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    Research progress of in vitro model of ulcerative colitis
    Jinxia BAI, Ting ZHANG, Meiqi LU, Zhen LU
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (8): 631-634. DOI:10.3969/j.issn.2097-0005.2022.08.016
    Abstract1869 HTML109 PDF(pc)(456KB)( 933 Save

    The incidence of ulcerative colitis (UC) is increasing year by year in the world and is listed as one of the refractory diseases by WHO. The cause of UC has not been thoroughly recognized. In addition to typical intestinal manifestations, such as abdominal pain, diarrhea, mucus pus and bloody stools, it can also be accompanied by multiple organ and multi-system parenteral manifestations, which seriously affects patients’ lives and work. In addition, patients with long-term UC have a higher risk of colon cancer, causing tremendous psychological stress on the patient and affecting physical and mental health. Therefore, the research on UC is getting deeper and deeper. Compared with clinical research and animal experiment research, the number of in vitro experiments of UC is small. By reviewing relevant literatures at home and abroad in recent years, the authors summarize the selection of UC model cell strains, inflammatory agents, and evaluation criteria for model establishment, aiming at a comprehensive understanding of UC in vitro experiments, and further development and innovation, thus providing a reference for the establishment and application of cell models in UC in vitro experiments.

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    The relationship of pyroptosis with autophagy and its role in pathogenesis and development of atherosclerosis
    Tianqi PAN, Hua TIAN, Shutong YAO
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (2): 156-160. DOI:10.3969/j.issn.2097-0005.2022.02.015
    Abstract427 HTML101 PDF(pc)(1019KB)( 613 Save

    Pyroptosis is different from other types of cell death in morphologically and mechanistically, and it is a type of cell death that relies on the inflammasome. Activated caspase-1 can induce pyroptosis, and cells secrete pro-inflammatory cytokines IL-1β and IL-18, which are widely involved in the progression of various chronic diseases, such as atherosclerosis and type 2 diabetes. Some studies have shown that defects in autophagy can stimulate pyroptosis and accelerate the process of atherosclerosis. This article summarizes the research progress of pyroptosis and its role in the development of atherosclerosis in recent years, and discusses whether the relationship between pyroptosis and autophagy can be used as a new target for the prevention and treatment of atherosclerosis.

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    Moderate intake of manganese benefits cardiovascular health: Based on NHANES 2011―2018
    Ruhui LIU, Kuan CHENG, Fangfang ZHENG, Zhaohui HU
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (4): 261-266. DOI:10.3969/j.issn.2097-0005.2022.04.004
    Abstract485 HTML11 PDF(pc)(851KB)( 522 Save
    Objective

    To explore the relationship between blood manganese concentration and the incidence of cardiovascular diseases (CVDs) as well as individual CVDs in adults.

    Methods

    We initially integrated the data in National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. 4 005 adults agd between 20 and 60 years old were recruited based on the inclusion and exclusion criteria. The relationship between manganese concentration and the prevalence of CVD was analyzed by constructing generalized linear models and restricted cubic spline curves.

    Results

    Compared with the lowest quartile, the modified odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the manganese quartiles were 1.066 (0.699,1.699), 1.105 (0.639,1.613), and 0.591 (0.376,0.930) respectively. In the full adjusted model, the incidence of total CVD decreased initially and increased when manganese concentration was over 9.59 μg/L. A restricted cubic spline curve was used to show a nonlinear “U” shape relationship between manganese concentration and CVD.

    Conclusion

    Based on adults, blood manganese concentration was associated with CVD prevalence. Maintaining manganese concentration at 9.59 μg/L can be beneficial for the heart.

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    Alleviation effects of drinking hydrogen-rich water on the oral mucosal ulcer induced by 5-fluorouracil in rats
    Danya Zhang, Junli Xue, Boyan Liu, Geru Tao, Yunzhi Shi, Shucun Qin
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2021, 42 (9): 662-666. DOI:10.3969/j.issn.2097-0005.2021.09.005
    Abstract582 HTML12797 PDF(pc)(3085KB)( 470 Save
    Objective

    To investigate the alleviation effects of drinking hydrogen-rich water on the oral mucosal ulcer induced by 5-fluorouracil (5-FU) and its possible biological mechanism.

    Methods

    Male SD rats were intraperitoneally injected with 5-FU (0.05 mg/g) for 2 consecutive days. On D3, rats were treated with NaOH particles or 20% acetic acid on buccal mucosa to establish oral ulcer model. From D5, the rats were given hydrogen-rich water, and the animals were sacrificed on the D10. The survival rates of rats in all experimental groups were counted, and the lesions of oral mucosa were measured by Image J software. The levels of TNF-α, IL-6 and IL-1β in serum were detected by ELISA, and the expressions of TNF-α, IL-6 and iNOS at buccal mucosa were detected by immunohistochemistry.

    Results

    Drinking hydrogen-rich water improved the survival rate of rats in the experimental groups. The damage area of ulcers produced by NaOH particles were larger than that caused by injection with 20% acetic acid (P< 0.05), but there was no significant difference in the damage area of ulcers with drinking hydrogen-rich water or not (P> 0.05). The serum levels of TNF-α, IL-6 and IL-1β of rats in model groups were significantly higher than those in the control group, while levels of the hydrogen-rich water group showed a downward trend compared with the model group. The expression of TNF-α and IL-6 at buccal mucosa were low in the healthy control and high in the model groups, while the expression in hydrogen-rich water groups showed a downward trend compared with the model group. The expression of iNOS at buccal mucosa was low in all groups.

    Conclusion

    Molecular hydrogen alleviates oral mucosal ulcers induced by 5-FU in rats possibly through inhibiting oxidative stress-related inflammation.

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    Joinpoint regression and age-period-cohort analysis of the incidence trends of depression in China from 1990 to 2019
    Haoyang GUO, Wei WANG, Xincan JI, Mengjun TAO, Hui YUAN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (6): 430-436. DOI:10.3969/j.issn.2097-0005.2023.06.006
    Abstract206 HTML3 PDF(pc)(2699KB)( 457 Save

    ObjectiveTo analyze the trends of depression in China from 1990 to 2019 and the impact resulting from age, period, and cohort effects.MethodsData on the incidence rate of depression among Chinese aged 10~94 years from 1990 to 2019 in the Global Burden of Disease (GBD) Study 2019 database were collated to analyze the time trend of depression standardized incidence rate using Joinpoint regression model; Age-period-cohort models were used to analyze the age, period, and cohort effects of depression.ResultsThe standardized incidence rate of depression among Chinese residents showed a decreasing trend from 1990 to 2019, and was higher in women than in men, with a gender difference. Joinpoint regression models showed that the standardized incidence rate of depression among women decreased by an average of 0.64% per year from 1990 to 2019 (AAPC = -0.64%,P< 0.001); the male depression standardized incidence rate decreased by an average of 0.26% per year from 1990 to 2019 (AAPC = -0.26%,P= 0.008). Age-period-cohort models showed that the overall risk of depression increased with age; The trend of change with the increase of period was not significant; there was an overall decreasing trend with the increase of birth cohort.ConclusionThe standardized incidence rate of depression among Chinese residents shows a decreasing trend from 1990 to 2019, and the focus should be on the elderly population and health policies should be developed to reduce the social burden and promote the mental health of the elderly population.

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    Construction of breast cancer protein risk prognosis model and identification of six key proteins
    Jian Li, Yuna Liang
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2021, 42 (10): 721-728. DOI:10.3969/j.issn.2097-0005.2021.10.001
    Abstract730 HTML2555 PDF(pc)(6457KB)( 398 Save
    Objective

    To optimize the prognosis assessment of breast cancer patients by developing proteomics signatures.

    Methods

    The protein expression profiles and clinical information of 879 breast cancer (BC) patient samples were downloaded from the TCPA and TCGA databases, respectively. We performed univariate Cox regression, lasso regression and multivariate Cox regression analysis to identify prognostic proteins and establish a prognostic model. Then, we further analyzed the differential expression and survival of the prognostic model protein, and analyzed the predictive performance of the model risk score. In addition, we analyzed all proteins related to prognostic model proteins.

    Results

    Based on the 224 proteins in the TCPA database, we constructed a prognostic model containing 6 proteins (CASPASE7CLIVEDD198, NFKBP65_pS536, PCADHERIN, P27, X4EBP1_pT70, EIF4G), and divided the patients into two groups according to the median of risk score. The overall survival rate was significantly different. Univariate and multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for patients (P< 0.001). In addition, the nomogram and ROC are used to demonstrate the predictive performance of the predictive model. The protein interaction relationship showed that the proteins CASPASE7CLEAVEDD198, PCADHERIN, X4EBP1_pT70 and EIF4G showed obvious correlation with other proteins (P< 0.001).

    Conclusion

    Studies have shown that six key proteins may be considered as new targets for BC treatment, and the protein risk model can be used to predict the overall survival of BC patients.

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    Mechanism ofLonicerae japonicaeflos in the treatment of diabetes based on netwwork pharmacology
    Mingli HAN, Dan TIAN, Xinyu CHE, Jinyi YU, Ang XIAO, Guojun PAN, Na XIAO
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (3): 172-177. DOI:10.3969/j.issn.2097-0005.2022.03.003
    Abstract515 HTML12 PDF(pc)(2750KB)( 386 Save
    Objective

    To elucidate the main active components and targets ofLonicerae japonicaeflos in the treatment of diabetes by network pharmacology, and to reveal the potential mechanism.

    Methods

    According to TCMSP, the active components and corresponding targets ofLonicerae japonicaeflos were analysis under the conditions of pharmacokinetic parameters [oral bioavailability (OB) ≥ 30%, drug-likeness (DL) ≥ 0.18]. The diabetic targets of active components ofLonicerae japonicaeflos were screened by Gene cards and OMIM database. The “component-target-disease” network was constructed by Cytoscape 3.8.2, and the protein-protein interaction (PPI) network was established by String database. Then, the potential diabetic targets ofLonicerae japonicaeflos analysis of gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed by R 4.0.4 language and Bioconductor. RCSB PDB and TMSCP database, Pymol and AutoDockTools-1.5.6 software were used for molecular docking ofLonicerae japonicaeflos core compounds and targets.

    Results

    A total of 16 main active components were screened fromLonicerae japonicaeflos, and 120 targets were predicted for the treatment of diabetes. Go function analysis and KEGG pathway enrichment analysis showed that the mechanism ofLonicerae japonicaeflos in the treatment of diabetes mainly involves the biological processes such as DNA binding transcription factor binding, RNA polymerase Ⅱ specific DNA binding transcription factor binding, and it plays a role through multiple pathways such as lipid and arteriosclerosis, PI3K-Akt and TNF signaling pathway signaling pathway. Molecular docking results showed that luteolin, quercetin and kaempferol in the core compounds ofLonicerae japonicaeflos had high affinity for AKT1.

    Conclusion

    The anti-diabetes mechanism by Lonicerae japonicae flos is the result of multi-component, multi-target and multi-channel, which provides a theoretical basis for the further study ofLonicerae japonicaeflos in the treatment of diabetes.

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    New advances in the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death from 2022 ESC guidelines
    Yujiao ZHANG, Zhan LI, Yinglong HOU
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (12): 886-890. DOI:10.3969/j.issn.2097-0005.2022.12.002
    Abstract230 HTML11 PDF(pc)(495KB)( 373 Save

    This paper presents an update of the 2015 European Society of Cardiology (ESC) Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death, which was issued by ESC in August, 2022, with many new contents and updated recommendations. The guidelines have added recommendations for public basic life support, genetic testing, risk assessment, and changed recommendations for the treatment of ventricular arrhythmias, to preferably guide clinical practice.

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    The research progress of HMGCS2 in diseases
    Wei CHU, Bing ZHANG, Hong JI
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (7): 546-551. DOI:10.3969/j.issn.2097-0005.2023.07.014
    Abstract185 HTML8 PDF(pc)(585KB)( 350 Save

    Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the first rate-limiting enzyme in the ketogenic pathway, plays an important role in pathophysiological processes. In recent years, the role of HMGCS2 in diseases has become the focus of researchers. Although it has been found that HMGCS2 has different roles in different stages of different diseases, the pathogenesis of HMGCS2 and its prognostic significance still need to be further explored. In this study, we summarize the effect and regulatory factors of HMGCS2 in diseases, and explore the mechanism of HMGCS2 in different diseases by reviewing domestic and foreign literatures.

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    Study advances in intestinal flora and intestinal mucosal immune tolerance
    Yifan JIANG, Yang SUN, Yan ZHANG, Jing LI
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (9): 711-715. DOI:10.3969/j.issn.2097-0005.2022.09.010
    Abstract929 HTML34 PDF(pc)(439KB)( 297 Save

    Intestinal flora forms a large symbiotic ecosystem with the host and regulates the immune status of the host by influencing the functions of various cells in the intestinal canal. The interaction between intestinal epithelial cells, immune cells and intestinal flora can induce specific immune response against harmful substances. Recent studies suggest that maintaining the balance between effector immunity and immune tolerance has become an important target for clinical treatment of immune diseases. Intestinal mucosal immune system forms immune tolerance by recognizing symbiotic bacteria in the intestinal tract, recognizes invading pathogens and activates effector immunity, so as to establish innate and adaptive immune systems in the intestinal tract. This review briefly summarizes the establishment mechanism of intestinal mucosal immune tolerance, the role and possible mechanism of intestinal microbiota in inducing intestinal mucosal immune tolerance, and the role of intestinal microbiota in inflammatory bowel disease, which can provide reference for the application prospect of symbiotic bacteria in the treatment of inflammatory bowel disease.

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    Changes of related biological factors before and after neoadjuvant chemotherapy for breast cancer and analysis of related predictors of MP grading
    Binbin Li, Xintong Wang, Xinli Wang
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2021, 42 (12): 899-902. DOI:10.3969/j.issn.2097-0005.2021.12.005
    Abstract449 HTML114 PDF(pc)(405KB)( 291 Save
    Objective

    To study whether the expression of biological factors is related to breast cancer changes during neoadjuvant chemotherapy, and to explore the clinical significance of such changes. To analyze whether the Miller-Payne grading of breast cancer after neoadjuvant chemotherapy is related to the expression of biological factors, so as to provide ideas for predicting the effects of neoadjuvant chemotherapy in different patients.

    Methods

    All 68 cases who accepted the preoperative neoadjuvant chemotherapy of breast cancer in our hospital from January 2019 to May 2021 were collected in this analysis. Significant changes of the expression of the endoplasmic reticulum ER, PR, Her-2, Ki-67 before and after the neoadjuvant chemotherapy were analyzed by the immunohistochemistry. Pathological Miller-Payne grading system evaluation was performed after chemotherapy, and the relationship between Miller-Payne grading system and the expression of biological factors ER, PR, Her-2 and Ki-67 in breast cancer before chemotherapy was analyzed.

    Results

    The positive rate of Ki-67 in 68 patients decreased to 34.1% after neoadjuvant chemotherapy compared with the prior 65.9%, which is statistically significant (P< 0.05). 15 (22.1%) patients had a grade 5 (G5) response after the neoadjuvant chemotherapy. There was a statistical difference in the expression of Her-2 between the G5 and G1 ~ 4 groups (P< 0.05). The results of the logistic regression analysis showed that the positive expression of Her-2 was a predictor for G5 in breast cancer treated with neoadjuvant chemotherapy [P< 0.05,OR= 0.214, 95%CI(0.056 ~ 0.816)].

    Conclusion

    The expression of Ki-67dose is significantly lowered in breast cancer patients after neoadjuvant chemotherapy, which can be used as a sensitive index for clinical chemotherapy evaluation. The positive expression of Her-2 can be used as a predictor of Miller-Payne grading (G5) in breast cancer patients treated with neoadjuvant chemotherapy.

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    Efficient construction and application of psiCHECK dual-luciferase reporter gene based on Golden Gate
    Yating DU, Wenjun YU, Yan LI, Yuanlei FU, Kaoxiang SUN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (3): 180-185. DOI:10.3969/j.issn.2097-0005.2023.03.004
    Abstract219 HTML6 PDF(pc)(1534KB)( 290 Save

    ObjectiveTo construct a dual-luciferase reporting system psiCHECK-CcdB for RNAinterference (RNAi) drug screeningbased on Golden Gate cloning (seamless cloning) technology, ed.MethodsThe BsmBI digestion sites needed for assembly of Golden Gate, the CcdB lethal gene and chloramphenicol gene was amplified by PCR and cloned into psiCHECK-2 vector to construct vector psiCHECK-CcdB. The lethal efficiency of the vector was detected by two kinds of E. coli DB3.1 and DH5α. The exogenous fragment of 1387 bp was cloned into psiCHECK-CcdB vector to detect its ligation efficiency, and investigated whether the psiCHECK-CcdB recombinant vector could be used as a dual-luciferase reporter system to monitor changes in target gene expression.ResultsThe recombinant plasmid psiCHECK-CcdB was successfully constructed by colony PCR and sequencing. The plasmid had significant lethal effect on E. coli DH5α strain which was not tolerant to CcdB toxic protein, and could grow normally in DB3.1 strain. Exogenous fragment could be easily and quickly cloned into the psiCHECK CcdB vector using the Golden Gate method with high ligation efficiency and low background cloning. By measuring the intensity of dual-luciferase expression, it was confirmed that the small interfering RNA(siRNA) sequence binded specifically to the target gene significantly reduced the expression of luciferase and successfully exerted the function of the dual-luciferase reporter gene.ConclusionThe recombinant double luciferase reporter vector psiCHECK-CcdB is successfully constructed. The application of Golden Gate assembly technology simplifies experimental operations, reduces experimental costs, has high positive clone rates and the potential to assemble multiple fragments at once, making it a promising candidate in the field of RNAi drug screening.

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    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2021, 42 (12): 881-882. DOI:10.3969/j.issn.2097-0005.2021.12.001
    Abstract270 HTML432 PDF(pc)(5310KB)( 283 Save
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    Ferroptosis suppressor protein 1: potential therapeutic targets for myocardial reperfusion injury
    Shujun WANG, Xiuqing TIAN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (2): 138-141. DOI:10.3969/j.issn.2097-0005.2022.02.012
    Abstract393 HTML206 PDF(pc)(441KB)( 252 Save

    Ferroptosis suppressor protein 1 (FSP1), a flavoprotein with an NADH/NAD oxidoreductase domain, which is involved in regulation of reactive oxygen species (ROS) and promotes mitochondrial electron transport, was recently confirmed to be a ferroptosis-resistant factor. Many studies have found that FSP1 plays a key role in many human diseases, such as breast cancer, rheumatoid arthritis, severe acute pancreatitis and Parkinson's syndrome. Based on the biological characteristics of FSP1, we speculate that FSP1 is a potential therapeutic target for myocardial reperfusion injury in the future. The relationship between FSP1 and myocardial reperfusion injury has been briefly described in this review, which provides a new target molecules for the treatment in the future.

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    Pericoronary adipose tissue and coronary atherosclerosis
    Qian ZHOU, Yibing SHAO, Zhaozhuo NIU, Xiaolei BI
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (4): 304-312. DOI:10.3969/j.issn.2097-0005.2023.04.014
    Abstract145 HTML8 PDF(pc)(540KB)( 250 Save

    Pericoronary adipose tissue (PCAT) is a part of epicardial adipose tissue (EAT) that directly neighbors coronary arteries. PCAT is not separated from the myocardium and vessels by fascia, which means that they share the same microcirculation. Therefore, PCAT has been reported to play an essential role in physiological and pathophysiological processes of coronary arteries according to its special location. It has been suggested that signaling between PCAT and coronary arteries is bidirectional. PCAT releases a panel of adipokines and cytokines that maintain vascular homeostasis, otherwise abnormal secretion of them may be primed to promote inflammation and angiogenesis. Therefore, PCAT has the ability of intervention in progression of the coronary atherosclerosis. This review will highlight the role of PCAT in regulating the progression of the coronary atherosclerosis and related research results.

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    Association between psychological stress response and IgG N-glycan among the students of a university in Shandong Province during COVID-19 epidemic
    Meng WANG, Peirui LI, Xinxia LU, Yingjie WANG, Long JI, Xiaomei LI, Guoyong DING, Yanbo QI, Weijia XING, Haifeng HOU, Fang WANG, Yang DENG, Dong LI
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (12): 911-917. DOI:10.3969/j.issn.2097-0005.2022.12.006
    Abstract240 HTML5 PDF(pc)(895KB)( 248 Save

    ObjectiveTo explore the correlation between psychological stress response and immunoglobulin G (IgG) N-glycan among the students of a university in Shandong Province during the epidemic.MethodsAccording to the inclusion and exclusion criteria, 150 students from Shandong First Medical University during the epidemic were selected as the research objects. SRQ questionnaire was used to investigate the psychological stress level of the college students, and ultra-high liquid chromatography was used to detect and analyze plasma IgG N-glycans. The Mann-WhitneyUrank-sum test was used for comparison of IgG N-glycans between groups; multivariate Logistic regression analysis was used to explore the association between psychological stress and IgG N-glycans after adjusting for confounding factors; Spearman rank correlation correlation was used to analyze the correlation between IgG N-glycan level and psychological stress level.ResultsCompared with the normal group, the levels of GP4 and GP8 in the high psychological stress group were higher, and the level of G2 was lower (P< 0.05). The degree of psychological stress was positively correlated with GP3, GP4, GP8 and G0, and negatively correlated with GP12, GP14, GP17, GP18, G2, Stotal and S1 (P< 0.05). On the whole, IgG galactosylation and salivary level of acidification modification were negatively correlated with the degree of psychological stress.ConclusionThere is a correlation between psychological stress response and IgG N-glycan among the students in a Shandong university during the epidemic. The level of galactosylation and sialylation reflected by IgG N-glycans may affect the degree of psychological stress response by altering the inflammatory potency of IgG.

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    Effects of dexmedetomidine for paravertebral nerve block on stress during thoracoscopic surgery
    Pengpeng YANG, Hua YAN, Maoliang TIAN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (10): 753-759. DOI:10.3969/j.issn.2097-0005.2022.10.006
    Abstract310 HTML3 PDF(pc)(539KB)( 242 Save

    ObjectiveTo investigate the effect of dexmedetomidine combined with ropivacaine hydrochloride on stress response in patients undergoing thoracoscopic surgery for paravertebral nerve block (TPVB).MethodsNinety patients undergoing thoracoscopic surgery were randomly divided into simple general anesthesia group (group C), ropivacaine group (group R), dexmedetomidine + ropivacaine group (group DR), with 30 cases in each group. TPVB (T4-8) was guided by ultrasound before general anesthesia induction in the group R and group DR. In group R, 0.5% ropivacaine 20 ml was injected into the paravertebral space. In the group DR, 0.5% ropivacaine + 1 μg/kg dexmedetomidine mixture was injected into the paravertebral space for 20 ml. Patients in the three groups were routinely connected with intravenous analgesia pump after operation. HR and mean blood pressure (MAP) were recorded in three groups immediately after tracheal intubation (t0), 2 hours after operation (t1), at the end of operation (t2) and 24 hours after operation (t3). The operation time, intraoperative dosage of propofol and remifentanil and the number of PCA self-controlled administration within 48 hours after operation were recorded. Cortisol (COR), epinephrine (E) and norepinephrine (NE) were measured at different time points in the three groups. Adrenaline (NE) and blood glucose levels were measured at 1 and 7 days after operation to observe the occurrence of pulmonary complications.ResultThe dosage of propofol and remifentanil during operation and the number of PCA self-controlled administration within 48 hours after operation in the group R and DR group were less than those in group C, while the dosage of propofol and remifentanil during operation and the number of PCA self-controlled administration within 48 hours after operation in group DR were less than those in group R (allP< 0.05); compared with t0, cortisol (COR), epinephrine (E) and norepinephrine (NE) in group 3 at t1-t3were lower than those in group R (allP< 0.05). The concentration of cortisol (COR), epinephrine (E), norepinephrine (NE) and blood sugar at t2and t3in DR group were significantly lower than those in the C group and R group (P< 0.05), and the incidence of hypoxemia, pulmonary infection and atelectasis in DR group were significantly lower than those in the C group and R group (P< 0.05).ConclusionDexmedetomidine for ultrasound-guided thoracic paravertebral nerve block can enhance the blocking effect of ropivacaine, prolong the blocking time, alleviate the stress reaction of patients undergoing thoracoscopic surgery, reduce postoperative complications, and improve the prognosis of patients, rapid recovery.

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    Expression and bioinformatics analysis of SOCS gene family in hepatocellular carcinoma
    Wenchao BU, Xianzhi ZENG, Yunqian GUAN, Siyuan XIE, Shixin CHEN, Tingbing TANG, Mingguo CAO
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (10): 740-747. DOI:10.3969/j.issn.2097-0005.2022.10.004
    Abstract266 HTML6 PDF(pc)(5333KB)( 240 Save

    ObjectiveTo systematically analyze the mechanism of suppressor of cytokine signaling (SOCS) gene family in hepatocellular carcinoma (HCC) based on high-throughput bioinformatics method.MethodsMultiple online databases, such as Oncomine, UNLCAN, cBioPortal, Kaplan-Meier plotter, David, etc. were used to comprehensively analyze the expression differences, clinicopathological characteristics, survival analysis, gene mutations, and biological functions of SOCS family molecules in hepatocellular carcinoma. The String online database was used to construct the protein-protein interaction network of SOCS family genes.ResultsMost SOCS family genes were differentially expressed in HCC. The expressions of SOCS5 and SOCS7 were significantly up-regulated (P< 0.05), while the expressions of SOCS2, SOCS3, SOCS6 and CISH were down-regulated (P< 0.05). The family gene prognosis analysis SOCS1, SOCS2, SOCS4, SOCS5, SOCS7, SOCS8 were associated with prognosis (P< 0.05). The gene alteration forms of SOCS family members in HCC patients mainly include amplification, mutation and multiple gene types. The biological processes related to the SOCS family in HCC are mainly enriched in Jak-STAT, inflammatory response and other aspects.ConclusionMost members of the SOCS gene family are differentially expressed in HCC, and may be potential new targets and prognosis-related genes for the treatment of hepatocellular carcinoma in the future.

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    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (12): 881-885. DOI:10.3969/j.issn.2097-0005.2022.12.001
    Abstract402 HTML1003 PDF(pc)(562KB)( 238 Save
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    Research progress of type Ⅱ innate lymphocytes
    Xinyue XU, Xiuli JING, Hua TANG
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (9): 666-673. DOI:10.3969/j.issn.2097-0005.2022.09.002
    Abstract1044 HTML37 PDF(pc)(894KB)( 232 Save

    Type Ⅱ innate lymphoid cells (ILC2s) are a group of innate immune cells that have similar functions to type Ⅱ helper T cells (Th2) and can rapidly secrete Th2 cytokines. They play an important role in type 2 immunity. ILC2s can receive signals from epithelial cells, stromal cells, nerve cells and other immune cells, and then regulate the function of downstream effector cells, thus exerting important effector functions in barrier tissues, such as lung and skin. In this paper, the classification, development and main functions of ILC2s will be summarized, and the main research progress of ILC2s in recent years will be reviewed.

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    Phenome-centered multiomics study in pituitary tumors
    Peixian ZHENG, Na LI, Xianquan ZHAN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (9): 641-665. DOI:10.3969/j.issn.2097-0005.2022.09.001
    Abstract268 PDF(pc)(1306KB)( 227 Save

    Pituitary tumor is a common, chronic, complex intracranial tumor, which in fact is a whole-body disease with multi-causing factors, multi-processes, multi-consequences, and highly heterogeneous characteristics. It is involved in a series of changes in molecules at the different levels of genome, transcriptome, proteome, peptidome, metabolome, and radiome in pituitary tumorigenesis, and these molecules are mutually associated in a molecular-network system. It is necessary to use muti-parameter systematic strategy but not the traditional single-factor strategy to elucidate the molecular mechanisms and manage pituitary tumors. Multiomics and systems biology is promoting this paradigm shift. However, the center of multiomics is moving from structural genomics to phenomics (proteomics and metabolomics). Of them, mass spectrometry-based proteomics and proteoformics studies take crucial part in the multiomics strategy of pituitary tumors. This review paper summarizes the current status of multiomics, multiomics-based molecular pathway networks, pattern biomarkers, and therapeutic targets/drugs, and future perspectives for predictive, preventive and personalized medicine (PPPM; 3PM) in pituitary tumors.

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    Advances in the pathogenesis of renal anemia
    Xia WANG, Lingyu XUE
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (2): 142-147. DOI:10.3969/j.issn.2097-0005.2022.02.013
    Abstract294 HTML305 PDF(pc)(465KB)( 223 Save

    Renal anemia (RA) is a common complication in patients with chronic kidney disease (CKD), which can accelerate disease progression, increase the risk of end-stage renal disease (ESRD) and improve patient mortality. It is generally believed that the occurrence of renal anemia is mainly related to the deficiency of erythropoietin (EPO), iron deficiency and metabolic disorder. This article reviews the latest progress in the pathogenesis of renal anemia by studying how hypoxia inducible factor (HIF) pathway, hepcidin ferroportin axis, inflammation, parathyroid hormone (PTH), fibroblast growth factor 23(FGF-23), B-type natriuretic peptides (BNP) and other factors play a role in the formation of EPO and the maintenance of iron homeostasis.

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    Preparation technology of plasmid DNA in laboratory scale
    Peiling BEN, Rongqian CHEN, Miao SUN, Xiangyang SHI
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (3): 202-208. DOI:10.3969/j.issn.2097-0005.2023.03.008
    Abstract174 HTML2 PDF(pc)(2471KB)( 215 Save

    ObjectiveTo explore the preparation technology of plasmid DNA (pDNA) in laboratory scale production.MethodsPlasmid pEGFP-N1E.coliStbl3 strain was selected, and the most significant factors affecting plasmid yield were screened by plackett-burman test, and the high yield fermentation conditions of recombinant bacteria were optimized by response surface method. The plasmid DNA was isolated and purified by alkaline lysis, concentration of plasmid, gel, affinity and ion chromatography, and the quality of purified pDNA was evaluated.ResultsThe key factors selected by steepest climbing test and response surface test design were yeast extract 20 g/L, glycerol 6 g/L and inoculum concentration OD = 0.014. Under the optimum conditions, the biomass OD 600 and plasmid yield were (28.07 ± 2.01) and (21.34 ± 1.31) mg/L respectively. The purity of plasmid DNA (A260 nm/A280 nm) was (1.91 ± 0.02). When the content of endotoxin was less than that of 0.005 EU/g DNA; there was almost no protein or bacterial genomic DNA residue. All the indicators met the relevant quality standards.ConclusionThe high quality pDNA can be produced by the preparation process.

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    Research progress of BIM deletion polymorphism and anti-tumor therapy in NSCLC patients
    Dai ZHANG, Xuanzong LI, Caimei HUANG, Linlin WANG
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (10): 788-791. DOI:10.3969/j.issn.2097-0005.2022.10.013
    Abstract219 HTML5 PDF(pc)(389KB)( 212 Save

    BIM belongs to bcl-2 family and is a key factor promoting apoptosis. Loss of BIM can lead to loss of the pro-apoptotic domain BH3, thus inhibiting apoptosis. It has been reported that the loss and decreased expression of BIM may lead to the resistance of patients to tumor therapy. This article aims to review the relationship between BIM deletion polymorphism and therapeutic efficacy of non-small cell lung cancer (NSCLC).

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    Niacin inpromoting small intestinal RORγt+Tregs homeostasis
    Yuxin GENG, Zhengtao CHEN, Zhongyun ZHANG, Bo DONG, Huiwen GU, Xinyu LI, Lingyun JIA, Xin WANG, Fangyuan SUN, Hua TANG
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (10): 728-733. DOI:10.3969/j.issn.2097-0005.2022.10.002
    Abstract254 HTML8 PDF(pc)(2538KB)( 197 Save

    ObjectiveTo explore the role of niacin in regulating the homeostasis of RORγt+Tregs in small intestine.MethodsThe mice model of antibiotic-induced microbiota imbalance was established, and the proportion of RORγt+Tregs in small intestinal lamina propria (SILP) was tested by flow cytometry. Niacin was added into drinking water containing antibiotics to detect the proportion of RORγt+Tregs and TH17 cells using flow cytometry.The expression of Ki67 in RORγt+Tregs and TH17 cells was also tested.ResultsAntibiotics treatment reduces RORγt+Tregs proportion in SILP. Niacin administration restores the proportion and proliferation of RORγt+Treg,but does not affect TH17 in SILP of antibiotic-treated mice.ConclusionThe microbiota modulates the homeostasis of RORγt+Tregs in SILP by promoting the proliferation of RORγt+Treg via niacin.

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    Application value of MRI in early screening of prostate cancer
    Yafei ZHANG, Ranran HUANG, Guowei ZHANG
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (12): 963-971. DOI:10.3969/j.issn.2097-0005.2022.12.016
    Abstract138 HTML4 PDF(pc)(764KB)( 194 Save

    Prostate cancer (PCa) is a common malignant tumor in men, with an increasing incidence rate and poor prognosis. Early screening can lead to early diagnosis and treatment, and significantly improve the quality of life and survival rate; MRI has proved to play an important role in PCa screening and active monitoring. However, multi parameter prostate MRI has many sequences, long examination time and high cost, which limits the popularity of prostate MRI screening. Therefore, it has become the focus of clinical attention to optimize the scanning sequence of MRI, shorten the examination time and improve the diagnostic coincidence rate. This article reviews the application progress of MRI in early screening of prostate cancer.

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    Distribution of PDE4 in the brain and its role in neurodegenerative diseases
    Hanbing YANG, Jiawei SHI, Yue HOU, Qiwei ZHANG, Haiyang YU, Yanmeng ZHOU
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (3): 186-190. DOI:10.3969/j.issn.2097-0005.2023.03.005
    Abstract193 HTML2 PDF(pc)(438KB)( 189 Save

    Aberrant changes in the second messenger cyclic adenosine monophosphate (cAMP) are involved in the development of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease. However, it is difficult to directly regulate cAMP signal. Therefore, targeted regulation of cAMP hydrolase is expected to be a new strategy to improve neurodegenerative diseases. Phosphodiesterase 4(PDE4), an enzyme that specifically catalyzes cAMP, has been shown to have an important role in the development of a variety of neurodegenerative diseases. Research into drugs targeting PDE4 will help in the treatment of neurodegenerative diseases. In this paper, we will describe the characteristics and function of PDE4, review its role and research into progress in neurodegenerative diseases and future development trend of its potential therapeutic effect in neurodegenerative diseases.

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    Psychological status and influencing factors of children with systemic lupus rythematosus
    Jinjiao Li, Yanjun Shi, Wei Zhou
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2021, 42 (10): 797-800. DOI:10.3969/j.issn.2097-0005.2021.10.016
    Abstract288 HTML33 PDF(pc)(431KB)( 188 Save

    Systemic lupus erythematosus (SLE) is a chronic multisystem diseases with rapid development and poor prognosis. Children have a more serious condition than adults and they also have serious psychological disorders. Some achievements have been made in the research and intervention of mental state of adult SLE patients at home and abroad, but the related research on children patients has not been carried out. This paper reviews the relevant literature at home and abroad to sort out the psychological status and influencing factors of children with systemic lupus erythematosus (cSLE) in order to explore the necessity of psychological intervention for cSLE patients.

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    Progress in clinical research on the use of hydrogen molecules in the treatment of diseases
    Xue JIANG, Boyan LIU, Fenglin WU, Yazhuo XUE, Shucun QIN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (7): 552-560. DOI:10.3969/j.issn.2097-0005.2023.07.015
    Abstract117 HTML3 PDF(pc)(945KB)( 174 Save

    Hydrogen molecules, as a physiological regulatory factor, have significant anti-inflammatory and antioxidant effects. In recent years, clinical trials of hydrogen molecule biomedicine have gradually increased, providing new avenues for the treatment of numerous diseases. This article provides a literature review on the clinical applications of hydrogen in the central nervous system, endocrine system and inflammation. It is found that hydrogen medicine has made rapid progress in human trials and clinical transformation in recent years, and it has preliminarily demonstrated the effectiveness and safety of hydrogen molecules in disease treatment, laying a preliminary foundation for the expansion of clinical indications.

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    Association between Fib and GP Ⅱb/Ⅲa gene polymorphisms and familial aggregation LAA cerebral infarction
    Hui KANG, Yanhua WANG, Min GAO, Jingjun ZHANG
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (7): 507-512. DOI:10.3969/j.issn.2097-0005.2022.07.006
    Abstract209 HTML3 PDF(pc)(1479KB)( 173 Save
    Objective

    To investigate the relationship between fibrinogen (Fib) and glycoprotein(GP) Ⅱb/Ⅲa gene polymorphisms and familial aggregation large?artery atherosclerosis (LAA) cerebral infarction.

    Methods

    Twenty-five patients with familial aggregation LAA cerebral infarction and 25 patients with sporadic LAA cerebral infarction were collected as family group and sporadic group respectively. Twenty-five healthy people were selected as the control group. Genomic DNA (gDNA) was extracted from the 75 cases, and the sequence to be tested was subjected to PCR reaction with gDNA as template. The PCR products were purified and sequenced directly to determine whether there were fibrinogen and platelet membrane glycoprotein IIb IIIa gene polymorphisms.

    Results

    There was no significant difference in Fib gene polymorphism among the three groups (P> 0.05), there was significant difference in GP IIb locus among the three groups (P< 0.05), and there was no significant difference in Gp IIIa locus among family group, sporadic group and control group.

    Conclusion

    GP IIb gene polymorphism is abnormal in familial aggregation LAA cerebral infarction, but Fib and Gp IIIa genotypes are not abnormal.

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    Preparation and in vitro and in vivo evaluation of linagliptin/metformin sustained-release tablets
    Huiya GAO, Shumeng KONG, Shuai SUN, Jin CHEN, Mengjun WANG, Kaoxiang SUN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (3): 166-171. DOI:10.3969/j.issn.2097-0005.2023.03.002
    Abstract265 HTML2 PDF(pc)(1669KB)( 172 Save

    ObjectiveTo prepare the sustained-release tablets of linagliptin and metformin with the same dissolution behavior as the reference preparation in vitro by screening the formulation and process, and to carry out the pharmacokinetics study of the two preparations in beagle dogs.MethodsWith dissolution, tablet hardness and tablet weight difference as factors of investigation, the dosage and preparation process of sustained-release matrix materials, adhesives, plasticizers in the formulation were investigated through single factor experiment, and the optimal formulation was selected. The dissolution curves of self-made preparation and reference preparation in four media and the pharmacokinetics in beagle dogs were compared.ResultsMetformin hydrochloride was used as the main drug, polyoxyethylene as the sustained-release skeleton material, hydroxypropyl methylcellulose as the adhesive, and magnesium stearate as the lubricant to prepare the sustained-release core. The sustained-release tablets of linagliptin and metformin were prepared by using linagliptin as the main drug, polyethylene glycol as the plasticizer, hydroxypropyl methylcellulose as the coating material. By comparing the dissolution curves of self-made preparation and reference preparation in four dissolution media, it was seen that their dissolution curve similarity factorf2was greater than 50. The pharmacokinetic experimental data in dogs were analyzed. The Cmaxof the two main drugs in the reference preparation and the self-made preparation in dogs was equivalent, indicating that they could reach the same effective concentration in the same time.ConclusionThe dissolution behavior of linagliptin metformin sustained-release tablets prepared by ourselves is consistent with that of reference tablets in vitro and in vivo, and the preparation method is simple and feasible, which can meet the needs of large-scale production.

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    Pathomechanism research of osteoporosis vertebral compression fractures after percutaneous kyphoplasty
    Qingfu Zhang, Jingguo Wu, Min Zhang, Xishan Zhang
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2021, 42 (11): 811-815. DOI:10.3969/j.issn.2097-0005.2021.11.003
    Abstract285 HTML170 PDF(pc)(1056KB)( 163 Save
    Objective

    To study the pathomechanism of osteoporosis vertebral compression fractures after percutaneous kyphoplasty.

    Methods

    Living adult sheep were purchased (4 male and female in each,40~50 kg in weight, all sacrificed on the same day), an anterioposterior and lateral X-ray was taken to rule out congenital malformation, tumor/fracture, etc., and dual-energy X-ray absorptiometry (dexa) was used to determine the bone density of each specimen. Ethylenediamine tetraacetic acid disodium salt decalcified in vitro was used to simulate vertebral osteoporosis, short-term manufacturing model of osteoporotic vertebral compression fractures, and the muscle and soft tissue on both sides of the vertebrae specimen connected to the thoracic spine specimen were removed and ribs. T3~T9, and T10~L4were the two groups, and preparation of 16 specimens of the experiments was made. In each group of a vertebral compression fractures (T6or L1), line PKP was used to restore the height of vertebral compression fractures. The artificial spinal vertebrae of the specimen were fixed at both ends. The test system (Mini Bionix) and spinal multi-channel test system were used for flexion/extension, axial load, rotation movement, as well as fatigue test of the specimens to obtain static and dynamic test data for statistical analysis. The recurrence of vertebral fractures and the relationship with strengthened vertebrae were observed.

    Results

    The vertebrae fracture incidence, cancellous bone maximum von Mises stress and the maximum von Mises stress of cortical bone vertebrae of T10~L4group were higher significantly than those in T3~T9groups, which were statistically significant (P< 0.05); In order to remain upright, vertical ridge strength of T10~L4group was obviously higher than that of T3~T9group, which was statistically significant (P< 0.05); The difference in intervertebral disc pressure, the maximum von Mises stress and endplate between T10~L4group and T3~T9groups was significant (P< 0.05).

    Conclusion

    The thoracolumbar osteoporotic vertebral compression fracture is more likely in T10~L4than that in T3~T9, and the recurrence of vertebral fracture is associated with the ability to withstand stress, which can guide the clinical prevention and treatment.

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    LAT1 expression and micro-PET tracing in breast cancer
    Xinliu SUN
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (1): 20-23. DOI:10.3969/j.issn.2097-0005.2022.01.006
    Abstract383 HTML588 PDF(pc)(1068KB)( 159 Save
    Objective

    To investigate the expression of LAT1 gene in breast cancer and the value of micro-PTE tracing in detection of breast cancer.

    Methods

    The expressions of LAT1 mRNA and protein in breast cancer cells were analyzed.18F-FACBC was used as the imaging agent of micro-PET to detect breast cancer in nude mice.

    Results

    MCF-10A, a non-tumorigenic breast cell line, expressed low level of LAT1 mRNA and protein, while MCF-7, a malignant breast cell line, expressed high level of LAT1 mRNA and protein; The inhibiting of LAT1 inhibited the proliferation of breast cancer cells, and micro-PET with18F-FACBC imaging agent could effectively detected the breast cancer in nude mice.

    Conclusion

    LAT1 is highly expressed in breast cancer and can be used as a biomarker for the diagnosis of breast cancer, and18F-FACBC and LAT1 can be used to trace breast cancer with micro-PET.

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    Advances in the study of intestinal flora in relation to obesity in adolescents
    Yuanqing DUAN, Hui NIU, Xinhuan ZHANG, Yan FU
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (12): 958-962. DOI:10.3969/j.issn.2097-0005.2022.12.015
    Abstract183 HTML10 PDF(pc)(443KB)( 158 Save

    With the development of economy and the changes of people's lifestyle, obesity in adolescents has become a global public health problem. Recently, it has been found that intestinal flora is widely involved in the fat metabolism of the host and plays an important role in the development of obesity in adolescents. This discovery provides a new possible way for the treatment of adolescent obesity, and makes it possible to treat adolescent obesity by intervening in the intestinal flora. This review aims to summarize the progress of research on adolescent obesity, intestinal flora, as well as its relevance and the feasibility of treatment, and to provide a theoretical support for the treatment of adolescent obesity through intervention of intestinal flora.

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    Research progress of tocilizumab in the treatment of refractory autoimmune encephalitis
    Fangyuan ZHANG, Shougang GUO
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (5): 396-400. DOI:10.3969/j.issn.2097-0005.2023.05.015
    Abstract171 PDF(pc)(430KB)( 158 Save

    Autoimmune encephalitis (AE) is associated with immune-mediated antigen-antibody reactions involving the central nervous system. With the advent of autoantibody-associated diseases, the therapy of AE has become a hot research frontier in neuroimmunology. The conventional treatments of AE include first-line therapy and second-line therapy. The first-line treatments of AE include steroids, intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and second-line therapy includes rituximab. However, current conventional therapy is ineffective for a considerable number of patients with AE. According to the current clinical trial evidence and single reports, tocilizumab is effective for refractory AE patients. With the current rapid research progress, a breakthrough in the treatment of AE is critical. This article aims to review tocilizumab in the treatment of refractory AE.

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    Technical difficulties of the CRISPR/Cas9 System: off-target effects and its optimization methods
    Zong-fei YU, Li-han WENG, Cheng-cheng SUN, Xiao-yu CAO, Zhen YE
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (1): 74-80. DOI:10.3969/j.issn.2097-0005.2023.01.014
    Abstract369 HTML12 PDF(pc)(1183KB)( 156 Save

    In recent years, CRISPR/cas9 (clustered regularly interspaced short palindromic repeats/associated nuclease 9), a novel gene editing technology, has gained considerable attention and can be utilized to edit single or multiple genes in a variety of cells in vivo or in vitro, which provides a new way for the study of gene function. Currently, CRISPR/Cas9-based gene editing technology is widely used in frontier medical fields such as tumour therapy, providing new and specific treatments for patients who are intolerant to radiotherapy and chemotherapy or are already in advanced stages of malignancy. The Cas9 nuclease can be targeted by altering its single-guide RNA (sgRNA) sequence to bind to a specific new gene sequence. It has been found that the CRISPR/Cas9 system is at risk of off-targeting, that is, the specific sgRNAs can form mismatches with non-target DNA sequences, resulting in unintended mutations at the gene locus, which has become a challenge in the practical application of this technology. This review gives an overview of the mechanism of CRISPR/Cas9 system and the clinical application in tumor treatment with a focus on the off-target effects, and summarizes the ways to reduce or avoid off-target effects, in order to provide reference for researchers in related fields.

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    Research progress of sepsis associated encephalopathy
    Wenyu LI, Hongna YANG, Wei FANG, Xuan SONG, Chunting WANG
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (9): 707-711. DOI:10.3969/j.issn.2097-0005.2023.09.014
    Abstract250 PDF(pc)(464KB)( 155 Save

    Sepsis associated encephalopathy (SAE) is a nervous system complication caused by systemic inflammatory reaction of sepsis, which is an important reason for the high mortality and poor long-term recovery of patients with sepsis. Clinically, it is divided into acute phase and chronic phase. The main clinical manifestations in the acute phase are changes in the level of consciousness, including attention deficit, delirium, lethargy and coma. In the chronic phase, cognitive dysfunction and even dementia occur. The clinical diagnosis of SAE lacks a unified clinical standard. Researchers should strive to better understand the pathophysiological mechanism of sepsis and explore possible effective intervention and treatment measures. This article reviews the pathophysiological mechanism, diagnosis, treatment and prevention of SAE.

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    Effects of recombinant human growth hormone on palmitic acid induced lipid deposition in HepG2 cells
    Fang ZHANG, Liyuan RAN, Jinjin ZHANG, Yingjie WU
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (9): 641-646. DOI:10.3969/j.issn.2097-0005.2023.09.001
    Abstract197 HTML744 PDF(pc)(4018KB)( 150 Save

    ObjectiveTo explore the effect of recombinant human growth hormone (rhGH) on the lipid metabolism of fatty liver cell model induced in vitro, and to provide theoretical support for further expanding the application of rhGH in clinical practice.MethodsPalmitic acid (PA) was combined to induce lipid accumulation in HepG2 cells, and a fatty liver cell model was constructed. The cell model was treated with different concentrations of rhGH, and CCK8 assay was used to detect the effects of different concentrations of PA and rhGH on the survival of HepG2 cells. The lipid accumulation level in HepG2 cells was evaluated by oil red O staining, the expression levels of genes and proteins related to lipid metabolism in HepG2 cell lines were evaluated by RT-qPCR and Western blot, and the mechanism of action of rhGH was preliminarily explored.ResultsIn this study, 0.2 mmol/L PA successfully induced a fatty liver cell model, which showed significant accumulation of lipid droplets in the cytoplasm. After being stimulated by rhGH, the accumulation of intracellular lipid droplets decreased with the increase of rhGH concentration, and the rhGH concentration of 40 ng/mL achieved a significant lipid-lowering effect. The results of RT-qPCR and Western blot showed that the expression of genes and proteins related to lipid synthesis in cells were significantly down-regulated after rhGH treatment, while the expressions of genes and proteins related to lipolysis had no significant changes.ConclusionrhGH can alleviate the lipid deposition in HepG2 cells induced by PA by inhibiting the de novo fatty acid synthesis pathway.

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    Effect of thalidomide on prevention and treatment of patients with reactive cutaneous capillary endothelial proliferation caused by carrizumab
    Meiyan ZHANG
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2022, 43 (8): 584-587. DOI:10.3969/j.issn.2097-0005.2022.08.006
    Abstract333 HTML9 PDF(pc)(422KB)( 148 Save

    ObjectiveTo investigate the effect of thalidomide in the prevention and treatment of reactive cutaneous capillary endothelial proliferation (RCCEP) caused by carrizumab.MethodsSixty patients treated with carrelizumab in the cancer treatment center from September 2020 to October 2021 were included as the research objects. They were randomly divided into groups. Thirty patients in the control group were graded according to the consensus of experts in the clinical diagnosis and treatment of RCCEP caused by carrelizumab according to the severity. Thirty patients in the experimental group took thalidomide simultaneously during the treatment, After RCCEP, thalidomide was adjusted from 50 mg QN to 100 mg QN, and local nursing was given. The incidence, occurrence and regression time and degree of RCCEP in the two groups were evaluated, and the post-treatment effects of the two groups were observed.ResultsThe incidence of RCCEP between the experimental group and the control group was 33.33%vs70.00%. There was significant difference between the two groups (P< 0.05); The time of regression in the experimental group was (79 ± 1.4) daysvs10.2 days after treatment, and the time of regression in the control group was (79 ± 1.2) days (P< 0.05); RCCEP in the two groups was mainly grades 1–2. There was significant difference in the degree of RCCEP between the two groups (P< 0.05). One in the control group had grade 3 RCCEP; After the emergence of RCCEP, the effective rates of thalidomide treatment were 96.67%vs70.67% respectively There was significant difference between the two groups (P< 0.05).ConclusionSimultaneous oral thalidomide during the treatment with carrelizumab can effectively prevent the occurrence of RCCEP and delay the occurrence time. Adjusting the dose of thalidomide after emergence can quickly and effectively promote the regression and improvement of RCCEP, which is worthy of clinical promotion.

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    Analysis for mortality trend and age-period-cohort of chronic obstructive pulmonary disease from 1990 to 2019
    Mengqi HAN, Wenpeng ZHU, Yunfei ZOU
    Journal of Shandong First Medical Unversity & Shandong Academy of Medical Sciences 2023, 44 (6): 424-429. DOI:10.3969/j.issn.2097-0005.2023.06.005
    Abstract191 HTML3 PDF(pc)(1349KB)( 146 Save

    ObjectiveTo study the death trend of lung disease in Chinese residents from 1990 to 2019 and its age, period and cohort effect.MethodsBased on the 2019 Global Burden of Disease Study (GBD 2019), the trend of mortality of chronic obstructive pulmonary disease was analyzed using Joinpoint regression model, and the age-period-cohort (APC) model was used to explore the age, period and cohort effects.ResultsFrom 1990 to 2019, the mortality rate of chronic obstructive pulmonary disease in China showed a downward trend (AAPC = 4.1%), and the annual average change rates of male and female were 3.6% and 4.7% respectively; the results of APC model analysis showed that the risk of death of chronic obstructive pulmonary disease in China increased with the increase of age from 1990 to 2019 (theRRvalue of male was 0.06 to 29.33; theRRvalue of female was 0.07 to 31.35); the risk of death decreases with the increase of years (RRvalue of male: 1.17~0.78;RRvalue of female: 1.46~0.63); the risk of death decreases with age (RRvalue for males: 3.75~0.15;RRvalue for females: 3.28~0.18).ConclusionThe mortality rate of chronic obstructive pulmonary disease (COPD) in China has a downward trend from 1990 to 2019. The older the population are and the earlier the birth is, the higher the risk of death is. It is necessary to strengthen the protection of high-risk groups to reduce the burden of COPD in China.

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