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.

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.

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.

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.

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.

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.

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.

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.

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.

急性心肌梗死即急性心肌缺血性坏死,是由于冠状动脉血供急剧减少或中断,使相应心肌因持久性缺血而发生局部坏死。发病机制通常是在冠状动脉粥样硬化病变的基础上继发血栓形成所致,其临床表现严重且持久,一般为数小时或数天的心绞痛,多伴有严重的心律失常、低血压或休克,是高死亡率的危急症。在临床实践过程中急性心肌梗死患者快速诊断标志物变得尤为重要。高敏肌钙蛋白T(high sensitivity cardiac troponin T,hs-cTnT)的高敏感性,可以更早发现心肌损伤。本研究结合近期发表的国内外相关研究,对急性心肌梗死的发生机制及诊疗作一综述。

Nuclear factor E2 related factor 2 （Nrf2） is the main regulator of cellular antioxidant response， and its activity is precisely regulated by the negative regulatory protein Keap1 （Kelch-like-ECH-associated protein 1）. The antioxidant effect of Nrf2 is inhibited by interaction with redox sensitive protein Keap1. The imbalance of Keap1/Nrf2 transcriptional activity is related to the pathogenesis of many diseases. Keap1/Nrf2 axis has become the most important regulator of intracellular homeostasis and plays an important role in the occurrence and development of many chronic diseases. Nrf2 can also mediate drug resistance by inducing antioxidant stress in tumor cells. Several studies have found that Keap1/Nrf2 mutation in NSCLC is related to the resistance of antitumor therapy （including chemotherapy， radiotherapy and targeted therapy）， and its impact on immunotherapy is not clear. Based on the dual role of Nrf2 in the process of tumor occurrence and development， targeted intervention of Nrf2 may not only prevent the occurrence of tumors in high-risk groups in the early stage， but also enhance the effect of anti-tumor treatment. This paper reviews the progress of Keap1/Nrf2 pathway changes in clinical research of NSCLC， suggesting that monitoring the changes of Keap1/Nrf2 pathway may be one of the important strategies to predict clinical prognosis and treatment resistance.

Diabetes as a complex metabolic disease， can cause complications of multiple systems. Incidence of diabetic encephalopathy has increased year by year in recent years， which has serious impact on the patient's quality of life. MiRNA as a small non-coding RNA molecules， stably exists in many biological fluids including serum and plasma in the form of cell-free circulation， and plays an important role in structure stability and progression of disease. Due to the fact that some changes in the miRNA are of cell type or tissue specificity， the analysis of circulating miRNA can be used to identify organizational dysfunction. In addition， the miRNA can be used as therapeutic targets in some diseases. This review summarizes miRNA in the early diagnosis and treatment of diabetic brain dysfunction.

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.

ObjectiveTo investigate the role and mechanism of HIF-1α in cardiac myocyte oxidative injury.MethodsThe classic oxidative injury model of cardiomyocytes with H₂O₂was established. The expression of HIF-1α and pathway-related genes were tested by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry analysis respectively. The protein levels were estimated by western blot.ResultsHIF-1α was expressed at a high level in human AC16 cardiomyocytes treated with hydrogen peroxide or hypoxia/reoxygenation. Knock down of HIF-1α restrained the Notch signaling pathway and aggravated H₂O₂-induced cardiomyocyte apoptosis.ConclusionHIF-1α protects cardiomyocytes from reactive oxygen species-induced apoptosis by regulating the Notch pathway.

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

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.

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）.

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.

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

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.

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.

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.

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.

Exosomes derived from mesenchymal stem cells are important carriers for mesenchymal stem cells to play biological effects. Exosomes can transport active proteins and various types of nucleic acids in stem cells into target cells by cell fusion. It has been confirmed that exosomes derived from mesenchymal stem cells can promote scarless wound healing by regulating inflammation， promoting cell proliferation and migrate， inhibiting cell apoptosis， promoting angiogenesis and regulating matrix remodelling. It has been proved that the exosome is a new biotherapy method to promote wound healing. In recent years， new studies have found that pretreatment of exosomes or adjusting the administration mode of exosomes can achieve more significant wound healing effects. In view of the positive role of mesenchymal stem cell exosomes in wound healing， this paper reviews the mechanism of the role of exosomes derived from mesenchymal stem cells in wound healing and the methods of engineering exosomes and administration methods in order to provide a comprehensive understanding of the role of exosomes in wound healing.

Neutrophil-to-high-density lipoprotein cholesterol ratio （NHR） has been widely reported as a novel inflammatory and oxidative stress marker that plays an important role in cardiovascular disease. The purpose of this article is to explore the predictive and prognostic value of NHR in cardiovascular disease. NHR is not only closely related to coronary artery stenosis， but also an independent predictor of severe coronary artery stenosis. In addition， several studies have shown a significant positive correlation between NHR and Gensini score， with a specificity of 94.2% and sensitivity of 61.0% in predicting Gensini score > 40. NHR can also be a useful indicator for predicting the risk of major adverse cardiovascular events in patients with cardiovascular disease. Numerous studies have provided strong statistical evidence that NHR is related to the development and prognosis of cardiovascular disease. This article reviews the research status of NHR and cardiovascular disease in recent years， to enhance its application value in cardiovascular disease and provide some assistance for future clinical research and decision-making.

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.

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.

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.

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

The natural herb Scutellaria baicalensis has a long history as a traditional Chinese medicine， with the efficacy of clearing heat and dampness， dipping fire and detoxifying the toxins. In recent years， research has shown that in addition to the pharmacological activities of Baicalin， it also has anti-inflammatory， antiviral， antioxidant and antitumor properties， especially in the protection and prevention of central nervous system diseases. Baicalin， as the most abundant compound， is the key indicator for quality control of Scutellaria baicalensis. Baicalin， as a natural flavonoid， can produce various medicinal effects， especially for neuropsychiatric disorders. This review will summarize the effects and clinical applications of baicalin and baicalin in the neuropsychiatric system， which can provide reference and reference for expanding the indications of baicalin and developing new neuroprotective drugs based on baicalin.

ObjectiveTo explore the expression ofACAT1and its immune cell infiltration of bladder cancer （BCa） by using bioinformatics and in vitro experiments.MethodsDifferential analysis of bladder cancer related expression data was performed in TCGA and GEO databases. The differentially expressed genes of bladder cancer was selected by Venn diagram. PubMed was used to search for genes related to ketone body metabolism. GO and KEGG enrichment analysis were performed in Metascape database to identify the pathway the genes involved. Ketone body related BCa differential expression gene was obtained by Venn diagram. Wilcoxon test was used in TIMER2.0 database to compare the expression ofACAT1between BCa and normal bladder tissues. Immunohistochemical staining ofACAT1in BCa was found in HAP database. Ualcan database was used to explore the relationship between the expression ofACAT1and the clinical character of BCa. Kaplan-Meier survival curve was used to explore the effect ofACAT1on the prognosis of BCa patients. Multivariate Cox regression of TIMER2.0 database was used to investigate the predictive ability ofACAT1for patients’ prognosis. TIMER2.0 was used to analyze the relationship betweenACAT1expression and immune cell infiltration. The biological function ofACAT1was verified by functional experiments in vitro.ResultsThe expression level ofACAT1in BCa was significantly lower than that in normal tissues （P< 0. 01）， and it positively related to some clinical character. Kaplan-Meier curve suggested that the overall survival rate of bladder cancer patients with highACAT1expression was lower than that of patients with lowACAT1expression （P< 0.01）. Combined with age and clinical stage， the multiple factors Cox regression suggested thatACAT1could be an independent risk factor for prognosis （P< 0.05）. TIMER2.0 analysis showed thatACAT1was positively correlated with the immunoinfiltration of bladder cancer （P< 0.01）. In vitro experiments proved that knockdown ofACAT1could promote the proliferation， migration and invasion of bladder cancer （P< 0.01）.ConclusionThe high expression ofACAT1may inhibit the occurrence of bladder cancer， but may have adverse effect on the prognosis of bladder cancer.

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.

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.

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.

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.

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.

Chronic obstructive pulmonary disease （COPD） is an important cause of death caused by chronic diseases worldwide. The rapid establishment of animal models with stable signs of COPD is the basis for further exploration of the disease mechanism of COPD. At present， there is still no recognized and standardized COPD rat modeling method at home and abroad. Referring to the relevant experimental literature and review literature on the application of rats to COPD preparation models in recent years， this paper summarizes the common modeling methods of rat models in recent years， which can be mainly divided into single factor COPD rat model preparation method and multi factor joint modeling method， in order to help standardize the establishment of COPD rat models.

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.

ObjectiveTo summarize the clinical pathological characteristics，immunohistochemistry， molecular genetic changes， treatment and prognosis of monomorphic epitheliotropic intestinal T-cell lymphoma （MEITL）.MethodsA total of 3 patients with MEITL in the Second Affiliated Hospital of Shandong First Medical University were collected from 2018 to 2022． Hematoxylin eosin staining， immunohistochemistry staining， in situ hybridization and clonal rearrangement of T cell receptor （TCR） gene were used to detect their histopathological features. The diagnosis and treatment as well as prognosis of the patients were reviewed， and their clinical pathological characteristics were analyzed.ResultsAll three patients lesions were located in the small intestine，and one of them infiltrated multisegmental small intestine， sigmoid colon， uterus and bladder. They had abdominal distension， abdominal pain， intestinal perforation and diffuse peritonitis at the time of admission， and two of them had fever. They were all treated by surgery， one patient also received chemotherapy， and all three patients died. Pathological characteristics showed that tumor cells grew diffusely and infiltrated the whole layer of the intestinal wall. The tumor cells had a single morphology， small to medium sizes， lightly stained cytoplasm， round nuclei， inconspicuous nucleoli， and exquisite chromatin. “Epitheliotropic phenomenon” were seen， together with mitotic figures and the formation of necrosis. Immunohistochemistry showed that CD3， CD8， CD56， Bcl-2 and TIA-1 were positive； CD4 was negative in 2 cases and partially positive in 1 case．CD20 was negative in 2 cases and partially weak positive in 1 case；Granzyme B was negative in 2 cases and scatteredly positive in 1 case；CD45RO was partially positive in all 3 cases；CD21， PAX-5 and CD5 were negative， the proliferation index of Ki-67 was 40% ~ 70% . In situ hybridization showed that small RNA encoded by Epstein Barr virus was negative and there was no EB virus infection．TCR rearrangement was positive in all 3 cases.ConclusionMETCL is a rare highly aggressive T-cell lymphoma， most of which is located in the small intestine， prone to intestinal perforation， with rapid progression and poor prognosis. The diagnosis should be comprehensively judged based on the combination of clinical manifestations， pathological features， immunohistochemistry， and gene detection results. The prognosis of patients with serious complications is very poor. The patients who have an early diagnosis， timely operation and good chemotherapy reaction have a relatively long survival time.

Objective: To study the clinical effect of auxiliary treatment by means of sputum suction with fiberoptic bronchoscope in patients with severe pneumonia. Methods: Forty-two patients with severe pneumonia in our hospital were randomly divided into control group and treatment group, with an average of 21 cases in each group. The control group received conventional anti infection and symptomatic treatment; the treatment group received auxiliary treatment by fiberoptic bronchoscope sputum suction on the basis of conventional anti infection and symptomatic treatment, and was given once a day or every other day according to the needs of the state of the illness,lasting for 1 week.And the levels of inflammatory markers (procalcitonin PCT, C-reactive protein CRP), the total effective rate of disease control and the total length of hospital stay were compared between the two groups before and after treatment. Results: The improvement of inflammatory markers in the treatment group was greater than that in the control group after the treatment. The total effective rate of disease control was 90.5%, which was higher than 71.4%,the rate of the control group; the total hospitalization time was (9.16± 1.02) d, which was lower than (13.62± 2.45) d in the control group, and the difference between the two groups was statistically significant( P＜0.001). Conclusion: In patients with severe pneumonia, auxiliary treatment by means of sputum aspiration with fiberoptic bronchoscope can significantly improve the level of inflammatory markers, shorten the total length of hospital treatment, and improve the total effective rate of disease treatment.

ObjectiveA stable cell line with overexpression and knockout of theOBSCNgene was constructed， and the effect ofOBSCNmutation on the proliferation and migration ability of hepatoma cells was preliminarily explored.MethodsqPCR technology was used to determine whether HepG2 cell hadOBSCNbackground expression， and HepG2 cell was infected by lentivirus to construct an overexpression cell line. Crispr cas9 technology was used to construct knockout cell lines； Western blot technology was used to detect the expression of Obscurin protein in knockout and overexpressed cells， and the proliferation and migration ability ofOBSCNmutant cell lines was explored by CCK-8 method and Transwell chamber method.ResultsqPCR verified that HepG2 cell had noOBSCNbackground expression， and HepG2 H21157 overexpression and HepG2 GL119 control empty vector stable cell line were obtained by lentivirus infection. The results of colony PCR， plasmid PCR and gene sequencing verified that the knockout recombinant plasmid reOBSCN was successfully constructed， and the HepG2 OBSCN KO stable cell line and the control empty vector HepG2 ecas stable cell line were transfected to obtainOBSCNknockout. Western blot technology verified the successful construction ofOBSCNknockout and overexpression cell lines. The results of CCK-8 method showed thatOBSCNoverexpression accelerated the proliferation of HepG2 cell （P< 0.000 1）， and knockout ofOBSCNgene could slow down the proliferation of HepG2 cell （P< 0.000 1）； the number of migratory cells of HepG2 H21157 and HepG2 GL119 were 150.30 ± 14.95 and 136.50 ± 15.02， respectively， and the number of migratory cells of HepG2 OBSCN KO and HepG2 ecas were 112.70 ± 20.30 and 147.8 ± 11.55， respectively， with statistical differences （P< 0.01）.ConclusionOverexpression ofOBSCNgene accelerates the proliferation and migration of HepG2 hepatoma cells， and knockout ofOBSCNgene slows down the proliferation and migration of HepG2 cell.

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.

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.

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.

With the improvement of living standards， the prevalence of metabolic associated fatty liver disease （MAFLD） is increasing， and MAFLD has become the most common chronic liver disease. In recent years， people's understanding of MAFLD has gradually deepened， and MAFLD has a high prevalence of type 2 diabetes mellitus （T2DM）， a significant proportion of them have non-alcoholic steatohepatitis （NASH）， people are paying more and more attention to the impact of MAFLD on T2DM-related complications， such as diabetic nephropathy， cardiovascular disease.and with the development of some new technologies in ultrasound， ultrasound is gradually being used in these complications. At present， ultrasound is the most common imaging method for the diagnosis of MAFLD and liver fibrosis， and this paper mainly reviews the diagnosis of MAFLD by ultrasound and the new progress of ultrasound in patients with MAFLD and T2DM.

ObjectiveTo explore the therapeutic efficacy of nebulized administration of Zhichuanling injection on allergic bronchial asthma in mice induced by ovalbumin （OVA）， and to investigate the safety of high-dose nebulization of Zhichuanling injection.MethodsAnimal welfare and experimental procedures followed the regulations of the Ethics Committee of China Pharmaceutical University. The severity of asthma symptoms was assessed by quantification of the latency and frequency of asthma-like behavior in mice. H&E staining was used to investigate histopathological changes in the lung. The total number of white blood cells （WBC）， eosinophil （Eos）， lymphocyte （Lym） and neutrophils （Neu） in bronchoalveolar lavage fluid were measured by automatic hematology analyzer to evaluate the allergic inflammatory response. Serum levels of interleukin-4 （IL-4） and immunoglobulin E （IgE） were quantified using ELISA. The safety of high-dose nebulization of Zhichuanlin injection was evaluated by examining the general behavior and nervous system response of animals.ResultsOur data demonstrated that the nebulized inhalation of different concentrations of Zhichuanling injection alleviated the asthma-like behavior of mice， improved the pathology of lung tissue， reduced the number of inflammatory cells in bronchoalveolar lavage fluid and the levels of IL-4 and IgG in the blood. Among the doses tested， the 1：1 dilution of Zhichuanling injection （the clinic dose） displayed the best efficacy that was comparable to the positive control， budesonide. Nebulized inhalation of a high dose （20 × clinic dose） Zhichuanling injection did not affect the general behavior， nervous and autonomic nervous system， urine， feces， saliva， body weight and food intake of mice.ConclusionConsidering these data together， nebulized inhalation of Zhichuanling injection may represent an effective and safe drug administration route for bronchial asthma treatment.

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）.