Lung cancer is one of the malignant tumors with the fastest increase in morbidity and mortality and the greatest threat to human life worldwide. Patients diagnosed with lung cancer usually receive a variety of treatments， including surgery， chemotherapy and/or radiation therapy， immunotherapy， and targeted therapy； However， the five-year survival rate for lung cancer remains low， especially when the cancer has reached an advanced stage or distant metastasis has occurred. Therefore， more effective and novel technologies must be developed to solve this problem. Inducer application of immunogenic cell death （ICD） has been proved to enhance immunity in patients receiving various types of therapy. The term ICD refers to a type of cell death that triggers an immune response to dead cell antigens， especially antigens derived from cancer cells. It was originally proposed about the effects of anti-cancer chemotherapy with traditional cytotoxic drugs. The purpose of this study is to review and discuss the role and mechanism of ICD as a promising combination immunotherapy for lung cancer.

ObjectiveTo investigate the effect of paclitaxel on the biological behavior of ovarian granulosa cells in rats with polycystic ovary syndrome （PCOS） by regulating TLR4/NF-κB/NLRP3 signaling pathway.MethodsA rat model of polycystic ovary syndrome was established and ovarian granulosa cells were isolated for culture and identification. Ovarian granulosa cells were randomly divided into PCOS group， PCOS+ paclitaxel low dose group， PCOS+ paclitaxel middle dose group， PCOS+ paclitaxel high dose group， PCOS+ paclitaxel +TLR4 inhibitor group， and normal granulosa cells were used as control group. Estradiol （E2）， testosterone （T）， progesterone （P）， luteinizing hormone （LH） and follicle-stimulating hormone （FSH） were detected by ELISA. CCK8 assay was used to detect the cell proliferation ability of each group. Transwell assay was used to detect the cell migration ability，. Flow cytometry was used to detect the cell apoptosis rate of each group， and Western blot was used to detect the protein levels of TLR4， NF-κB， NLRP3 and caspase‐3.ResultsAll doses of paclitaxel and TLR4 inhibitor had no effect on the proliferation of normal granulosa cells， but significantly increased the proliferation of PCOS cells. Compared with the PCOS group， the levels of E2， T and LH in the paclitaxel treatment groups and TLR4 inhibitor group significantly decreased， the cell migration ability enhanced significantly， and the number of apoptosis significantly reduced. The protein expression levels of TLR4， NF-κB， NLRP3 and Caspase3 in the cells were significantly down-regulated （P< 0.05）.ConclusionPaclitaxel can promote the proliferation， migration and inhibit the apoptosis of ovarian granulosa cells in rats with PCOS， and its regulatory mechanism may be related to the regulation of TLR4/NF-κB/NLRP3 signaling pathway.

ObjectiveThis article is to explore the role and mechanism of macrophage subsets in lung metastases， and to explore the differential genes and signaling pathways expressed by alveolar macrophages and interstitial macrophages in mouse lung metastases.MethodsSingle-cell RNA sequencing （seRNAseq） data GSM5235892 were obtained from the gene expression database of mouse melanoma lung metastasis. Bioinformatic analysis techniques were used to screen potential differential genes of and to conduct gene ontology enrichment analysis， Kyoto Encyclopedia of Genes and Genes pathway analysis， protein interaction analysis and screening to identify the top 10 genes with high scores. Finally， the expression levels of core genes in mouse melanoma lung metastasis model alveolar macrophages and interstitial macrophages were detected by qPCR.ResultsA total of 1 975 differentially expressed genes of alveolar macrophages and interstitial macrophages were identified， including 1 511 up-regulated genes and 464 down-regulated genes. Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes pathway analysis showed that the genes were mainly involved in immune response， tumor cell immune regulation， neuronal synaptic immune synapse， growth factor receptor activity， etc. The signaling pathways involved were NF-κB， TNF-α， MAPK， etc. The top 10 hub genes in PPI analysis were related to cellular oxidative phosphorylation， includingNdufa8，Cox6b1，Uqcr11，Cox5a，Ndufs6，Ndufs5，Uqcr10，Uqcrq，Ndufb6，Ndufab1； Through qPCR detection， we found that the expressions of hub geneUqcr11，Ndufa5were higher in alveolar macrophages and interstitial macrophages， which was consistent with the results of bioinformatics analysis. Survival analysis showed that the expression of the key geneCox5awas associated with the survival of patients with skin melanoma.ConclusionThrough scRNAseq data bioinformatics analysis method， the key genes and signaling pathways expressed by alveolar macrophages and interstitial macrophages in mice with melanoma lung metastasis were screened so as to provide references for the study of the pathogenesis of melanoma lung metastasis.

ObjectiveTo investigate the anti-inflammatory effect of bone marrow mesenchymal stem cell exosomes （MSC-Exo） in lipopolysaccharide （LPS）-stimulated RAW 264.7 cells and its possible mechanisms.MethodsMesenchymal stem cells （MSCs） were extracted from mouse bone marrow and cultured with the primary culture method. Mesenchymal stem cell conditioned medium （MSC-CM） and exosomes were extracted to verify the inhibitory effect of MSC-CM and MSC-Exo on LPS-induced inflammation in RAW 264.7 cells. RAW 264.7 cells were stimulated by LPS for 4 - 6 h， and cell proliferation activity was detected by cell counting and MTT assay. The exosomes in MSC-CM were detected by Western blot. The morphology and particle size of the exosomes were observed with the particle size analyzer. The morphological changes of cells were observed by inverted fluorescence microscope. Real-time fluorescence quantitative polymerase chain reaction （RT-qPCR） was used to detect mRNA transcription levels of IL-6 and Arg-1 in RAW 264.7 cells induced by LPS. Enzyme-linked immunosorbent assay （ELISA） was used to evaluate the secretion of IL-6 and IL-10 in LPS-induced RAW 264.7 cells.ResultsCompared with LPS group， MSC-Exo inhibited cell differentiation and significantly decreased the secretion of the cytokine IL-6 in LPS-induced cells after 30 h （P< 0.001）. MSC-Exo inhibited IL-6 mRNA transcription， and promoted Arg-1 mRNA transcription， and increased IL-10 expression.ConclusionThis study preliminarily demonstrated that bone marrow mesenchymal stem cell exosomes can inhibit lipopolysaccharide-induced RAW 264.7 cell inflammation.

In the field of tissue regeneration and repair， biomaterials are essential， and their use can enhance patient outcomes and prognoses. A class of materials known as smart-responsive biomaterials is able to react and change in response to various environmental stimuli， including light， temperature， pH， electric and magnetic fields， and biomolecules. Because of these materials' special qualities， tissue engineering could benefit greatly from their use. An overview of smart response and smart responsive biomaterials' mechanism for encouraging tissue healing will be provided in this study， along with an analysis of the difficulties and potential applications of smart responsive biomaterials in tissue regeneration and repair.

Gastric cancer is the most common gastric malignant tumor， and the incidence is getting higher in our country. Most patients are diagnosed with gastric cancer when it is in the advanced stage with poor treatment effect and high mortality. The therapeutic effect and prognosis of patients with early gastric cancer are better than those with advanced gastric cancer， so early diagnosis and treatment become the key to the diagnosis and treatment of gastric cancer. At present， the gold standard for the diagnosis of early gastric cancer is biopsy， which is invasive， painful to patients， expensive and easy to miss， so it is not suitable as a screening method. Detection of serum markers， a non-invasive method， provides a new strategy for the diagnosis of early gastric cancer. This article reviews the progress of serum markers in the detection of early gastric cancer.

ObjectiveTo study the relationship between physiologic ability and surgical stress score （E-PASS） and perioperative complications of radical hepatectomy in patients with primary liver cancer.Methods124 primary hepatocellular carcinoma patients admitted to our hospital from March 2022 to May 2023 were retrospectively selected as the study subjects， all of whom underwent radical hepatectomy in our hospital. The perioperative complications of these patients were statistically analyzed， and then they were divided into two groups based on the presence or absence of complications， namely the occurrence group （n= 29） and the non-occurrence group （n= 95）. The clinical data and disease-related characteristics of the two groups of patients were compared and E-PASS evaluation was conducted. The multifactorial Logistic regression equation was taken to analyze the relationship between perioperative complications of radical hepatectomy and various indictors， and then ROC curve graphs were drawn to predict the value of E-PASS in evaluating perioperative complications of radical hepatectomy in patients with primary liver cancer.ResultsA total of 124 patients were included in this paper who underwent radical hepatectomy， and 29 patients （23.39%） had perioperative complications， including 2 cases of liver failure （1.61%）， 6 cases of pleural effusion （4.84%）， 4 cases of abdominal abscess （3.23%）， 8 cases of postoperative hemorrhage （6.45%）， and 9 cases of abdominal cavity infection （7.26%）. In addition， patients with no complications were 95 cases （76.61%）. The difference between the occurrence group and the non-occurrence group was significant in terms of age， intraoperative bleeding， preoperative total bilirubin， and preoperative albumin （P< 0.05）. The preoperative risk score （PRS）， surgical stress score （SSS）， and composite risk score （CRS） scores were all higher in the occurrence group than those in the non-occurrence group （P< 0.05）. After multifactorial logistic regression analysis， it was found that PRS， SSS， and CRS would all have a significant positive influence relationship on perioperative complications of radical hepatectomy in patients with primary hepatocellular carcinoma （P< 0.05）. Meanwhile， by drawing ROC curves， it was found that E-PASS has certain value in predicting perioperative complications of radical liver resection with AUCs of 0.617， 0.614， and 0.601 respectively.ConclusionThe perioperative complications of primary hepatocellular carcinoma patients after radical hepatectomy are high， which need to be paid attention to. And the value of predicting perioperative complications by E-PASS is higher， which is worth being popularized in clinic use.

As a significant challenge to women's health globally， the research of breast cancer has shown increasingly prominence and urgency. Interferon regulatory factor 3 （IRF3）， a member of the human interferon regulatory factor （IRF） family， serves as a crucial transcription factor. IRF3 plays a significant role in regulating the signal transduction process of the innate immune response. Recent research advancements have discovered IRF3’s pivotal role in the field of tumor immunology， particularly its significant impact on breast cancer. IRF3 regulates the growth and apoptosis of breast cancer cells and influences tumor cell behavior by inducing the production of type I interferons （IFN-I） and other critical cytokines. However， in breast cancer， the activation of IRF3 is suppressed by various mechanisms， including the obstruction of IRF3-dependent apoptosis pathways and the inhibition of stimulator of interferon genes （STING） expression through the modulation of microRNA expression. Under certain circumstances， IRF3 may also promote the occurrence and recurrence of breast cancer. This review comprehensively explores the fundamental characteristics of IRF3， its signaling pathways， roles in developing breast cancer， the latest research progress， and summarizes potential therapeutic strategies based on the mechanism of action of IRF3.

ObjectiveTo conduct visualized analysis on the current situation and hotpots of domestic and overseas research on social participation of older people， so as to provide references for related research in China.MethodsBased on text mining technology and bibliometrics， this paper searched literature on the social participation of the older people published in Chinese and English in Web of Science， CNKI， Wanfang， Cqvip databases. CiteSpace was used to visually analyze the number of published documents， institutions， keywords and other aspects.ResultsFinally， 571 papers were included， including 269 in English and 302 in Chinese， respectively. The number of annual publications in the area of social participation of older people has been on a wave-like upward trend. Compared with foreign countries， the cooperation network between domestic publishing institutions is looser， and the contact density is lower. Most domestic papers focus on the influencing factors， while most foreign counterparts concentrate on the effects of social participation on different health outcomes. The same research focus at home and abroad is mainly about the interaction between social participation of older people and mental health disorders and active aging health policies.ConclusionAt present， the research on the social participation of older people in China is still in a stage of continuous development， but the depth and breadth of the study are insufficient， and the research on influencing factors and current status is still the core of the study. It is hoped to promote the exchange and cooperation between institutions， learn from foreign research hotspots， deepen the research content， and provide both theoretical and empirical reference to empower social participation in the future.

Diabetic macular edema （DME） is a manifestation of diabetic retinopathy （DR）， which can occur at any stage of DR and is one of the most common causes of vision loss in patients with DR. The choroid is the only source of blood supply to the macular fovea， so choroidal abnormalities can damage retinal function. The commonly used choroidal biomarkers are subfoveal choroidal thickness （SFCT） and choroidal vascularity index （CVI）. SFCT and CVI reflect the choroidal blood flow， especially CVI， which has a great application prospect in monitoring the progress of DME and evaluating the prognosis. Understanding the baseline choroidal characteristics and the changes of choroidal vessels after anti-vascular endothelial growth factor （VEGF） treatment has important guiding significance for evaluating the therapeutic effect and prognosis of DME.

Parthenolide， a sesquiterpene lactone extracted from chamomile， is considered a highly potential anticancer candidate drug due to its unique chemical properties and complex molecular effects on various tumor cells. This review focuses on exploring the mechanisms of parthenolide in tumor models， particularly its impact on gene expression， signal transduction， and different types of cell death in tumor cells. The latest research findings reveal that parthenolide can not only effectively inhibit key transcription factors such as NF-κB and STAT-3 but also trigger specific cell death pathways leading to an increase in intracellular reactive oxygen species and changes in Bcl-2 family proteins. Moreover， parthenolide has shown specific targeting capabilities against cancer stem cells. Given the significant efficacy of parthenolide， this compound is promised to be a new drug targeting cancer therapy.

ObjectiveTo investigate the clinical significance ofSOX10 expression in triple negative breast cancer （TNBC） tissues and its correlation with epithelial‐mesenchymal transition （EMT）.MethodsTo use Immunohistochemical methods to detect the expression levels ofSOX10 protein in 80 cases of TNBC and 60 cases of non TNBC tissues， as well as the expression levels of EMT key markers Vimentin and E-cadherin in TNBC tissues and to analyze the relationship between SOX10， Vimentin and E-cadherin in TNBC and clinicopathological parameters and the correlation betweenSOX10 and EMT markers.ResultsSOX10 expression was significantly higher in TNBC than that in non-TNBC （P< 0.001）. The expression ofSOX10 was associated with tumor classification， histological grade， Ki67 high value-added expression （Ki67 ≥ 30%） and lymph node metastasis in TNBC patients （P< 0.05）， and has no relationship with age or tumor diameter. The expression ofSOX10 was positively correlated with Vimentin expression （r= 0.398，P< 0.001） and negatively correlated with E-cadherin expression （r= -0.337，P< 0.01）.ConclusionSOX10 is specifically and highly expressed in TNBC and can be used as a useful biological marker for the differential diagnosis and prognosis of TNBC.SOX10 may promote tumor invasion and metastasis by regulating the expression of EMT-related proteins.

Being a common and frequently occurring gynecological disease， Endometriosis （EMS） seriously affects women's reproductive health and quality of life. Actually， the etiology and pathogenesis of EMS are still unclear at present. Research has revealed that patients suffering EMS have an imbalance in their microbiota， which participates the formation and development of EMS through mechanisms such as inflammation， immune， endocrine， and metabolic effects. Microbial balance is a key factor in maintaining normal local barrier function， and restoring bacterial homeostasis is beneficial for improving the prognosis of EMS patients. This article reviews the research progress on EMS and bacterial imbalance， hoping to provide new ideas for the clinical diagnosis and treatment of patients with EMS.

ObjectiveTo analyze the relationship between nutritional intervention and clinical prognosis by studying the nutritional status and nutritional intervention in elderly hospitalized patients.MethodsThe miniature nutritional assessment-short form （MNA-SF） was used to assess the nutritional risk and nutritional status of patients who were admitted to a Grade-A tertiary hospital in Shandong Province （hereinafter referred to as our department） from August 2020 to July 2021 and met the inclusion criteria， and to obtain the nutritional interventions during hospitalization， and to statistically analyze the clinical prognosis of the patients after nutritional interventions.Results422 patients were included in the study， of whom 156 patients were at nutritional risk （malnutrition + risk of malnutrition） with a prevalence of 36.9%， and the prevalence increases with age and number of disease types. All patients with malnutrition received nutritional intervention （50/50） and none of the patients with normal nutrition received nutritional intervention （0/266）. Among the patients who received nutritional intervention， enteral nutrition （EN） was the main mode of intervention， and the application ratio of EN， parenteral nutrition （PN）， and combined nutrition （EN+PN） was 1.68∶1.00∶1.09. 67 patients received the 2nd nutritional risk assessment after 1 week of admission， and 42 patients received the 3rd nutritional risk assessment after 2 weeks. The results of the 2 assessments showed that the patients who received nutritional intervention had significant improvement in nutritional indicators （prealbumin， hemoglobin， and lymphocyte count）.ConclusionElderly hospitalized patients have a high incidence of nutritional risk， and rational nutritional intervention has a significant effect on the improvement of nutritional status of elderly patients， and it is extremely important to select appropriate nutritional interventions in an individualized and detailed way.

Transient receptor potential channel vanilloid 3 （TRPV3） is a Ca²⁺permeable channel， located in plasma membrane. Except physical regulation of warmth （≥ 32℃）， the activity of TRPV3 is regulated by various endogenous and exogenous chemicals. With these chemicals， recent studies reveal physiological and pathological functions of TRPV3 including temperature sensing， hair growth， pain transduction， and skin inflammation， suggesting that TRPV3 is a potential drug development target. This article reviews the research progress of TRPV3 modulators， providing reference for subsequent researches on TRPV3.

The standard treatment of locally advanced rectal cancer （LARC） is the mode of neoadjuvant chemoradiotherapy （CRT） followed by total mesorectal excision （TME） plus adjuvant chemotherapy （ACT）. Neoadjuvant therapy significantly improves prognosis. However， the rate of distant metastasis is still kept high. The usual neoadjuvant chemotherapy is FOLFOX or FOLFIRI two-drug regimens， while FOLFOXIRI three-drug regimen remains stronger. This article has summarized the application of three-drug chemotherapy in neoadjuvant therapy for LARC， hoping to provide reference for clinical diagnosis and treatment.

ObjectiveTo investigate the clinical characteristics and factors influencing progression-free survival （PFS） of 78 cases thymic squamous cell carcinoma （TSCC）.MethodsWe retrospectively analyzed the clinical data of 78 patients with TSCC diagnosed for the first time in the Affiliated Hospital of Qingdao University from March 15^th， 2018 to March 15th， 2023 and followed them until March 15， 2024. Kaplan-Meier （KM） curve was used for survival analysis. Log rank test and Cox univariate and multivariate regression were used for the analysis of factors influencing prognosis.ResultsThe median PFS of the 78 patients were 66.0 months. The 1-year， 3-year， and 5-year PFS rates were 91.0%， 69.0%， and 54.3%， respectively. In the overall patient cohort， Univariate analysis showed that the tumor diameter （χ²= 7.43，P= 0.006）， N stage （χ²= 6.00，P= 0.050）， M stage （χ²= 8.18，P= 0.004）， TNM stage （χ²= 4.91，P= 0.027）， surgery （χ²= 4.10，P= 0.043）， and treatment method （χ²= 10.19，P= 0.017） were associated with PFS； Multivariate analysis showed that tumor diameter （HR= 1.30， 95%CI： 1.08 - 1.58，P= 0.007）， chemotherapy （HR= 0.22， 95%CI： 0.06 - 0.77，P= 0.018）， surgery alone （HR= 0.04， 95%CI： 0.01 - 0.29，P= 0.001）， and surgery with adjuvant therapy （HR= 0.23， 95% CI： 0.06 - 0.86，P= 0.029） were independent influencing factors of PFS. As for patient subgroups stratified according to the TNM stage， Multivariate analysis showed that surgery alone （HR= 0.06， 95%CI： 0 - 0.74，P= 0.028） and surgery with adjuvant therapy （HR= 0.08， 95%CI： 0.01 - 0.79，P= 0.031） were independent influencing factors of PFS in stage Ⅰ/Ⅱ patients； Tumor diameter （HR= 1.35， 95%CI： 1.03 - 1.78，P= 0.031） and radiotherapy （HR= 0.21， 95%CI： 0.05 - 0.92，P= 0.039） are independent influencing factors of PFS in stage Ⅲ/Ⅳ patients.ConclusionTSCC is a malignancy with a poor prognosis. Both tumor diameter and tumor stage are associated with PFS. It is recommended to choose the UICC/AJCC 9th TNM staging as the staging method. Patients who undergo surgery， radiotherapy， or chemotherapy have a lower risk of progression. It is recommended that stage Ⅰ/Ⅱ patients should undergo surgical treatment， and postoperative adjuvant therapy would be feasible. Stage Ⅲ/Ⅳ patients are recommended to try to add radiotherapy， and chemotherapy should be considered for selected patients.

ObjectiveHepatocellular carcinoma （HCC） has high genetic heterogeneity， while the survival rate is poor. Recent studies have suggested that pyroptosis is closely connected to the development of tumours， including genesis， invasion and metastasis， but whether these genes are associated with pyroptosis could provide information for prognosis prediction in HCC is unknown.MethodsAll HCC patients from The Cancer Genome Atlas （TCGA） database were divided randomly into a training group and a validation group at a 1：1 ratio. Then， we analysed the expression levels of 33 pyroptosis-related genes retrieved from influential studies. Univariate Cox analysis and the following LASSO algorithm of overall survival （OS） were conducted to identify candidate prognostic genes. Finally， multivariable Cox analysis was utilized to form a prognostic model that could distinguish all patients into high-risk or low-risk groups.ResultsFive pyroptosis-related genes （GPX4， CASP8， NLRP6， GSDMC and PLCG1） were enrolled in the prediction model， while the median cut-off value of the risk score could stratify the training and validation group patients into the high-risk or low-risk group. A lower probability of death was found in the low-risk group than in the high-risk group in the training group and was confirmed in the validation group （allP< 0.05）. The time-dependent ROC curves for OS were analyzed， and the area under the curve （AUC） was found to be 0.775， 0.713， and 0.677 in the training group and 0.671， 0.614， and 0.624 in the validation group at 1， 2， and 3 years， respectively. Functional enrichment analyses showed that carbohydrate and lipid metabolism pathways， macrophage subgroups and immune reactions were associated with the risk model.ConclusionThe five pyroptosis-related gene models have a significant prognostic prediction effect. The potential mechanism， including the interaction between pyroptosis and cell metabolism and macrophage and immune reactions in the HCC immune microenvironment needs further exploration.

ObjectiveTo investigate the application value of three-dimensional （3D） laparoscopy in sleeve gastrectomy.MethodsA total of 101 obese patients who underwent laparoscopic sleeve gastrectomy in the First Affiliated Hospital of Wannan Medical College from September 2022 to September 2023 were selected for retrospective analysis. According to the choice of laparoscopic system， the patients were divided into 2D group and 3D group. The surgical method was standard laparoscopic sleeve gastrectomy， Compare two groups of the total operation time， stomach cut edge and greater omentum suture time， intraoperative blood loss， postoperative related indicators.ResultsThere were 47 patients in the 2D laparoscopic group and 54 patients in the 3D laparoscopic group. All patients successfully underwent laparoscopic sleeve gastrectomy without conversion to open surgery. There was no conversion to 2D laparoscopic surgery in the 3D group. Compared with the 2D group， the 3D group had shorter total operation time， shorter suture time of gastric resection margin and greater omentum （P< 0.05）， and less intraoperative blood loss （P< 0.05）. There was no significant difference in postoperative related indicators between the two groups （P> 0.05）.Conclusion3D laparoscopy can shorten the operation time， reduce intraoperative blood loss and improve the quality of operation， which has high clinical application value.

Thyroid nodules are quite common in clinical practice. In recent years， with the continuous progress of ultrasonography technology and people's increasing attention to their own health， the detection rate of thyroid nodules has gradually increased. At the same time， new ultrasound diagnostic techniques such as ultrasonography， microvascular flow imaging， ultrasound elastography and artificial intelligence have been developed in recent years， which have significantly improved the accuracy of benign and malignant diagnosis of thyroid nodules. The purpose of this article is to review the value of new ultrasound technologies in the benign-malignant differential diagnosis of thyroid nodules.

ObjectiveA Meta-analysis was conducted to systematically analyze the efficacy and safety of apatinib combined with SOX regime（oxaliplatin+tegafur）in patients with advanced gastric cancer.MethodsPubMed， Embase， Cochrane Library， ClinicalTrials.gov， WANFANG DATA and CNKI were searched for randomized controlled trials studying the efficacy and safety of apatinib combined with SOX in the treatment of advanced gastric cancer patients. Data were extracted from the included literature， and the main outcome indicators were as follows： objective response rate （ORR）， disease control rate （DCR）； secondary outcome indicators： partial response rate （PRR） and safety related indicators， including hypertension， proteinuria， hand-foot syndrome， diarrhea， oral mucositis， fatigue， leukopenia， thrombocytopenia. All statistical analyses were performed using meta package for R version 4.0.3.Results1699 articles were retrieved and 28 articles with a total of 2110 subjects were ultimately included. Compared with SOX regimen， apatinib combined with SOX regimen improved DCR （OR= 3.90， 95%CI： 3.15 - 4.83，P< 0.001） and ORR （OR= 2.73， 95%CI： 2.26 - 3.31，P< 0.001）， PRR （OR= 2.33， 95%CI： 1.94 - 2.81，P< 0.001）， but increased hypertension （OR= 2.47， 95%CI： 1.26-4.83，P= 0.008）， proteinuria （OR= 2.16， 95%CI： 1.46-3.21，P< 0.001）， hand-foot syndrome （OR= 2.19， 95%CI： 1.44 - 3.32，P< 0.001）. The difference was statistically significant.ConclusionThe results of this meta-analysis showed that apatinib combined with SOX regime was effective in the treatment of advanced gastric cancer with relatively mild adverse events， which is expected to be applied in clinical practice.

ObjectiveTo investigate the mechanism of high mobility group box 1 （HMGB1） in chemotaxis of neutrophils in occupational asthma induced by toluene diisocyanate （TDI） in vitro.MethodsTDI and human serum albumin （TDI-HSA） conjugate were prepared， and the contents of TDI and HSA in the conjugate were determined by Gutmann method and BCA method， respectively. On 0， 40， 80， 120 mg/L TDI-HSA infected human bronchial epithelial cells （human bronchial epithelial cells， HBECs） 12 h， ELISA method to detect cell culture supernatant of interleukin 8 （interleukin-8， IL-8） and C-X-C motif chemokine 12 （CXCL12） levels； Western blot was used to detect the expression of HMGB1， CXCL12 and nuclear factor kappa-B （NF-κB） related proteins in cells. The level of reactive oxygen species （ROS） was detected by live cell fluorescent probe method. The nuclear translocation of HMGB1 was observed by immunofluorescence. HBE cells were pretreated with different concentrations （100 and 200 mmol/L） of glycyrrhizin （GL） for 24 h to inhibit HMGB1， and then treated with TDI-HSA for 12 h. The level of IL-8 in cell culture supernatant was detected. The expression of HMGB1， CXCL12 and NF-κB related proteins， the level of ROS release and the nuclear translocation of HMGB1 were observed.ResultsHBE cells were exposed to different concentrations of TDI-HSA （0， 40， 80， 120 mg/L） for 12 h. The results showed that nuclear translocation of HMGB1 occurred in HBECs with the increase of TDI-HSA concentration. ROS in the cells and the cell supernatant of IL-8 levels increased significantly （P< 0.05）； Compared with the control group， the 120 mg /L exposure group had significant increases in the protein expression of HMGB1 and phosphorylated P65 in HBECs cells （P< 0.05）. Not found HBE cells CXCL12 protein expression in cells with TDI-HSA infected concentration increase is on the rise， in cell supernatant CXCL12 levels are not checked out. In order to further verify the regulatory role of HMGB1， useing different concentrations （100， 200 mmol/L） GL medium and 120 mg/L TDI-HSA on cells after 12 h， the results showed that compared with the control group， 100 and 200 mmol/L GL effected on HBE cells can inhibit the nuclear transfer caused by TDI-HSA， HMGB1 can significantly inhibit suppression ROS in the HBE cells and rise the level of IL-8 in the supernatant. The expression of HMGB1 and phosphorylated P65 protein in the cells was significantly reduced （P< 0.05）.ConclusionsTDI can increase the expression and nuclear translocation of HMGB1， activate NF-κB and promote the release of IL-8 in HBE cells， but does not affect the expression of CXCL12. GL can reduce the expression of HMGB1， inhibit the activation of NF-κB， and reduce the release of IL-8.

ObjectiveTo evaluate the clinical efficacy of porcelain bonded bridge in repairing patients with deep overbite and single anterior tooth loss.MethodsThirty patients with deep overbite and single anterior tooth loss who were treated in our hospital from January 2023 to June 2023 were selected as the study subjects. A cast ceramic adhesive bridge was made on the lip side. The restoration detachment， restoration fracture， edge sealing， secondary caries， edge staining， and periodontal health status were examined one week and six months after surgery，ResultsThe restoration effect was good one week after surgery， with no loss or breakage of the restoration body， good edge closure， no discoloration， and healthy periodontium. After 6 months of examination， 2 cases of restoration were found to have fallen off. After rebonding， they continued to be used. One probe could detect the edge， with mild gingival inflammation. The remaining 27 cases showed no abnormalities， and there was no loss or fracture of the restoration. The edge fit was good， and the abutment teeth had no caries， and the periodontium was healthy.ConclusionThe short-term clinical effect of using porcelain bonded bridge to repair deep overbite with single anterior tooth loss is good.

Breast cancer （BC） is one of the most common malignant tumors in women and is also a major cause of death. Currently， BC treatment involves a multidisciplinary approach， including surgery， radiotherapy， chemotherapy， and so on. Anthracyclines， taxanes， and 5-fluorouracil， among other chemotherapeutic drugs， are widely used in the treatment of BC and can significantly reduce the risk of death and recurrence. However， chemoresistance caused by various complex factors severely affects the clinical efficacy of drug treatment， leading to poor prognosis for patients. The mechanisms of drug resistance to these medications are complex and not yet fully elucidated. Non-coding RNA mainly includes microRNA， long non-coding RNA， circular RNA， etc. Different types of chemotherapeutic drugs and non-coding RNAs regulate and interact with each other in a complex manner， intricately linked to precisely mediate chemoresistance in BC. In this review， the involvement of non-coding RNA in drug resistance to different chemotherapy drugs is detailed， with the hope of providing new potential targets for the diagnosis and treatment of BC.

ObjectiveTo investigate the clinical effect of six-step microscopic varicocelectomy.MethodsThere is a retrospective analysis of 102 patients with varicocele underwent microscopic varicocelectomy from September 2021 to December 2022，47 patients in the control group （from September 2021 to June 2022） underwent routine microscopic varicocelectomy， and 55 patients in the observation group （from July 2022 to to December 2022） underwent microscopic varicocelectomy based on the six-step method.The indicators of surgery and surgical complications of the two groups were compared.ResultsThe operation time of observation group（32.54 ± 1.68）min was shorter than control group（47.76 ± 1.43）min， and the difference between the two groups was significant（P< 0.05）。There was no significant difference between two groups in terms of preoperative indexes， intraoperative other indexes（the amount of internal spermatic vein complexes，operation time， intraoperative bleeding），postoperative indexes（P> 0.05）.ConclusionBased on the six-step method， the microscopic spermatic vein ligation by establishing the correct surgical level， standardizing the surgical steps and procedures， thus reducing the operation time， effectively ligation the veins and preserving the arteries and lymphatics， with fewer postoperative complications and good clinical efficacy.

ObjectiveTo observe and analyze the clinical efficacy of the combined treatment of Three-dimensional balanced chiropractic therapy and McKenzie therapy on lumbar disc herniation （LDH）， and its impact on the reabsorption of protrusions.MethodsFrom January 2022 to June 2023， Clinical data of patients with lumbar disc herniation who received three-dimensional balanced chiropractic therapy combined with McKenzie therapy at the Neck， Shoulder and Back Pain Hospital affiliated to Shandong First Medical University. Clinical data of patients with lumbar disc herniation were included in the treatment of three-dimensional balanced chiropractic technique， massage， acupuncture， and McKenzie therapy. All patients underwent MRI examination before treatment and during follow-up treatment， with an interval of ≥ 6 months between two MRI examinations and compared the clinical efficacy evaluation， VAS， JOA， SAS， and lumbar disc herniation resorption among the three groups.Results（1） The overall efficacy rate， as well as the VAS， JOA， and SAS scores of the comprehensive treatment group， were superior to those of the McKenzie treatment group， with statistically significant differences （allP< 0.05）； （2） The JOA and SAS scores of the comprehensive treatment group were superior to those of the three-dimensional balance therapy group， with statistically significant differences （allP< 0.05）， with a statistically significant difference（allP< 0.05）. （3） The comprehensive treatment group had 43.3% reabsorption of lumbar discherniation， which was higher than the three-dimensional balanced chiropractic therapy group and the Mackenzie treatment group，however， the difference was not statistically significant （P> 0.05）.ConclusionsThe combination of Three-dimensional balanced chiropractic therapy and McKenzie therapy has a good therapeutic effect on lumbar disc herniation， and the probability of protrusion reabsorption and complete absorption after treatment is higher than that of the three-dimensional balanced chiropractic therapy group and McKenzie therapy group.

ObjectiveBy studying the effect of PHLPP2 gene over-expression on Burkitt lymphoma grafts and its effect on AKT signaling pathway related protein expression， the mechanism of action of PHLPP2 on Burkitt lymphoma is further explored， providing experimental basis for the development of gene targeted therapy.MethodsThe stable over-expression model of PHLPP2 is established in Burkitt lymphoma cell line （CA46） and inoculated into NCG mice to construct Xenograft tumor model. Tumor formation in mice is observed， tumor size is measured， and tumor growth curve is drawn. At the end of the experiment， the mice are euthanized to collect the samples of Xenografted tumor. The tumor volume and weight of the two groups are compared to evaluate the inhibitory effect of PHLPP2 on tumor growth. The expression of PHLPP2， p-AKT is detected by immunohistochemistry staining.and the expression levels of PHLPP2， AKT and S6K1 protein and the phosphorylation levels of AKT and S6K1 protein are detected by Western blot.Results1.The NCG mouse model of Burkitt lymphom Xenograft model is successfully established： subcutaneous tumor formation is observed in all 10 mice， the tumor-forming rate is 100%. 2. Effect of PHLPP2 gene on transplanted tumor in mice： the time of subcutaneous tumor formation in control group and treatment group are （10.60 ± 1.95） and（15.00 ± 1.58）respectively. Compared with the control group （2.00 ± 1.01） mm³， the tumor volume of the treatment group （0.63 ± 0.18） mm³is significantly reduced （P< 0.05）. The average tumors weight in control group and treatment group are （0.83 ± 0.33）g and （0.31 ± 0.03）g （P< 0.05）. 3.Western blot and immunohistochemical results： the results of Western blot indicate that the expression of PHLPP2 in the treatment group is significantly higher than that in the control group， while the expression of p-AKT and p-S6K1 in the treatment group is decreased comparing with the control group （P< 0.05）. Immunohistochemical results show that PHLPP2 protein and p-AKT protein are expressed in the cell membrane and cytoplasm in the experimental group and the control group. In the treatment group， PHLPP2 protein is strongly positive and p-AKT protein is weakly positive， while in the control group， PHLPP2 protein is weakly positive and p-AKT is strongly positive（P< 0.05）.ConclusionPHLPP2 plays an important inhibitory role in the development of Burkitt lymphoma， which may be realized by inhibiting the phosphorylation level of downstream proteins related to the AKT signaling pathway.

ObjectiveUnderstand and master the epidemic trends of the main pathogens of foodborne diseases， and provide a basis for the formulation of prevention and control measures for foodborne diseases in Taian.MethodsStatistical analysis of case information and pathogen detection results reported through the foodborne disease active monitoring system in Taian from 2019 to 2023.ResultsThe detection rate of pathogens was 28.11% from 2019 to 2023， and the highest rate was 45.02% after the COVID-19 （2023）；The detection rates of various pathogens from high to low were Norovirus （13.50%）， Salmonella （10.54%）， Escherichia coli causing diarrhea （3.61%）， Vibrio parahaemolyticus （0.46%）， and Shigella was not detected； Bacterial pathogens are more prevalent in summer， with a higher detection rate from May to August. Norovirus is more prevalent in winter and spring， with peak detection rates in November and February； The pathogen detection rate is higher in the group aged 1 to 3 （31.49%） and the group aged 0 to 1 （30.14%）； Farmers （35.54%）， scattered children （31.31%）， and students （30.36%） are the occupations with a high detection rate of pathogens in physical examinations； The exposed foods that cause a high detection rate of pathogens are aquatic animals and their products （43.21%）， eggs and egg products （37.65%）， and fruits and their products （36.63%）； The place with the highest detection rate of pathogens in physical examinations is the home （30.54%）.ConclusionThe pathogen detection rate in Taian varies seasonally， with the main pathogens being Norovirus and Salmonella. The key population is farmers， and the main suspicious foods are aquatic animals and their products. In the future， targeted prevention and control should be carried out according to the high incidence season of the main pathogens， popular science promotion should be carried out for key populations， active monitoring and food supervision should be strengthened， and the risk of foodborne diseases should be reduced.

ObjectiveTo explore the clinical characteristics and prognosis analysis of multiple cerebral hemorrhage involving the brainstem.MethodsA retrospective analysis was conducted on the clinical data of SMICH patients with brainstem involvement admitted to the Second Affiliated Hospital of Shandong First Medical University from January 2020 to March 2024， to explore their clinical characteristics， treatment strategies， and prognosis.ResultsThere were 11 patients with multiple cerebral hemorrhage involving the brainstem， including 7 males and 4 females， with an average onset age of （60.7 ± 12.0） years. 6 cases received conservative treatment.There were 5 patients who underwent surgical treatment， including 3 patients undergoing ventricular drainage and hematoma puncture drainage， 1 patient undergoing ventricular drainage， and 1 patient who underwent hematoma removal and decompressive craniectomy. Among 11 SMICH patients with brainstem involvement， 3 died and 8 survived. Follow-up of surviving patients showed that 5 patients scored 4－5 on the GOS score and 3 patients scored 3 on the GOS score.ConclusionThe symptoms of SMICH involving the brainstem lack specificity， and a comprehensive analysis of its etiology and severity is needed. Individualized treatment plans should be adopted， and early intervention can improve patient prognosis.

In recent years， there has been a gradual increase in the incidence of carotid artery stenosis. The relationship between cognitive function and carotid artery stenosis has always been an area of interest. Numerous studies have demonstrated that symptomatic carotid stenosis （SCS） leads to cognitive impairment. However， the impact of asymptomatic carotid stenosis （ACS） on cognitive function and its extent are still inconclusively determined. Possible mechanisms include cerebral hypoperfusion， cerebral microembolism， and cerebral white matter hyperintensities. Definitive evidence regarding whether carotid revascularization can improve cognitive impairment caused by carotid artery stenosis is still lacking. Early detection and proactive intervention before the onset of significant symptoms in patients with carotid artery stenosis can prevent cognitive decline， thereby benefiting patient prognosis. Based on an extensive review of domestic and foreign literature sources， this article reviews the association between carotid artery stenosis and cognitive function as well as its pathogenesis and explores the impact of ACS on cognitive function along with potential improvements through carotid revascularization.

ObjectiveTo optimize the prescription of Paeoniae Radix Alba and Glycyrrhiza umbilical patches （referred to as umbilical patches）.MethodsSing transdermal penetration test in vitro and high performance liquid chromatography （HPLC） with the appearance， cumulative release of 8 indicator ingredients and that of total ingredients as evaluation indexes and optimizing the drug loading， penetration enhancer dosage and the ratio of PEG6000 and PEG4000 to micro-powder silica gel by single factor test and Box-Behnken response surface method combined with GA-BP neural network to determine the best prescription.ResultsThe comprehensive evaluation indexes of Box-Behnken response surface method and GA-BP neural network optimization were 1.2808 （n= 3，RSD = 3.05%） and 1.1937 （n= 3，RSD = 2.26%）， respectively. After comparison and verification， the optimal prescription process for Paeoniae Radix Alba and Glycyrrhiza was 9.71% of micro-powder silica gel to PEG， 24.56% of drug loading and 2.87% of penetration enhancer.ConclusionThe optimal prescription of umbilical patches was determined by Box-Behnken response surface test combined GA-BP neural network. The umbilical patches prepared by this prescription have moderate softness and hardness， and good skin permeability.

With the increasing knowledge of gastrointestinal endoscopy， the number of patients undergoing gastrointestinal endoscopy is increasing year by year， but the diagnosis and treatment of gastrointestinal endoscopy requires a lot of experience accumulation， and the correct diagnosis is a challenge for junior doctors. At present， the artificial intelligence model based on deep learning technology is widely used in the field of gastrointestinal endoscopy， which can improve the consistency between observers， improve the detection rate and diagnostic accuracy of clinical diseases， and reasonable application can improve the clinical work efficiency and reduce the economic burden of patients. This article reviews the application of artificial intelligence in gastrointestinal endoscopy， in order to provide ideas for the diagnosis and treatment of gastrointestinal endoscopy.

ObjectiveTo investigate the relationship between dietary patterns and hyperuricemia （HUA） in American adults.MethodsThis study was based on population data of the National Health and Nutrition Examination Survey （NHANES） 2007—2018 year. According to the inclusion and exclusion criteria， 25，526 US adult residents were finally included in this study. Principal component analysis was used to extract the dietary patterns of the survey respondents. Restricted cubic spline （RCS） regression model was applied to detect the possible linear or non-linear dependency of the relationship between dietary patterns and the prevalence risk of HUA with 3 knots adjusting for all confounders. The association between different dietary patterns and the risk of prevalence of hyperuricemia was analyzed by multifactorial logistic regression after quartiles of dietary pattern factor scores， with the lowest quartile as the reference. The covariates in the logistic regression model include age， gender， race， education， family income poverty rate， BMI， smoking， drinking， physical activity， dietary supplement use， Healthy Eating Index， total energy， and high-purine food intake.ResultsThree patterns were extracted by principal component analysis. These are labeled as fat-processed grain-cheese-added sugar （FPCS）， oil-vegetables-nuts-whole grains （OVNW） pattern and oil-white potatoes-drink-seafood （OPDS） pattern. RCS analysis showed that FPCS pattern score was linearly related to the risk of HUA （P-linear < 0.001）， and the higher the FPCS pattern score， the lower the prevalence of HUA. The OVNW pattern score was linearly related to the risk of HUA （P-linear < 0.001） and the higher the OVNW pattern score， the lower the prevalence of HUA. There was a linear relationship between the OPDS pattern score and the risk of HUA （P-linear < 0.001） and the higher the OPDS pattern score， the higher the prevalence of HUA. In logistic regression， FPCS and OVNW patterns were negatively associated with prevalence risk of hyperuricemia （Q4：OR= 0.74， 95%CI0.62－0.87） and （Q4：OR= 0.76，95%CI0.66－0.87） respectively. However， OPDS pattern was positively associated with prevalence risk of hyperuricemia （Q4：OR= 1.54，95%CI1.41－1.70）.ConclusionFPCS and OVNW patterns were associated with decreased prevalence risk of hyperuricemia in the Adults of United States， whereas OPDS patterns were associated with increased prevalence risk of hyperuricemia.

ObjectiveThe aim of this study was to screen neutralizing monoclonal antibodies against Coxsackievirus A group 16 （CVA16） through single-cell sequencing and to validate their functions.MethodsCVA16 capsid protein VP1 was used as the antigenic protein， and specific B cells recognizing VP1 were then sorted by flow cytometry and sequenced by BCR library single-cell sequencing. Based on the analysis of the IgG antibody light and heavy chain sequences from the sequencing data， CVA16 candidate monoclonal antibodies were screened according to the abundance ranking and expressed. Thein vivoandin vitrofunctions of the identified CVA16 monoclonal antibodies were verified by enzyme-linked immunosorbent assay （ELISA） and micro-neutralization assays.ResultsThe CVA16-VP1-His recombinant protein was successfully expressed. Approximately 50 000，12.00 viable VP1-specific B cells were sorted out by flow cytometry， and the BCR library was constructed and sequenced. 19 candidate monoclonal antibodies against CVA16 were screened. Monoclonal antibodies 7-2， 7-4， 7-8， 8-8， and 8-9 have neutralizing activity， with IC₅₀values of 9.09， 12.00， 5.56， 9.68， and 9.67 μg/mL， respectively. Monoclonal antibody 7-8 showed strong neutralization at the cellular levelin vitroand also showed good neutralization in thein vivochallenge protection assay in Suckling mice. In addition， monoclonal antibody 7-1 had neutralizing ability against EVA71 virus， and 7-5 showed neutralizing ability against CVA6 virus.ConclusionThis study successfully established a pipeline for screening CVA16 monoclonal antibodies based on single-cell sequencing and found that antibody 7-8 had a strong neutralizing activity.

ObjectiveTo investigate the effect of signal transcription and activation factor 3 （STAT3） inhibitor WP1066 on the proliferation of human airway BEAS-2B cells and explore the potential molecular mechanism of WP1066 in the treatment of bronchial asthma.MethodsAfter pretreatment with WP1066， the proliferation of BEAS-2B cells was determined by MTT assay. The level of STAT3 phosphorylation and its downstream target Cyclin D1 were measured by Western Blot.ResultsWP1066 inhibited the proliferation of BEAS-2B cells in a concentration-dependent manner. WP1066 did not reduce the total STAT3 protein level， but inhibited the phosphorylation of STAT3 and down-regulated the expression of Cyclin D1 protein.ConclusionWP1066 can inhibit the proliferation of human airway epithelial cells by blocking the STAT3 signaling pathway.

Lung cancer is the malignant tumor with the highest morbidity and mortality rate in China. Surgery， radiotherapy， and chemotherapy were the primary means of treatment for non-small cell lung cancer in the past.Immunotherapy and targeted therapy， such as immune checkpoint inhibitors against tumor immune escapealso play a vital role in its treatment. However， some patients are not sensitive to the treatment， so finding biomarkers to predict the efficacy of treatment is significant in achieving the precision treatment of lung cancer. Peripheral blood lymphocytes are critical to human systemic immunity as an essential complement of immune cells in the tumor microenvironment. In this paper， we systematically review the changes of peripheral blood lymphocytes in the development of lung cancerduring and after treatmentto further understand the progression of non-small cell lung cancer， thusproviding new ideas for developing therapeutic strategies.