BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.

Objective To analyze the current status,hotspots,and trends in the research field of traditional Chinese medicine and pharmacy combined with transcatheter arterial chemoembolization(TACE)for the treatment of hepatocellular carcinoma.Methods The relevant literatures on traditional Chinese medicine and pharmacy combined with TACE treatment for hepatocellular carcinoma collected by China National Knowledge Infrastructure from January 1994 to December 2022,and use CiteSpace 6.1.R6 software to analyze its publication volume,authors,research institutions,and key words.Results This study included a total of 686 articles.The publication volume showed a fluctuating upward trend from 1994 to 2015,but it had decreased since 2016,indicating that further breakthrough research was needed in this field.The communication between authors and research institutions needed to be strengthened,with low levels of cross institutional and cross regional cooperation and uneven geographical distribution.Cooperation should be strengthened.High frequency key words included hepatocellular carcinoma,Chinese materia medica,interventional therapy,therapeutic,etc.,resulting in 9 key word clustering labels.Conclusion Currently,there is a lack of experimental research and related mechanism research,the future research hotspots of traditional Chinese medicine and pharmacy combined with TACE treatment for hepatocellular carcinoma will focus more on traditional Chinese medicine and pharmacy,interventional therapy,clinical observation,and cell apoptosis,which provides new ideas for researchers conducting related research in the future.

Objective By using the bibliometrics method,the literature about Yinchenhao decoction was visualized and analyzed to explore its research hot spot and frontier.Methods The related literatures on Yinchenhao decoction were retrieved from CNKI database,and CiteSpace 6.1.R6 software was used to analyze the authors,institutions and key words,and the key words were clustered to draw a visual atlas.Results A total of 856 articles were included,and the number of articles showed a fluctuating upward trend.There were 764 authors and 513 related key words,including clinical application,experimental study and signaling pathway of Yinchenhao decoction.Conclusion Although Yinchenhao decoction is a commonly used clinical prescription for liver disease,there is a lack of studies on the mechanism of action and molecular level.Future research hot spot should focus more on large sample randomized controlled clinical studies and experimental studies,so as to provide new directions for researchers.

ObjectiveTo comprehensively analyze the impact of health literacy on fourth-grade students in a primary school in Changning District through the implementation of interactive interventions， providing a theoretical basis for the effective implementation of school health literacy initiatives. MethodsUsing a cluster random sampling method， the effects of a 6-month interactive intervention were assessed among all fourth-grade students through two rounds of health literacy questionnaires conducted before and after the intervention. ResultsFollowing the intervention， there was a significant increase in the overall rate of health literacy （86.80%）， knowledge of health beliefs （71.57%）， adherence to a healthy lifestyle （92.89%）， and basic health skills （76.14%） （P<0.001）. The rate of formation of student health behaviors after the intervention （90.10%） increased by 16.02% compared to the pre-intervention level （P<0.05）. ConclusionConducting interactive interventions can stimulate students’ enthusiasm for self-directed learning， facilitate the formation of health behaviors， and reduce the risk of disease occurrence. This approach plays a positive role in promoting students’ physical and mental health development and enhancing their level of health literacy.

Objective: To analyze the semen quality parameters of sperm donor volunteers, so as to provide insights into male infertility control and related research. Methods: A total of 155 sperm donors were recruited from the Human Sperm Bank of Zhejiang Province using the convenience sampling method from January to March 2021. Demographic information were collected through questionnaire surveys. Semen were collected, and parameters including semen volume, sperm concentration, total number of sperm, forward motility rate and total sperm viability were measured. Semen quality was evaluated according to the WHO Laboratory Manual for the Examination and Processing of Human Semen. : Results Conclusion There were 20.65% of the 155 sperm donors with unqualified semen, and the unqualified rates of forward motility rate and total sperm viability were relatively high.

Tbx18,Wt1,and Tcf21 have been identified as epicardial markers during the early embryonic stage.However,the gene markers of mature epicardial cells remain unclear.Single-cell transcriptomic analysis was performed with the Seurat,Monocle,and CellphoneDB packages in R software with standard pro-cedures.Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides(10x Genomics)and Visium Spatial Gene Expression Slides(10x Genomics).Spatial transcriptomics analysis was performed with Space Ranger software and R software.Immunofluorescence,whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results.Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue.Several gene markers specific to postnatal epicardial tissue were identified,including Msln,C3,Efemp1,and Upk3b.Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts(from embryonic day 9.5 to postnatal day 9)could be categorized into six major cell types,which included epicardial cells.Throughout epicardial development,Wt1,Tbx18,and Upk3b were consistently expressed,whereas genes including Msln,C3,and Efemp1 exhibited increased expression during the mature stages of development.Pseudotime analysis further revealed two epicardial cell fates during maturation.Moreover,Upk3b,Msln,Efemp1,and C3 positive epicardial cells were enriched in extracellular matrix signaling.Our results suggested Upk3b,Efemp1,Msln,C3,and other genes were mature epicardium markers.Extracellular matrix signaling was found to play a critical role in the mature epicardium,thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.

AIM: To observe the effects of single-dose of fentanyl on sedation and agitation during recovery after pediatric adenotonsillectomy day surgery during anesthesia induction. METHODS: A total of 157 children undergoing elective adenotonsillectomy, with ASA physical status I or II, aged 3-10 years were selected during January and March in 2022 in the Second Affiliated Hospital of Wenzhou Medical University. The children were divided into two groups according to random number table method: remifentanil combined with fentanyl group (group RF, n = 78) and remifentanil group (group R, n = 79). Children in group RF received a single-dose injection of 1 μg/kg of fentanyl and 2.5 μg/kg of remifentanil during induction, children in group R received an equal volume of normal saline and 2.5 μg/kg of remifentanil injection. Children in both groups were intubated after propofol induction and anesthetized with combination of sevoflurane-remifentanil. The incidence and severity of emergence agitation (EA), Ramsay sedation score and FLACC pain score in post-anesthesia care unit (PACU), extubation time, recovery time, PACU stay time, discharge time were recorded. RESULTS: Compared with group R, the incidence of EA was significantly lower (38.0% vs. 18.0%, P = 0.005), the maximum PAED score during recovery was significantly lower (7.7 ±3.3 vs. 8.9 ± 3.4, P = 0.027), and the Ramsay sedation score was significantly higher at 15 min after admission of PACU (4.4 ± 1.1 vs. 3.8 ± 1.4, P = 0.01), as well as discharge of PACU (2.0 ± 0.3 vs. 1.8 ±0.4, P = 0.03) in RF group . There was no significant difference in extubation time, recovery time, PACU stay time, discharge time, pain score (discharge of PACU and 2 h after operation) between two groups (P > 0.05). CONCLUSION: A single-dose injection of fentanyl (1 μg/kg) during anesthesia induction can increase the degree of sedation and reduce the incidence of EA in PACU after pediatric daytime adenotonsillectomy.

Objective:To estimate the mental symptoms in malignant tumor patients undergoing chemotherapy using DSM-5 cross cutting symptom measure.Methods:A total of 314 patients who undergoing chemotherapy in oncology department of Zhongshan Hospital, Fudan University who met all standards were chosen. The DSM-5 cross cutting symptom measure Level 1 Scale was used to assess the mental symptoms of the patients. SPSS 25.0 software was used for χ 2 test, Pearson correlation analysis and multiple regression analysis. Results:The most common symptoms in the patients were depressive symptoms(85/314, 27.1%), somatic symptoms (79/314, 25.2%), manic symptoms (78/314, 24.5% ) and anxiety symptoms (76/314, 24.3%). The proportion of anxiety symptoms in malignant tumor patients who were taken care of by other personnel(26/64, 40.6%) was significantly higher than that in patients who were taken care of by immediate relatives(50/250, 20.0%)(χ 2=12.23, P<0.05). Patients with unstable working conditions were more likely to have depressive symptoms (χ 2=7.64, P<0.05). There was a significant negative correlation between the patients' understanding of the disease and their scores of depressive symptoms, somatic symptoms, manic symptoms, anxiety symptoms and the total score of mental symptoms( r= -0.26, -0.15, -0.12, -0.25, -0.22, all P<0.05). In addition, the total score of mental symptoms of malignant tumor patients was significantly positively correlated with family burden and family status( r=0.11, 0.11, both P<0.05), and negatively correlated with patients' education ( r=-0.13, P<0.05). Multiple regression analysis showed that the degree of understanding of the disease( β=-0.203) and family status( β=0.197) were the influencing factors of mental symptoms of inpatients malignant tumors undergoing chemotherapy in general hospital ( F=13.653, P<0.001). Conclusion:Malignant tumor patients undergoing chemotherapy may have a variety of mental symptoms. The high incidence mainly includes depressive symptoms, somatic symptoms, manic symptoms and anxiety symptoms. The understanding of the patients to the disease and family situation are the main influencing factors.

Background and Objectives: Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. Methods: and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. Conclusions Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.