ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

Purpose To study the expression of of mono-clonal and polyclonal TRPS1 antibodies in synovial sarcoma,and to explore the value of TRPS1 in the diagnosis and differen-tial diagnosis of synovial sarcoma and the sensitivity and speci-ficity of polyclonal TRPS1 for the diagnosis of synovial sarcoma.Methods Immunohistochemical EnVision method was used to detect the expression of monoclonal and polyclonal TRPS1 anti-bodies in the synovial sarcomas and its mimickers.Results A-mong 31 cases of synovial sarcoma,the positive rates of poly-clonal and monoclonal TRPS1 antibodies were 54.8％and 93.5％,respectively.Of 30 synovial sarcoma mimicking le-sions,2 were positive for TRPS1(polyclonal antibody),which was 6.67％,and TRPS1 was more frequently expressed in syno-vial sarcoma than in non-synovial sarcoma(P＜0.05).The sensitivity of polyclonal TRPS1 antibody for the diagnosis of syn-ovial sarcoma was 93.5％,and the specificity was 93.3％.Conclusion Polyclonal TRPS1 antibody has a higher sensitivity and specificity for the diagnosis of synovial sarcoma and it there-fore is recommended in routine pathologic diagnosis.

Tumor microenvironment(TME)is a complex cellular environment where tumor cells reside,along with various types of cells and extracellular components surrounding the tumor cells.Immune cells are key components of TME,including tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),lymphocytes,regulatory T cells(Tregs),natural killer cells(NK cells),dendritic cells(DCs),and many others.It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy,radiotherapy,targeted therapy,and immunotherapy,and a leading cause of treatment failure.Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME.Consequently,overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment.In recent years,with in-depth research into immune cells within TME,significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells.Furthermore,therapeutic strategies that target these immune cells,signaling pathways,or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment.This article reviews the research advancements regarding the roles of TAMs,MDSCs,Tregs,and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance.Additionally,we explore the relationship of tumor-associated neutrophils(TANs)and B regulatory cells(Bregs)with tumor drug resistance.It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies.

Objective:To survey the status quo and influencing factors of contracted family doctor pay services in urban communities of Suzhou city.Methods:This study was a cross-sectional study. A questionnaire survey on the status quo and influencing factors of contracted family doctor pay services was conducted from July to October 2022 among 750 residents from 40 communities of 4 subdistricts in Suzhou Gusu District, selected by stratified random sampling method. A self-designed questionnaire was used for the survey, which included demographic information, status quo of pay services among residents and factors influencing the service contracting. Chi-square test and binary logistic regression were used to analyze the influencing factors of contracted family doctor pay services.Results:A total of 750 questionnaires were distributed, with 720 valid ones returned at a recovery rate of 96.0%. Among the 720 residents, 370 (51.4%) were female, and 300 (41.7%) were between the age of 35 and 60 years old. There were 71 residents who had contracted pay services with a contracting rate of 9.9% (71/720), and the renewal rate was 80.3% (57/71). The top 3 reasons for signing the contract were health guidance (67.6%, 48/71), medical counselling (63.4%, 45/71) and 3 free consultations (57.7%, 41/71). The top 3 reasons for not signing a contract were not needing services (49.9%, 324/649), not knowing about contracted services (41.9%, 272/649) and rarely visiting the community health service center (25.6%, 166/649). Age ( χ2=21.072), marital status ( χ2=10.969), knowing the family doctor team ( χ2=145.954), knowing the family doctor contract system ( χ2=133.981), knowing the content and the rights of the contracted services ( χ2=132.905), using primary medical institutions as first choice for common and chronic diseases ( χ2=13.532), multiple comorbid chronic diseases ( χ2=30.024), being agreed by family members ( χ2=46.258), signing contract in family members ( χ2=108.833) or relatives and friends ( χ2=47.492), and experience in community health service centers ( χ2=26.116) were significantly associated with the contract signing (all P<0.05). Logistic regression analysis showed that knowing family doctor team well ( OR=23.13,95% CI:5.05-105.97) or very well( OR=95.28,95% CI: 10.71-847.68); having ≥3 chronic diseases compared to no chronic diseases ( OR=5.60, 95% CI: 1.88-16.75, P<0.05); contracting agreed by family members compared to not agreed ( OR=2.66, 95% CI: 1.03-6.84, P<0.05); signing contract in family members compared to not signing ( OR=4.42, 95% CI:2.05-9.55, P<0.05) were independent influencing factors of signing contract of family doctor pay services. Conclusions:The rate of contracted of family doctor pay services in Gusu District of Suzhou City is relatively low. Knowing the family doctor team, having multiple comorbid chronic diseases, agreement among family members, and signing contract in family members are influencing factors of contracted family doctor pay services.

Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients,detect their related resistance genes,and provide reference for the clinical treatment of carbapenem resistant Enterobacteria(CRE)infections and the rational use of antibiotics.Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected.The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method.The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR.Results Among the 400 strains,51 strains were identified as CRE,accounting for 12.75%.Among these,49 strains produced carbapenemases,with 41 strains(80.39%)being CR Klebsiella pneumoniae and 10 strains(19.61%)being CR Escherichia coli.Among the CRE strains,34 strains(66.67%)carried blaKPC,13 strains(25.49%)carried blaNDM,and 2 strains(3.92%)carried blaOXA-48.Conclusion Compared with other commonly used antibiotics,colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli.In addition,there was good concordance between drug resistance phenotype testing and genotyping.Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.

Objective:To evaluate the risk factors for pulmonary embolism in patients with spinal injury.Methods:Literature on risk factors for pulmonary embolism after spinal injury was searched on CNKI, Wanfang database, VIP Chinese Science, PubMed, Embase, Cochrane Library, Up to Date databases from inception through November 2023. A Meta-analysis was performed with the software of RevMan 5.4 after two researchers screened the literature independently according to the inclusion and exclusion criteria, extracted the data and evaluated their quality. Correlations of gender, age, surgical duration, intervertebral disc fusion, body mass index, comorbidity, medicine prophylaxis, deep venous thrombosis (DVT) history, and length of hospital stay with the incidence of pulmonary embolism in patients with spinal injury were evaluated.Results:A total of 10 studies were enrolled, including 2 prospective cohort studies and 8 cross-sectional studies. The total sample size was 401 698 patients, with 525 in the pulmonary embolism group and 401 173 in the non-pulmonary embolism group. The Meta analysis showed that gender ( OR=1.59, 95% CI 1.20, 1.97), age ( OR=1.58, 95% CI 1.19, 2.10), surgical duration ( OR=2.56, 95% CI 1.84, 3.56), DVT history ( OR=15.84, 95% CI 1.88, 133.25) and length of hospital stay ( OR=1.08, 95% CI 1.07, 1.09) were statistically significantly correlated with the incidence of pulmonary embolism in patients with spinal injury ( P<0.01), while intervertebral fusion, body mass index, comorbidity, and medicine prophylaxis were not correlated with the incidence of pulmonary embolism ( P>0.05). Conclusion:Gender, age, surgical duration, DVT history and length of hospital stay are risk factors for pulmonary embolism in patients with spinal injury.

Objective:To test the practical effect of the research projects outpatient strategy for application of the National Natural Science Foundation (NSFC) in a hospital of Chinese medicine.Methods:We compared the number and success rate of the National Natural Science Foundation of China grant awards before and after the implementation of the research projects outpatient strategy, and further analyzed the promotional effect of the research projects outpatient strategy on general programs and youth scientists funds through univariate analysis and multivariate Logistic regression.Results:Since the implementation of the research projects outpatient strategy, both the number of NSFC grant awards and the success rate continuously increased, indicating that the strategy played a positive role in improving the overall success rate of the hospital. However, this effect was primarily reflected in the assistance provided to applications for youth scientists funds. The main favorable factor for winning general programs was the applicant′s preliminary foundation. Applicants who have previously received NSFC funding had a higher success rate.Conclusions:The strategy of research projects outpatient can promote the winning of NSFC youth scientists funds.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Organophosphorus flame retardants (OPFRs) pollution and its impacts on human health are of global concern. The review briefly reviewed the current state-of-knowledge on exposure assessment and epidemiological evidence of OPFRs-related health effects. Specifically, this paper provided an overview and comparison of the levels of respiratory and gastrointestinal exposure to OPFRs and their body burden in different populations worldwide; summarized potential adverse effects of long-term low-level OPFRs exposure on children's neurodevelopment, adults' reproductive system, and thyroid function. Available epidemiological studies have revealed that the OPFRs exposure level of Chinese population is low, and rice consumption may be a potential source of exposure to OPFRs; OPFRs such as tris (1-chloro-2-propyl) phosphate (TCIPP) and tris (2-chloroethyl) phosphate (TCEP) have both neurotoxicity and reproductive toxicity, and possibly affect the thyroid function in adults and increase the risk of wheezing and eczema in children. Finally, the future research focus on population exposure and health effects of OPFRs was prospected.

Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.