OBJECTIVE To evaluate the efficacy and safety of rituximab （RTX） in the treatment of primary Sjögren syndrome （pSS）. METHODS Randomized controlled trials （RCTs） on the effects of RTX （trial group） versus placebo （control group） in the treatment of pSS were searched from the Cochran Library， PubMed， Embase， Medline， Web of Science， VIP， CNKI， Wanfang， and other databases during the inception to February 2024. After literature screening and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS Seven RCTs were finally included， involving a total of 518 patients. Results of meta-analysis showed that European League Against Rheumatism Sjögren syndrome disease activity index （ESSDAI） score [MD＝－1.17， 95%CI（－1.52， －0.82）， P＜0.000 01] and oral dryness visual analogue scale （VAS） score [MD＝－3.97， 95%CI （－5.08， －2.86）， P＜0.000 01] in the trial group were significantly lower than the control group； unstimulated salivary flow rate [SMD＝0.64， 95%CI（0.41， 0.87）， P＜0.000 01] and Schirmer score [MD＝0.19， 95%CI（0.18， 0.20）， P＜0.000 01] were significantly higher than the control group. There was no statistical significance in response rate [RD＝0.10， 95%CI（－0.04， 0.23）， P＝0.16]， fatigue VAS score [MD＝－12.50， 95%CI（－35.14， 10.15）， P＝0.28]， European League Against Rheumatism Sjögren syndrome patient reported index （ESSPRI） score [MD＝0.33， 95%CI（－0.53， 1.18）， P＝0.46]， Short-form 36 health survey physical component summary （SF36-PCS） score [MD＝0.90， 95%CI（－2.97， 4.78）， P＝0.65]， SF-36 mental component summary （SF36-MCS） score [MD＝0.11， 95%CI（－0.41， 0.63）， P＝0.68]， total salivary gland ultrasound score [SMD＝－1.91， 95%CI（－4.01， 0.19）， P＝0.07] or the incidence of adverse drug reactions [OR＝1.15，95%CI（0.62，2.13），P＝0.66] between 2 groups. CONCLUSIONS RTX has advantages in the improvement of ESSDAI score， unstimulated salivary flow rate， Schirmer score and oral dryness VAS score in pSS patients， and has a good safety profile. However， it did not exhibit significant improvement in fatigue VAS score， ESSPRI score， SF36-PCS score， SF36-MCS score or response rates.

Objective: To assess the awareness and associated factors of wild mushroom poisoning among students in Guizhou Province, so as to provide a scientific foundation for wild mushroom poisoning prevention and control among students. Methods: By a multi stage stratified cluster random sampling method, 1 162 students from Guizhou Province were selected in May 2024. The questionnaire survey was administered to evaluate knowledge regarding wild mushroom poisoning. Data were analyzed employing the χ 2 test and Logistic regression model. Results: Among the nine questions assessing awareness of wild mushroom poisoning, only three had the awareness rate exceeding 70%. Binary Logistic regression analysis revealed that students who "actively learn about the prevention of wild mushroom poisoning" ( OR=0.48, 95%CI =0.26-0.92) and "spread knowledge about wild mushroom poisoning to others" ( OR=0.47, 95%CI =0.33-0.69) scored higher on the wild mushroom poisoning knowledge questions ( P <0.05). Conversely, students with a habit of consuming wild mushrooms ( OR=1.52, 95%CI =1.15-2.02) scored lower ( P < 0.05 ). 42.3% of the students suggested that scientific dissemination and publicity about wild mushrooms should be intensified. Conclusions The awareness rate of wild mushroom poisoning knowledge among students in Guizhou Province requires further attention. Comprehensive knowledge should be disseminated systematically through various channels to further improve students awareness of the prevention and control of wild mushroom poisoning.

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

Objective To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer(NSCLC)cells.Methods CCK-8 assay,colony formation assay,and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation,survival,and apoptosis of PC-9 and HCC827 cells,and their synergistic effect was evaluated using the SynergyFinder model.In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib,the changes in cell invasion and migration abilities were assessed with Transwell assay,and the expressions of apoptosis-and invasion/migration-related proteins(Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9)and the key PI3K-Akt pathway proteins were detected using Western blotting.Results In PC-9 cells,the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L,respectively,with a synergy score(ZIP)of 19.112;in HCC827 cells,their IC50 was 2.961 μmol/L and 7.934 μmol/L,respectively,with a ZIP of 12.325.Compared with aumolertinib and anlotinib used alone,their combined treatment more strongly inhibited the proliferation and survival,enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells.Western blotting showed that in both PC-9 and HCC827 cells,the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins,downregulated the expressions of Bcl-2,vimentin,MMP2,and MMP9 proteins,and reduced phosphorylation levels of PI3K and Akt.Conclusion Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway,suggesting a potentially new option for NSCLC treatment.

Objective To investigate the expression of Acyl-CoA synthetase long-chain family member 4(ACSL4)in liver cancer and its role in regulating ferroptosis and proliferation of liver cancer cells.Methods Clinical samples of liver cancer and adjacent normal liver tissues were examined for malondialdehyde(MDA)contents and for expressions of mRNA and protein expressions of ACSL4 and proliferating cell nuclear antigen(PCNA)using RT-qPCR and Western blotting.Human liver cancer Huh-7 cells were treated with Erastin(a ferroptosis inducer),Fer-1(a ferroptosis inhibitor),or both,and the changes in expression levels of MDA,ACSL4 and PCNA were detected,and the cell proliferation was assessed with plate cloning assay.Results MDA contents were lower and ACSL4 and PCNA expressions were higher significantly in liver cancer tissues than in adjacent liver tissues.In Huh-7 cells,Erastin treatment significantly inhibited mRNA and protein expressions of ACSL4 and PCNA,suppressed cell proliferation,and increased MDA contents.Fer-1 alone did not produce significant effect on cell viability but reversed the effect of Erastin on ACSL4 and PCNA expressions,cell proliferation and MDA contents.Conclusion ACSL4 level is significantly overexpressed in liver cancer.Erastin increases MDA contents and down-regulates ACSL4 expression,thereby promoting ferroptosis and inhibiting proliferation of liver cancer cells,and these effects can be reversed by Fer-1.

Objective To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer(NSCLC)cells.Methods CCK-8 assay,colony formation assay,and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation,survival,and apoptosis of PC-9 and HCC827 cells,and their synergistic effect was evaluated using the SynergyFinder model.In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib,the changes in cell invasion and migration abilities were assessed with Transwell assay,and the expressions of apoptosis-and invasion/migration-related proteins(Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9)and the key PI3K-Akt pathway proteins were detected using Western blotting.Results In PC-9 cells,the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L,respectively,with a synergy score(ZIP)of 19.112;in HCC827 cells,their IC50 was 2.961 μmol/L and 7.934 μmol/L,respectively,with a ZIP of 12.325.Compared with aumolertinib and anlotinib used alone,their combined treatment more strongly inhibited the proliferation and survival,enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells.Western blotting showed that in both PC-9 and HCC827 cells,the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins,downregulated the expressions of Bcl-2,vimentin,MMP2,and MMP9 proteins,and reduced phosphorylation levels of PI3K and Akt.Conclusion Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway,suggesting a potentially new option for NSCLC treatment.

Objective To investigate the expression of Acyl-CoA synthetase long-chain family member 4(ACSL4)in liver cancer and its role in regulating ferroptosis and proliferation of liver cancer cells.Methods Clinical samples of liver cancer and adjacent normal liver tissues were examined for malondialdehyde(MDA)contents and for expressions of mRNA and protein expressions of ACSL4 and proliferating cell nuclear antigen(PCNA)using RT-qPCR and Western blotting.Human liver cancer Huh-7 cells were treated with Erastin(a ferroptosis inducer),Fer-1(a ferroptosis inhibitor),or both,and the changes in expression levels of MDA,ACSL4 and PCNA were detected,and the cell proliferation was assessed with plate cloning assay.Results MDA contents were lower and ACSL4 and PCNA expressions were higher significantly in liver cancer tissues than in adjacent liver tissues.In Huh-7 cells,Erastin treatment significantly inhibited mRNA and protein expressions of ACSL4 and PCNA,suppressed cell proliferation,and increased MDA contents.Fer-1 alone did not produce significant effect on cell viability but reversed the effect of Erastin on ACSL4 and PCNA expressions,cell proliferation and MDA contents.Conclusion ACSL4 level is significantly overexpressed in liver cancer.Erastin increases MDA contents and down-regulates ACSL4 expression,thereby promoting ferroptosis and inhibiting proliferation of liver cancer cells,and these effects can be reversed by Fer-1.

Objective:To explore the optimum opportunity for lumbodorsal muscles exercises of patients undergoing posterior lumbar decompression and instrumentation, and investigate its effect on the rehabilitation outcomes and kinesiophobia.Methods:A randomized controlled trial was used. By convenient sampling method, a total of 120 lumbar disc herniation patients were prospectively selected from Affiliated Nantong Hospital of Shanghai(Nantong Sixth People′s Hospital) from February 2020 to December 2021. The paitients were assigned to early group, middle group and late group, with 40 cases in each group. All patients were given routine postoperative care and lumbodorsal muscles exercises. The early group started to exercise 10th day after operation, the middle group started to exercise 3 weeks after operation, and the late group started to exercise 6 weeks after operation. The intervention effect was respectively evaluated by Japanese Orthopaedics Association (JOA) and Tampa Scale for Kinesiophobia (TSK).Results:There were 3, 1 and 1 missing cases in the early, middle and late group respectively, the age in the 3 groups were (56.05 ± 11.77), (57.33 ± 14.64) and (54.23 ± 15.73) years old in turn. Three months after exercising, the total score of JOA in the early, middle and late group were (25.32 ± 2.45), (24.44 ± 2.19) and (22.13 ± 1.58) in turn, the difference was significant ( F=23.64, P<0.05); the score of TSK in the early, middle and late group were (37.95 ± 6.81), (34.18 ± 6.39) and (33.33 ± 7.36) in turn, the difference was significant ( F=4.82, P<0.05). Conclusions:Lumbodorsal muscles exercises start at 3 weeks after operation can significantly improve the rehabilitation outcome of lumbar disc herniation patients undergoing posterior lumbar decompression and instrumentation, and will not increase the level of kinesiophobia, its can be consider as optimum opportunity for lumbodorsal muscles exercises.

Objective:Based on the accounting results of total health expenditure in different regions since the 18th National Congress of the Communist Party of China,to analyze the regional disparity and evolution trend of health financing level and financing structure in 2012-2022,so as to provide references for subsequent adjustment and improvement.Methods:Range,standard deviation and coefficient of variation were used to analyze the degree of absolute and relative differences of total regional health expenditure in China and the changing characteristics of regional total health expenditure differences since the New Era(2012-2022).Results:Since 2012,the total health expenditure in various regions has been increasing continuously,and the average annual growth rate of total health expenditure is higher than that of the economy in this region.The relative difference of the proportion of total health expenditure to GDP in 31 provinces has converged in the fluctuation,but the absolute difference is still very large;the relative gap and absolute gap of per capita total health expenditure are expanding;the absolute difference in the proportion of out-of-pocket payments to total health expenditure has narrowed,while the relative difference has gradually narrowed.Conclusion:There are obvious differences in the growth rate of total health expenditure in different regions,so it is suggested that"appropriate growth"and"accurate control of health expenditure"should be carried out in parallel;the regional disparity of health investment in China has not improved,especially the regional disparity of per capita investment level continues to increase,so narrowing the regional disparity is a long-term task.The gap of regional financing structure has converged,but the gap is still large.

Objective:To investigate the diagnostic value of nucleic acid matrix-assisted laser desorption ionization-time of flight mass spectrometry（MALDI-TOF MS）in sputum smear-negative patients with nontuberculous Mycobacterial（NTM）pulmonary disease.Methods:Clinical data of 123 patients suspected of NTM pulmonary disease admitted in Public Health Clinical Center Affiliated to Shandong University between July 2022 and November 2023 were retrospectively analyzed. Bronchoalveolar lavage fluid（BALF）specimens were collected for MALDI-TOF MS assay and MGIT 960 culture. The diagnostic efficacy of MALDI-TOF MS for NTM pulmonary disease in patients with negative sputum smears for acid-fast bacilli was evaluated with receiver operating characteristic（ROC）curve. Statistical analysis was performed using SPSS 26.0 software and MedCalc statistical software.Results:Diagnosis of NTM pulmonary disease was finally confirmed in 66 out of the 123 suspected patients. It took 8 to 24 h for MALDI-TOF MS to identify NTM species and resistance. By MALDI-TOF MS，72 NTM strains were identified，with the Mycobacterium avium complex being the most prevalent（34 strains，47.22%），followed by the Mycobacterium abscessus complex（13 strains，18.06%）；resistance to macrolides was detected in 6 cases，while no resistance to aminoglycosides was found. It took 9 to 45 days for BALF MGIT 960 culture to identify NTM，and took 7 to 15 days for NTM typing and drug sensitivity testing. By BALF MGIT 960 culture，28 NTM strains were identified；and 1 case was found to be resistant to macrolides. Using confirmed diagnosis as the gold standard，MALDI-TOF MS demonstrated higher sensitivity，negative predictive value，and agreement rate compared to MGIT 960 culture（84.85% vs. 42.42%，81.13% vs. 56.32%，80.49% vs. 62.60%， χ2=25.667，8.998，9.664， P<0.05 or <0.01）. The area under ROC curve（AUC）for MALDI-TOF MS was significantly higher than that of MGIT 960 culture（0.801 vs. 0.642， Z=3.300， P=0.001）. Conclusion:Compared to MGIT 960 culture，MALDI-TOF MS exhibits superior diagnostic efficiency in detecting NTM pulmonary disease in patients with acid-fast bacilli smear-negative sputum，with advantage of rapidly identifying NTM species and resistance.