Objective To investigate the mechanism by which Shenqi Xiaozheng Decoction-medicated serum regulates c-Myc/SLC1A5/GLS1 signaling axis to inhibit glutamine(Gln)metabolism and activate immunogenic cell death(ICD)in non-small cell lung cancer(NSCLC)cells.Methods A549 cells were divided into control group,model group,Shenqi Xiaozheng Decoction-medicated serum low-,medium-and high-dosage groups and positive control group.A Gln-dependent growth model was established,and cells were treated with different concentrations of Shenqi Xiaozheng Decoction-medicated serum or the SLC1A5 inhibitor V-9302.Cell proliferation was assessed by CCK-8,EdU and colony formation assays;Cell invasion and migration were evaluated using Transwell and wound-healing assays;intracellular Gln,glutathione(GSH),and α-ketoglutarate(α-KG)contents were determined by colorimetric assay;reactive oxygen species(ROS)contents were measured with fluorescent probes;Western blot was used to detect the protein expressions of E-cadherin,N-cadherin,c-Myc,SLC1A5 and GLS1;c-Myc/SLC1A5 colocalization and high mobility group box 1(HMGB1)expression were assessed by dual immunofluorescence staining;flow cytometry was used to evaluate calreticulin(CRT)exposure on the cell surface,and ATP and HMGB1 contents in cell supernatants were quantified by ELISA.Results Compared with the control group,the model group showed significantly increased A549 cell viability,EdU-positive rate and migration rate(P<0.05),as well as higher colony counts and invasion cell numbers(P<0.05);cellular Gln,GSH and α-KG contents were significantly elevated(P<0.05,P<0.01),while ROS content were not significantly different(P>0.05),E-cadherin protein expression significantly decreased,whereas the protein expressions of N-cadherin,c-Myc,SLC1A5 and GLS1 significantly increased(P<0.05,P<0.01).c-Myc and SLC1A5 colocalization was enhanced,HMGB1 expression was significantly increased(P<0.01),CRT exposure significantly increased(P<0.01),and ATP and HMGB1 contents in cell supernatant were significantly elevated(P<0.05,P<0.01).Compared with the model group,Shenqi Xiaozheng Decoction-medicated serum at different concentrations significantly inhibited Gln-stimulated A549 cell proliferation,migration and invasion in a dosage-dependent manner.Mechanistic studies indicated that Shenqi Xiaozheng Decoction could reduce Gln uptake and synthesis of its metabolic products GSH and α-KG,induce ROS accumulation,up-regulate protein expression of E-cadherin,down-regulate the protein expressions of N-cadherin,c-Myc,SLC1A5 and GLS1(P<0.05,P<0.01),and enhance CRT exposure,ATP release and HMGB1 secretion(P<0.01).Conclusion Shenqi Xiaozheng Decoction may exert a synergistic"metabolism-immunity"antitumor effect by inhibiting c-Myc/SLC1A5/GLS1 axis-mediated Gln uptake,inducing ROS accumulation,and activating ICD signaling.

Background:With the widespread use of vonoprazan-based dual therapy for Helicobacter pylori(Hp)eradication,a comparative analysis of its efficacy and safety against bismuth-containing quadruple therapy is warranted.Aims:To compare the efficacy and safety of vonoprazan and amoxicillin-based 14-day dual therapy and 10-day bismuth-containing quadruple therapy for eradication of Hp infection.Methods:This study is a single-center,prospective,randomized,controlled,open-label,non-inferiority trial.Patients with chronic gastritis,diagnosed with Hp infection and scheduled for eradication therapy at Yuancheng District People's Hospital between December 2023 and December 2025 are planned to enroll in this study and randomly assigned into two groups.Patients in the control group received bismuth-containing quadruple therapy(vonoprazan 20 mg+bismuth potassium citrate 220 mg+amoxicillin 1.0 g+furazolidone 0.1 g,all twice daily)for 10 days,and those in the treatment group received dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1.0 g three times daily)for 14 days.Both groups were supplemented with compound lactobacillus capsule.Adverse events were recorded during the treatment period.Hp eradication was assessed by 13C-or 14C-urea breath test at least four weeks after the completion of therapy.Results:As of the interim analysis,a total of 160 patients have been enrolled in the study,with 80 in each group.The per-protocol(PP)Hp eradication rates were 93.6%(95%CI:85.6%-97.9%)for the treatment group and 94.7%(95%CI:86.8%-98.5%)for the control group,with an intergroup difference of-1.147%(95%CI:-8.5%-6.1%).While in intention-to-treat(ITT)analysis,the Hp eradication rates were 91.2%(95%CI:82.9%-96.4%)for the treatment group and 90.0%(95%CI:81.2%-95.6%)for the control group,with an intergroup difference of 1.25%(95%CI:-7.8%-10.4%).Non-inferiority was confirmed for both PP and ITT analyses(P=0.012,P=0.021).No significant difference in symptoms relieve was observed between the two groups(92.1%vs.91.0%,P=0.81).The incidence of adverse events was significantly lower in the treatment group(7.7%vs.18.4%,P=0.043).The symptoms were mild and required no intervention.Conclusions:The 14-day vonoprazan-amoxicillin dual therapy is non-inferior to 10-day bismuth-containing quadruple therapy in Hp eradication rate with fewer adverse events,making it a preferred option for family-based management and primary care settings for Hp eradication.

Objective:To explore the association between serum selenium levels and total cancer risk in humans.Methods:A systematic search was conducted for Chinese and English literature on the association between selenium and cancer risk published up to December 2023 in the Chinese National Knowledge Infrastructure (CNKI), Wanfang, PubMed, EMbase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases by using “neoplasms” “selenium” “prospective-studies” (both in English and Chinese) as keywords. The meta-analysis was performed using a random-effect model. The linear dose-response relationship was analyzed using a generalized least squares regression model, and the non-linear dose-response relationship was analyzed using a restricted cubic spline regression model. Publication bias was assessed by funnel plots and Egger′s regression asymmetry test.Results:A total of 12 prospective studies were included from 16 408 articles retrieved, including seven studies from Europe, four from America, and one from Asia, with a total of 4 586 cancer cases reported. Meta-analysis revealed an inverse association between baseline serum selenium levels and total cancer risk ( RR=0.68, 95% CI: 0.57-0.82, P=0.000). Furthermore, serum selenium was found to have a protective effect on both the incidence ( RR=0.66, 95% CI: 0.53-0.84, P=0.001) and mortality ( RR=0.70, 95% CI: 0.50-0.98, P=0.035) of total cancer. The inverse association between serum selenium and the incidence of total cancer was more pronounced in populations with low baseline serum selenium levels ( RR=0.65, 95% CI: 0.48-0.89, P=0.007). Additionally, dose-response meta-analysis showed that for every 10 μg/L increase in baseline serum selenium concentration, there was a 26% reduction in incidence of total cancer ( RR=0.74, 95% CI: 0.46-0.83, P=0.229) and a 6% reduction in mortality of total cancer ( RR=0.94, 95% CI: 0.86-0.96, P=0.229). Conclusion:Serum selenium is negatively associated with the incidence and mortality of total cancer.

Under the current situation of "low prevalence and low infection" of schistosomiasis in China, and to provide a basis for achieving the goal of eliminating schistosomiasis by 2030 proposed by the Healthy China Action (2019 - 2030) as scheduled, the Hunan Provincial Corps Hospital of the Chinese People's Armed Police Force established a schistosomiasis monitoring and early warning index system based on the previous studies on schistosomiasis early warning index system and the recent literature analysis, combined with the current potential risk factors affecting the transmission and prevalence of schistosomiasis, and organized two rounds of expert consultation and carried out project promotion meetings. The experts reached a consensus on the comprehensiveness and practicability of the index system, aiming to lay a solid foundation for construction of China's schistosomiasis prevention and control early warning system.

Background:With the widespread use of vonoprazan-based dual therapy for Helicobacter pylori(Hp)eradication,a comparative analysis of its efficacy and safety against bismuth-containing quadruple therapy is warranted.Aims:To compare the efficacy and safety of vonoprazan and amoxicillin-based 14-day dual therapy and 10-day bismuth-containing quadruple therapy for eradication of Hp infection.Methods:This study is a single-center,prospective,randomized,controlled,open-label,non-inferiority trial.Patients with chronic gastritis,diagnosed with Hp infection and scheduled for eradication therapy at Yuancheng District People's Hospital between December 2023 and December 2025 are planned to enroll in this study and randomly assigned into two groups.Patients in the control group received bismuth-containing quadruple therapy(vonoprazan 20 mg+bismuth potassium citrate 220 mg+amoxicillin 1.0 g+furazolidone 0.1 g,all twice daily)for 10 days,and those in the treatment group received dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1.0 g three times daily)for 14 days.Both groups were supplemented with compound lactobacillus capsule.Adverse events were recorded during the treatment period.Hp eradication was assessed by 13C-or 14C-urea breath test at least four weeks after the completion of therapy.Results:As of the interim analysis,a total of 160 patients have been enrolled in the study,with 80 in each group.The per-protocol(PP)Hp eradication rates were 93.6%(95%CI:85.6%-97.9%)for the treatment group and 94.7%(95%CI:86.8%-98.5%)for the control group,with an intergroup difference of-1.147%(95%CI:-8.5%-6.1%).While in intention-to-treat(ITT)analysis,the Hp eradication rates were 91.2%(95%CI:82.9%-96.4%)for the treatment group and 90.0%(95%CI:81.2%-95.6%)for the control group,with an intergroup difference of 1.25%(95%CI:-7.8%-10.4%).Non-inferiority was confirmed for both PP and ITT analyses(P=0.012,P=0.021).No significant difference in symptoms relieve was observed between the two groups(92.1%vs.91.0%,P=0.81).The incidence of adverse events was significantly lower in the treatment group(7.7%vs.18.4%,P=0.043).The symptoms were mild and required no intervention.Conclusions:The 14-day vonoprazan-amoxicillin dual therapy is non-inferior to 10-day bismuth-containing quadruple therapy in Hp eradication rate with fewer adverse events,making it a preferred option for family-based management and primary care settings for Hp eradication.

Objective:To explore the association between serum selenium levels and total cancer risk in humans.Methods:A systematic search was conducted for Chinese and English literature on the association between selenium and cancer risk published up to December 2023 in the Chinese National Knowledge Infrastructure (CNKI), Wanfang, PubMed, EMbase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases by using “neoplasms” “selenium” “prospective-studies” (both in English and Chinese) as keywords. The meta-analysis was performed using a random-effect model. The linear dose-response relationship was analyzed using a generalized least squares regression model, and the non-linear dose-response relationship was analyzed using a restricted cubic spline regression model. Publication bias was assessed by funnel plots and Egger′s regression asymmetry test.Results:A total of 12 prospective studies were included from 16 408 articles retrieved, including seven studies from Europe, four from America, and one from Asia, with a total of 4 586 cancer cases reported. Meta-analysis revealed an inverse association between baseline serum selenium levels and total cancer risk ( RR=0.68, 95% CI: 0.57-0.82, P=0.000). Furthermore, serum selenium was found to have a protective effect on both the incidence ( RR=0.66, 95% CI: 0.53-0.84, P=0.001) and mortality ( RR=0.70, 95% CI: 0.50-0.98, P=0.035) of total cancer. The inverse association between serum selenium and the incidence of total cancer was more pronounced in populations with low baseline serum selenium levels ( RR=0.65, 95% CI: 0.48-0.89, P=0.007). Additionally, dose-response meta-analysis showed that for every 10 μg/L increase in baseline serum selenium concentration, there was a 26% reduction in incidence of total cancer ( RR=0.74, 95% CI: 0.46-0.83, P=0.229) and a 6% reduction in mortality of total cancer ( RR=0.94, 95% CI: 0.86-0.96, P=0.229). Conclusion:Serum selenium is negatively associated with the incidence and mortality of total cancer.

Under the current situation of "low prevalence and low infection" of schistosomiasis in China, and to provide a basis for achieving the goal of eliminating schistosomiasis by 2030 proposed by the Healthy China Action (2019 - 2030) as scheduled, the Hunan Provincial Corps Hospital of the Chinese People's Armed Police Force established a schistosomiasis monitoring and early warning index system based on the previous studies on schistosomiasis early warning index system and the recent literature analysis, combined with the current potential risk factors affecting the transmission and prevalence of schistosomiasis, and organized two rounds of expert consultation and carried out project promotion meetings. The experts reached a consensus on the comprehensiveness and practicability of the index system, aiming to lay a solid foundation for construction of China's schistosomiasis prevention and control early warning system.

Objective To investigate the mechanism by which Shenqi Xiaozheng Decoction-medicated serum regulates c-Myc/SLC1A5/GLS1 signaling axis to inhibit glutamine(Gln)metabolism and activate immunogenic cell death(ICD)in non-small cell lung cancer(NSCLC)cells.Methods A549 cells were divided into control group,model group,Shenqi Xiaozheng Decoction-medicated serum low-,medium-and high-dosage groups and positive control group.A Gln-dependent growth model was established,and cells were treated with different concentrations of Shenqi Xiaozheng Decoction-medicated serum or the SLC1A5 inhibitor V-9302.Cell proliferation was assessed by CCK-8,EdU and colony formation assays;Cell invasion and migration were evaluated using Transwell and wound-healing assays;intracellular Gln,glutathione(GSH),and α-ketoglutarate(α-KG)contents were determined by colorimetric assay;reactive oxygen species(ROS)contents were measured with fluorescent probes;Western blot was used to detect the protein expressions of E-cadherin,N-cadherin,c-Myc,SLC1A5 and GLS1;c-Myc/SLC1A5 colocalization and high mobility group box 1(HMGB1)expression were assessed by dual immunofluorescence staining;flow cytometry was used to evaluate calreticulin(CRT)exposure on the cell surface,and ATP and HMGB1 contents in cell supernatants were quantified by ELISA.Results Compared with the control group,the model group showed significantly increased A549 cell viability,EdU-positive rate and migration rate(P<0.05),as well as higher colony counts and invasion cell numbers(P<0.05);cellular Gln,GSH and α-KG contents were significantly elevated(P<0.05,P<0.01),while ROS content were not significantly different(P>0.05),E-cadherin protein expression significantly decreased,whereas the protein expressions of N-cadherin,c-Myc,SLC1A5 and GLS1 significantly increased(P<0.05,P<0.01).c-Myc and SLC1A5 colocalization was enhanced,HMGB1 expression was significantly increased(P<0.01),CRT exposure significantly increased(P<0.01),and ATP and HMGB1 contents in cell supernatant were significantly elevated(P<0.05,P<0.01).Compared with the model group,Shenqi Xiaozheng Decoction-medicated serum at different concentrations significantly inhibited Gln-stimulated A549 cell proliferation,migration and invasion in a dosage-dependent manner.Mechanistic studies indicated that Shenqi Xiaozheng Decoction could reduce Gln uptake and synthesis of its metabolic products GSH and α-KG,induce ROS accumulation,up-regulate protein expression of E-cadherin,down-regulate the protein expressions of N-cadherin,c-Myc,SLC1A5 and GLS1(P<0.05,P<0.01),and enhance CRT exposure,ATP release and HMGB1 secretion(P<0.01).Conclusion Shenqi Xiaozheng Decoction may exert a synergistic"metabolism-immunity"antitumor effect by inhibiting c-Myc/SLC1A5/GLS1 axis-mediated Gln uptake,inducing ROS accumulation,and activating ICD signaling.

The pathogenesis of ulcerative colitis(UC)is still unclear,and the pathogenesis based on intestinal mucosal immune imbalance is now widely recognized."Spleen as the defense"refers to the function of the spleen to protect the body and defend against pathogenic factors,which is highly consistent with modern mucosal immunology theory.The abnormal function of"Spleen as the defense"is the key reason for the immune imbalance of UC intestinal mucosa.In this paper,"spleen as the defense"as the starting point,to explore the mechanism of UC intestinal mucosal immune dysfunction,to consolidate the theoretical basis for the treatment of UC based on spleen,and to provide a theoretical basis for the treatment of UC from the perspective of restoring intestinal mucosal immune homeostasis.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.