ObjectiveQi deficiency and phlegm dampness syndrome is a common type of clinical traditional Chinese medicine（TCM） syndrome. However， there is no standard， scientific， and accurate report on the construction of animal models of Qi deficiency and phlegm dampness syndrome. This study aims to construct a mouse model of Qi deficiency and phlegm dampness syndrome by using a multi-factor composite modeling method and to evaluate the model. MethodsTwenty-one C57BL/6 mice were randomly divided into three groups with seven mice in each group， which were the normal group， model group， and Shenling Baizhusan （SLBZ） group. The control group was fed with ordinary diet and kept in a normal environment. The model group and SLBZ group were fed with a high-fat diet in a high-humidity environment. Swimming with heavy weights until exhaustion and gavage with cold water or lard were used to establish the mouse model of Qi deficiency and phlegm dampness syndrome. In order to test the syndrome by prescription， mice in the SLBZ group were treated with SLBZ for 14 days after model construction. The exhaustive swimming time， body weight， serum lipid levels， tongue changes， "Qi deficiency and phlegm dampness" assessment scale score， and cecal index of mice in each group were measured. The feces of each group of mice were sent for metagenomics and metabolome sequencing， and the changes in intestinal flora and metabolites were analyzed. ResultsAfter the modeling of Qi deficiency and phlegm dampness syndrome， the exhaustive swimming time of mice was obviously shortened （P<0.01）. The serum total cholesterol， low density lipoprotein cholesterol， and non-high density lipoprotein cholesterol of mice were significantly increased （all P<0.01）. The tongue of mice was significantly different from that of the normal group， and the score of the assessment scale was significantly higher than that of the control group （P<0.01）. Cecal index decreased significantly （P<0.01）. The serum lipid level， tongue image， assessment scale score， and cecal index were reversed in the SLBZ group. Metagenomic and metabolome sequencing results showed that intestinal flora and fecal metabolites were significantly changed in mice with Qi deficiency and phlegm dampness syndrome. Akkermansia_muciniphila， Faecalibaculum_rodentium， Eubacterium_plexicaudatum， Eubacterium sp 14_2， Candida glabrata， Romboutsia_ilealis， Turicibacter sp TS3， and other bacteria had significant changes， and the expressions of intestinal metabolites such as chenodeoxycholic acid， choline， L-phenylalanine betaine， and 2-phenylbutyric acid were significantly changed. Related metabolic pathways such as linoleic acid metabolism， primary bile acid biosynthesis， lysine degradation， arginine biosynthesis， and alpha-linolenic acid metabolism were affected. ConclusionThe Qi deficiency and phlegm dampness model of mice can be constructed by the multi-factor composite modeling method of high-fat diet feeding， high-humidity environment feeding， exhaustive swimming with heavy weight， and intragastric administration with cold water or lard. The blood lipid level， tongue change， score of "Qi deficiency and phlegm dampness assessment scale"， cecal index， and changes in related intestinal flora and metabolites of mice can be used as key indicators for model evaluation.

Immune complex deposition is a critical factor in early renal damage associated with lupus nephritis (LN), and targeting plasma cell aggregation offers a promising therapeutic strategy. Ginsenoside compound K (i.e., 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol) (CK), a derivative of ginsenoside, has indicated significant potential in alleviating renal damage in lupus-prone mice, potentially by modulating B cell dynamics in response to endoplasmic reticulum (ER) stress. In this study, CK (20 or 40 mg/kg) was orally administered to female MRL/lpr mice for 10 weeks. The effects of CK on B cell subpopulations, renal function, and histopathological changes were evaluated. Single-cell ribonucleic acid sequencing was employed to analyze gene expression profile and pseudotime trajectories during B cell-mediated renal injury. Additionally, in vitro B cell assays were conducted to explore the role of the sirtuin-1 (SIRT1)-X-box binding protein 1 (XBP1) axis in ER stress. Our findings demonstrated that CK effectively reduced anti-double stranded DNA (dsDNA) antibody levels, alleviated systemic inflammation, improved renal function, and facilitated the clearance of deposited immune complexes. CK likely suppressed the unfolded protein response (UPR), delaying the differentiation of renal-activated B cells into plasma cells. It promoted B cell-specific SIRT1 activation and inhibited the splicing of XBP1 into its active form, XBP1s. CK also restored ER morphology by interacting with calmodulin (CALM) to maintain ER calcium storage, reinforcing SIRT1 functional integrity and promoting XBP1 deacetylation, thereby limiting plasma cell differentiation. In conclusion, CK mitigates plasma cell accumulation in the renal microenvironment by preventing SIRT1-mediated XBP1 splicing, offering a potential therapeutic approach for LN.

Background and purpose:The treatment of recurrent,metastatic,and treatment-na?ve advanced cervical cancer remains challenging.Immunotherapy in combination with chemotherapy and targeted therapy has shown preliminary clinical benefits,however,current evidence remains limited.This study aimed to evaluate the impact of camrelizumab combined with chemotherapy and targeted therapy on the prognosis of patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer.Methods:In this study,we conducted a retrospective analysis of the clinical data from 130 patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer admitted to Minhang Branch of Fudan University Shanghai Cancer Center from 2019 to 2025.The patients were categorized into the observation group(n=70),which included those who received camrelizumab with or without chemotherapy and targeted therapy,and the control group(n=60),including those who received chemotherapy and targeted therapy.Survival analysis was performed using the log-rank test,and univariate and multivariate Cox regression analyses were conducted to explore prognostic factors.This study was approved by the Ethics Committee of the Minhang Branch of Fudan University Shanghai Cancer Center[Approval number:(2024)Review No.(015)]and all informed consents were exempted.Results:The objective response rate(ORR)in the observation group was 72.9%,and the disease control rate(DCR)was 80.0%,which were significantly higher than those in the control group with an ORR of 20.0%(χ2=36.1,P＜0.001)and a DCR of 40.0%(χ2=21.8,P＜0.001).The median progression-free survival(PFS)in the observation group was not reached,significantly longer than that in the control group of 7.0 months(P＜0.001).Multivariate Cox regression analysis identified camrelizumab treatment as an independent protective factor for PFS(P＜0.001).Age,site of recurrence/metastasis,initial treatment approach,and histopathological type were not significantly associated with PFS.In the observation group,adverse events of grade 3 or higher were reported in 29 patients(41.4%),which primarily included vasculitis,hypothyroidism,hypersensitivity reactions,and diarrhea.Conclusion:The use of camrelizumab significantly improved treatment outcomes and prognosis for patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer,with significantly improved progression-free survival.Although a certain proportion of patients experienced adverse events of grade 3 or higher,the overall safety profile was acceptable.In clinical practice,immunotherapy offers a more effective treatment option for patients.

Background and Aims:Autoimmune thyroid disease(AITD)are closely associated with metabolic dysregulation,but the causal role of specific metabolites remains unclear.This study aimed to systematically evaluate the causal relationships between approximately 1 400 blood metabolites and two major AITD subtypes-Graves'disease(GD)and Hashimoto's thyroiditis(HT)-using a two-sample Mendelian randomization(MR)approach,to identify potential risk or protective metabolites and provide genetic evidence for mechanistic studies and targeted metabolic interventions.Methods:Summary-level genome-wide association study(GWAS)data for blood metabolites and AITDs were analyzed using inverse-variance weighted MR as the primary method,supplemented by MR-Egger,weighted median,and mode-based methods.Heterogeneity,pleiotropy,and robustness were assessed through Cochran's Q test,horizontal pleiotropy test,and leave-one-out analyses.Results:Forty-nine metabolites showed significant causal associations with GD and 89 with HT.Hexanoylglutamine and ceramide(d18∶1/16∶0)were identified as GD risk factors,while N2,N2-dimethylguanosine and β-hydroxyisovalerylcarnitine were protective.Pregnanediol sulfate and theobromine were associated with increased HT risk,whereas dihomo-linolenate(20:3n3 or n6)and caprylate appeared protective.The α-ketoglutarate/succinate ratio was positively associated with both diseases,suggesting a shared metabolic risk pathway.Conclusion:This MR study provides genetic evidence supporting causal links between multiple blood metabolites and GD or HT.Several metabolites may serve as predictive or protective biomarkers,offering novel insights into the pathophysiology,early screening,and personalized metabolic intervention strategies for AITDs.

Objective To establish the fingerprint of Xuemai Shutong granules by UPLC-ELSD and determine the contents of 9 components in the preparation simultaneously.Methods The UPLC-ELSD was used to establish the fingerprint of Xuemai Shutong granules,and determine the content of its 9 components.The similarity evaluation system,systematic,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate the quality of different batches of preparation.Results The similarity degrees of UPLC-ELSD fingerprints of 11 batches of Xuemai Shutong granules were from 0.929 to 0.978,17 common peaks were calibrated,of which 11 peaks were identified:peak 3(notoginsenoside R1),peak 4[ginsenoside Rg,(Re)],peak 5(notoginsenoside R2),peak 6(ginsenoside Rb,),peak 9(astragaloside Ⅳ),peak 10(ginsenoside Rk3),peak 11(ginsenoside Rh4),peak 12[20(S)-ginsenoside Rg3],peak 13[20(R)-ginsenoside Rg3],peak 14(ginsenoside Rk1),peak 15(ginsenoside Rg5).The stoichiometric analysis divided 11 batches of samples into 2 classes,and the 2 principal components in PCA analysis reflected the information of 17common peaks,10 peaks which affected the quality difference are screened out.The linear relationship of the 9 components was good in their respective quality ranges in the content analysis(r＞0.999 2),the average recovery rate were between 95.02％-97.78％and the RSD were 0.69％-1.70％(n=6).The contents of notoginsenoside R1,notoginsenoside R2,ginsenoside Rb1,astragaloside Ⅳ,ginsenoside Rh4,20(S)-ginsenoside Rg3,20(R)-ginsenoside Rg3,ginsenoside Rk1 ginsenoside Rg5 in the 11 batches of Xuemai Shutong granules were 0.087 5-0.187 6,0.494 3-0.688 6,0.448 1-0.705 5,0.192 2-0.270 8,1.492 5-2.077 6,0.316 0-0.463 8,0.254 5-0.382 0,0.117 6-0.163 9,3.407 7-4.706 4 mg·g-1,respectively.Conclusions The established fingerprint and content determination method was accurate and reliable,which can improve the quality standard of Xuemai Shutong granules,and provide reference for its overall quality evaluation.

Objective To establish the fingerprint of Xuemai Shutong granules by UPLC-ELSD and determine the contents of 9 components in the preparation simultaneously.Methods The UPLC-ELSD was used to establish the fingerprint of Xuemai Shutong granules,and determine the content of its 9 components.The similarity evaluation system,systematic,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used to evaluate the quality of different batches of preparation.Results The similarity degrees of UPLC-ELSD fingerprints of 11 batches of Xuemai Shutong granules were from 0.929 to 0.978,17 common peaks were calibrated,of which 11 peaks were identified:peak 3(notoginsenoside R1),peak 4[ginsenoside Rg,(Re)],peak 5(notoginsenoside R2),peak 6(ginsenoside Rb,),peak 9(astragaloside Ⅳ),peak 10(ginsenoside Rk3),peak 11(ginsenoside Rh4),peak 12[20(S)-ginsenoside Rg3],peak 13[20(R)-ginsenoside Rg3],peak 14(ginsenoside Rk1),peak 15(ginsenoside Rg5).The stoichiometric analysis divided 11 batches of samples into 2 classes,and the 2 principal components in PCA analysis reflected the information of 17common peaks,10 peaks which affected the quality difference are screened out.The linear relationship of the 9 components was good in their respective quality ranges in the content analysis(r＞0.999 2),the average recovery rate were between 95.02％-97.78％and the RSD were 0.69％-1.70％(n=6).The contents of notoginsenoside R1,notoginsenoside R2,ginsenoside Rb1,astragaloside Ⅳ,ginsenoside Rh4,20(S)-ginsenoside Rg3,20(R)-ginsenoside Rg3,ginsenoside Rk1 ginsenoside Rg5 in the 11 batches of Xuemai Shutong granules were 0.087 5-0.187 6,0.494 3-0.688 6,0.448 1-0.705 5,0.192 2-0.270 8,1.492 5-2.077 6,0.316 0-0.463 8,0.254 5-0.382 0,0.117 6-0.163 9,3.407 7-4.706 4 mg·g-1,respectively.Conclusions The established fingerprint and content determination method was accurate and reliable,which can improve the quality standard of Xuemai Shutong granules,and provide reference for its overall quality evaluation.

Background and purpose:The treatment of recurrent,metastatic,and treatment-na?ve advanced cervical cancer remains challenging.Immunotherapy in combination with chemotherapy and targeted therapy has shown preliminary clinical benefits,however,current evidence remains limited.This study aimed to evaluate the impact of camrelizumab combined with chemotherapy and targeted therapy on the prognosis of patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer.Methods:In this study,we conducted a retrospective analysis of the clinical data from 130 patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer admitted to Minhang Branch of Fudan University Shanghai Cancer Center from 2019 to 2025.The patients were categorized into the observation group(n=70),which included those who received camrelizumab with or without chemotherapy and targeted therapy,and the control group(n=60),including those who received chemotherapy and targeted therapy.Survival analysis was performed using the log-rank test,and univariate and multivariate Cox regression analyses were conducted to explore prognostic factors.This study was approved by the Ethics Committee of the Minhang Branch of Fudan University Shanghai Cancer Center[Approval number:(2024)Review No.(015)]and all informed consents were exempted.Results:The objective response rate(ORR)in the observation group was 72.9%,and the disease control rate(DCR)was 80.0%,which were significantly higher than those in the control group with an ORR of 20.0%(χ2=36.1,P＜0.001)and a DCR of 40.0%(χ2=21.8,P＜0.001).The median progression-free survival(PFS)in the observation group was not reached,significantly longer than that in the control group of 7.0 months(P＜0.001).Multivariate Cox regression analysis identified camrelizumab treatment as an independent protective factor for PFS(P＜0.001).Age,site of recurrence/metastasis,initial treatment approach,and histopathological type were not significantly associated with PFS.In the observation group,adverse events of grade 3 or higher were reported in 29 patients(41.4%),which primarily included vasculitis,hypothyroidism,hypersensitivity reactions,and diarrhea.Conclusion:The use of camrelizumab significantly improved treatment outcomes and prognosis for patients with recurrent,metastatic,and treatment-na?ve advanced cervical cancer,with significantly improved progression-free survival.Although a certain proportion of patients experienced adverse events of grade 3 or higher,the overall safety profile was acceptable.In clinical practice,immunotherapy offers a more effective treatment option for patients.

Background and Aims:Autoimmune thyroid disease(AITD)are closely associated with metabolic dysregulation,but the causal role of specific metabolites remains unclear.This study aimed to systematically evaluate the causal relationships between approximately 1 400 blood metabolites and two major AITD subtypes-Graves'disease(GD)and Hashimoto's thyroiditis(HT)-using a two-sample Mendelian randomization(MR)approach,to identify potential risk or protective metabolites and provide genetic evidence for mechanistic studies and targeted metabolic interventions.Methods:Summary-level genome-wide association study(GWAS)data for blood metabolites and AITDs were analyzed using inverse-variance weighted MR as the primary method,supplemented by MR-Egger,weighted median,and mode-based methods.Heterogeneity,pleiotropy,and robustness were assessed through Cochran's Q test,horizontal pleiotropy test,and leave-one-out analyses.Results:Forty-nine metabolites showed significant causal associations with GD and 89 with HT.Hexanoylglutamine and ceramide(d18∶1/16∶0)were identified as GD risk factors,while N2,N2-dimethylguanosine and β-hydroxyisovalerylcarnitine were protective.Pregnanediol sulfate and theobromine were associated with increased HT risk,whereas dihomo-linolenate(20:3n3 or n6)and caprylate appeared protective.The α-ketoglutarate/succinate ratio was positively associated with both diseases,suggesting a shared metabolic risk pathway.Conclusion:This MR study provides genetic evidence supporting causal links between multiple blood metabolites and GD or HT.Several metabolites may serve as predictive or protective biomarkers,offering novel insights into the pathophysiology,early screening,and personalized metabolic intervention strategies for AITDs.

[Objective]To introduce the clinical characteristics and experience of Professor GE Linyi(hereinafter referred to as Professor GE),a master of traditional Chinese medicine,in the treatment of spleen and stomach diseases with wind herbs at different levels.[Methods]Through the theoretical traceability,following up with teachers,it summarizes Professor GE's ideas and experiences in the skillful use of wind herbs for the differentiation and treatment of spleen and stomach diseases based on the theory of gasification,as well as the characteristics of her medication,and provides a medical case as evidence.[Results]Gasification is a fundamental activity of life,and abnormal gasification is an important cause of disease,In terms of the diagnosis and treatment ideas,Professor GE believes that"gasification failure"is the basic pathogenesis of spleen and stomach diseases.In clinical practice,Professor GE treats spleen and stomach diseases from"gasification",to regulate Qi movement and maintain the function of spleen ascending and stomach descending,and skillfully applies wind herbs to soothe the liver with wind,strengthen Qi with wind,dry dampness with wind,and search wind and dredge collaterals.The commonly used wind herbs are Bupleurum chinense,Saposhnikoviae Radix,Astragali Radix,Cimicifugae Rhizoma,Citri Sarcodactylis Fructus,Perillae Radix,Atractylodes Rhizome,Aesculi Rhizoma,Morus alba Linn.,Agastache rugosa,Amomum tsaoko,Magnolia officinalis,Eupatorium fortunei,Cynanchum paniculatum,Bombyx Batryticatus and herb strings,herb pairs.[Conclusion]Professor GE is good at syndrome differentiation in clinical practice,skillfully applies wind herbs to regulate Qi according to different levels in treating spleen and stomach diseases.The academic thought has distinct characteristics and remarkable curative effect,which is worthy of clinical reference and promotion.

Objective:To analyze the characteristics of inhibitory control and cognitive flexibility in hearing-impaired children.Methods:From March to April 2023, a convenience sampling method was used to select 33 hearing-impaired children from a special education school in Meizhou City, Guangdong Province, and 35 normal-hearing children from two ordinary schools as participants. Inhibitory control and cognitive flexibility of the participants were assessed by the Flanker task and the dimensional change card sorting (DCCS) task. Statistical analysis was conducted using SPSS 26.0 software, and independent sample t-test was used to compare the differences in reaction time and accuracy rate between two groups of participants. Results:There were no significant differences in the Flanker task reaction time ((558.39±123.65) ms vs (566.11±118.20) ms) and accuracy rate((0.93±0.10) vs (0.96±0.04))between hearing-impaired children and normal-hearing children ( t=-0.295, -1.645, both P>0.05). The hearing-impaired children had significantly longer reaction time ((1 019.60±131.08) ms)than the normal-hearing children ((857.85±129.19) ms) ( t=4.046, P=0.001) in the DCCS task, while there was no statistically significant difference in the accuracy rate between hearing-impaired children (0.62±0.16) and normal-hearing children (0.57±0.15) ( t=-1.602, P>0.05). Conclusion:There is no difference in inhibitory control ability between hearing-impaired children and normal-hearing children, but the hearing-impaired children have a lag in cognitive flexibility.