ObjectiveTo investigate the mechanism of action of modified Shaofu Zhuyutang in antagonizing cellular pyroptosis and fibrosis in ectopic endometrial tissues of endometriosis through the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3 （TRL4/NF-κB/NLPR3） signaling pathway. MethodsSeventy-two SPF-grade female SD rats were randomly divided into a sham-operated group （n = 12） and a modeling group （n = 60）. The rats in the sham-operated group underwent a caesarean section， while the rats in the modeling group were used to establish an endometriosis model through the auto-transplantation method. After successful modeling， the animals were randomly divided into the model group， progesterone group （0.25 mg·kg^-1）， and modified Shaofu Zhuyutang low-， medium-， and high-dose groups （7.5， 15， 30 g·kg^-1）， with 12 animals in each group. After 4 weeks of drug administration， voluntary activity and heat pain latency were observed. The rats were sacrificed for tissue collection， and Masson staining were used to observe histopathological changes in the endometrial tissues. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of interleukin-18 （IL-18）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） was used to detect the protein expression area of tumor necrosis factor-related factor 6 （TRAF6） and NLPR3 in the endometrial tissues. Immunofluorescence （IF） was used to detect the relative fluorescence intensity of Caspase-1 and gasdermin D （GSDMD） in the endometrial tissues. Western blot was employed to measure the relative expression of TRL4， myeloid differentiation factor 88 （MyD88）， TRAF6， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， and NLPR3 proteins in endometrial tissues. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 in the endometrial tissues. ResultsCompared with the sham-operated group， rats in the model group showed reduced voluntary activity and shorter heat pain latency. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were elevated. The relative expression areas of TRAF6 and NLPR3 proteins were increased， and the relative fluorescence intensity of Caspase-1 and GSDMD was enhanced. The relative expression of TRL4， MyD88， TRAF6， NF-κB p65， p-NF-κB p65， and NLPR3 proteins， along with the expression of TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA， were significantly increased （P<0.01）. Compared with the model group， rats in the progesterone group and the modified Shaofu Zhuyutang medium- and high-dose groups exhibited improved voluntary activity， longer heat pain latency， the fibrosis of endometrial tissue is alleviated. Serum levels of IL-18， IL-1β， TNF-α， and TGF-β were decreased. The relative expression areas of TRAF6 and NLPR3 proteins decreased， and the relative fluorescence intensity of Caspase-1 and GSDMD weakened. The relative expression of TRL4， MyD88， TRAF6， p-NF-κB p65， NLPR3 proteins， and TRL4， MyD88， TRAF6， NF-κB， and NLPR3 mRNA expression were reduced （P<0.05， P<0.01）. ConclusionModified Shaofu Zhuyutang may play a therapeutic role in endometriosis by interfering with key proteins in the TRL4/NF-κB/NLPR3 signaling pathway， reducing NLRP3 inflammasome-induced cellular pyroptosis， antagonizing the fibrosis process in ectopic endometrial tissues， improving the inflammatory microenvironment in the pelvic cavity， and alleviating pain.

ObjectiveTo investigate the developmental characteristics of gross motor skills and executive functions, and the correlation between them in school-age children with attention deficit hyperactivity disorder (ADHD). MethodsFrom November, 2020 to May, 2021, 90 children with ADHD were recruited from Peking University Sixth Hospital and Beijing Haidian Wanquan Primary School, and other 90 children with normal development from this primary school were recruited matched their age and gender. Gross motor skills were assessed with the Test of Gross Motor Development in Children, Third Edition (TGMD-3), and inhibitory control, working memory, and cognitive flexibility were assessed with Stroop Color Words Test (SCWT), Rey-Osterrich Complex Figure Test (ROCFT) and Trail Making Test (TMT), respectively. ResultsThe TGMD-3 score was significantly lower in children with ADHD than in normal children (t = -6.275, P < 0.001), while the test results of SCWT, ROCFT and TMT were worse (|t| ≥ 1.986, P ≤ 0.05). The TGMD-3 score of children with ADHD was negatively correlated with the word sense reaction time (r = -0.261), the number of word sense errors (r = -0.404) and the number of color errors (r = -0.326) (P < 0.05), positively correlated with the delayed structural memory scores (r = 0.228) (P < 0.05), and negatively correlated with the TMT-A reaction time (r = -0.255), the number of TMT-A errors (r = -0.329), TMT-B reaction time (r = -0.214) and the number of TMT-B errors (r = -0.474) (P < 0.05). Stratified linear regression analyses showed that the TGMD-3 score of children with ADHD was significant only in predicting test results for inhibitory control and cognitive flexibility (P < 0.05), with explanations of 8.7% and 22.5%, respectively. ConclusionDevelopments of both gross motor skills and executive function delay in children with ADHD, and there is a relation between them, especially the level of gross motor skills relating to the developments of inhibitory control and cognitive flexibility.

Objective:To investigate the mid-to-long term therapeutic effects of allogeneic bone composite prosthesis reconstruction in patients with large bone defects after the resection of distal femoral tumors.Methods:From June 2013 to December 2018, a total of 19 patients with malignant tumors of the distal femur who underwent reconstruction with allogeneic bone composite prosthesis in the Department of Bone Tumor, Shanghai General Hospital were retrospectively collected. There were 10 males and 9 females, aged 22.3±11 years (range, 11-42 years). The mean body mass index was 19.3±3.4 kg/m 2 (range, 14-27 kg/m 2). There were 18 cases of osteosarcoma and 1 case of Ewing's sarcoma. According to Ennecking staging, there were 17 cases of stage IIB and 2 cases of stage III. The intraoperative blood loss and operation time were recorded, and the prosthesis and patient survival conditions and postoperative complications were observed. The limb function was evaluated by the Musculoskeletal Tumor Society (MSTS) 93 function score. Results:All patients successfully completed the operation. The operation time was 187.3±39.8 min (range, 110-260 min), the intraoperative blood loss was 284.9±87.0 ml (range, 200-500 ml), and the blood transfusion volume was 327±213 ml (range, 100-800 ml). The remaining length of the proximal femur was 153.7±26.6 mm (range, 93-190 mm), and the length of allogeneic bone was 84.1±24.6 mm (range, 39-134 mm). Among the 19 patients, 9 patients (47%) achieved bony union with an average healing time of 16.7±4.8 months (range, 10-25 months), and 7 patients had delayed healing with an average healing time of 18.4±4.0 months (range, 15-25 months). The remaining 10 cases were nonunion between allogeneic bone and host bone. All patients were followed up for 80.7±20.2 months (range, 56-121 months). During the follow-up, 3 cases died due to pulmonary metastasis of bone tumors, and the time of death was 57 months, 63 months, and 59 months after surgery, respectively. At the last follow-up, the patient survival rate was 84% (16/19), and the MSTS 93 function score of the 16 patients was (24.3±2.4) points (range, 21-28 points), with an excellent rate of 100% (16/16). Seven patients underwent revision surgery, 3 cases were aseptic loosening, 3 cases were prosthesis stem fracture at the junction of the allograft bone and the host bone, and 1 case was periprosthetic infection, among which the patient with periprosthetic infection had poor local soft tissue conditions due to preoperative radiotherapy, and the infection was controlled after two revision surgeries. Five cases were revised with allogeneic bone composite prosthesis, and 2 cases were revised with short-stem giant prosthesis with cortical steel plate or locking nail. After revision, the remaining length of the proximal femur was 143.4±31 mm (range, 91-175 mm), and the length of the allograft bone was 92.6±26.6 mm (range, 61-123 mm). The 7 revised patients were still in follow-up. There were no cases of pulmonary infection, nerve injury, deep vein thrombosis or other complications after surgery.Conclusion:The survival period of patients after the surgery to reconstruct large bone defects following the resection of malignant tumors at the distal end of the femur using allogeneic bone composite prosthesis is satisfactory, and the limb function is good. However, the incidence of prosthesis complications is high, which can be reconstructed through revision.

Objective To investigate the efficacy of antibacterial photodynamic therapy(aPDT)as an adjunct to subgingival scaling and root planning in the treatment of chronic periodontitis.Methods This study followed medical ethics guidelines,and informed consent was obtained from all patients.Sixteen patients were recruited for this random-ized split-mouth controlled trial.The control group underwent subgingival scaling and root planning(SRP),while the ex-perimental group received subgingival scaling and root planing plus aPDT treatment using Perowave? with a toluidine blue O solution photosensitizer.The probing pocket depth(PD),recession,plaque index(PLI),bleeding index(BI)and proportion of positive sites of bleeding on probing(BOP)(BOP%)at all sites were examined at baseline(before treat-ment)and at 1,3 and 6 months after treatment.Results Follow-up was completed for 13 patients.On the control side,356 teeth were tested at 2 136 sites.A total of 360 teeth on the test side and 2 160 sites were included in the study.Before treatment,there was no significant difference in the baseline indicators between the two groups.After treatment,both groups showed significant improvement in clinical parameters,including PD,PLI,BI,and BOP%,compared with baseline.At 3 months,the BOP%and PLI in the experimental group were significantly lower than those in the control group(P＜0.05).The improvement in BOP%and PLI in the experimental group was significantly greater than that in the control group 3 months after treatment(P＜0.05).Conclusion aPDT,as an adjuvant treatment to SRP for chronic periodontitis,can improve gingival bleeding and control periodontal inflammation in the early stage.

Objective To explore the clinical significance of serum cytokine expression in the hepatitis B surface antigen(HBsAg)sero-clearance in patients with severe hepatitis B.Methods A nested case-control trial was conducted on 14 inpatients with severe hepatitis B admitted in our hospital from 2006 to 2020.Of them,7 patients(aged 36.57±3.15 years)achieved HBsAg sero-clearance within 1 year after the onset of hepatitis B flares(with abrupt rise of ALT level to＞5 times the upper limit of normal during HBV infection)and were assigned into HBsAg clearance group,while the other 7 patients(aged 34.14±2.97 years)only obtained HBsAg decreased less than 1 g within 1 year after the onset(HBsAg non-clearance group).Then,multiplex liquid-chip assay based on Luminex xMAP was used to detect the expression levels of 48 cytokines such as IFN-γ and IL-2 in serum samples of these 14 patients.Results The serum levels IFN-γ,IL-2Ra and SDF-1α were significantly lower in the HBsAg clearance group than the HBsAg non-clearance group(P＜0.05),but no statistical differences were observed in other 39 cytokines between the 2 groups.And there were 5 cytokines having no mutual expression in both groups.The copy number of HBV DNA was positively correlated with serum HGF(r=0.675,P=0.008)and SDF-1α levels(r=0.587,P=0.027),while negatively with IP-10(r=-0.600,P=0.023)and MIG level(r=-0.640,P=0.014).Meanwhile,a positive correlation was found between HBsAg titer and IL12-p70 level(r=0.593,P=0.025),and a negative correlation between HBsAg titer and TNF-α level(r=-0.609,P=0.021).In addition,the serum total bilirubin level was positively correlated with the expression of SCGF-β(r=0.543,P=0.045).Conclusion Three differentially expressed cytokines and some cytokines related to HBV DNA level and HBsAg titer are found,which may provide new insights into the underlying immunological mechanism of HBV virus clearance caused by hepatitis flares.Meanwhile,it also provides potential biomarkers for HBsAg serological clearance in patients with severe hepatitis B.

Objective:To explore the causal relationship between blood metabolites and keloids.Methods:The study was a two-sample bidirectional Mendelian randomization (MR) analysis-based study. Blood metabolites of 7 824 adult volunteers and 8 299 participants and data related to 481 912 keloid patients were obtained from the genome-wide association studies (GWAS) Catalog database. Single nucleotide polymorphisms (SNPs) significantly associated with blood metabolites and keloids were screened for inclusion as instrumental variables in the MR analysis by setting a significance threshold of P<1.0×10 -5, chain imbalance analysis [ r2 = 0.001, kilobase pairs (kb) = 10, 000)], and the F statistic ( F≥10) . Five method of MR analysis, i.e., inverse variance weighting (IVW) as the main method and MR-Egger regression, weighted median, simple modeling, and weighted modeling as auxiliary method, were used to analyze the causal relationship between blood metabolites (exposure factors) and keloids (outcome variables) . Sensitivity analyses were performed on eligible blood metabolite SNPs to assess the reliability and stability of the findings: heterogeneity was assessed by Cochran Q-test and MR-Egger regression test, MR Egger intercept test to rule out horizontal pleiotropy, leave-one-out test to determine if the presence of a single SNP significantly affected the result of the MR analyses, MR-PRESSO method was used to test for outliers of SNPs, which were corrected by false discovery rate (FDR) (FDR <0.2) to control the false positive rate. Reverse MR analysis was performed with keloid as the exposure factor, and blood metabolites screened by the aforementioned MR analysis were used as outcome variables for effect analysis and sensitivity analysis. The data were analyzed using R 4.3.2 software and the TwoSampleMR program package therein, and the causal effect values of the MR analysis were expressed as the ratio ( OR) and 95% CI, with P<0.05 being considered as a statistically significant difference, i. e., the evidence of a potential causal effect was substantial. Forest plots, funnel plots, and scatter plots were constructed to visualize the result of MR analysis and sensitivity analysis. Results:A total of 1 400 blood metabolites with 34 843 SNPs were obtained from the GWAS Catalog database, all of which were consistent with the hypothesis that genetic variants are closely associated with exposure factors; a total of 24 197 210 SNPs were obtained from the keloid dataset. IVW analysis revealed that one blood metabolite, succinyl taurine (16 ∶ 1n-7), had 28 SNPs with keloid with a causal relationship ( OR=1.13, 95% CI 1.06-1.19, P<0.001, FDR=0.070) ; MR-Egger regression method ( OR = 1.11, 95% CI 1.04-1.19, P=0.005), weighted median method ( OR = 1.11, 95% CI 1.02-1.20, P=0.014) and weighted modeling method ( OR=1.12, 95% CI 1.04 to 1.20, P=0.004) analyses also showed that succinyl taurine (16 ∶ 1n-7) was a risk factor for keloid disease; the result of the simple modeling method only showed that the causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid disease was not significant ( OR=1.10, 95% CI 0.85-1.41, P=0.485) . MR overall analysis showed a significant positive causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid, i.e., elevated levels of succinyl taurine (16 ∶ 1n-7) were associated with an increased risk of keloid disease. Cochran Q-test ( Q = 26.98, P=0.465), MR-Egger regression test ( Q = 26.65, P = 0.428), MR-Egger intercept test ( P = 0.574), and MR-PRESSO composite test ( P=0.569) showed that there was no heterogeneity and horizontal pleiotropy among SNPs ( P>0.05) ; the leave-one-out test confirmed that individual SNPs did not have a significant effect on the overall result, indicating that the result had reliability and stability. The inverse MR analysis suggested that there was no causal relationship between keloid on succinyl taurine (16 ∶ 1n-7) (IVW: OR=0.98, 95% CI 0.93-1.04, P=0.490) . Conclusions:There is a significant positive causal relationship between the blood metabolite succinyl taurine (16 ∶ 1n-7) and keloids, and succinyl taurine (16 ∶ 1n-7) is a risk factor for keloid disease.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Objective:To explore the causal relationship between blood metabolites and keloids.Methods:The study was a two-sample bidirectional Mendelian randomization (MR) analysis-based study. Blood metabolites of 7 824 adult volunteers and 8 299 participants and data related to 481 912 keloid patients were obtained from the genome-wide association studies (GWAS) Catalog database. Single nucleotide polymorphisms (SNPs) significantly associated with blood metabolites and keloids were screened for inclusion as instrumental variables in the MR analysis by setting a significance threshold of P<1.0×10 -5, chain imbalance analysis [ r2 = 0.001, kilobase pairs (kb) = 10, 000)], and the F statistic ( F≥10) . Five method of MR analysis, i.e., inverse variance weighting (IVW) as the main method and MR-Egger regression, weighted median, simple modeling, and weighted modeling as auxiliary method, were used to analyze the causal relationship between blood metabolites (exposure factors) and keloids (outcome variables) . Sensitivity analyses were performed on eligible blood metabolite SNPs to assess the reliability and stability of the findings: heterogeneity was assessed by Cochran Q-test and MR-Egger regression test, MR Egger intercept test to rule out horizontal pleiotropy, leave-one-out test to determine if the presence of a single SNP significantly affected the result of the MR analyses, MR-PRESSO method was used to test for outliers of SNPs, which were corrected by false discovery rate (FDR) (FDR <0.2) to control the false positive rate. Reverse MR analysis was performed with keloid as the exposure factor, and blood metabolites screened by the aforementioned MR analysis were used as outcome variables for effect analysis and sensitivity analysis. The data were analyzed using R 4.3.2 software and the TwoSampleMR program package therein, and the causal effect values of the MR analysis were expressed as the ratio ( OR) and 95% CI, with P<0.05 being considered as a statistically significant difference, i. e., the evidence of a potential causal effect was substantial. Forest plots, funnel plots, and scatter plots were constructed to visualize the result of MR analysis and sensitivity analysis. Results:A total of 1 400 blood metabolites with 34 843 SNPs were obtained from the GWAS Catalog database, all of which were consistent with the hypothesis that genetic variants are closely associated with exposure factors; a total of 24 197 210 SNPs were obtained from the keloid dataset. IVW analysis revealed that one blood metabolite, succinyl taurine (16 ∶ 1n-7), had 28 SNPs with keloid with a causal relationship ( OR=1.13, 95% CI 1.06-1.19, P<0.001, FDR=0.070) ; MR-Egger regression method ( OR = 1.11, 95% CI 1.04-1.19, P=0.005), weighted median method ( OR = 1.11, 95% CI 1.02-1.20, P=0.014) and weighted modeling method ( OR=1.12, 95% CI 1.04 to 1.20, P=0.004) analyses also showed that succinyl taurine (16 ∶ 1n-7) was a risk factor for keloid disease; the result of the simple modeling method only showed that the causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid disease was not significant ( OR=1.10, 95% CI 0.85-1.41, P=0.485) . MR overall analysis showed a significant positive causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid, i.e., elevated levels of succinyl taurine (16 ∶ 1n-7) were associated with an increased risk of keloid disease. Cochran Q-test ( Q = 26.98, P=0.465), MR-Egger regression test ( Q = 26.65, P = 0.428), MR-Egger intercept test ( P = 0.574), and MR-PRESSO composite test ( P=0.569) showed that there was no heterogeneity and horizontal pleiotropy among SNPs ( P>0.05) ; the leave-one-out test confirmed that individual SNPs did not have a significant effect on the overall result, indicating that the result had reliability and stability. The inverse MR analysis suggested that there was no causal relationship between keloid on succinyl taurine (16 ∶ 1n-7) (IVW: OR=0.98, 95% CI 0.93-1.04, P=0.490) . Conclusions:There is a significant positive causal relationship between the blood metabolite succinyl taurine (16 ∶ 1n-7) and keloids, and succinyl taurine (16 ∶ 1n-7) is a risk factor for keloid disease.

Public hospitals bear the responsibility of ensuring people's health and promoting their healthy lives.New media have emerged as a pivotal platform for health science popularization in public hospitals.Under these contexts,the Science Popularization Base for Health and Chronic Disease Prevention of the First Hospital of Lanzhou University established a multidisci-plinary team model for science popularization,mainly relying on the WeChat official account to disseminate health knowledge and dispel rumors.This article explored the experiences and practices of health science popularization under this model,focusing on the"meticulous selection for science popularization"strategy employed on their WeChat official account.