ObjectiveTo evaluate the comprehensive intervention effects of Huangqin Qingre Chubi Capsule （黄芩清热除痹胶囊， HQC） on self-perception of patients （SPP） and immune inflammation in patients with rheumatoid arthritis （RA）， and to explore its potential mechanisms. MethodsClinical data of 452 RA patients were retrospectively collected. Patients were divided into a control group （274 cases）， treated with conventional western medicine， and an observation group （178 cases）， treated with HQC for at least 2 weeks in addition to conventional western medicine. The treatment duration was 2 weeks for both groups. Propensity score matching （PSM） was performed at a ratio of 1∶1 to match patients between groups. SPP including the Chinese version of the short form-36 health survey （SF-36）， self-rating anxiety scale （SAS）， self-rating depression scale （SDS）， visual analog scale （VAS）， and Chinese patient-reported index for rheumatoid arthritis （CPRI-RA）， as well as immune inflammatory indicators， including erythrocyte sedimentation rate （ESR）， high-sensitivity C-reactive protein （hs-CRP）， rheumatoid factor （RF）， anti-cyclic citrullinated peptide antibody （anti-CCP）， interleukin-6 （IL-6）， immunoglobulin A （IgA）， immunoglobulin G （IgG）， immunoglobulin M （IgM）， complement C3， and complement C4， were collected before and after treatment. Spearman correlation analysis was used to assess the relationships between SPP and immune inflammatory indicators. Logistic regression， association rule analysis， and mediation analysis were performed to evaluate the effects and potential pathways of HQC on SPP and immune inflammatory indicators. Network pharmacology was applied to identify the active components and core targets of HQC in the treatment of RA， followed by molecular docking verification. In cell experiments， cells were divided into normal group， model group， 20% medicated serum group， and 80 nmol/L control group. Human synovial fibroblasts （FLS） were cultured with complete medium in the normal group， while human rheumatoid arthritis fibroblast-like synoviocytes （RA-FLS） were cultured in the model group. In the 20% medicated serum group， RA-FLS were cultured with medium containing 20% HQC-medicated serum， and in the 80 nmol/L control group， RA-FLS were cultured with complete medium containing 80 nmol/L methotrexate suspension. After 48 h of culture， cell viability was detected by cell counting kit-8 （CCK-8） assay. Levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and interleukin-10 （IL-10） in the cell supernatant were measured by enzyme-linked immunosorbent assay （ELISA）. Protein levels of matrix metalloproteinase 9 （MMP9）， transcription factor AP-1 subunit （JUN）， vascular endothelial growth factor A （VEGFA）， and C-X-C motif chemokine ligand 8 （CXCL8） were detected by Western Blot， and cell migration ability was evaluated using Transwell assay. ResultsAfter PSM， 178 cases were included in each group. After treatment， SF-36 scores increased， while scores of SAS， SDS， VAS and CPRI-RA， levels of ESR， hs-CRP， IL-6， complement C3， and complement C4 levels decreased in both groups； IgG and IgM levels were also reduced in the observation group （P＜0.05）. Physical functioning （correlation coefficient -0.19， P＜0.05） and social functioning （correlation coefficient -0.18， P＜0.05） of SF-36 were negatively correlated with hs-CRP， while VAS score was positively correlated with hs-CRP （correlation coefficient 0.19， P＜0.05）. HQC showed high associations with improvements in multiple indicators of SPP and immune inflammatory， and acted as a protective factor for the improvement of several SPP； hs-CRP and ESR played partial mediating roles in the improvement of SPP induced by HQC （P＜0.05）. Network pharmacology analysis identified baicalein， quercetin， α1-sitosterol， β-sitosterol， stigmasterol， baicalin， and crocetin as the core active components， and JUN， IL-6， VEGFA， MMP9， IL-1β， and CXCL8 as the core targets. Molecular docking results showed strong binding affinities of quercetin with VEGFA， JUN， MMP9， IL-6， and IL-1β， of baicalin with VEGFA and MMP9， and of wogonin with CXCL8. Cell experiments demonstrated that HQC and methotrexate inhibited RA-FLS viability and migration， reduced levels of IL-1β， IL-6， and IL-8， decreased protein levels of MMP9， JUN， VEGFA， and CXCL8， and increased IL-10 levels （P＜0.05）. ConclusionHQC can improve SPP in RA by regulating immune inflammatory responses. Its mechanism may be related to multi-pathway and multi-target inhibition of synovial cell inflammation and migration.

Objective:To explore the effects of high-intensity interval training(HIIT)and semaglutide on cardiomyopathy and glycophagy in db/db mice.Method:Forty male db/db mice were randomly divided into diabetic control group(DC,n=10),diabetic+exercise group(DE,n=10),diabetic+semaglutide group(DM,n=10)and diabetic+exercise+semaglutide group(EM,n=10).DE mice and EM mice were conducted a 8-week HIIT treadmill protocol,DM mice and EM mice received daily subcutaneous neck injections of semaglutide at 0.05mg/kg.Body weight and fasting blood glucose were measured regularly.Echocardiography was used to detect cardiac function at the end of the intervention.Myocardial morphology was evaluated by H&E staining;The H&E staining was used to observe the myocardial morphological changes;fibrosis by Masson staining;glycogen accumulation by periodic acid-Schiff staining;and cardiomyocyte hypertrophy by wheat germ agglutinin(WGA)staining.The glycophagy was observed by transmission electron microscopy.Western Blot quantified the IRS-1,P-PI3K,PI3K,p-AKT,AKT,p-GSK3β,GSK3β,p-AMPK,AMPK,p-mTOR,mTOR,LC3Ⅱ/Ⅰ,TFEB and GABARAPL1 in myocar-dial tissue.Result:Compared with DC group,HIIT and/or semaglutide intervention reduced body weight and fasting glu-cose,improved cardiac function and myocardial morphology,decreased fibrosis and cardiomyocyte hypertrophy(reduced cross-sectional area,P<0.05),and lowered glycogen accumulation.Autophagosomes and autophagy vac-uoles containing different amounts of glycogen granule were observed by transmission electron microscopy.Compared with DC group,the protein level of p-mTOR/mTOR in DE mice was significantly decreased,and the protein levels of LC3Ⅱ/Ⅰ,TFEB and GABARAPL1 in DE mice were significantly increased(P<0.05).The phosphorylation levels of AKT and GSK3β in DM mice was significantly increased,and the protein level of TFEB and GABARAPL1 in DM mice was significantly increased(P<0.05).The protein levels of IRS-1,LC3Ⅱ/Ⅰ,TFEB and GABAPARAL1 in EM mice significantly increased,the phosphorylation levels of PI3K,AKT,GSK3β and AMPK were significantly increased.The p-mTOR/mTOR ratio of autophagy negative regula-tor in EM mice was decreased(P<0.05).Compared with single treatment group,the AMPK phosphorylation and LC3Ⅱ/Ⅰ protein expression in EM group were significantly increased(P<0.05).Conclusion:HIIT and semaglutide can improve myocardial fibrosis,glycogen accumulation and cardiac func-tion in db/db mice,and the combined intervention group yields the most pronounced effects,which may be re-lated to AMPK/mTOR pathway activation,enhanced cardiac glycophagy,and reduced myocardial injury.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Objective:To explore the effects of high-intensity interval training(HIIT)and semaglutide on cardiomyopathy and glycophagy in db/db mice.Method:Forty male db/db mice were randomly divided into diabetic control group(DC,n=10),diabetic+exercise group(DE,n=10),diabetic+semaglutide group(DM,n=10)and diabetic+exercise+semaglutide group(EM,n=10).DE mice and EM mice were conducted a 8-week HIIT treadmill protocol,DM mice and EM mice received daily subcutaneous neck injections of semaglutide at 0.05mg/kg.Body weight and fasting blood glucose were measured regularly.Echocardiography was used to detect cardiac function at the end of the intervention.Myocardial morphology was evaluated by H&E staining;The H&E staining was used to observe the myocardial morphological changes;fibrosis by Masson staining;glycogen accumulation by periodic acid-Schiff staining;and cardiomyocyte hypertrophy by wheat germ agglutinin(WGA)staining.The glycophagy was observed by transmission electron microscopy.Western Blot quantified the IRS-1,P-PI3K,PI3K,p-AKT,AKT,p-GSK3β,GSK3β,p-AMPK,AMPK,p-mTOR,mTOR,LC3Ⅱ/Ⅰ,TFEB and GABARAPL1 in myocar-dial tissue.Result:Compared with DC group,HIIT and/or semaglutide intervention reduced body weight and fasting glu-cose,improved cardiac function and myocardial morphology,decreased fibrosis and cardiomyocyte hypertrophy(reduced cross-sectional area,P<0.05),and lowered glycogen accumulation.Autophagosomes and autophagy vac-uoles containing different amounts of glycogen granule were observed by transmission electron microscopy.Compared with DC group,the protein level of p-mTOR/mTOR in DE mice was significantly decreased,and the protein levels of LC3Ⅱ/Ⅰ,TFEB and GABARAPL1 in DE mice were significantly increased(P<0.05).The phosphorylation levels of AKT and GSK3β in DM mice was significantly increased,and the protein level of TFEB and GABARAPL1 in DM mice was significantly increased(P<0.05).The protein levels of IRS-1,LC3Ⅱ/Ⅰ,TFEB and GABAPARAL1 in EM mice significantly increased,the phosphorylation levels of PI3K,AKT,GSK3β and AMPK were significantly increased.The p-mTOR/mTOR ratio of autophagy negative regula-tor in EM mice was decreased(P<0.05).Compared with single treatment group,the AMPK phosphorylation and LC3Ⅱ/Ⅰ protein expression in EM group were significantly increased(P<0.05).Conclusion:HIIT and semaglutide can improve myocardial fibrosis,glycogen accumulation and cardiac func-tion in db/db mice,and the combined intervention group yields the most pronounced effects,which may be re-lated to AMPK/mTOR pathway activation,enhanced cardiac glycophagy,and reduced myocardial injury.

Objective:To investigate the effects of growth hormone combined with triptoreline acetate on growth and sex hormone in girls with central precocious puberty.Methods:Sixty-two girls with central precocious puberty who received treatment in Xin'an International Hospital from January 2017 to December 2019 were included in this study. They were randomly assigned to receive treatment with either triptorelin acetate (control group, n = 31) or triptorelin acetate plus growth hormone (observation group, n = 31) for 12 successive months. Before and after treatment, bone age difference/chronological age difference (△BA/△CA), body height, body weight, uterine and ovarian volume and sex hormone level were compared between the control and observation groups. Results:△BA/△CA in the observation group was significantly lower than that in the control group [(0.64 ± 0.17) vs. (0.95 ± 0.13), t = 8.065, P < 0.05). Body height and weight in the observation group were (127.32 ± 1.08) cm and (33.42 ± 2.37) kg, respectively, which were significantly higher than those in the control group [(126.34 ± 0.87) cm and (31.01 ± 2.15) kg, t = 3.934 and 4.193, both P < 0.05]. Uterine and ovarian volume in the observation group were (1.68 ± 0.29) cm 3 and (1.26 ± 0.18) cm 3, respectively, which were significantly lower than those in the control group [(2.41 ± 0.46) cm 3 and (1.83 ± 0.26) cm 3, t = 7.474 and 10.036, both P < 0.05). After treatment, there were no significant differences in serum estradiol and luteinizing hormone levels between the two groups (both P > 0.05). Conclusion:Growth hormone combined with triptoreline acetate has a good effect on central precocious puberty in girls because it can improve the growth and development of girls and reduce serum levels of estradiol and luteinizing hormone.

Objective:To investigate the effect of montelukast sodium combined with glucocorticoid on acute attack of children with bronchial asthma and its influence on cytokines and immune function.Methods:A total of 122 children with acute asthma attack admitted to Xin'an International Hospital from September 2018 to September 2019 were divided into observation group(61 cases) and control group(61 cases) according to the random digial table mrethod.The control group was treated with glucocorticoid, and the observation group was treated with montelukast sodium on the basis of the control group.The course of treatment in both two groups was 7 days.The therapeutic effect, lung function, cytokines and immune function of the two groups were compared before and after treatment.Results:The total effective rate of the observation group(91.80%) was higher than 73.77% of the control group (χ 2=6.960, P<0.05). The peak expiratory flow rate(PEFR)[(2.93±0.21)L/s], forced expiratory volume in the first second(FEV 1%)[(82.54±5.37)%] and forced expiratory volume/forced vital capacity in the first second(FEV 1/FVC)[(90.32±4.36)%] in the observation group were higher than those in the control group[(2.48±0.16)L/s, (75.42±3.28)% and (83.98±3.42)%] ( t=13.313, 8.837, 8.936, all P<0.05). The levels of VEGF[(129.83±17.64)ng/L], TGF-β1[(83.21±16.79)ng/L] and IL-6[(24.32±4.19)ng/L] in the observation group were lower than those in the control group [(210.37±25.43)ng/L, (176.48±23.12)ng/L and (48.39±5.47)ng/L] ( t=20.325, 25.494, 27.284, all P<0.05). The CD 3+ [(75.72±3.46)%], CD 4+ [(42.56±3.18)%] and CD 4+ /CD 8+ (1.97±0.19) in the observation group were higher than those in the control group [(66.81±4.80)%, (37.87±2.63)% and (1.62±0.16)] ( t=11.761, 8.877, 11.005, all P<0.05). Conclusion:Montelukast sodium combined with glucocorticoid has obvious therapeutic effect on children with acute attack of asthma.It can reduce inflammatory reaction and enhance immune function, which is worthy of clinical reference.

PURPOSE: Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. MATERIALS AND METHODS: Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRI was determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. RESULTS: The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. CONCLUSION: Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.
Alanine Transaminase ; Aspartate Aminotransferases* ; Aspartic Acid* ; Biomarkers ; Blood Platelets ; Carcinoembryonic Antigen ; Cholangiocarcinoma* ; Disease-Free Survival ; Hepatectomy* ; Hepatitis B ; Humans ; Leukocytes ; Lymph Nodes ; Lymphocytes ; Multivariate Analysis ; Neoplasm Metastasis ; Neutrophils* ; Prognosis* ; Recurrence ; Retrospective Studies ; ROC Curve

Objective To investigate the evaluation index of melasma staging by clinical manifestations and non-invasive skin detection technology.Methods A total of 195 patients with a clinical diagnosis of melasma were enrolled from the First Affiliated Hospital of Kunming Medical University.The skin with lesion enlarged,color darker,erythema,red occured after scratching or lesion faded after compressing with glass belonged to the active stage;on the contrary,it was in the stable stage.Reflectance confocal microscopy (RCM),dermoscopy,Mexameter 18 and LAB were used to observe skin lesions of different stage of melasma.Results There were 115 patients (59.0 ％) in the active stage of melasma and 80 patients (41.0 ％) in the stable stage.DMA score in active stage 35.08± 10.59 were significantly higher than that of the stable stage 15.06-4-9.20 (P＜0.05).There were statistically significant difference in the quantity of inflammatory cell and blood vessels between two stages of melasma (P＜0.05).Erythema index (EI) in active stage of melasma 376.35±61.39 were high-er than that of the stable stage 320.364± 62.40 (P＜0.05).A-value in active stage of melasma 13.28± 1.75 were higher than that of the stable stage 12.34± 1.78 (P＜0.05).However,there were no siginificant differences in the quantity of melenin,melanin index (MI),L-value and B-value.Conclusions Melasma could be divided into active stage or stable stage,respectively,according to its clinical manifestations.DMA score,quantity of inflammatory cells and blood vessels,EI and A-value could be used as the reference index of melasma staging.

The ketoreductase (KR) domain in the first extending module of the polyketide synthase (PKS) catalyzes the reductions of both an α-keto group and a β-keto group in the biosynthesis of bacillaene, suggesting the intrinsic substrate promiscuity. In order to further investigate the substrate specificity, the KR domain (BacKR1) was heterologously overexpressed in Escherichia coli. In vitro enzymatic analysis showed that only one of the four diastereomers was formed in the reduction of the racemic (±)-2-methyl-3-oxopentanoyl-N-acetylcysteamine thioester catalyzed by BacKR1. In addition, BacKR1 was revealed to catalyze the reductions of cyclohexanone and p-chloroacetophenone, indicating the potential of KR domians of PKSs as biocatalysts.
Bacterial Proteins ; genetics ; metabolism ; Catalysis ; Cyclohexanones ; metabolism ; Escherichia coli ; enzymology ; Polyketide Synthases ; genetics ; metabolism ; Protein Structure, Tertiary ; Substrate Specificity ; omega-Chloroacetophenone ; metabolism