This study investigated the mechanism by which Jianpi Bushen Yiqi Decoction promotes acetylcholine receptor(AChR) clustering in myasthenia gravis through the Agrin/low-density lipoprotein receptor-related protein 4(LRP4)/muscle-specific receptor tyrosine kinases(MuSK) signaling pathway. A total of 114 female C57BL/6J mice were divided into the normal group, modeling group, and solvent control group. The normal group and the solvent control group were immunized with phosphate-buffered saline(PBS), while the modeling group was established as an experimental autoimmune myasthenia gravis(EAMG) model using the murine-derived AChR-α subunit R97-116 peptide fragment. After successful modeling, the mice were randomly assigned to the model group, the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups, and the prednisone group. After four weeks of continuous treatment, muscle strength was assessed using Lennon scores and grip strength tests. Immunofluorescence staining was conducted on differentiated C2C12 myotubes incubated with a drug-containing serum to observe the number of AChR clusters. The integrity of AChR on myofilaments in mouse gastrocnemius muscles was further assessed by immunofluorescence staining. Hematoxylin-Eosin(HE)staining was applied to examine pathological changes in the gastrocnemius muscles of EAMG mice treated with Jianpi Bushen Yiqi Decoction. Western blot was utilized to detect the expression of key proteins in the Agrin/LRP4/MuSK signaling pathway in both C2C12 myotubes and mouse gastrocnemius muscles. The results demonstrated that compared to the model group, the prednisone group exhibited a significant decrease in the body weights of mice, whereas no significant differences in the body weights of mice were observed among the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups. All treatment groups showed significantly improved grip strength and Lennon scores. Additionally, the formula promoted AChR clustering on myotubes and enhanced AChR integrity in gastrocnemius myofilaments and reduced inflammatory infiltration between muscle tissue and fibrous hyperplasia. Furthermore, Jianpi Bushen Yiqi Decoction upregulated the protein expression of AChRα1, Agrin, and p-MuSK in C2C12 myotubes and increased the protein expression of AChRα1, Agrin, MuSK, p-MuSK, LRP4, and docking protein 7(Dok-7)in gastrocnemius tissue. In conclusion, Jianpi Bushen Yiqi Decoction may promote AChR clustering by targeting key proteins in the Agrin/LRP4/MuSK signaling pathway, thereby improving neuromuscular junction function and enhancing muscle strength.
Animals ; Agrin/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Receptors, Cholinergic/genetics* ; Female ; Mice, Inbred C57BL ; Receptor Protein-Tyrosine Kinases/genetics* ; Neuromuscular Junction/metabolism* ; Myasthenia Gravis, Autoimmune, Experimental/physiopathology* ; Humans ; LDL-Receptor Related Proteins

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency＞100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.

Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.

Objective:To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis.Methods:A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group(n=68)and a control group(n=64),the former following the Mediterranean dietary pattern,the latter adhering to their own dietary habits,and meanwhile both receiving lifestyle guidance,psychological counseling,symptomatic medication and physiotherapy according to their specific symptoms.The patients were followed up for 4 weeks,therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment.Re-sults:Compared with the baseline,the quality of life(QOL)scores,pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment(P<0.05),even more decreased in the former than in the latter,but with no statistically significant difference between the two(P>0.05).The rate of therapeutic effective-ness was higher in the observation group than in the control(87.1%vs 79.7%,but showed no statistically significant difference be-tween the two groups(P>0.05).Conclusion:Multimodal therapy is suitable for the management of different clinical manifesta-tions of individual patients,while dietary habits vary from person to person as well as from region to region.Therefore,scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.

Objective:To investigate the selection of the modality of transperineal surgery and its effect in the treatment of pel-vic fracture-induced posterior urethral atresia(PUA).Methods:This study included 116 cases of PUA caused by pelvic fractures treated in our hospital from January 2012 to December 2021.We used transperineal resection of the urethral stricture and end-to-end u-rethral anastomosis(EEUA)as the first choice in the treatment of 79 cases.For the patients with the urethral atresia segment longer than 3 cm and evident urethral involution tension,we incised the penile septum,separated and removed the muscle tendon and scar tis-sue attached to the lower border of the pubis,and anastomosed with 4-0 absorbable thread for 8 stitches.For the other 37 cases for which we were not sure of effective suture of the membrane due to obvious scarring of the proximal urethra,the remaining urethra shor-ter than 5 mm or incomplete urethral mucosa,we selected conventional urethral pull-through operation(UPTO).We followed up the patients for 3-24 months postoperatively.Results:The total success rate of surgery was 78.4％(91/116),81.1％(30/37)in the UPTO and 77.2％(61/79)in the EEUA group,significantly higher in the former than in the latter(P=0.05).The rate of post-operative dysuria was remarkably lower in the UPTO than in the EEUA group(13.5％[5/37]vs 16.5％[13/79],P=0.05),and so was that of surgical failure(5.4％[2/37]vs 6.3％[5/79],P=0.05).The main causes of postoperative dysuria in the EEUA group included restenosis resulting from incomplete scar resection and the two sides of the anastomosed urethral segment not being at the coaxial level,while those in the UPTO group included the formation of mucosal flaps in the pulled-through urethra,and re-scarring leading to stricture or the pulled-through urethra not being at the coaxial level.Among the 7 cases of surgical failure due to recurrence,1 refused reoperation and opted for cystostomy tube drainage,and the other 6 underwent EEUA again 6 months later.Conclusion:EEUA is preferred as the first-choice surgery for PUA,while UPTO remains an effective treatment option in hospitals with preliminary skills and less experience in the management of PUA.

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL^-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

OBJECTIVE: To observe the effect of acupuncture combined with infantile tuina on intestinal flora and its efficacy in children with tic disorders (TD), and to explore its mechanism. METHODS: A total of 15 children with TD were recruited as an observation group and 10 healthy children as a healthy control group. Regulating spleen and stomach acupuncture combined with infantile tuina were received in the observation group. First, acupuncture was applied to Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Hegu (LI 4), Zusanli (ST 36), etc., and then abdominal massage and other tuina techniques were applied, once a day, 6 times a week, 2 weeks as a course of treatment, a total of 2 courses of treatment were required. No intervention was given in the healthy control group. In the observation group, Yale global tic severity scale (YGTSS) score and TCM syndrome score were compared before treatment and after 1 and 2 courses of treatment. 16S rRNA sequencing technology was used to detect the intestinal flora in the healthy control group and before and after treatment in the observation group. RESULTS: After 1 and 2 courses of treatment, the scores of YGTSS and TCM syndrome in the observation group were lower than those before treatment (P<0.01, P<0.05). Compared with the healthy control group, the number of operational taxonomic units (OTU) and indexes of Chao1, Sobs, Ace and Shannon were decreased in the observation group before treatment (P<0.05, P<0.01). Compared with before treatment, the number of OTU and indexes of Chao1, Sobs, Ace and Shannon were increased in the observation group after treatment (P<0.01, P<0.05). Compared with the healthy control group, the relative abundance of Firmicutes in the observation group before treatment was decreased (P<0.001), while the relative abundance of Bacteroidetes, Bacteroides and Erysipelatoclostridium was increased (P<0.001, P<0.05). Compared with before treatment, the relative abundance of Bacteroidetes in the observation group was decreased (P<0.001) after treatment, while the relative abundance of Actinobacteria, Bifidobacterium and Atopobium was increased (P<0.05, P<0.01). CONCLUSION Acupuncture combined with infantile tuina based on the principle of regulating spleen and stomach could effectively improve TD symptoms in children, which may be related to regulating the diversity of intestinal flora, increasing beneficial bacteria, maintaining intestinal microecological balance, and playing a role in improving neurological disorders.
Child ; Humans ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Acupuncture Therapy ; Spleen ; Tic Disorders