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

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

Objective:To analyze intestinal microecological differences and their correlation with psychological status in patients with constipated irritable bowel syndrome(IBS-C)and functional constipation(FC).Methods:A total of 160 patients with IBS-C and FC attending the outpatient and inpatient departments of the Department of Gastroenterology at the General Hospital of Ningxia Medical University from January 2021 to January 2024 were selected and grouped according to the type of disease into the IBS-C group(80 patients)and the FC group(80 patients),and 80 patients who had a health checkup during the same period were selected as the control group.Fresh fecal specimens were taken from all subjects,and 16S rRNA sequencing was used to detect the intestinal flora,and the indices of intestinal microecological diversity(Ace index,Chao index,Shannon index,and Sobs index)were detected,and the psychological state of the subjects was assessed by using the Self-Assessment Scale for Anxiety(SAS)and the Self-Depression Scale(SDS).Pearson's correlation method was used to analyze the correlation between intestinal microecology and correlation with psychological state in IBS-C and FC patients.Result:Bifidobacteria and Lactobacillus levels were lower in both the FC and IBS-C groups compared with the control group,and the decrease was more pronounced in the IBS-C group(P＜0.05).Enterobacteriaceae and Enterococci contents were higher in patients in the FC and IBS-C groups(P＜0.05),with the greatest increase in the IBS-C group(P＜0.05);Microbial diversity analysis showed that there were differences in Ace,Chao,Shannon and Sobs indices among the three groups(P＜0.05).All diversity indices were lower in the FC and IBS-C groups than in the control group,and the degree of reduction was more pronounced in the IBS-C group than in the FC group(P＜0.05);The SAS and SDS scores of both FC and IBS-C groups were higher than those of the control group,and the scores of the IBS-C group were higher than those of the FC group(P＜0.05);correlation analysis showed that,in the IBS-C and FC groups,Bifidobacterium and Lactobacillus,Ace index,Chao index,Shannon index,and Sobs index were negatively correlated with SAS and SDS scores.Enterobacteriaceae and Enterococci were positively correlated with SAS and SDS scores(P＜0.05).Conclusion:There are possible differences in the gut microbiota between IBS-C and FC patients.The imbalance of gut microbiota is more significant in IBS-C patients,and gut microbiota is closely related to psychological status.Clinical treatment of IBS-C and FC should pay attention to the regulation of gut microbiota and intervention of psychological status.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Objective:To analyze intestinal microecological differences and their correlation with psychological status in patients with constipated irritable bowel syndrome(IBS-C)and functional constipation(FC).Methods:A total of 160 patients with IBS-C and FC attending the outpatient and inpatient departments of the Department of Gastroenterology at the General Hospital of Ningxia Medical University from January 2021 to January 2024 were selected and grouped according to the type of disease into the IBS-C group(80 patients)and the FC group(80 patients),and 80 patients who had a health checkup during the same period were selected as the control group.Fresh fecal specimens were taken from all subjects,and 16S rRNA sequencing was used to detect the intestinal flora,and the indices of intestinal microecological diversity(Ace index,Chao index,Shannon index,and Sobs index)were detected,and the psychological state of the subjects was assessed by using the Self-Assessment Scale for Anxiety(SAS)and the Self-Depression Scale(SDS).Pearson's correlation method was used to analyze the correlation between intestinal microecology and correlation with psychological state in IBS-C and FC patients.Result:Bifidobacteria and Lactobacillus levels were lower in both the FC and IBS-C groups compared with the control group,and the decrease was more pronounced in the IBS-C group(P＜0.05).Enterobacteriaceae and Enterococci contents were higher in patients in the FC and IBS-C groups(P＜0.05),with the greatest increase in the IBS-C group(P＜0.05);Microbial diversity analysis showed that there were differences in Ace,Chao,Shannon and Sobs indices among the three groups(P＜0.05).All diversity indices were lower in the FC and IBS-C groups than in the control group,and the degree of reduction was more pronounced in the IBS-C group than in the FC group(P＜0.05);The SAS and SDS scores of both FC and IBS-C groups were higher than those of the control group,and the scores of the IBS-C group were higher than those of the FC group(P＜0.05);correlation analysis showed that,in the IBS-C and FC groups,Bifidobacterium and Lactobacillus,Ace index,Chao index,Shannon index,and Sobs index were negatively correlated with SAS and SDS scores.Enterobacteriaceae and Enterococci were positively correlated with SAS and SDS scores(P＜0.05).Conclusion:There are possible differences in the gut microbiota between IBS-C and FC patients.The imbalance of gut microbiota is more significant in IBS-C patients,and gut microbiota is closely related to psychological status.Clinical treatment of IBS-C and FC should pay attention to the regulation of gut microbiota and intervention of psychological status.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the effects of esketamine on respiration,complications and acute phase inflammatory factors in patients undergoing single-port thoracoscopic surgery under general anesthesia with preserved spontaneous respiration.Methods Ninety patients,aged 16～74 years,BMI 18～28 kg/m2,ASA physical status Ⅰ or Ⅱ,who were scheduled to undergo single-port thoracoscopic surgery under general anesthesia were selected.Patients were randomly divided into two groups by random number table:esketamine group(group E,n=45)and control group(group C,n=45).Esketamine 0.5 mg/kg was given for induction of anesthesia,and 0.25 mg/kg again before cutting skin.In group C,sufentanilwas given at 0.15 μg/kg for induction of anesthesia.Other anesthesia induction and maintenance durgs in both groups were the same.SP02,PaCO2 and PaO2 were recorded at the patient's entrance(T0),before pleuraopening(T1),15 min after pleuraopening(T2),30 min after pleuraopening(T3),and beforelaryngeal mask removal(T4).3 mL of blood was extracted from themedian cubital vein at T0 and 24 h after surgery(T5)todetect the concentrations of TNF-α and IL-6.The length of spontaneous respiration recovery and laryngeal mask removal,the number of respiratory intervention,the incidence of body movement during operation,nausea,vomiting,psychiatric symptom,awareness,the length of hospital stay was recorded.Results Compared with group C,PaO2was significantly decreased and PaCO2was significantly increased in group E at T1,PaO2was significantly increased and PaCO2was significantly decreased at T2(P<0.01).Compared with group C,the length of spontaneous respiration recovery was significantly shortened and the number of respiratory intervention was significantly decreased in group E(P<0.01).Compared with group C,the concen-trations of TNF-α and IL-6 in venous blood in group E at T5 was significantly decreased(P<0.01).There were no significant difference in the length of laryngeal mask removal,and the incidenceofcomplications,hospitalstay between the two groups.Conclusion Esketamine reducesintraoperative respiratory depression,shortens spontaneous respiration recovery,maintains respiratory stability and reduces acute inflammatory response in patients under general anesthesia with preserved spontaneous respiration for single-port thoracoscopic surgery.

This study investigated the characteristics of gut microbiota imbalance in patients with infectious diarrhea caused by various pathogenic infections,and the role of Bacteroides in maintaining homeostasis in the intestinal environment.The gut microbiota in patients with diarrhea caused by pathogenic infections,such as viral and bacterial infections,was determined through full-length 16S rRNA amplicon sequencing.Patients with diarrhea were grouped and analyzed according to the presence of single bacterial infection,single viral infection,mixed infection,or Clostridioides difficile infection.Bacteroides had the highest absolute number and relative abundance in the gut microbiota in healthy people,whereas patients with infectious diar-rhea showed lower relative abundance of Bacteroides at each phylum/order/family/genus taxonomic level.Alpha diversity anal-ysis indicated no significant differences among groups.NMDS and PCoA indicated formation of distinct clusters in the control group compared with the different infectious diarrhea groups.The diversity of the gut microbiota was higher in the control group than the infectious diarrhea groups.Patients with infec-tious diarrhea caused by different pathogens showed differing predominant gut microbiota.Bifidobacterium predominated in the single viral infection group,Streptococcus predominated in the single bacterial infection group,and Lachnoclostridium predominated in the mixed infection group.Escherichia and Klebsiella were the major gut microbiota in the C.difficile infection group.Meanwhile,the dominant gut microbiota in the healthy population was Bacteroides.COG function prediction revealed that the healthy control group formed a distinct cluster from the different infection groups.The functions of defense mechanisms,cell wall synthesis,protein modification,cellular differentiation,and replication and recombination were signifi-cantly diminished in all infectious diarrhea groups.In general,patients with infectious diarrhea caused by different pathogens showed dysbiosis,with diminished gut microbiota diversity and the emergence of related biomarkers.Our findings indicated that Bacteroides has a key role in maintaining the homeostasis of the human intestinal environment,thus providing new ideas for the subsequent treatment of infectious diarrhea and research in other fields.