ObjectiveThis study aims to systematically analyze the blood-absorbed components and metabolic profiles of Xiebaisan（XBS） in normal and chronic bronchitis （CB） mice using ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， while comparing differences between the two states. MethodsThirty female BABL/c mice were randomly divided into the normal group， the normal drug administration group， the CB group， the CB drug administration group and the dexamethasone group， with 6 mice in each group. The CB mouse model was established by inducing with ovalbumin （OVA）. The mice in the normal drug administration group and the CB drug administration group started to be gavaged with XBS（13.2 g·kg^-1） from the 21^st day， and the dexamethasone group mice were simultaneously gavaged with dexamethasone （0.5 mg·kg^-1） until the end of the 35^th day of the experiment. Subsequently， serum samples were collected and evaluated for their efficacy， based on the pharmacological evaluation indicators， to determine the efficacy of XBS in treating CB. Then the UPLC-Q-Exactive Orbitrap MS was employed to identify and analyze the chemical constituents， blood-absorbed components， and metabolites of XBS. Chemometric analysis was conducted to reveal metabolic profile differences under "dual states". Concurrently， Real-time PCR technology was utilized to detect the expression levels of key liver metabolic enzymes CYP2E1， CYP3A1， UGT1A1， and UGT1A6. ResultsA total of 28 prototype components and 158 metabolites （including 48 phase Ⅰ metabolites and 110 phase Ⅱ metabolites） of XBS were unambiguously identified in the serum of normal mice. Additionally， a comprehensive characterization was performed on a total of 32 prototype components and 178 metabolites （including 50 phase Ⅰ metabolites and 128 phase Ⅱ metabolites） of XBS in the serum of CB mice. Among them， 27 prototype components were detected in both states， including 12 flavonoids， 2 alkaloids， 3 triterpenes， 4 organic acids， 3 amides， 1 stilbene and 2 other compounds. The chemometrics analysis revealed no significant difference in the prototype components and metabolites of XBS between normal and CB mice； however， there was a significant increase in the in-vivo exposure of XBS in CB mice. Compared to normal mice， the levels of phase Ⅰ metabolites such as oxidation， reduction and methylation of blood components of XBS as well as phase Ⅱ metabolites of glucuronidation showed significant changes in CB mice. Real-time PCR further confirmed that these alterations were attributed to the upregulation of CYP2E1 （P<0.05）， CYP3A1 （P>0.05）， UGT1A1 （P<0.01） and UGT1A6 （P<0.01） enzymes expression in the liver of CB mice. ConclusionThis study elucidated the disparities in the levels of the blood-absorbed components and metabolic profiles of XBS in normal and CB mice， especially in oxidation， reduction， methylation in phase Ⅰ metabolism and glucoaldehyde acidification in phase Ⅱ metabolism. And there are related to the differences in the expression levels of phase Ⅰ and phase Ⅱ metabolic enzymes CYP2E1， CYP3A1， UGT1A1 and UGT1A6 in the liver.

Objective To explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P＜0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P＜0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.

Objective:To explore effect of Astragalus polysaccharides(APS)through TLR4/NF-κB signal pathway on intesti-nal immune inflammation of rats with dampness stagnancy due to spleen deficiency syndrome based on fecal microbiota transplantation.Methods:Rats with dampness stagnancy due to spleen deficiency syndrome were fed with high-fat and low-protein diet and subjected to exhaustive swimming,transplant flora microbiota after intervention of APS.General condition,changes in weight gain,time of weight exhaustion swimming,spleen index and thymus index were tested.Pathological manifestations of duodenal tissue inflammation were observed by HE staining.Serum IL-1β,IL-6 and TNF-α concentrations of rats were determined by ELISA.Protein levels of TLR4,NF-κB p65 and IκBα in colon were determined by Western blot.Results:Compared with model group,general condition rating,changes in weight gain and time of weight exhaustion swimming in APS-FTG group were increased significantly(P<0.01);spleen index and thymus index were increased;pathological manifestations of duodenal inflammation were significantly relieved;serum IL-1β,IL-6 and TNF-α concentrations were decreased significantly(P<0.01),TLR4 and NF-κB p65 levels in colon were decreased significantly(P<0.05 and P<0.01),IκBα level was in colon increased significantly(P<0.01).Conclusion:APS improves intestinal microbiota of rats with dampness stagnancy due to spleen deficiency syndrome and inhibits TLR4/NF-κB pathway activation through intestinal flora,thus improving intestinal immune inflammation status in rats with dampness stagnancy due to spleen deficiency syndrome.

Objective:To analyze the risk factors associated with intradialytic hypotension (IDH) in patients undergoing maintenance hemodialysis (MHD).Methods:This study used a cross-sectional design and included 150 adult patients who underwent MHD at The Third Affiliated Hospital of Anhui Medical University from January 2023 to March 2024. Relevant clinical data were collected to analyze the occurrence of IDH in patients undergoing MHD over 3 months, and the associated risk factors.Results:Among the 150 patients undergoing MHD, there were 67 in the IDH group and 83 in the non-IDH group. The IDH group had a higher fibrinogen/albumin ratio (FAR) [89.41 (73.30, 114.50) vs. 76.56 (65.80, 89.60), χ2 = -3.55, P < 0.001], an older age [(68.46 ± 14.10) years vs. (61.30 ± 12.23) years, t = -3.33, P = 0.001], a longer dialysis duration [(4 (3.5, 4.0) hours vs. (4 (4.0, 4.0) hours), U = -2.11, P = 0.044], a greater ultrafiltration volume [(2.20 ± 0.74) L vs. (1.92 ± 0.82) L, t = -2.16, P = 0.032], a higher ultrafiltration rate [(8.90 ± 2.64) mL·h?1·kg?1 vs. (7.75 ± 2.91) mL·h?1·kg?1, t = -2.51, P = 0.013], and a higher ultrafiltration volume/dry body mass ratio [(33.75 ± 9.76) mL/kg vs. (30.21 ± 11.39) mL/kg, t = -2.11, P = 0.046] compared with the non-IDH group. In the IDH group, the proportion of patients with primary chronic glomerulonephritis was lower (19.4% vs. 37.3%, χ2 = 5.76, P = 0.016), fibrinogen levels were higher [(3.63 (3.15, 4.50) μg/L vs. (3.34 (2.90, 3.74) μg/L, U = -2.61, P = 0.009], albumin levels were lower [(41.26 ± 4.03) g/L vs. (43.42 ± 4.29) g/L, t = 3.15, P = 0.002], high-density lipoprotein cholesterol (HDL-C) levels were lower [0.90 (0.77, 1.09) mmol/L vs. 1.05 (0.84, 1.34) mmol/L, U = -2.77, P = 0.006], and C-reactive protein levels were higher [5.92 (2.79, 9.61) mg/L vs. 2.70 (0.99, 6.49) mg/L, U = -2.27, P = 0.023] compared with the non-IDH group. Multivariate logistic regression analysis indicated that higher FAR values ( OR = 1.030, P = 0.025), a history of chronic glomerulonephritis ( OR = 10.408, P = 0.012), older age ( OR = 1.062, P = 0.043), a high ultrafiltration volume/dry body mass ratio ( OR = 1.072, P = 0.037), and low HDL-C levels ( OR = 0.046, P = 0.015) are independent risk factors for IDH. The area under the receiver operating characteristic curve for FAR predicting IDH was 0.699 (95% CI: 0.571-0.827, P = 0.003). The combination of age, chronic glomerulonephritis, ultrafiltration volume/dry body mass ratio, HDL-C levels, and FAR for predicting IDH resulted in a receiver operating characteristic curve area of 0.839 (95% CI: 0.750-0.929, P < 0.001). Conclusions:Among the risk factors for IDH in patients undergoing MHD, FAR is independently associated with an increased risk of IDH and serves as a valuable predictor for its occurrence in these patients.

Objective To investigate the risk factors associated with onset of vertebrobasilar doli-choectasia(VBD)symptoms in elderly patients.Methods A retrospective study was conducted on 206 elderly VBD patients admitted in Chinese PLA General Hospital between July 2014 and July 2024.Based on the presence of VBD-related symptoms or not,they were divided into a symptom-atic group(112 cases)and an asymptomatic group(94 cases).All patients underwent cranial mag-netic resonance angiography(MRA)and MRI.And routine blood tests were performed and related indicators were detected,including following parameters:neutrophil-to-lymphocyte ratio(NLR),systemic immune-inflammation(SII)index,total cholesterol(TC),low-density lipoprotein choles-terol(LDL-C),and C-reactive protein(CRP).Multivariate logistic regression analysis was per-formed to identify risk factors associated with symptomatic progression in elderly VBD patients.Results The symptomatic group showed significantly higher SII index and NLR,longer bilateral vertebral artery length,and larger proportion of elevated vertebral artery confluence when compared with the asymptomatic group(P＜0.05,P＜0.01).Significant differences were also observed be-tween the two groups in basilar artery height grade and proportion of basilar artery hyperintensity of vessel wall signal(BA-HVS,P＜0.01).Multivariate logistic regression analysis revealed that elevated vertebral artery confluence and high-grade basilar artery hyperintensity of vessel wall signal were risk factors for symptomatic onset in elderly VBD patients.The risk of symptomatic onset in elderly VBD patients with elevated confluence of the vertebral artery was 2.143 times higher than in those without elevation(95％CI:1.144-4.013,P=0.017).Similarly,the risk in elderly VBD patients with high-grade basilar artery hyperintensity of vessel wall signal was 4.113 times higher than in those without such signal(95％CI:2.213-7.646,P=0.000).Conclusion Elevated vertebral artery confluence and high-grade basilar artery hyperintensity of vessel wall signal may serve as clinical indicators for monitoring disease progression in elderly patients with VBD,thereby facilitating the optimization of clinical management strategies in the patients.

Objective:To investigate the role of rheum tanguticum polysaccharide(RTP)in treating ulcerative colitis(UC)by improving intestinal flora.Methods:UC model was established,rats were divided into normal control group,model group and RTP treatment group.The integrity of colonic mucosa,submucosa and muscularis were observed by HE staining.Expressions of TNF-α,IL-6,IL-8 and IL-1β in serum were assessed by ELISA.16S rRNA sequencing was performed to analyze the composition and differences of intestinal flora in rats.Results:UC rats had symptoms such as loose stools,blood in the stool,anal filth,chills and mental malaise.RTP treatment could significantly improve the symptoms and reduce DAI scores(P<0.05).HE staining showed that the colonic struc-ture of UC rats was necrotic and inflammatory cells infiltrated submucosa.RTP treatment could significantly promote the repair and regeneration of mucosal epithelium.RTP could significantly inhibit inflammatory response and downregulate the expression of inflam-matory factors in UC rats(P<0.05).Composition and abundance of intestinal flora in UC rats were significantly different from that of normal control group.Staphylococcus was significantly increased,while Collinsella,Allobaculum,Chlamydia and Holdemanella were significantly decreased.RTP treatment could improve intestinal flora,reduce the abundance of Staphylococcus,and increase the abundance of Collinsella,Allobaculum,Chlamydia and Holdemanella.Conclusion:RTP can be used to treat UC in rats by inhibiting inflammation and improving intestinal flora.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective To explore the therapeutic effect and mechanism of electroacupuncture on depressive model mice based on the phosphatase and tensin homolog-induced kinase 1(PINK1)/Parkin pathway.Methods Specific pathogen-free grade male C57BL/6J mice were used.For experiment 1,60 mice were randomly divided into blank,model,sham electroacupuncture,and electroacupuncture groups using the random number table method,with 15 rats per group.For experiment 2,30 mice were randomly divided into normal,cyclosporine A(CsA),and electroacupuncture+CsA groups using the same method,with 10 rats per group.The chronic restraint stress(CRS)was used to establish a depression model.After successful modeling,CRS was continued to maintain model stability.After modeling,1 h before daily CRS stimulation,the electroacupuncture and electroacupuncture+CsA groups received electroacupuncture interventions at the"Baihui"(GV20)and"Zusanli"(ST36)acupoints,using continuous wave stimulation at a frequency of 2 Hz and an intensity of 1 mA for 20 min,once daily for 7 consecutive days.Mice in the sham electroacupuncture group received superficial needling at non-meridian,non-acupoint locations under the axilla 1 h before CRS,with the electroacupuncture device connected but not powered on once a day for 7 consecutive days.Mice in the CsA and electroacupuncture+CsA groups received an intraperitoneal injection of CsA solution(0.2 mg/g)30 min before electroacupuncture intervention,once daily for 7 consecutive days.In experiment 1,depressive-like behavior was assessed using the open field,tail suspension,and sucrose preference tests.The spontaneous excitatory postsynaptic currents(sEPSC)and spontaneous inhibitory postsynaptic currents(sIPSC)parameters of hippocampal neurons were evaluated using brain slice patch clamp techniques.Western blotting was conducted to measure the expression levels of mitochondrial autophagy-related proteins PINK 1,phosphorylated PINK1(p-PINK1),Parkin,microtubule-associated protein 1A/1B-light chain 3-Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),ubiquitin-binding protein(p62),and mitochondrial markers,including translocase of outer mitochondrial membrane 20(TOMM20),heat shock protein 60(HSP 60),and cytochrome c oxidase Ⅳ(COX Ⅳ).Immunofluorescence was used to detect PINK1 protein expression in the CA3 region of the hippocampus.Transmission electron microscopy was used to examine the ultrastructure of mitochondria in hippocampal neurons.On the basis of experiment 1,experiment 2 evaluated depressive-like behavior in mice using sucrose preference,open field,and tail suspension tests;Western blotting was used to detect the expressions of PINK1,p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,p62,TOMM20,HSP 60,and COX Ⅳ proteins of hippocampus in mice.The mitochondrial ultrastructure was observed in hippocampal neurons using transmission electron microscopy.Results In experiment 1,compared with the blank group,the model and sham electroacupuncture groups exhibited a decrease in sucrose consumption rate,a decrease in the time spent in the center area,a reduced proportion of distance moved in the center area,and an increase in immobility time of tail suspension(P＜0.05).The sEPSC and sIPSC in hippocampal neurons decreased in both amplitude and frequency(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus were reduced,whereas the p62 expression level was increased(P＜0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus decreased(P＜0.05).The number of healthy mitochondria in hippocampal neurons was reduced,with numerous damaged mitochondrial structures observed.Compared to the model and sham electroacupuncture groups,the electroacupuncture group showed an increased in the time spent in the center area,a higher proportion of distance moved in the center area,and an elevated sucrose consumption rate.In contrast,the immobility time in the tail suspension test decreased(P＜0.05),whereas the amplitude and frequency of sEPSC and sIPSC in hippocampal neurons increased(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COXⅣ expression levels in the hippocampus increased,whereas the p62 expression level decreased(P＜0.05).The average fluorescence intensity of PINK1 in the CA3 region of the hippocampus increased(P＜0.05).Additionally,mitochondrial damage in hippocampal neurons was alleviated,and a notable presence of autophagosomes mitophagy lysosomes was observed.In experiment 2,compared with the normal group,the mice in the CsA and electroacupuncture+CsA groups showed a decrease in the time spent in the center area and the proportion of distance moved in the center area,a decrease in sucrose consumption rate,and an increase in the immobility time in the tail suspension test(P＜0.05).p-PINK1,Parkin,LC3-Ⅱ/Ⅰ,TOMM20,HSP 60,and COX Ⅳ expression levels in the hippocampus decreased,whereas p62 expression increased(P＜0.05).Many damaged mitochondria were observed in hippocampal neurons.Conclusion Electroacupuncture may exert its antidepressant effects by promoting PINK1/Parkin pathway-mediated mitophagy to eliminate damaged mitochondria,thereby restoring the function of hippocampal neurons in depressive model mice.

Objective: To analyze the current status of clinical trial registration for childhood and adolescent obesity, so as to provide insights for the registration and implementation of related trials. Methods: ClinicalTrials.gov and the ChiCTR database were searched for obesity related clinical trial registrations up to 1 June 2025. Data included basic characteristics (registration region, date, funding source, status, sample size), trial design features, participant demographics, interventions, outcome measures, methodology, and reporting quality. Statistical and descriptive analyses were conducted. Results: A total of 1 450 registered studies were included, covering 59 regions globally. North America hosted the highest number of registrations (876, 60.41%), with the United States accounting for the largest share (771, 53.17%). The earliest registered study dated to 1985, while 2016 saw the highest annual registrations ( n =87). Funding sources predominantly originated from universities (834 studies, 57.52%). Currently, completed trials accounted for the majority (1 003 trials, 69.17%). Globally, the majority of studies employed sample sizes within the 11-50 range (331 studies, 22.83%). Interventional studies predominated in design type (1 186, 81.79%), predominantly employing randomized parallel group controlled trials. Main interventions included comprehensive lifestyle interventions, physical activity and exercise interventions, and diet and nutrition interventions. High frequency outcome indicators primarily involved body composition and anthropometric measurements, metabolic and biochemical indicators, etc. Methodology and reporting quality required improvement. Conclusions The registration of clinical trials related to childhood and adolescent obesity globally shows a positive development trend, but issues of regional imbalance and methodological limitations exist. It is necessary to strengthen clinical trial registration norms, optimize study designs, and focus on the innovation of interventions and the systematicity of outcome indicators.

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.