Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2＜BMI≤23 kg/m2), a group B (23 kg/m2＜BMI≤29 kg/m2) and a group C (BMI＞29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

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.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective:To construct and validate a depression risk prediction model for middle-aged and elderly patients with diabetes.Methods:Data were extracted from the fifth wave (2020) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 900 diabetic patients were identified, and after excluding those with missing data or invalid questionnaires, 769 patients were included in the analysis. Patients were randomly divided into a training set and a validation set in a 7∶3 ratio. Univariate analysis and logistic regression analysis were performed to screen the optimal predictors of depression in diabetic patients, and a nomogram model was developed. The predictive performance of the model was assessed by the area under the receiver operating characteristic curve ( AUC). Model calibration and accuracy were evaluated using bootstrap resampling, calibration plots, and the Hosmer-Lemeshow test. The clinical utility was further assessed by decision curve analysis (DCA) and clinical impact curves (CIC) . Results:Among the 769 patients, 366 (47.59%) had depression. Logistic regression analysis showed that place of residence, pain, difficulty in toileting, difficulty in bathing, sleep duration, physical exercise, life satisfaction, and children's satisfaction were independent predictors of depression in diabetic patients. A nomogram was constructed based on these variables, yielding an AUC of 0.775. At the optimal cutoff value of 0.557, the model demonstrated a sensitivity of 59.1% and a specificity of 84.8%, indicating good discriminative ability. The Hosmer-Lemeshow test showed (χ 2=15.821, P=0.105), suggesting good agreement between predicted and observed outcomes. In the validation set, the AUC was 0.778, with Hosmer-Lemeshow (χ 2=8.557, P=0.575). DCA and CIC indicated favorable clinical applicability of the model. Conclusions:The depression risk prediction model constructed in this study demonstrated good predictive performance. It can assist clinicians in early identification of high-risk individuals with diabetes and provide a theoretical basis for targeted interventions.

Objective:To compare the clinical efficacy of catheter-directed thrombolysis (CDT) via the contralateral femoral vein approach (CFVA-CDT) and the calf deep vein approach (CVA-CDT) in the treatment of acute mixed-type lower extremity deep vein thrombosis (DVT).Methods:Patients treated with CFVA-CDT and CVA-CDT for acute mixed-type DVT were retrospectively collected from January 2018 to December 2021, totaling 49 and 32 patients, respectively. The relevant technical indicators, thrombolysis rates in the iliac-femoral vein segment and femoral-popliteal vein segment, clinical efficacy, and the incidence of lower extremity deep vein patency, venous valve insufficiency, and post-thrombotic syndrome (PTS), as well as the severity of chronic venous disease in the affected limb (VCSS score) during a 2-year follow-up period were retrospectively compared between the two venous access CDT groups. The t-test was used for comparing quantitative data, while the chi-square test or Fisher′s exact test was used for categorical data.Results:During CFVA-CDT procedure, 6-8 F vascular sheaths were used, and balloon dilation of 2~6 mm was more frequently employed (65.31%, 32/49) to expand venous stenosis/occlusion segments before successful sheath placement compared to the CVA-CDT group (37.50%, 12/32), and the difference was statistically significant ( P=0.014). In the CVA-CDT group, 31.25% (10/32) of patients had a maximum sheath size of 6 F, while the remainder used 4 or 5 F sheaths. Among them, 34.38% (11/32) of patients required re-puncture of the popliteal or femoral vein for larger sheaths (≥8 F) for thrombus aspiration and subsequent endovascular treatment during or after thrombolysis. The effective thrombolysis rates (≥50%) in the iliac-femoral vein segment were not significantly different between the two groups ( P=0.778). The effective thrombolysis rate of the femoral-popliteal venous segment is related to the presence or absence of popliteal vein opacification on lower extremity venous antegrade venography. There was no significant difference between the groups when the popliteal vein was visualized ( P=1.000). While the popliteal vein was not visualized, the CVA-CDT group (75.0%, 15/20) was significantly better than the CFVA-CDT group (34.38%, 11/32), and the difference was statistically significant ( P=0.004). There was no significant difference in clinical efficacy between the two groups ( P=0.819). During follow-up, the femoral-popliteal vein patency rate in the CVA-CDT group (87.50%, 28/32) was significantly higher than in the CFVA-CDT group (44.90%, 22/49), the difference was statistically significant ( P<0.001). Conclusions:Successful CFVA-CDT requires the assistance of more ancillary devices, while the use of larger sheaths is more limited in CVA-CDT due to the smaller caliber of the calf deep veins. The presence or absence of popliteal vein opacification on lower extremity venous antegrade venography may influence the effective thrombolysis of the femoral-popliteal venous segment thrombus in patients with acute mixed deep vein thrombosis (DVT) treated with CFVA-CDT and CVA-CDT. Compared to CFVA-CDT, CVA-CDT can improve the patency rate of the femoral-popliteal venous segment.

AIM To investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α.levels(P＜0.05,P＜0.01);decreased HDL-C level and activities of SOD and GSH-Px(P＜0.05,P＜0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P＜0.01)and increased lipid deposition area(P＜0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α levels(P＜0.05,P＜0.01);increased HDL-C level and SOD,GSH-Px activities(P＜0.05,P＜0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P＜0.05,P＜0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P＜0.05)as well.CONCLUSION PCPs can improve mouse NAFLD,and its mechanism may lie in their function in reversing abnormal lipid metabolism via Akt/mTOR/SREBP-1c signaling pathway.

Objective To construct and preliminary verify a postoperative pulmonary rehabilitation nursing programme for children with double lung transplantation,aiming to promote early recovery and provide references for clinical nursing practice.Methods A convenience sampling approach was employed to select 25 cases pediatric patients who underwent bilateral lung transplantation at a tertiary teaching hospital in Hangzhou between January 2020 and September 2024,and they were divided into an experimental group and a control group according to the time of admission to the hospital.The experimental group received the newly developed post-transplant rehabilitation nursing program,which encompassed fluid management,mechanical ventilation,sequential oxygen therapy,pulmonary function training,exercise management,and process facilitation.In contrast,the control group received the standard post-lung transplantation rehabilitation protocol.Key outcomes,including mechanical ventilation duration,ICU stay,total hospitalization time,activity level,pulmonary function,incidence of adverse events and rehabilitation adherence,were compared between the 2 groups.Results Finally,24 cases completed the study,including 11 cases in the experimental group and 13 cases in the control group.After the intervention,the experimental group exhibited significantly shorter mechanical ventilation time compared to it in the control group(P=0.009).Additionally,at discharge,the intervention group demonstrated higher activity levels and better rehabilitation compliance(P＜0.05).Conclusion The pulmonary rehabilitation nursing program for children with double lung transplantation is scientifically sound,safe,and feasible.The implementation of this program is beneficial for the early discontinuation of mechanical ventilation,improving postoperative mobility,and enhancing compliance with pulmonary rehabilitation.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.