Background/Aims: Non-pharmacological treatments are crucial for managing irritable bowel syndrome (IBS), yet patient engagement remains a challenge. Understanding patients' knowledge, attitudes, and practices regarding these treatments is essential for improving care. Methods: A cross-sectional study was conducted across 5 hospitals, from October 2023 to February 2024. A self-designed knowledge, attitudes, and practices questionnaire along with the IBS quality of life and IBS severity scoring system was administered, and 496 valid responses were analyzed. Statistical analyses included correlation tests, multivariate linear regression, and mediation effect analysis. Results: The median scores for knowledge, attitude, and practice were 28, 25.5, and 21, respectively. Significant positive correlations were found between knowledge-attitude (r = 0.195), knowledge-practice (r = 0.364), and attitude-practice (r = 0.151). The multivariate linear regression analysis further indicated that knowledge (β = 0.399, P < 0.001) and attitude (β = 0.219, P = 0.022) positively correlated with the practical performance. SEM revealed that knowledge had a significant direct effect on both attitude (β = 0.186, P = 0.013) and practice (β = 0.356, P = 0.006). However, the direct effect of attitude on practice was not significant, and attitude did not mediate the relationship between knowledge and practice. Conclusions IBS patients exhibit a significant gap between their positive attitudes and their actual practices concerning non-pharmacological treatments. Knowledge is a direct driver of practice, but positive attitudes alone are insufficient to translate into behavior. Healthcare providers must move beyond simply fostering positive attitudes and focus on targeted educational interventions that provide actionable knowledge and skills to improve patient outcomes.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To explore and analyze the feasibility and efficacy of the 22G needle-guided suture for orbital septum fat flap fixation on the periosteum.Methods:The retrospective study was conducted. From January 2022 to November 2023, patients with tear trough deformity and eyelid bags underwent surgery of releasing the orbicularis retaining ligament (ORL) complex, orbital septum fat pad combined with 22G needle-guided suture in Department of Burn and Plastic Surgery, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology. Postoperative follow-up was conducted to observe the occurrence of complications. The lacrimal depression deformity was classified according to the Hirmand standard and the degree of lower eyelid bags was graded to evaluate the surgical outcome. Patients were evaluated their satisfaction using the visual analogue scale (very dissatisfied, dissatisfied, average, satisfied, very satisfied).Results:A total of 32 patients (30 females and 2 males) were included in this study. The age range was 31-62 years old with an average of 50.2 years. All patients were followed up for 6 months postoperatively. None of the patients had any severe complications, such as inferior eyelid ectropion, inferior eyelid retraction, scar hyperplasia, and diplopia. Four patients showed mild eyelid-eyeball separation, two patients had conjunctival edema, and all recovered in 1 month. The orbital fat protrusion, tear trough depression deformity, and lower eyelid skin laxity were significantly improved compared to before the operation. Postoperative satisfaction was 22 cases, very satisfied 10 cases, and patient satisfaction rate was 100% (32/32) after surgery.Conclusion:The method of 22G needle-guided suture to fix orbital septum fat pad represents a technically feasible, easy, and suitable for promotion.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Objective To develop an ultra-high performance liquid chromatography-mass spectrometry method(UPLC-MS/MS)for the determination of nirmatrelvir concentration in mouse plasma.Methods The ACQUITY UPLC system was used in tandem with an API 4000 triple quadrupole mass spectrometer.The analytical column was Waters BEH C18(2.1 mm×5.0 mm,1.7 μm)column,and the mobile phases consisted of water(containing 0.1％formic acid)and methanol(containing 0.1％formic acid)under gradient elution at the flow rate of 0.4 mL·min-1.The column temperature was set at 40 ℃,and the injection volume was 5 μL.Electrospray ionization was used as ion source,and positive multiple reaction monitoring mode was adopted to quantitatively analyze the ionization pairs m/z 500.3→110.3(nirmatrelvir)and m/z 237.3→193.3(carbamazepine).Carbamazepine was employed as an internal standard.Results The linear range of nirmatrelvir was from 10 ng·mL-1 to 2 560 ng·mL-1.For the quality control nirmatrelvir samples,the accuracies of intra-and inter-batch were less than±15％,and the precisions of intra-and inter-batch were lower than 15％.Nirmatrelvir in plasma was stable at room temperature for 24 h and remained stable after three freeze-thaw cycles.The extracted nirmatrelvir solution could be stored at 4℃ for 3 d without any visible change.Conclusion The method was characterized by good specificity,high sensitivity,and appropriate linear range.The methodological validation was in accordance with the 2020 edition of the Chinese Pharmacopoeia and could be applied to the quantitative detection of nirmatrelvir in plasma.

Objective:To evaluate the clinical efficacy of individualized postural management guided by lung ultrasound (LUS) in neonates with grade Ⅲ bronchopulmonary dysplasia (BPD).Methods:This prospective randomized controlled trial enrolled neonates diagnosed with grade Ⅲ BPD at Guangdong Second People's Hospital Affiliated to Jinan University from July 2022 to December 2024, who were randomly assigned to control or intervention groups. The control group received conventional postural management (head elevation 15°-30°, supine-left lateral-right lateral-prone positioning with 2-hour rotations), while the intervention group underwent additional LUS examinations every 12 hours for dynamic posture adjustment based on pulmonary findings. Outcomes included LUS signs (pleural line abnormalities, A-line disappearance, B-line increases, cystic hyperaeration, alveolar-interstitial syndrome, consolidation) and primary endpoints (post-diagnosis oxygen therapy duration, invasive mechanical ventilation duration, and hospital stay). Secondary outcomes comprised new complications (pulmonary hemorrhage, necrotizing enterocolitis, BPD-associated pulmonary hypertension, grade Ⅲ-Ⅳ intracranial hemorrhage, retinopathy of prematurity). Intergroup comparisons used two independent samples t-tests and Chi square tests. Results:Among 49 eligible neonates, 47 were randomized (intervention group=24; control group=23), with 40 completing the study (20 per group after exclusions). At day 7, the intervention group showed significantly lower rates of pleural line abnormalities [55% (11/20) vs. 90% (18/20), χ2=6.14, P=0.013], A-line disappearance [50% (10/20) vs. 80% (16/20), χ2=3.95, P=0.046], B-line increases [50% (10/20) vs. 85% (17/20), χ2=5.58, P=0.018], alveolar-interstitial syndrome [65% (13/20) vs. 95% (19/20), χ2=5.62, P=0.017], and consolidation [50% (10/20) vs. 80% (16/20), χ2=3.95, P=0.046]. The intervention group also demonstrated shorter invasive ventilation [(9.5±2.3) vs. (11.6±3.5) days, t=2.18, P=0.035] and hospital stay [(58.9±4.9) vs. (63.2±6.4) days, t=2.33, P=0.025] post-diagnosis, with no significant differences in new complication rates (all P>0.05). Conclusion:LUS-guided postural management improves pulmonary pathology, reduces respiratory support duration and hospitalization, without increasing complications in grade Ⅲ BPD neonates.