Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Diabetic sarcopenia (DS) is a common but often ignored skeletal muscle complication in individuals with diabetes mellitus. It is characterized by progressive loss of skeletal muscle mass, reduced muscle strength, and impaired physical performance, which may further increase the risk of falls, disabilities, metabolic disorders, and adverse clinical outcomes. Traditionally, DS has been attributed mainly to hyperglycemia, insulin resistance, aging-related muscle decline, and chronic complications of diabetes. However, increasing evidence suggests that lipid metabolic disturbance and pathological lipid metabolic reprogramming are not merely secondary consequences of diabetes, but may actively participate in the initiation and progression of DS. Under diabetic conditions, impaired fatty acid uptake, transport, oxidation, and storage disrupt skeletal muscle metabolic homeostasis, leading to ectopic lipid deposition and accumulation of lipotoxic intermediates. These lipid-derived metabolites can aggravate insulin resistance, impair mitochondrial energy production, enhance oxidative stress, activate chronic low-grade inflammation, and disturb protein synthesis and degradation balance, thereby accelerating skeletal muscle atrophy and functional decline. Lipid metabolic dysregulation may also interact with multiple pathological processes involved in DS, including mitochondrial dysfunction, inflammatory signaling, oxidative damage, impaired autophagy, and gut microbiota imbalance. These mechanisms do not occur independently; instead, they form a complex bidirectional vicious cycle with diabetes-related metabolic disorders. Specifically, mitochondrial dysfunction reduces fatty acid oxidative capacity, which further promotes lipid accumulation and lipotoxicity. Inflammatory activation can impair insulin signaling and muscle protein metabolism, while lipid overload may in turn amplify inflammatory responses. Similarly, gut microbiota dysbiosis and altered microbial metabolites may influence systemic inflammation, lipid metabolism, and skeletal muscle homeostasis. Therefore, lipid metabolic reprogramming provides an important mechanistic perspective for understanding the progression of DS from metabolic disturbance to structural and functional muscle impairment. Exercise intervention is an effective and clinically feasible non-pharmacological strategy for the prevention and management of DS. Both aerobic exercise and resistance training have been shown to improve insulin sensitivity, enhance fatty acid oxidation, increase mitochondrial biogenesis, reduce ectopic lipid deposition, and attenuate lipotoxic metabolite accumulation. These adaptations not only improved glucose and lipid metabolism, but also increased the preservation of muscle mass, muscle strength, and physical function. Moreover, combined exercise strategies may provide complementary benefits by integrating the metabolic advantages of aerobic exercise with the anabolic and functional effects of resistance training. Based on analyses of publicly available datasets and literature evidences, this review systematically summarizes the role of lipid metabolic disorders in the pathogenesis of DS, with particular attention to the molecular mechanisms linking lipid dysregulation to insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota disturbance. Furthermore, this review discusses the potential mechanisms by which exercise intervention improves DS through the regulation of lipid metabolic reprogramming, and outlines exercise prescription strategies in terms of modality, intensity, frequency, and duration. Understanding the interaction between lipid metabolism and skeletal muscle dysfunction may provide new theoretical evidence for early identification, mechanistic research, and precision exercise therapy in DS. Overall, targeting pathological lipid metabolic reprogramming through exercise intervention represents a promising and clinically actionable approach for improving muscle health and prognosis in individuals with DS.

OBJECTIVES: To investigate the effects of formulated granules of Tianma Gouteng Yin (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms. METHODS: Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment. RESULTS: Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum. CONCLUSIONS TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
Animals ; Mice, Inbred C57BL ; Mice ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Parkinson Disease/drug therapy* ; Disease Models, Animal ; Male

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

OBJECTIVE: To evaluate the effectiveness of Poster Fusion Cage combined with xenogeneic bone graft augmentation for bone defect management in distal radius fractures. METHODS: A retrospective analysis was conducted on 20 patients with bone defects complicating distal radius fractures who met the selection criteria and were treated between June 2022 and June 2024. The cohort comprised 2 males and 18 females, aged 54-87 years (mean, 63.3 years). Etiologies included falls in 17 cases, traffic accidents in 2 cases, and crush injury in 1 case. According to AO classification, there were 5 cases of type A, 8 cases of type B, and 7 cases of type C. The interval from injury to operation ranged from 2 to 10 days (mean, 5.8 days). All patients underwent volar plate fixation augmented with Poster Fusion Cage and demineralized xenogeneic bone matrix grafting. The operation time, intraoperative blood loss, fracture healing time, and postoperative complications were recorded. Radiographic parameters, including radial height, volar tilt, and ulnar deviation, were measured on standardized X-ray films obtained immediately postoperatively and at last follow-up, and whether secondary reduction loss occurred was judged. At last follow-up, wrist range of motion (extension, flexion, radial deviation, ulnar deviation, pronation, and supination) and grip strength (expressed as a percentage of the contralateral side) were measured. Wrist function was assessed using the Disabilities of the Arm, Shoulder, and Hand (DASH) score and Patient-Rated Wrist Evaluation (PRWE) score. RESULTS: The operation time was 70-200 minutes (mean, 116.4 minutes), and the intraoperative blood loss was 10-80 mL (mean, 36.5 mL). All surgical incisions healed by first intention, with no neurovascular complications documented. All patients were followed up 9-12 months (mean, 11.6 months). All fractures healed normally, with a healing time of 8-14 weeks (mean, 9.95 weeks). No significant difference was observed in radial height, volar tilt, or ulnar deviation between immediate postoperatively and last follow-up ( P>0.05). All fractures achieved satisfactory reduction, with no secondary loss of reduction or implant failure occurring during follow-up. At last follow-up, the range of motion of the affected wrist joint was 60°-65° (mean, 62.5°) in extension, 67°-75° (mean, 71.1°) in flexion, 18°-23° (mean, 20.4°) in radial deviation, 28°-33° (mean, 30.1°) in ulnar deviation, 69°-80° (mean, 74.7°) in pronation, and 69°-82° (mean, 75.6°) in supination. Grip strength recovered to 75%-85% (mean, 80%) of the contralateral side. Functional scores showed a DASH score of 5-15 (mean, 9.4) and PRWE score of 8.0-12.5 (mean, 10.2). CONCLUSION The combination of Poster Fusion Cage and xenogeneic bone graft augmentation provides a safe and effective treatment for bone defects in distal radius fractures.
Retrospective Studies ; Humans ; Male ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Treatment Outcome ; Wrist Fractures/surgery* ; Heterografts ; Transplantation, Heterologous/methods* ; Bone Transplantation/methods* ; Operative Time ; Blood Loss, Surgical ; Radius/surgery* ; Fracture Healing ; Time Factors ; Postoperative Complications/etiology* ; Range of Motion, Articular ; Follow-Up Studies ; Internal Fixators ; Fracture Fixation, Internal/methods* ; Combined Modality Therapy

OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:This multicenter retrospective study aimed to analyze the clinicopathological features of duodenal adenocarcinoma (DA) and identify prognostic factors for postoperative survival.Methods:Demographic characteristics, clinicopathological features, treatment outcomes and survival of DA patients undergoing surgical treatment at 18 Chinese medical centers from January 2012 to December 2023 were retrospectively analyzed.Results:Among the 2 056 DA patients included, 46.8% (963) had extra-ampullary DA (EA-DA), and 53.2% (1 093) had peri-ampullary DA (PA-DA). The 1-, 3-, and 5-year overall survival (OS) rates for patients who underwent radical surgery were 93.2%, 71.0%, and 57.2%, respectively. The median overall survival was 76 months, and the median progression-free survival (PFS) was 65 months. No differences in survival were observed between the laparotomy group and minimally invasive surgery (MIS) group either before or after propensity score matching (OS: 76 vs. 75 months before PSM, P=0.986; OS: 75 vs. 75 months after PSM, P=0.602). Furthermore, there were no significant differences between-group in operation time and postoperative complications ( P＞0.05). The MIS group experienced less intraoperative blood loss and shorter hospital stays. The multivariate Cox regression analysis revealed that advanced age ( HR=1.43,95% CI:1.18-1.73), elevated carbohydrate antigen 19-9 levels ( HR=1.24,95% CI:1.02-1.51), perineural invasion ( HR=1.44,95% CI:1.14-1.81), vascular invasion ( HR=1.35,95% CI:1.07-1.71), advanced T stage (T3-4 vs. T1-2: HR=1.86,95% CI:1.49-2.31), regional lymph node metastasis ( HR=1.93,95% CI:1.58-2.36), preoperative biliary drainage ( HR=1.26,95% CI:1.04-1.53), intraoperative blood loss ( HR=1.34,95% CI:1.11-1.62), clinically significant postoperative pancreatic fistulas ( HR=1.53,95% CI:1.12-2.09), and postoperative hemorrhage ( HR=1.62,95% CI:1.14-2.29) were independent risk factors for poor prognosis after surgery (all P＜0.05). Conclusions:Radical surgery is associated with favorable overall survival among DA patients, and no difference in survival is observed between EA-DA and PA-DA patients. MIS is a reliable alternative for DA treatment.