To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

OBJECTIVE: To investigate the effects of 4-methylcatechol (4MC) on the migration and inflammatory response in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), as well as its underlying mechanisms of action. METHODS: RA-FLS was isolated from synovial tissue donated by RA patients, and the optimal concentration of 4MC was determined by cell counting kit 8 method for subsequent experiments, and the effect of 4MC on the migratory ability of RA-FLS was evaluated via a cell scratch assay. An inflammation model of RA-FLS was induced by tumor necrosis factor α (TNF-α). Real-time fluorescence quantitative PCR and ELISA were employed to detect the gene and protein expression levels of interleukin-1β (IL-1β) and IL-6 in RA-FLS and their culture supernatants, respectively, thereby investigating the anti-inflammatory effects of 4MC. Western blot was used to examine the expressions of nuclear factor κB (NF-κB) signaling pathway-related proteins, including inhibitor of NF-κB-α (IKBα), phosphorylated (P)-IκBα, NF-κB-inducing kinase α (IKKα), P-IKKαβ, P-p65, and p65. Cellular immunofluorescence was utilized to detect the expression and localization of p65 in RA-FLS, exploring whether 4MC exerts its anti-inflammatory effects by regulating the NF-κB signaling pathway. Finally, a collagen-induced arthritis (CIA) mouse model was established. The anti-RA effect of 4MC in vivo was evaluated by gross observation and histological examination. RESULTS: 4MC inhibited RA-FLS migration in a concentration-dependent manner. In the TNF-α-induced RA-FLS inflammation model, 4MC significantly decreased the gene and protein expression levels of IL-1β and IL-6. Furthermore, 4MC markedly reduced the ratios of P-IΚBα/IΚBα, P-IKKαβ/IKKα, and P-p65/p65, thereby blocking the transcriptional activity of p65 by inhibiting its nuclear translocation. This mechanism effectively suppressed the activation of the TNF-α-mediated NF-κB signaling pathway. Animal studies demonstrated that 4MC [10 mg/(kg·day)] significantly lowered serum levels of IL-1β, IL-6, and TNF-α, and alleviated arthritis severity and bone destruction in CIA mice. CONCLUSION 4MC not only inhibits the migration of RA-FLS but also mitigates their inflammatory response by suppressing the NF-κB signaling pathway, thereby effectively exerting its anti-RA effects.
Synoviocytes/metabolism* ; Arthritis, Rheumatoid/metabolism* ; Animals ; Cell Movement/drug effects* ; Humans ; Catechols/therapeutic use* ; Fibroblasts/drug effects* ; Mice ; Tumor Necrosis Factor-alpha/pharmacology* ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/cytology* ; Cells, Cultured ; Male ; Arthritis, Experimental ; Anti-Inflammatory Agents/pharmacology* ; NF-KappaB Inhibitor alpha ; Inflammation

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Objective To evaluate the efficacy and safety of Mirabegron combined with transcutaneous tibial nerve stimulation (TTNS) in the treatment of drug-refractory overactive bladder (OAB), so as to alleviate patients'symptoms, improve their quality of life with optimized treatment plan, and provide reference for clinical practice. Methods A retrospective analysis was conducted on 56 patients with drug-refractory OAB treated at the Department of Urology of Gansu Provincial Hospital during Jan.2023 and Dec.2024. Based on the treatment methods, the patients were divided into two groups:the TTNS group and the combined treatment group, with 28 patients in either group. The daytime urination frequency, nocturia frequency, urgency episodes, urinary incontinence, functional bladder capacity (FBC), OAB symptom scores (OABSS), and incontinence quality of life questionnaire (I-QoL) scores were collected before and after treatment. The therapeutic efficacy was evaluated using the Nimodipine method. Results After 12 weeks of treatment, the 24-hour urination indicators in both groups including daytime urination frequency, nocturia frequency, urgency episodes and FBC, as well as OABSS and I-QoL scores, showed a significant improvement compared to baseline (P<0.001). The combined treatment group exhibited fewer urgency episodes than the TTNS group [ (1.07±0.66) times/24 h vs. (1.64±0.62) times/24 h, P<0.05]. However, no statistically significant differences were observed between the two groups in other urinary parameters (P>0.05). The total effective rate in the combined treatment group was 96.43%, which was significantly higher than that in the TTNS group (82.14%, P<0.05). During treatment, one patient (3.57%) in the TTNS group experienced mild skin allergy, which recovered following symptomatic management. Conclusion The combination of TTNS and Mirabegron in drug-refractory OAB not only alleviates clinical symptoms and improves quality of life, but also shows superior efficacy in reducing urgency episodes. This approach is a safe and effective treatment option.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a refractory condition characterized by chronic inflammation of the bladder wall, disruption of the urothelial barrier, and neural sensitization. Current therapies, such as oral pentosan polysulfate sodium (PPS) or intravesical hyaluronic acid instillations, offer limited efficacy due to transient effects and an inability to reverse tissue fibrosis. Platelet-rich plasma (PRP), a regenerative medicine approach, has demonstrated significant therapeutic potential in urological disorders through the synergistic actions of its multiple growth factors. This review summarizes the latest advances in PRP therapy for IC/BPS, revealing that the underlying mechanisms primarily involve the release of diverse growth factors, suppression of inflammatory responses, restoration of the urothelial barrier, and modulation of nerve axonal regeneration. Clinically, PRP therapy significantly alleviates symptoms including pelvic/bladder pain, urinary frequency, nocturia episodes, and improves patients'quality of life. Furthermore, it offers advantages such as convenient administration, a favorable safety profile, and strong feasibility, presenting new therapeutic methods and options for the clinical treatment of IC/BPS.

Objective:To investigate the correlation between urinary electrolyte level and detrusor overactivity (DO) in children with primary monosymptomatic nocturnal enuresis (PMNE).Methods:In this case control study, a retrospective analysis was performed on 60 PMNE children aged 5-12 years who were admitted to the First Affiliated Hospital of Zhengzhou University from February 2015 to January 2020.According to the results of ambulatory urodynamic monitoring (AUM), there were 36 patients in the nocturnal DO group [(19 males and 17 females, mean age(9.4±2.1) years, mean body mass index (BMI)(18.90±2.66) kg/m 2], and 24 patients in the non-nocturnal DO group [16 males and 8 females, mean age(9.0±1.9) years, mean BMI(18.85±2.50) kg/m 2].Daytime and nighttime urine volume and average urine electrolyte levels were measured. t-test, Chi-square test or Mann-Whitney U test were used for comparison between groups.Spearman rating coefficient was used to evaluate the correlation between average electrolyte level and maximum detrusor pressure during nighttime bladder storage. Results:There were no statistically significant differences in age, gender ratio, and BMI between the two groups (all P>0.05).The nocturnal urine volume [0.291(0.194, 0.408) L] and the frequency of nocturnal polyuria (33.0%) in the nocturnal DO group were significantly lower than those [0.420 (0.298, 0.673) L and 62.5%](all P<0.05) in the non-nocturnal DO group.The levels of nocturnal urine sodium [(181.13±102.39) mmol/L], calcium [(3.68±2.44) mmol/L], and chloride [(147.89±57.21) mmol/L] in the nocturnal DO group were significantly higher than those [levels of nocturnal urine sodium [(132.15±67.42) mmol/L], calcium [(1.98±2.07) mmol/L], and chloride [(110.95±54.27) mmol/L] in the non-nocturnal DO group (all P<0.05).However, there was no statistically significant difference in the level of nocturnal urine potassium between the two groups ( P>0.05).The levels of diurnal urine sodium, potassium, calcium, and chloride showed no statistically significant differences between the two groups (all P>0.05).The levels of nocturnal urine sodium [(181.13±102.39) mmol/L] and calcium [(3.68±2.44) mmol/L] in the nocturnal DO group were significantly higher than the levels of diurnal urine sodium [(132.48±79.84) mmol/L] and calcium [(1.48±1.20) mmol/L](all P<0.05); however, there was no statistically significant difference in the levels of nocturnal urine potassium and chloride compared to diurnal levels (all P>0.05).In the non-nocturnal DO group, there were no statistically significant differences in the levels of diurnal and nocturnal urine sodium, potassium, calcium, and chloride (all P>0.05).Additionally, the level of nocturnal urine calcium in the nocturnal DO group was positively correlated with the maximum detrusor pressure during the bladder storage period ( r=0.501, P<0.05). Conclusions:The increased nocturnal urine sodium, calcium, and chloride levels in children with PMNE may be one of the important reasons for the occurrence of nocturnal bladder dysfunction.

Cervical cancer is a prevalent gynecological malignancy worldwide,and despite established mea-sures for prevention,detection,and treatment at different stages,limited success has been achieved in effectively reducing its incidence.While treatments such as surgery for early-stage patients,adjuvant chemoradiotherapy based on postoperative pathology assessment of high-risk factors and intermediate risk factors,combined radiochemotherapy for patients at all stages,and systemic treatment for advanced cervical cancer have demonstrated effectiveness in numerous cases.Recent advancements in surgical pathology staging,selection of surgical approaches,options available for early-stage cases,utilization of neoadjuvant chemotherapy,novel approaches to radiotherapy adminis-tration,as well as clinical trials investigating new drugs targeting recurrent and metastatic cervical cancer have con-tributed to more precise and individualized treatment strategies while providing a wider range of choices.Therefore,this manuscript comprehensively discusses important developments concerning the diagnosis and treatment of cervi-cal cancer with the aim of offering an improved reference for clinical practice.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA