Objective To explore the potential role and underlying mechanism of the functionally uncharacterized gene Gm49394 on regulating β-cell apoptosis under diabetic conditions.Methods The expression and translational activity of Gm49394 in pancreatic β-cell lines and non-β-cell lines were validated using RNA fluorescence in situ hybridization(RNA-FISH),quantitative real-time PCR(qPCR),Western blotting,and immunofluorescence(IF)assay.The β-cell lines(NIT-1/Min6)with Gm49394 overexpression or knockdown were constructed.The proliferation,apoptosis,mitochondrial function,as well as oxidative stress and endoplasmic reticulum stress markers in these β-cell lines under physiological homeostasis or pathological stress conditions,such as high glucose(30 mmol/L),inflammation(10 ng/mL IFN-γ alone or combined with 10 ng/mL IL-6),and hydrogen peroxide(100 μmol/L H2O2)were detected by flow cytometry and Western blotting.Results RNA-FISH and qPCR indicated that Gm49394 was specifically expressed in pancreatic β-cell lines and up-regulated under high glucose or inflammatory stimulation.IF assay and Western blotting showed that Gm49394 had protein-coding activity.Flow cytometry and Western blotting identified that Gm49394 overexpression did not affect β-cell proliferation,but promoted β-cell apoptosis and increased reactive oxygen species(ROS)and mitochondrial superoxide(MitoSOX)levels in β cells under physiological homeostasis or pathological stress conditions(P<0.05).Under physiological conditions,Gm49394 knockdown failed to induce significant alterations on β-cell apoptosis,ROS,or MitoSOX levels.Under pathological stress conditions,Gm49394 knockdown significantly suppressed β-cell proliferation,apoptosis,as well as oxidative and endoplasmic reticulum stress(P<0.05).Conclusion Gm49394 may promote β-cell apoptosis via oxidative stress and endoplasmic reticulum stress.

By combining the origin and research progress of the combination of disease and syndrome, the core pathogenesis, this article explored the research ideas and methods of the core pathogenesis of TCM. It is found that modern TCM is mostly guided by the idea of classification-staging-syndrome differentiation, the main prescription of the main disease, the special prescription of the special disease, and the idea of "dynamic-fixed sequential". The tongue image syndrome differentiation method, clustering analysis method, drug test syndrome method, compound pathogenesis method, "evidence-based pathogenesis-syndrome treatment system" research model, and the integration of traditional Chinese and Western medicine theory were used to explore the core pathogenesis of TCM under the condition of disease. Combined with the advantages of modern medical disease differentiation and TCM syndrome differentiation, the individualized diagnosis and treatment methods of integrated traditional Chinese and Western medicine have been continuously improved, in order to solve the stage contradictions of different clinical stages, effectively delay the progression of the disease and improve the prognosis of the disease.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

OBJECTIVES: We propose a multi-feature fusion model based on manually extracted features and deep learning features from endoscopic images for grading rebleeding risk of peptic ulcers. METHODS: Based on the endoscopic appearance of peptic ulcers, color features were extracted to distinguish active bleeding (Forrest I) from non-bleeding ulcers (Forrest II and III). The edge and texture features were used to describe the morphology and appearance of the ulcers in different grades. By integrating deep features extracted from a deep learning network with manually extracted visual features, a multi-feature representation of endoscopic images was created to predict the risk of rebleeding of peptic ulcers. RESULTS: In a dataset consisting of 3573 images from 708 patients with Forrest classification, the proposed multi-feature fusion model achieved an accuracy of 74.94% in the 6-level rebleeding risk classification task, outperforming the experienced physicians who had a classification accuracy of 59.9% (P<0.05). The F1 scores of the model for identifying Forrest Ib, IIa, and III ulcers were 90.16%, 75.44%, and 77.13%, respectively, demonstrating particularly good performance of the model for Forrest Ib ulcers. Compared with the first model for peptic ulcer rebleeding classification, the proposed model had improved F1 scores by 5.8%. In the simplified 3-level risk (high-risk, low-risk, and non-endoscopic treatment) classification task, the model achieved F1 scores of 93.74%, 81.30%, and 73.59%, respectively. CONCLUSIONS The proposed multi-feature fusion model integrating deep features from CNNs with manually extracted visual features effectively improves the accuracy of rebleeding risk classification for peptic ulcers, thus providing an efficient diagnostic tool for clinical assessment of rebleeding risks of peptic ulcers.
Humans ; Deep Learning ; Peptic Ulcer ; Risk Assessment ; Peptic Ulcer Hemorrhage ; Recurrence

Objective Meta-analysis was used to summarize the current status of medication adherence in patients with type 2 diabetes mellitus and to clarify the characteristics of people with low medication adherence.Methods Relevant literatures were searched in Pubmed,Cochrane Library,Web of Science,Embase,CINAHL,CBM,China National Knowledge Infrastructure,Wanfang Data,and VIP.Two researchers conducted literature screening,data extraction and quality evaluation.Stata 16.0 software was used for subgroup analysis,sensitivity analysis,offset analysis.Results A total of 42 papers were included,and the overall medication adherence of middle-aged and elderly type 2 diabetes patients ranged from 18.37%-96.53%.The medication adherence was higher among those with high education level(63%),married(61%),not living alone(50%),monthly income>3000 RMB/month(64%),having medical insurance(49%),good psychological status(61%),no chronic co-morbidities(66%),having knowledge about the disease(53%),taking≤3 types of medication(58%),convenient access to medical care(58%),and good doctor-patient relationship(50%).Conclusion The medication adherence of patients with type 2 diabetes mellitus varies greatly among different subgroups.In the future,the specific influencing factors should be further explored to formulate targeted policies and intervention measures to improve patients'medication adherence and improve their health and quality of life.

Objective To systematically evaluate the efficacy and acceptability of non-pharmaceutical intervention(NPI)for depression in patients with mild cognitive impairment(MCI).Methods Randomized controlled trials of NPI in treatment of depression patients with MCI published in PubMed,Embase,Web of Science,CINAHL,Cochrane Library,CNKI,Wanfang Data,VIP and CBM databases were searched from self-built databases to January 6,2024,and performed a network Meta-analysis using Stata 14.0 software.Results A total of 55 literatures were included,involving 10 NPIs.According to the surface under the cumulative ranking curve(SUCRA),the top 3 curative effects were cognitive behavioral therapy(CBT),Chinese traditional sport(CTS)and art therapy,the top 3 acceptability were CBT,CTS,and health education.Conclusion CBT and CTS may be effective and acceptable NPI for improving depression in patients with MCI,and individualized interventions can be tailored to the patient's situation to achieve the best results.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

OBJECTIVE: To explore the immunological mechanisms underlying spermatogenetic malfunction in patients with non-obstructive azoospermia (NOA) based on bioinformatics and machine learning, and to screen out the key genes associated with spermatogenesis failure. METHODS: NOA-related datasets were obtained from the GEO database, and the differentially expressed genes identified by differential analysis and weighted gene co-expression network analysis (WGCNA). A model of spermatogenesis scoring was established for analysis of the immunological microenvironment and cell interaction networks related to spermatogenesis failure. The key genes were screened out by machine learning, followed by analysis of their correlation with T cells and macrophages. An NOA mouse model was constructed for validation of transcriptome sequencing. RESULTS: Seventy-five differentially expressed genes were identified for the establishment of the spermatogenesis scoring model. The low spermatogenesis score group showed a higher infiltration of the immune cells, with an increased proportion of T cells and macrophages and a correlation of cell interaction signals with immunity. SOX30, KCTD19, ASRGL1 and DRC7 were identified by machine learning as the key genes related to spermatogenesis, with down-regulated expressions in the NOA group, and their expression levels negatively correlated with the infiltration of T cells and macrophages. The accuracy of the spermatogenesis scoring and machine learning models, as well as the trend of the expression levels of the key genes, was successfully validated with the transcriptome sequencing data on the NOA mouse testis. CONCLUSION The development of NOA is closely associated with enhanced immunological microenvironment in the testis. T cells and macrophages may play important roles in spermatogenesis failure. SOX30, KCTD19, ASRGL1 and DRC7 are potential biomarkers for the diagnosis and treatment of NOA.
Male ; Azoospermia/genetics* ; Machine Learning ; Animals ; Computational Biology ; Mice ; Humans ; Spermatogenesis/genetics* ; Gene Expression Profiling ; Macrophages/immunology* ; Gene Regulatory Networks ; T-Lymphocytes/immunology* ; Transcriptome