Objective To analyze the epidemiological characteristics of statutory infectious diseases in Yichang City from 2015 to 2023 and evaluate the effectiveness of non-pharmaceutical interventions (NPIs) in infectious disease prevention and control, and to provide a basis for formulating prevention and control strategies. Methods Descriptive epidemiological methods were used to analyze annual incidence rates. SARIMA and SARIMA intervention models were constructed to predict the incidence rates of infectious diseases. Interrupted time series analysis (ITS) was applied to assess the control effectiveness. Results The average annual incidence rate from 2015 to 2023 was 787.47/100 000, with the top five diseases being influenza, hand-foot-and-mouth disease, hepatitis B, tuberculosis, and diarrheal diseases. The average incidence rate from 2015 to 2019 (654.31/100 000) was significantly higher than that from 2020 to 2022 (489.01/100 000) (χ²= 3 499.6, P < 0.05). The total incidence rate in 2023 (2 396.51/100 000) was significantly higher than the average annual incidence rates from 2015-2019 (χ²= 108 186.1, P < 0.05) and 2020-2022 (χ²= 112 869.4, P < 0.05). SARIMA model results indicated that the actual incidence rate from 2020 to 2022 decreased by 73.49% compared to the predicted rate without intervention, with the highest decline observed in respiratory infectious diseases (79.57%). The SARIMA-intervention model showed a 55.48% relative decrease in the total incidence rate for 2023, with the largest reduction in respiratory infectious diseases (63.28%) and a slight increase in intestinal infectious diseases (5.48%). Conclusion NPIs effectively reduce the incidence of statutory infectious diseases in the short term, especially for acute respiratory and intestinal infectious diseases. However, long-term effectiveness faces challenges, necessitating the development of differentiated prevention and control strategies.

Objective: To develop a clinical decision and prescription generation system (CDPGS) specifically for diarrhea in traditional Chinese medicine (TCM), utilizing a specialized large language model (LLM), Qwen-TCM-Dia, to standardize diagnostic processes and prescription generation. Methods: Two primary datasets were constructed: an evaluation benchmark and a fine-tuning dataset consisting of fundamental diarrhea knowledge, medical records, and chain-of-thought (CoT) reasoning datasets. After an initial evaluation of 16 open-source LLMs across inference time, accuracy, and output quality, Qwen2.5 was selected as the base model due to its superior overall performance. We then employed a two-stage low-rank adaptation (LoRA) fine-tuning strategy, integrating continued pre-training on domain-specific knowledge with instruction fine-tuning using CoT-enriched medical records. This approach was designed to embed the clinical logic (symptoms → pathogenesis → therapeutic principles → prescriptions) into the model’s reasoning capabilities. The resulting fine-tuned model, specialized for TCM diarrhea, was designated as Qwen-TCM-Dia. Model performance was evaluated for disease diagnosis and syndrome type differentiation using accuracy, precision, recall, and F1-score. Furthermore, the quality of the generated prescriptions was compared with that of established open-source TCM LLMs. Results: Qwen-TCM-Dia achieved peak performance compared to both the base Qwen2.5 model and five other open-source TCM LLMs. It achieved 97.05% accuracy and 91.48% F1-score in disease diagnosis, and 74.54% accuracy and 74.21% F1-score in syndrome type differentiation. Compared with existing open-source TCM LLMs (BianCang, HuangDi, LingDan, TCMLLM-PR, and ZhongJing), Qwen-TCM-Dia exhibited higher fidelity in reconstructing the “symptoms → pathogenesis → therapeutic principles → prescriptions” logic chain. It provided complete prescriptions, whereas other models often omitted dosages or generated mismatched prescriptions. Conclusion By integrating continued pre-training, CoT reasoning, and a two-stage fine-tuning strategy, this study establishes a CDPGS for diarrhea in TCM. The results demonstrate the synergistic effect of strengthening domain representation through pre-training and activating logical reasoning via CoT. This research not only provides critical technical support for the standardized diagnosis and treatment of diarrhea but also offers a scalable paradigm for the digital inheritance of expert TCM experience and the intelligent transformation of TCM.

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer

A single-center, randomized, double-blind, dose-controlled trial of modified Sini Powder in treating mild to moderate generalized anxiety disorder(GAD) in the patients with syndrome of liver depression transforming into fire was conducted at Xiyuan Hospital, China Academy of Chinese Medical Sciences. A total of 80 patients with mild to moderate GAD and the syndrome of liver depression transforming into fire were included. Patients were assigned by the central randomization system at a ratio of 3∶1 into an observation group(n=60, receiving a conventional-dose of granules of modified Sini Powder) and a control group(n=20, receiving low-dose granules with the active ingredients being 50% of that in observation group). Assessments were conducted before treatment(baseline), after 2 weeks of introduction, after 2/4/8 weeks of treatment, and after 4 weeks of follow-up. The results were summarized as follows. In terms of primary outcome indicators, the observation group(62.2%) showed higher total response rate than the control group(26.6%)(P<0.05), and greater Hamilton anxiety scale(HAMA) score reduction after 8 weeks of treatment(P<0.05). In terms of secondary outcome indicators, the HAMA score(somatic anxiety score), traditional Chinese medicine(TCM) syndrome scores, Pittsburgh sleep quality index(PSQI) scale, and clinical global impression(CGI) scale score in the observation group showed a significant compared to the control group at each visit points(P<0.05). Adverse events occurred in 10 cases, including 9(16.9%) cases in the observation group and 1(6.6%) case in the control group. No adverse reaction was observed. In conclusion, conventional-dose modified Sini Powder demonstrated superior efficacy and favorable safety for mild and moderate GAD in the patients with the syndrome of liver depression transforming into fire over low-dose treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety Disorders/drug therapy* ; Treatment Outcome ; Young Adult ; Powders ; Aged ; Liver/drug effects* ; Generalized Anxiety Disorder

Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Urethral length has been identified as a factor affecting postoperative continence recovery. In this meta-analysis, we examined the association between use of the maximal urethral length preservation (MULP) technique and postoperative urinary continence in patients undergoing RARP. We conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to synthesize data and calculate the odds ratio (OR) from eligible studies on continence and MULP. Six studies involving 1869 patients met the eligibility criteria. MULP was positively associated with both early continence (1 month after RARP; Z = 3.62, P = 0.003, OR = 3.10, 95% confidence interval [CI]: 1.68-5.73) and late continence (12 months after RARP; Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13-3.90). Oncological outcomes indicated that MULP did not increase the overall positive surgical margin rate or the positive surgical margin status at the prostate apex (both P > 0.05). In conclusion, the use of the MULP technique in RARP significantly improved both early and late postoperative continence outcomes without compromising oncological outcomes.
Humans ; Prostatectomy/adverse effects* ; Robotic Surgical Procedures/methods* ; Male ; Urethra/surgery* ; Urinary Incontinence/prevention & control* ; Postoperative Complications/etiology* ; Prostatic Neoplasms/surgery* ; Organ Sparing Treatments/methods*

OBJECTIVES: To investigate the efficacy and safety of empagliflozin in patients with glycogen storage disease (GSD)-associated inflammatory bowel disease (IBD). METHODS: A cross-sectional study was conducted, enrolling 25 patients with GSD-associated IBD who received empagliflozin treatment. General data, details of empagliflozin use, and adverse events were collected. Clinical symptoms and biochemical parameters before and after empagliflozin therapy were compared. RESULTS: Twenty-five patients with GSD-associated IBD were included, with a median age at diagnosis of 0.7 years, and a mean age at initiation of empagliflozin therapy of (11 ± 6) years. The initial dose of empagliflozin was (0.30 ± 0.13) mg/(kg·d), with a maintenance dose of (0.40 ± 0.21) mg/(kg·d), and a treatment duration of (34 ± 6) months. Seventy-eight percent (18/23) of patients' parents reported that empagliflozin therapy reduced the frequency of infections and oral ulcers, and increased neutrophil counts. Clinically, the number of patients with anorexia decreased from 12 to 5 after treatment, and 30% showed improved appetite (P<0.05). The numbers of patients with diarrhea, mucus/bloody stools, perianal disease, and oral ulcers decreased from 19, 9, 11, and 21 before treatment to 7, 1, 0, and 10 after treatment, respectively (P<0.05). Laboratory findings showed that absolute neutrophil counts increased, while platelet counts, lactate, and uric acid levels decreased significantly after empagliflozin treatment (P<0.05). Adverse reactions occurred in 7 patients (28%) during empagliflozin treatment. Two cases occurred in the treatment initiation phase, presenting as hypotension or profuse sweating with dehydration, along with urinary tract infections (UTIs); empagliflozin was discontinued in both cases. During the maintenance phase, 3 cases of UTIs and 2 cases of hypoglycemia (one with profuse sweating) were reported. CONCLUSIONS Empagliflozin therapy can increase neutrophil counts, reduce the incidence of infections and oral ulcers, alleviate diarrhea and abdominal pain, improve appetite, and ameliorate platelet count, lactate, and uric acid levels in patients with GSD-associated IBD, demonstrating significant clinical benefit. UTIs, hypoglycemia, hypotension, profuse sweating, and dehydration may be potential adverse reactions associated with empagliflozin therapy.
Humans ; Benzhydryl Compounds/adverse effects* ; Male ; Female ; Glucosides/adverse effects* ; Inflammatory Bowel Diseases/etiology* ; Child ; Child, Preschool ; Cross-Sectional Studies ; Adolescent ; Glycogen Storage Disease/drug therapy* ; Infant

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

ObjectiveTo investigate the effect and mechanism of cordycepin in inhibiting fat infiltration after rotator cuff injuries in rats by regulating the Wnt/β-catenin signaling pathway， providing a theoretical basis for clinical treatment of rotator cuff injuries. MethodsFifty SPF-grade female SD rats were used in this study， with 10 randomly selected as the blank group. A rotator cuff injury repair model was established by supraspinatus tendon and suprascapular nerve compression. The successfully modeled rats were randomized into model and low-dose （20 mg·kg^-1）， medium-dose （40 mg·kg^-1）， and high-dose （80 mg·kg^-1） cordycepin groups. After 6 weeks of treatment， the gait analysis was performed to assess the limb function in rats. Oil red O staining and Masson staining were employed to observe pathological changes in the muscle tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the serum. Immunohistochemistry （IHC） was employed to detect the expression of peroxisome proliferator-activated receptor γ （PPARγ） and CCAAT/enhancer-binding protein α （C/EBPα）， which are markers of adipogenesis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of Wnt3a， Wnt10b， and β-catenin. ResultsCompared with the blank group， the model group showed decreases in stride length and paw print area （P<0.01）， an increase in ratio of wet muscle mass reduction and a decrease in muscle fiber cross-sectional area （P<0.05）， and decreased ratios of fat infiltration area and collagen fiber area （P<0.01）. Additionally， the model group showed elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， up-regulated protein levels of PPARγ and C/EBPα （P<0.01）， and down-regulated mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. Compared with the model group， the low-， medium-， and high-dose cordycepin groups showed increases in stride length and paw print area （P<0.01）， a decrease in ratio of wet muscle mass reduction and an increase in muscle fiber cross-sectional area （P<0.05）， and increases in ratios of fat infiltration area and collagen fiber area （P<0.05， P<0.01）. In addition， cordycepin lowered the serum levels of IL-1β， IL-6， and TNF-α （P<0.05， P<0.01）， down-regulated the protein levels of PPARγ and C/EBPα （P<0.01）， and up-regulated the mRNA and protein levels of Wnt3a， Wnt10b， and β-catenin （P<0.05， P<0.01）. ConclusionCordycepin can improve the limb function， alleviate rotator cuff muscle atrophy， fat infiltration， and fibrosis， and inhibit inflammation in rats by regulating the Wnt/β-catenin signaling pathway.