Objective: To investigate the epidemiological and spatio-temporal characteristics of influenza in Jiaxing City, Zhejiang Province, so as to provide insights into perfecting the prevention and control strategies of influenza. Methods: Data of influenza in Jiaxing City from 2019 to 2023 were collected from the Chinese Disease Prevention and Control Information System. Population data of the same period were collected from the Zhejiang Health Information Network Reporting System. The epidemiological characteristics of influenza were analyzed using descriptive analysis. Vector map information was collected from the Open Street Map, and the spatio-temporal clustering characteristics of influenza were analyzed using spatial autocorrelation and spatio-temporal scanning. Results: A total of 181 501 cases of influenza were reported in Jiaxing City from 2019 to 2023, with an average annual reported incidence of 653.93/105. The majority of cases were aged 5 to <15 years (59 785 cases, 32.94%). The majority of the occupations were students (78 239 cases, 43.11%) and pre-school children (33 715 cases, 18.58%). The county (city, district) with the highest reported incidence was Haining City (1 451.70/105), and the town (street) with the highest reported incidence was Chang'an Town (1 932.78/105). Spatial autocorrelation analysis showed that the incidence of influenza in Jiaxing City from 2019 to 2023 had positive spatial correlations (all Moran's I>0, all P<0.05), with a high-high clustering in the southern region. Spatio-temporal scanning analysis showed that there was a spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with the southern region being the primary-type clustering area and the period between November and January of the following year being the clustering time. Conclusion There was a significant spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with winter being the peak season and the southern region being the primary area.

Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:To explore the clinical effect of precise intraepiphyseal wedge osteotomy for the treatment of congenital hypertrophic epiphysis of the distal phalanx of the thumbs in children.Methods:A retrospective analysis was conducted on the data of children with congenital hypertrophic epiphysis deformity of the distal phalanx of the thumb treated by precisely located intraepiphyseal wedge osteotomy in Dongguan Integrated Traditional Chinese and Western Medicine Hospital from January 2020 to January 2023. Preoperative X-ray films all showed asymmetric thickening of the secondary ossification centers, presenting as triangular, elliptical, unequal trapezoidal, and bipartite epiphyseal fusion shapes respectively. During the operation, precise localization was performed, and wedge osteotomy was conducted at 1.5 mm from the articular surface. The osteotomy angle and volume were adjusted according to the morphology of the hypertrophic epiphysis and the comprehensive condition of the distal and proximal phalanges, with axial over-correction of approximately 10° for fixation. Six months after surgery, the ulnar deviation angle of the distal phalanx with the interphalangeal joint of the thumb, the maximum passive flexion angle, and the thickness of the distal epiphyseal plate on X-ray were followed up. Statistical analysis was conducted using paired t-tests before and after surgery, and P<0.05 was considered statistically significant. Results:A total of 32 children with 34 thumbs were included, aged from 6 months to 8 years old, with an average age of 2.1 years old. There were 27 thumbs accompanied by radial polydactyly, the main and accessory thumbs were clear, and the epiphysis of the distal phalanx of the main thumb was thickened. The lateral deviation angle of the distal phalanx of the thumb before surgery was (35.6±13.2)° (15.0°-67.0°), the maximum passive flexion range was (62.8±7.7)° (38.0°-80.0°), and the maximum thickness of the distal phalanx epiphysis in the X-ray was (3.7±0.9) mm (2.3-5.9 mm). All surgeries of all children were successfully completed, the wounds healed well without redness, swelling or infection. Patients were discharged smoothly. The average follow-up time after surgery was 13 month (rang from 6-22 months), with an average deviation angle of (7.6±5.6)° (1.8°-13.4°) in the distal phalanx with the interphalangeal joint, compared with before surgery, the difference was statistically significant ( t=10.36, P=0.012). Five thumbs had residual ulnar deviation after surgery, with an average deviation of (16.6±2.3)° (12.0°-20.0°), two cases had corrected positive radial deviation (15°, 18°), while the other cases had no significant ulnar deviation in the distal phalanx of the thumb. The average maximum angle of passive flexion of the distal thumb after surgery was (62.9±7.5)° (35.0°-80.0°), compared with before surgery, the difference was not statistically significant ( t=0.16, P=0.359). The average maximum thickness of the distal epiphyses on postoperative X-rays was (1.9±0.5) mm (1.2-3.1 mm), compared with before surgery, the difference was statistically significant ( t=17.04, P=0.012). The epiphyses were flat and round, and the growth lines were normal. Conclusion:Using precise intraepiphyseal wedge osteotomy, combined with postoperative fixation with mild overcorrection for the treatment of congenital hypertrophic epiphysis at distal phalanx of the thumb in children, can achieve satisfactory correction of deviation, significantly shorten and improve the morphology of the epiphysis without affecting the growth plate, and cause minimal impact on joint flexion activity.

Objective:To investigate the value of quantitative parameters of dual-layer detector spectral CT (DLCT) in preoperative prediction of lymphovascular invasion (LVI) in invasive lung adenocarcinoma.Methods:This study employed a cross-sectional design. The data of 91 patients with primary lung adenocarcinoma confirmed by postoperative pathology who underwent DLCT enhanced scanning in the First Affiliated Hospital of Zhengzhou University from March 2022 to July 2024 were retrospectively collected. The patients were divided into LVI positive group and LVI negative group according to the postoperative pathology. Gender, age, smoking status, and lesion location were recorded,the clinical T-stage and N-stage were evaluated. Spectral base data images were generated based on the spectral reconstruction algorithm. Conventional CT features such as the size and density of the lesions were analyzed. The DLCT quantitative parameters such as 40 keV single-energy CT value (CT 40 keV), iodine density (ID), standardized iodine density (NID), and effective atomic number (Z eff) were measured. The differences of parameters between the two groups were compared using t-test, Mann-Whitney U test, or χ2 test. Multivariate logistic regression analysis was used to identify independent factors for predicting invasive lung adenocarcinoma LVI. The predictive performance of individual parameters and their combinations for LVI in invasive lung adenocarcinoma was evaluated using receiver operating characteristic curve analysis and area under the curve (AUC) measurements. Results:There were significant differences in age, T stage, N stage, maximum diameter, focal density, and arteriovenous stage NID and Z eff between the LVI positive group and the LVI negative group ( P<0.05). Multiple logistic regression analysis showed that age ( OR=0.890, 95% CI 0.821-0.966), N stage( OR=12.721, 95% CI 2.676-60.473) and venous stage Z eff( OR=0.012,95% CI 0-0.668) were independent factors for predicting invasive lung adenocarcinoma LVI ( P<0.05). The combination of age, N stage, and venous-phase Z eff values demonstrated the highest predictive efficacy for LVI in invasive lung adenocarcinoma, with an AUC of 0.916. Conclusions:The quantitative parameters of DLCT are helpful for preoperative prediction of LVI status of invasive lung adenocarcinoma. The Z eff in the venous stage is an independent predictor, the combination of multiple parameters can further improve the diagnostic efficiency.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To observe the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) at different frequencies on cognitive impairment due to high-altitude hypoxia.Methods:Sixty officers and soldiers displaying cognitive impairment in a hypoxic high-altitude environment were randomly divided into 15Hz, 20Hz and 25Hz groups, each of 20. They were given rTMS at those frequencies for 30 days. Before the stimulation and after 15 and 30 days, event-related potentials, latencies of mismatched negativity (MMN) and P300 signals were recorded. The participants′ cognition was also evaluated using the Montreal Cognitive Assessment Scale (MoCA). Correlation between the electrophysiological indexes and the MoCA scores was computed.Results:After 15 days, all had shorter MMN latencies, higher total MoCA scores and better memory scores. The only significant difference among the three groups was in the average memory scores. After 15 days, MMN latency was significantly negatively correlated with the memory scores in all three groups ( r=0.44 to -0.54). Conclusions:rTMS at frequencies above 15Hz can effectively relieve cognitive impairment, especially memory dysfunction, resulting from high-altitude hypoxia.

AIM:This study aimed to utilize network pharmacology and an anxiety rat model to investigate the intervention targets and underlying mechanisms of Baixiangdan capsule(BXD)in the treatment of anxiety-like behavior.METHODS:We screened the action targets of BXD on the anxiety model using network pharmacology,followed by Gene Ontology(GO)enrichment and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the identified targets.Additionally,we evaluated the effects of BXD on rat anxiety behaviors induced by foot shock,with measurement of serum level of c-Jun N-terminal kinase inhibitor(JIK),and the protein levels of c-Jun N-terminal kinase(JNK),phos-phorylated JNK(p-JNK)and JIK in the left hippocampus and hypothalamus.RESULTS:A total of 97 targets,including the dopamine D1/D3 receptors,were identified as intersection targets.GO enrichment analysis indicated that target pro-teins were significantly involved in molecular functions such as catecholamine binding,receptor activation,and signal transduction.KEGG pathway analysis revealed that neural receptor-ligand pathways,including dopaminergic synapses(15%)and neuroactive ligand-receptor interaction(18%),were notably represented.In behavioral experiments,BXD and diazepam treatments significantly reduced total path in the open-field test(P＜0.01),while the number of entries into the central region increased(P＜0.05).Additionally,the percentage of entry times of the open arm and the percentage of time spent in the open arm were also increased(P＜0.01).Furthermore,BXD treatment led to decreased ratio of p-JNK/JNK and increased level of JIK(P＜0.05).CONCLUSION:The traditional Chinese medicine BXD demonstrates a promising efficacy in alleviating anxiety-like behaviors in model rats.It operates through a multi-component,multi-target,and multi-pathway approach,primarily by modulating the JIK/JNK signaling pathway.

Objective:To compare the clinicopathological characteristics and prognostic outcomes between patients with clear cell renal cell carcinoma(ccRCC)and non-clear cell renal cell carcinoma(nccRCC)accompanied by venous tumor thrombus.Methods:A retrospective analysis was conducted on clinical and pathological data from patients with RCC and venous tumor thrombus treated in the Depart-ment of Urology at Peking University Third Hospital between January 2014 and February 2024.Patients were stratified into two groups based on pathological type:ccRCC and nccRCC.Comparisons of baseline characteristics,intraoperative situation,and prognosis between the two groups were performed using t-tests,Mann-Whitney U tests,chi-square tests,and Log-rank tests.Survival curves were generated using the Kaplan-Meier method.Results:A total of 437 patients were included,with a median age of 58 years,including 317 males and 120 females.The cohort comprised 366 cases of ccRCC and 71 cases of nccRCC.The non-clear cell group included 38 cases(53.5％)of papillary renal cell carcinoma,2 cases(2.8％)of chromophobe renal cell carcinoma,11 cases(15.5％)of unclassified renal cell carcinoma,19 cases(26.8％)of molecularly defined renal cell carcinoma,and 1 case(1.4％)of collecting duct carcinoma.Compared with the clear cell renal carcinoma group,patients in the non-clear cell carcinoma group demonstrated a younger age at diagnosis(59 years vs.55 years,P=0.010),larger tumor size(8.4 cm vs.9.5 cm,P=0.025),higher rates of lymph node metastasis(56.8％vs.70.6％,P=0.034),more advanced tumor thrombus(P＜0.001)and pathological grading(P=0.010),longer surgical duration(272 minutes vs.289 minutes,P=0.023),and shorter overall survival(80 months vs.35 months,P＜0.001).Multivariate Cox analysis indicated that histologic type,distant metastasis,tumor thrombus grading,and sarcomatoid/rhabdoid differentiation were prognostic factors in the renal cell carcinoma patients with venous tumor thrombus.No significant differences were observed between the two groups in terms of gender,body mass index,tumor laterality,distant metastasis,sarcomatoid or rhabdoid differentiation,American Society of Anesthesiologists(ASA)score,surgical approach,conversion to open surgery,blood loss,or transfusion of red blood cells and plasma.Conclusion:Compared with pa-tients with clear cell renal carcinoma and venous tumor thrombus,those with non-clear cell carcinoma and venous tumor thrombus exhibit earlier onset,more aggressive disease progression,and poorer prognosis.