Driven by the growing practical need to accelerate drug development and the continuous innovation of trial design in recent years， the number of protocol amendments during clinical trials have gradually increased， and the changed contents have become more flexible and complex， which significantly heightens the difficulty of ethical review on amendments. Against this backdrop， it is of great importance to fully leverage the role and responsibilities of ethics committees， effectively control clinical trial risks， and ensure subject safety. This paper analyzed development trends of protocol amendments in recent years， sorted out requirements for protocol amendments in Chinese regulations and guiding principles， and examined difficulties of amendment ethical review in practical work. Based on these， targeted strategies and recommendations were proposed， namely， strengthening the integration with scientific review， enhancing the formal review， adjusting the scope of review according to approval notifications， and adopting appropriate review methods， with a view to providing insights and references for the management of the amendment ethical review in drug clinical trials.

PURPOSE: To screen laboratory markers with predictive value in early spinal surgical site infections (SSI) that are diagnosed within 30 days postoperatively. METHODS: Patients who underwent surgical treatment for internal spinal fixation between March 2022 and March 2023 in our hospital were retrospectively studied. The inclusion criteria were aged >18 years, undergoing internal fixation surgery, complete medical records with >30 days of postoperative follow-up, diagnosis was made within 30 days postoperatively, and an informed consent form was obtained. The exclusion criteria were abnormal white blood cell count or neutrophil percentage in the preoperative blood routine and combined diseases that may affect the C-reactive protein (CRP) or procalcitonin (PCT) values, including lower respiratory tract infection, renal insufficiency, and liver disease. We collected patients' personal information, surgical information, and blood laboratory data, including CRP, PCT, lymphocyte-neutrophil ratio, platelet-neutrophil ratio, and routine blood tests on preoperative and postoperative days 3, 5, and 7, from these patients. These data were statistically analyzed to determine which laboratory markers were statistically significant. The diagnostic value and optimal diagnostic threshold of these laboratory markers were further determined by receiver operating characteristic curve analysis. RESULTS: A total of 106 patients were enrolled in this study, of whom 8 patients were diagnosed with early SSI. A total of 4 laboratory markers were screened, namely, CRP on postoperative day 7 (optimal diagnostic threshold of ≥64.1 mg/L, sensitivity of 100%, specificity of 76.5%, area under the curve (AUC) of 0.908), PCT on postoperative day 7 (optimal diagnostic threshold of ≥0.2 ng/mL, sensitivity of 87.5%, specificity of 94.1%, AUC of 0.967), lymphocyte count on postoperative day 5 (optimal diagnostic threshold of ≤0.67 × 10⁹/L, sensitivity of 50%, specificity of 95.9%, AUC of 0.760), and lymphocyte count on postoperative day 7 (optimal diagnostic threshold of ≤1.32 × 10⁹/L, sensitivity of 87.5%, specificity of 55.1%, AUC of 0.721). CONCLUSION We concluded that CRP and PCT levels on postoperative day 7 and lymphocyte counts on postoperative days 5 and 7 are useful markers in screening for early spinal SSI.
Humans ; Retrospective Studies ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; C-Reactive Protein/analysis* ; Surgical Wound Infection/blood* ; Procalcitonin/blood* ; Adult ; Aged ; Postoperative Period ; ROC Curve ; Predictive Value of Tests ; Spine/surgery*

Background While A few studies have suggested associations between ambient temperature and cardiac autonomic function, the relationship between hourly temperature variations and heart rate variability (HRV) remains unclear. Objective To examine the acute effects and lag patterns of short-term ambient temperature exposure on HRV at an hourly temporal resolution during cold and warm seasons, and to further characterize the exposure-response relationships. Methods We conducted a longitudinal panel study involving 1047 eligible participants who ordered repeated 24 h ambulatory electrocardiogram monitoring at the First Affiliated Hospital of Xinjiang Medical University in Urumqi, Xinjiang Uygur Autonomous Region, China, between March 2020 and March 2022. Twelve HRV parameters were extracted, including standard deviation of all NN intervals (SDNN), standard deviation of the 5 min averages of NN intervals (SDANN), standard deviation of NN intervals index (SDNNIDX), root mean square of successive differences of adjacent NN intervals (rMSSD), triangle index (TI), percent of NN50 in the total number of NN intervals (pNN50), total power (TP), ultralow frequency (ULF), very low frequency (VLF), low frequency (LF), high frequency (HF), and ratio of low frequency to high frequency (LF/HF). Hourly meteorological data (mean temperature and relative humidity) were obtained from the nearest monitoring stations to participants' residences. Linear mixed effects models (LME) and generalized additive mixed effects models (GAMM) were employed to assess temperature-HRV associations and lag patterns during cold (from October to March next year) and warm (from April to September) seasons, with stratification by sex and age. Results A total of 1047 Urumqi residents who had repeated 24 h ambulatory electrocardiograms were included in this study. In both cold and warm seasons, the exposure-response relationship between ambient temperature and HRV showed an approximately linear negative correlation with no threshold effect; HRV parameters decreased as ambient temperature increased. The correlation between ambient temperature and HRV usually began at a lag of 6 h and disappeared around 24 h lag. The cold season induced a stronger effect on HRV decline, and for every 1 °C increase in ambient temperature during the cold season from lag 0 to 6 h, SDNN decreased by 0.72%, SDNNIDX decreased by 1.46%, TI decreased by 0.07%, SDANN decreased by 1.23%, rMSSD decreased by 1.00%, pNN50 decreased by 2.74%, TP decreased by 3.30%, ULF decreased by 3.74%, VLF decreased by 3.76%, LF decreased by 2.75%, HF decreased by 2.49%, and LF/HF decreased by 0.74%; for every 1 °C increase in ambient temperature during the warm season, SDNN decreased by 0.56%, SDNNIDX decreased by 1.08%, TI decreased by 0.29%, SDANN decreased by 0.56%, rMSSD decreased by 0.68%, pNN50 decreased by 2.11%, TP decreased by 2.64%, ULF decreased by 3.14%, VLF decreased by 2.74%, LF decreased by 1.85%, HF decreased by 1.68%, and LF/HF decreased by 0.47%. Conclusion Elevated ambient temperatures in Urumqi are significantly associated with decreased HRV in the residents, affecting cardiac autonomic function.

Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Purpose To develop and validate a nomogram incorporating high-resolution MRI and clinicopathological indicators for predicting distant metastasis after curative resection of mid-low rectal cancer.Materials and Methods This retrospective study analyzed 219 patients with pathologically confirmed mid-low rectal cancer from Tianjin Union Medical Center(December 2016 to December 2021).Patients were categorized into metastasis(n=46)and non-metastasis(n=173)groups based on postoperative distant metastasis occurrence.All patients underwent preoperative pelvic MRI with measurement of posterior mesangial thickness(PMT),mesentery fat area(MFA)and mesenteric fascia envelopment volume(MFEV)on high-resolution T2WI.Clinicopathological and imaging data were collected.Cox proportional hazards model identified predictive factors for distant metastasis,and a risk probability nomogram was constructed.Predictive performance,goodness-of-fit and clinical applicability were evaluated.Results Kaplan-Meier analysis demonstrated significantly higher distant metastasis risk in patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 compared to those with higher values(χ2=29.07,8.71,19.05;all P<0.05).Cox regression identified tumor differentiation(HR=0.536,95％CI 0.290-0.990),pathological N stage(HR=0.397,95％CI 0.210-0.747),perirectal structure invasion(HR=0.242,95％CI 0.068-0.865)and PMT(HR=0.334,95％CI 0.168-0.664)as independent predictors.The nomogram achieved a concordance index of 0.775 with good calibration.Decision curve analysis demonstrated substantial net benefit across wide probability thresholds,indicating excellent clinical applicability.Conclusion Patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 exhibit elevated distant metastasis risk.The nomogram incorporating tumor differentiation,pathological N stage,perirectal structure invasion and PMT effectively predicts distant metastasis after curative resection of mid-low rectal cancer.

Objective To quantitatively assess the correlation between the skeletal muscle index(SMI)of patients and the occur-rence of anastomotic leakage(AL)in rectal cancer patients after surgery,and to analyze the risk factors for AL in rectal cancer patients and the influencing factors of sarcopenia.Methods The clinical,pathological,and related imaging data of 362 patients who under-went radical surgery for rectal cancer were retrospectively analyzed.All patients underwent pelvic MRI and abdominal CT scans(plain/enhanced)within one month before surgery,and the third lumbar vertebra skeletal muscle area(L3-SMA)was measured from the images.All patients were divided into AL group(56 cases)and control group(306 cases)based on the presence or absence of postoperative complications.The differences in clinical characteristics and imaging parameters between the two groups were analyzed.A logistic risk prediction model was established.Results Significant differences were observed between the two groups in sarcopenia,type of surgery,surgical approach,serum albumin level,operation duration,stoma type,and extramural vascular invasion(EMVI)(P＜0.05).These factors were incorporated in a multivariate logistic regression analysis model,the area under the curve(AUC)of receiver operating characteristic(ROC)curve of the model was 0.810[95％confidence interval(CI)0.743-0.876,P＜0.001],with a sensitivity of 0.865 and specificity of 0.669.Conclusion Sar-copenia is a significant risk factor for AL after rectal cancer surgery.It enhances the predictive efficacy for postoperative AL and serves as a basis for identifying high-risk populations for AL in clinical practice.

Myasthenia gravis(MG)is an autoimmune disease characterized primarily by skeletal muscle weakness and,in severe cases,respiratory involvement.Western medical treatment predominantly relies on immunosuppressants,but long-term administration often leads to notable side effects.In contrast,traditional Chinese medicine(TCM)offers the advantage of multi-target interventions.However,the pathogenesis of MG has not been fully elucidated,and the establishment of animal models that accurately reflect the clinical characteristics of both Chinese and Western medicine is essential for mechanism research and new drug development.This paper systematically reviews the etiology and pathogenesis,diagnostic criteria,and progress of animal model research for MG from both Chinese and Western medicine perspectives.In Western medicine,the pathogenesis of MG is closely related to genetic susceptibility,environmental factors,and autoantibody-mediated postsynaptic membrane damage.In TCM,MG is classified under the category of"flaccidity syndrome",attributed to congenital deficiencies and acquired malnourishment.Western diagnostic criteria involve a combination of clinical symptoms,fatigue testing,serum antibody assays,and electrophysiological evaluation.In contrast,TCM diagnosis emphasizes the integration of primary and secondary symptoms with tongue and pulse pattern differentiation.Currently available animal models mainly include experimental autoimmune myasthenia gravis(EAMG)and passive transfer myasthenia gravis(PTMG).The Toredo acetylcholine receptor(AChR)induced EAMG model aligns well with Western diagnostic criteria,but poorly matches secondary symptoms in TCM.The synthetic AChR peptide model is widely used,but shows low conformity with TCM syndromes.Models induced by muscle-specific tyrosine kinase(MuSK),low-density lipoprotein receptor-related protein 4(LRP4),and transgenic models demonstrate high innovation but exhibit low clinical conformity.Evaluation of these models requires integration of behavioral,electrophysiological,and immunological indicators.However,a systematic framework for modelling TCM syndromes is still lacking.Future research should integrate TCM-based etiological modelling methods with the Western pathological mechanisms to construct disease-syndrome combination models.Additionally,it is crucial to establish a TCM syndrome evaluation system based on"validation by prescription",as well as to improve the scientific rigor and practicality of animal models by the incorporation of emerging technologies.This review provides a theoretical foundation for optimizing MG animal model design,advancing the research on the combination of Chinese and Western medicine,and supporting efficacy assessment and mechanism exploration of Chinese herbal prescriptions.

Objective:To explore the categories and characteristics of health behaviors of community residents in Dongfang City, Hainan Province, and to analyze the influencing factors of different categories.Methods:From March to May 2023, 795 community residents of Dongfang City were selected for the study using a simple random sampling method. General Information Questionnaire, Chinese version Short of Health Promotion Lifestyle Profile-Ⅱ, Health Conception Scale, and Self-rated Abilities for Health Practice Scale were used to conduct the survey. Cluster analysis was used to explore the health behavior categories of community residents, and a decision tree model was applied to analyze the influencing factors of different categories.Results:A total of 830 questionnaires were distributed, and 795 valid questionnaires were recovered, with a valid recovery rate of 95.78%. The health behaviors of 795 community residents in Dongfang City were divided into four categories of comprehensive behavior group (26.04%, 207/795), healthy behavior group (37.23%, 296/795), risky behavior group (18.99%, 151/795), and poor health behavior group (17.74%, 141/795). The decision tree model showed that exercise efficacy, gender, ethnicity, and clinical health concepts were the factors influencing different health behavior categories of community residents in Dongfang City ( P<0.05), with exercise efficacy being the core factor. Conclusions:There is heterogeneity in the health behavior of community residents in Dongfang City. Community healthcare workers can implement targeted health promotion measures according to the behavioral characteristics of the population.

Purpose To develop and validate a nomogram incorporating high-resolution MRI and clinicopathological indicators for predicting distant metastasis after curative resection of mid-low rectal cancer.Materials and Methods This retrospective study analyzed 219 patients with pathologically confirmed mid-low rectal cancer from Tianjin Union Medical Center(December 2016 to December 2021).Patients were categorized into metastasis(n=46)and non-metastasis(n=173)groups based on postoperative distant metastasis occurrence.All patients underwent preoperative pelvic MRI with measurement of posterior mesangial thickness(PMT),mesentery fat area(MFA)and mesenteric fascia envelopment volume(MFEV)on high-resolution T2WI.Clinicopathological and imaging data were collected.Cox proportional hazards model identified predictive factors for distant metastasis,and a risk probability nomogram was constructed.Predictive performance,goodness-of-fit and clinical applicability were evaluated.Results Kaplan-Meier analysis demonstrated significantly higher distant metastasis risk in patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 compared to those with higher values(χ2=29.07,8.71,19.05;all P<0.05).Cox regression identified tumor differentiation(HR=0.536,95％CI 0.290-0.990),pathological N stage(HR=0.397,95％CI 0.210-0.747),perirectal structure invasion(HR=0.242,95％CI 0.068-0.865)and PMT(HR=0.334,95％CI 0.168-0.664)as independent predictors.The nomogram achieved a concordance index of 0.775 with good calibration.Decision curve analysis demonstrated substantial net benefit across wide probability thresholds,indicating excellent clinical applicability.Conclusion Patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 exhibit elevated distant metastasis risk.The nomogram incorporating tumor differentiation,pathological N stage,perirectal structure invasion and PMT effectively predicts distant metastasis after curative resection of mid-low rectal cancer.