Objective To analyze the problems in the operation and management of drug clinical trials and put forward targeted suggestion. Methods An electronic questionnaire survey was conducted among medical staff in about 80 hospitals in the yangtze river delta region. Results 606 valid questionnaires were received. 71% of the respondents expressed their willingness to study and participate in drug clinical trials. There were significant differences in the cognitive demands, willingness and motivation of the respondents with different occupations and educational backgrounds about the drug clinical trial work （P<0.05）. During the operation of drug clinical trials, respondents reported the main factors affecting the quality of clinical trials which including good clinical practice (GCP) awareness and subjective enthusiasm of investigators （response rate 27%）, job stability of supervisors and research coordinators （27%）, compliance of subjects （45%）, quality control of the whole process of the circulation of test drugs, medical devices and biological samples （52%）, and the informatization level of clinical trial institutions （30%）. Conclusion Hospitals, institutions and project teams could take measures to cultivate and stabilize the drug clinical trial talent team, improve the quality management system of drug clinical trials, improve work efficiency, and promote the high-quality development of drug clinical trials in medical institutions.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Objective To analyze the clinical features of premature rupture of membrane(PROM)complicated with histologic chorioamnionitis(HCA),and to provide insights for clinical management of such pregnant women and their newborns.Methods A total of 202 cases of PROM pregnant women who gave birth and performed placental pathological examination in the Affiliated Hospital of Southwest Medical University from January to December 2021 were retrospectively analyzed.According to the histopathological results,the pregnant women were divided into HCA group(n=151)and control group(n=51),and the prenatal factors and short-term maternal-fetal pregnancy outcomes of two groups were compared and analyzed.Results The amniotic fluid contamination rate,white blood cell count,neutrophil count and serum amyloid A levels in HCA group were significantly higher than those in control group(P＜0.05).There was a higher incidence of early neonatal septicemia in HCA group than in control group(P＜0.05).Conclusion The risk of early-onset sepsis in neonates with PROM complicated with HCA significantly increases.It is necessary to strengthen the screening and early intervention in such cases.Amniotic fluid contamination and increased maternal infection indicators are associated with the occurrence of HCA,which may has potential value in predicting HCA occurrence.

Objective:To investigate the changes in and correlations between melanin-concentrating hormone (MCH) and androgen levels in the serum of patients with polycystic ovary syndrome (PCOS), aiming to provide a novel research perspective for its diagnosis.Methods:A cross-sectional study. A total of 307 subjects were enrolled from the physical examination center and endocrinology clinic of the Affiliated Hospital of Zunyi Medical University from June 2023 to June 2024. The cohort comprised 114 healthy controls and 193 patients with PCOS, diagnosed according to the Rotterdam criteria. The patients were grouped into four phenotypes: Phenotype A (hyperandrogenemia [HA]+ovulatory dysfunction [OA]+polycystic ovarian morphology [PCOM], n=44), Phenotype B (HA+OA, n=50), Phenotype C (HA+PCOM, n=46), and Phenotype D (OA+PCOM, n=53). Clinical data were collected for all subjects. Serum MCH levels were determined by enzyme-linked immunosorbent assay. The relationship between MCH and androgen-related risk factors for PCOS was analyzed using Spearman partial correlation analysis and stepwise multiple linear hierarchical regression. Binary logistic regression was used to analyze factors influencing PCOS onset. The diagnostic value of MCH for PCOS was evaluated using a receiver operating characteristic (ROC) curve. Results:There were no significant differences in age and height between the healthy control group and the PCOS phenotypic groups (both P>0.05). MCH levels [17.63 (12.69, 22.00), 17.31 (11.05, 20.09), 17.82 (11.47, 19.40), 16.50 (11.14, 19.41) μg/L vs. 12.14 (9.78, 15.05) μg/L], homeostatic model assessment of insulin resistance, fasting plasma glucose, fasting serum lisulin, body mass index, and weight were significantly higher across all four PCOS phenotypes (A, B, C, and D) than in healthy controls (all P<0.05), whereas sex hormone-binding globulin (SHBG) contents were significantly lower ( P<0.05). Free androgen index (FAI), total testosterone (TES) and dehydroepiandrosterone (DHEA) levels were significantly higher in PCOS phenotypes A, B, and C than in the control group and PCOS phenotype D (all P<0.05). Spearman partial correlation analysis revealed no significant correlation between MCH and TES, DHEA, or FAI in healthy controls and patients with non-HA PCOS (all P>0.05). However, in PCOS patients with HA, MCH showed a significant positive correlation with TES and DHEA ( r=0.227 and 0.196, respectively; both P<0.05), but not FAI ( P>0.05). Stepwise multiple linear hierarchical regression analysis showed that MCH was positively correlated with TES, DHEA and luteinizing hormone and negatively correlated with SHBG (all P<0.05). Binary logistic regression indicated that an increase in MCH may be a potential risk factor for PCOS occurrence ( OR=1.113, 95% CI 1.012-1.224, P=0.028). ROC analysis showed that MCH has diagnostic value for PCOS ( P<0.05), with an area under the curve of 0.713. Conclusion:Serum MCH is closely related to FAI, TES, and DHEA levels in PCOS patients and may play an important role in the etiology and progression of the syndrome.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective To explore the effects of physical activity(PA)on carotid intima-media thickness(CIMT)thickening in patients with type 2 diabetes mellitus(T2DM)with poor HbA1c control.Methods A total of 2505 T2DM inpatients with poor HbA1c control who visited the Endocrinology Department of the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine and Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2019 to February 2022 were enrolled in this study.The patients were categorized into the mild-intensity PA(1～599 MET-min/w,n=795),moderate-intensity PA(600～1499 MET-min/w,n=1107)and high-intensity PA(≥1500 MET-min/w,n=603)based on the metabolic equivalence level(MET).Logistic regression was performed to analyze the relationship between PA and CIMT thickening.Statified analysis was used to investigate the effects of blood pressure(BP)and low-density lipoprotein cholesterol(LDL-C)target status on CIMT thickness in different PA groups.Results Restricted cubic spline plots showed a nonlinear relationship between PA levels and the risk of CIMT thickening(P<0.05).Logistic regression showed that with moderate-intensity PA as the control,while high-intensity PA was the influence factor of CIMT thickening(OR 1.581,95%CI 1.244～2.010,P<0.05).Statified analyses showed that under mild-intensity PA,using neither BP nor LDL-C on target as reference,achievement of either index and both were the influence factor of CIMT thickening.Using BP on target as reference,achievements of both indexes,achievements of neither of both indexes,and achievement of LDL-C only were the influence factor of CIMT thickening.Using LDL-C on target as reference,achievement of neither of them and achievement of BP only were the influence factor of CIMT thickening.Under high-intensity PA,achievement of both indexes was negatively associated with CIMT thickening.Conclusions Moderate-intensity PA is the recommended scheme to prevent CIMT thickening in T2DM patients whose HbA1c is not up to standard.Mild-intensity PA is not related to the risk of CIMT thickening,while high-intensity PA is positively related to the risk of CIMT thickening,and focusing on LDL-C compliance is particularly important to avoid CIMT thickening.

Objective:To investigate the effect of skin care based on the National Cancer Institute (NCI) grading on breast cancer patients with chemotherapy-related hand-foot syndrome (HFS) .Methods:A convenience sampling method was used to select 72 female breast cancer patients with chemotherapy-induced HFS treated at Nantong Tumor Hospital from January 2019 to December 2021. Patients were randomly divided into an observation group ( n=36) and a control group ( n=36) using a random number generator. The control group received routine nursing intervention, while the observation group received skin care intervention based on NCI grading. The Numerical Rating Scale (NRS) , European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) , Morisky Medication Adherence Scale-8 (MMAS-8) , and Healthy Eating Index (HEI) were used for evaluation. Comparisons were made between the two groups before and after intervention in terms of NCI grading, main symptoms of HFS (numbness, skin erythema) grading, NRS score, and EORTC QLQ-C30 score, and the time to first HFS relief, as well as adherence to medication and diet, were assessed. Results:After nursing intervention, the distribution of NCI grades differed between the two groups, and the difference was statistically significant ( P<0.05) . The time to first relief of HFS in the observation group was earlier than in the control group, and the difference was statistically significant ( P<0.05) . The distribution of skin erythema grades between the two groups also differed, and the difference was statistically significant ( P<0.05) . The observation group had lower NRS scores, while MMAS-8, HEI, and EORTC QLQ-C30 scores were higher than those of the control group, and the differences were all statistically significant ( P<0.05) . Conclusions:Skin care based on NCI grading can improve symptoms of chemotherapy-related HFS in breast cancer patients, shorten the time to HFS relief, enhance quality of life, and improve treatment adherence. It is worthy of clinical application.

Objective:To investigate the effect of skin care based on the National Cancer Institute (NCI) grading on breast cancer patients with chemotherapy-related hand-foot syndrome (HFS) .Methods:A convenience sampling method was used to select 72 female breast cancer patients with chemotherapy-induced HFS treated at Nantong Tumor Hospital from January 2019 to December 2021. Patients were randomly divided into an observation group ( n=36) and a control group ( n=36) using a random number generator. The control group received routine nursing intervention, while the observation group received skin care intervention based on NCI grading. The Numerical Rating Scale (NRS) , European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) , Morisky Medication Adherence Scale-8 (MMAS-8) , and Healthy Eating Index (HEI) were used for evaluation. Comparisons were made between the two groups before and after intervention in terms of NCI grading, main symptoms of HFS (numbness, skin erythema) grading, NRS score, and EORTC QLQ-C30 score, and the time to first HFS relief, as well as adherence to medication and diet, were assessed. Results:After nursing intervention, the distribution of NCI grades differed between the two groups, and the difference was statistically significant ( P<0.05) . The time to first relief of HFS in the observation group was earlier than in the control group, and the difference was statistically significant ( P<0.05) . The distribution of skin erythema grades between the two groups also differed, and the difference was statistically significant ( P<0.05) . The observation group had lower NRS scores, while MMAS-8, HEI, and EORTC QLQ-C30 scores were higher than those of the control group, and the differences were all statistically significant ( P<0.05) . Conclusions:Skin care based on NCI grading can improve symptoms of chemotherapy-related HFS in breast cancer patients, shorten the time to HFS relief, enhance quality of life, and improve treatment adherence. It is worthy of clinical application.

Objective To explore the effects of physical activity(PA)on carotid intima-media thickness(CIMT)thickening in patients with type 2 diabetes mellitus(T2DM)with poor HbA1c control.Methods A total of 2505 T2DM inpatients with poor HbA1c control who visited the Endocrinology Department of the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine and Changzhou Second People's Hospital Affiliated with Nanjing Medical University from January 2019 to February 2022 were enrolled in this study.The patients were categorized into the mild-intensity PA(1～599 MET-min/w,n=795),moderate-intensity PA(600～1499 MET-min/w,n=1107)and high-intensity PA(≥1500 MET-min/w,n=603)based on the metabolic equivalence level(MET).Logistic regression was performed to analyze the relationship between PA and CIMT thickening.Statified analysis was used to investigate the effects of blood pressure(BP)and low-density lipoprotein cholesterol(LDL-C)target status on CIMT thickness in different PA groups.Results Restricted cubic spline plots showed a nonlinear relationship between PA levels and the risk of CIMT thickening(P<0.05).Logistic regression showed that with moderate-intensity PA as the control,while high-intensity PA was the influence factor of CIMT thickening(OR 1.581,95%CI 1.244～2.010,P<0.05).Statified analyses showed that under mild-intensity PA,using neither BP nor LDL-C on target as reference,achievement of either index and both were the influence factor of CIMT thickening.Using BP on target as reference,achievements of both indexes,achievements of neither of both indexes,and achievement of LDL-C only were the influence factor of CIMT thickening.Using LDL-C on target as reference,achievement of neither of them and achievement of BP only were the influence factor of CIMT thickening.Under high-intensity PA,achievement of both indexes was negatively associated with CIMT thickening.Conclusions Moderate-intensity PA is the recommended scheme to prevent CIMT thickening in T2DM patients whose HbA1c is not up to standard.Mild-intensity PA is not related to the risk of CIMT thickening,while high-intensity PA is positively related to the risk of CIMT thickening,and focusing on LDL-C compliance is particularly important to avoid CIMT thickening.

Objective To analyze the clinical features of premature rupture of membrane(PROM)complicated with histologic chorioamnionitis(HCA),and to provide insights for clinical management of such pregnant women and their newborns.Methods A total of 202 cases of PROM pregnant women who gave birth and performed placental pathological examination in the Affiliated Hospital of Southwest Medical University from January to December 2021 were retrospectively analyzed.According to the histopathological results,the pregnant women were divided into HCA group(n=151)and control group(n=51),and the prenatal factors and short-term maternal-fetal pregnancy outcomes of two groups were compared and analyzed.Results The amniotic fluid contamination rate,white blood cell count,neutrophil count and serum amyloid A levels in HCA group were significantly higher than those in control group(P＜0.05).There was a higher incidence of early neonatal septicemia in HCA group than in control group(P＜0.05).Conclusion The risk of early-onset sepsis in neonates with PROM complicated with HCA significantly increases.It is necessary to strengthen the screening and early intervention in such cases.Amniotic fluid contamination and increased maternal infection indicators are associated with the occurrence of HCA,which may has potential value in predicting HCA occurrence.