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.

Objective To investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

AIM: To investigate the influence of relevant inflammatory markers in peripheral blood on the progression of neovascular glaucoma(NVG)secondary to diabetic retinopathy(DR)patients.METHODS: Retrospective case-control study. Patients were categorized into two groups based on the presence or absence of NVG: those with proliferative diabetic retinopathy(PDR)alone(PDR group, n=148)and those with NVG secondary to PDR(NVG secondary to PDR group, n=142). Peripheral blood inflammatory markers were evaluated, including white blood cell-related indices, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), monocyte-to-lymphocyte ratio(MLR), and systemic immune-inflammation index(SII). The distinctions in peripheral blood inflammatory markers between the two groups of patients and their relationships with NVG secondary to PDR were analyzed.RESULTS:No statistically significant differences were observed in basic characteristics between the two groups, confirming their comparability. However, significant differences were found in eosinophil percentage and MLR between the PDR group and the NVG secondary to PDR group(all P<0.05), with both values being significantly higher in the NVG secondary to PDR group. Multivariate Logistic regression analysis revealed that the eosinophil percentage and the MLR were factors influencing the development of patients with NVG secondary to PDR.CONCLUSION: Eosinophil percentage and MLR may be associated with the progression of PDR to NVG, and could serve as potential predictive markers for NVG development in PDR patients.

Objective: To investigate the association between overweight, obesity, central obesity and hypertension, so as to provide the basis for formulating targeted hypertension prevention and control strategies. Methods: Permanent residents aged ≥18 years were selected in Wenzhou City, Zhejiang Province from June 2023 to August 2024 by a multistage cluster random sampling method. Data on demographic information, lifestyle, height, weight, waist circumference (WC), blood pressure, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. The prevalence of hypertension was calculated and standardized using the data of the Sixth National Population Census in 2010. Body mass index (BMI) was calculated to determine overweight and obesity, while WC was used to identify central obesity. The association between overweight, obesity, central obesity and hypertension were analyzed using multivariable logistic regression models. Results: A total of 38 593 residents were surveyed, including 19 481 (50.48%) males and 19 112 (49.52%) females. The median age was 46.00 (interquartile range, 26.00) years. The rates of overweight, obesity, and central obesity were 32.74% (12 634 individuals), 10.27% (3 963 individuals), and 27.87% (10 755 individuals), respectively. There were 11 813 cases of hypertension, with a prevalence and standardized prevalence of 30.61% and 24.41%, respectively. Multivariable logistic regression analysis showed that after adjusting for demographic information, lifestyle, diabetes and dyslipidemia, the likelihood of hypertension in the overweight and obesity groups was 1.927 (95%CI: 1.815-2.045) times and 3.724 (95%CI: 3.404-4.073) times that of the normal BMI group, respectively. The likelihood of hypertension in the central obesity group was 2.346 (95%CI: 2.214-2.486) times that of the normal WC group. The likelihood of hypertension in the central obesity only, overweight only, overweight with central obesity, obesity only and obesity with central obesity groups was 1.586 (95%CI: 1.391-1.809), 1.704 (95%CI: 1.582-1.835), 2.433 (95%CI: 2.254-2.626), 1.768 (95%CI: 1.424-2.194), and 4.466 (95%CI: 4.053-4.921) times that of the normal BMI and WC group, respectively. Conclusions Overweight, obesity and central obesity were all associated with hypertension among adult residents. The highest likelihood of hypertension was observed among adult residents with both general obesity and central obesity.

ObjectiveTo analyse the efficacy and mechanism of Guizhi Fulingwan in regulating sex hormone disorders in rats with benign prostatic hyperplasia （BPH）. MethodsThirty male SD rats were randomly divided into a sham group， a model group， a finasteride group （0.45 mg·kg^-1·d^-1）， and low-dose and high-dose groups of Guizhi Fulingwan （0.135， 0.337 5 g∙kg^-1∙d^-1）， with six in each group. The BPH model was prepared by subcutaneous injection of 3.5 mg∙kg^-1∙d^-1 testosterone propionate after debridement surgery in all groups except the sham group. The rats in the sham group and the model group were administered with an equal volume of saline by gavage， and the rest of the groups were administered with the corresponding medicinal solution by gavage for 35 days. Histopathology in rats was evaluated by prostate wet weight， volume， index， and hematoxylin-eosin （HE） staining. The serum sex hormone levels of testosterone （T）， dihydrotestosterone （DHT）， and estradiol （E₂） were determined by enzyme-linked immunosorbent assay. The protein expression of the androgen receptor （AR） was detected by immunohistochemistry. The serum metabolism profiles of rats in the sham group， the model group， and the high-dose group of Guizhi Fulingwan were compared by ultra-high performance liquid chromatography tandem Fourier transform mass spectrometry （UHPLCQ Exactive） to screen for metabolic markers and to obtain relevant metabolic pathways. ResultsCompared with those in the sham group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the model group were all elevated （P<0.05， P<0.01）， and the histomorphology showed pathological changes. Compared with those in the model group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the intervention groups showed a decreasing trend （P<0.05， P<0.01）， and histopathology was improved. Serum metabolomics analysis obtained a total of 40 metabolic markers related to the intervention effect of Guizhi Fulingwan， such as dehydrosafynol， hyoscyamine， and lumichrome， which were involved in the pathways of autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling. ConclusionGuizhi Fulingwan can effectively regulate sex hormone disorders in BPH rats， and its mechanism may be related to autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling.

Objective To explore the regulatory effects of cytokines interleukin(IL)-1β,IL-6,tumor necrosis factor alpha(TNF-ɑ),gamma interferon(IFN-γ),granulocyte colony-stimulating factor(G-CSF),and granulocyte-macrophage colony-stimulating factor(GM-CSF)on spontaneous pyroptosis in neutrophils.Methods Neutrophils isolated from mouse bone marrow by density-gradient centrifugation were cultured in vitro for 20 h with or without 10,50 or 100 ng/mL IL-1β,IL-6,IFN-γ,G-CSF or GM-CSF,or for 12 h with or without 1,10 or 50 ng/mL TNF-α.After incubation,cells were stained with annexin Ⅴ(AV)/propidium iodide(PI),and the proportions and absolute number of neutrophils undergoing different forms of cell death were determined by fluorescence microscopy combined with manual counting.Pyroptotic neutrophils were identified by cell morphology in conjunction with AV/PI staining.Flow cytometry with counting beads was employed to measure the proportions and number of AV/PI-stained Ly6g⁺neutrophils in different forms of cell death.Western blotting was employed to assess the cleavage and activation levels of cysteinyl aspartate-specific proteinase-3(caspase-3)and gasdermin E(GSDME).Results Treatment with IL-1β or IL-6 had no significant effect on the proportion or number of neutrophils undergoing spontaneous pyroptosis.After 12 h of treatment with TNF-α at 1,10,and 50 ng/mL,the proportions of pyroptotic neutrophils were(14.79±0.45)%,(19.99±3.02)%,and(20.66±1.99)%,respectively,higher than that[(10.22±1.12)%]in the untreated control(P=0.024,P<0.001,and P<0.001,respectively).Treatment with 10,50,and 100 ng/mL IFN-γ for 20 h reduced the proportion of pyroptotic neutrophils from(17.43±1.88)%to 12.00%(all P<0.001).G-CSF at 10,50,and 100 ng/mL reduced the proportion of pyroptotic cells to around 6.00%and greatly inhibited the cleavage of both caspase-3 and GSDME.After 20 h of treatment with 10,50,and 100 ng/mL GM-CSF,the proportions of pyroptotic neutrophils decreased to(7.52±0.53)%,(5.27±2.30)%,and(0.64±1.11)%,respectively.Conclusions Neither IL-1β nor IL-6 affects GSDME-mediated spontaneous pyroptosis in neutrophils.TNF-ɑ induces spontaneous pyroptosis in neutrophils,whereas IFN-γ,G-CSF,and GM-CSF demonstrate inhibitory effects.
Pyroptosis/drug effects* ; Animals ; Neutrophils/cytology* ; Mice ; Cytokines/pharmacology* ; Interleukin-1beta/pharmacology* ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology* ; Cells, Cultured ; Granulocyte Colony-Stimulating Factor/pharmacology* ; Tumor Necrosis Factor-alpha/pharmacology* ; Interferon-gamma/pharmacology* ; Interleukin-6/pharmacology*

Objective To explore the predictive value of combined detection of serum CXC chemokine lig-and 12(CXCL12),caspase-cleaved cytokeratin 18(CCCK-18)and matrix metalloproteinase-9(MMP-9)for short-term poor prognosis in patients with acute hemorrhagic stroke.Methods A total of 138 patients with a-cute hemorrhagic stroke admitted to a hospital from October 2021 to March 2023 were selected as the study objects.Serum CXCL12,CCCK-18 and MMP-9 levels were detected after admission and before treatment.Pa-tients were followed up for 6 months after treatment and were divided into good prognosis group and poor prognosis group according to the modified Rankin scale score.Clinical data and serum CXCL12,CCCK-18 and MMP-9 levels of the two groups were compared to analyze the factors affecting the short-term poor prognosis of patients with acute hemorrhagic stroke.Receiver operating characteristic(ROC)curve was drawn to evalu-ate the predictive value of single and combined detection of serum CXCL12,CCCK-18 and MMP-9 in patients with acute hemorrhagic stroke.Results Among 138 patients,there were 52 cases in the poor prognosis group and 86 cases in the good prognosis group,and the poor prognosis rate was 37.68%.Serum CXCL12,CCCK-18 and MMP-9 levels,age,blood loss at admission,National Institutes of Health Stroke Scale(NIHSS)score at admission,systolic blood pressure and diastolic blood pressure at admission in the poor prognosis group were higher than those in the good prognosis group.The score of Glasgow Coma Scale(GCS)at admission was lower than that of good prognosis group,and the difference was statistically significant(P<0.05).Multivari-ate Logistic regression analysis showed that high level of serum CXCL12,high level of CCCK-18,high level of MMP-9,older age,large amount of blood loss upon admission,high NIHSS score and high systolic blood pres-sure were all risk factors for short-term poor prognosis of acute hemorrhagic stroke(P<0.05).High GCS score on admission was a protective factor(P<0.05).ROC curve analysis showed that the area under the combined prediction curve of serum CXCL12,CCCK-18 and MMP-9 was higher than that of the single and pairwise combined prediction of each index(P<0.05).Conclusion The combined detection of serum CX-CL12,CCCK-18 and MMP-9 has a good value in predicting the short-term poor prognosis of patients with a-cute hemorrhagic stroke.

Objective To investigate the expression of serum micro ribonucleic acid(miR)-423-5p and fer-ritin in elderly osteoporosis(OP)and their relationship with hip fragility fracture.Methods A total of 79 eld-erly OP patients admitted to the hospital from March 2020 to March 2024 were selected as the observation group,and 62 healthy elderly patients with complete physical examination records and reports were selected as the control group during the same period.Patients in the observation group were divided into fracture group(42 cases)and non-fracture group(37 cases)according to the occurrence of hip fragility fracture.Serum miR-423-5p and ferritin levels were compared between the observation group and the control group and between the fracture group and the non-fracture group.The difference of bone mineral density(BMD)at different sites between the fracture group and the non-fracture group was compared.The correlation between serum miR-423-5p and ferritin and BMD at different sites was analyzed by Pearson,and the predictive value of serum miR-423-5p and ferritin in elderly hip fragility fractures was analyzed by receiver operating characteristic(ROC)curve.Results Serum miR-423-5p and ferritin in observation group were higher than those in control group,the differences were statistically significant(P＜0.05).The levels of serum miR-423-5p and ferritin in frac-ture group were higher than those in non-fracture group,and the differences were statistically significant(P＜0.05).Greater trochanteric BMD and total hip BMD in the non-fracture group were higher than those in the fracture group,and the differences were statistically significant(P＜0.05).According to Pearson correlation analysis,serum miR-423-5p and ferritin levels in elderly OP patients were negatively correlated with BMD de-tected in lumbar spine,femoral neck,greater trochanter,intertrochanter and total hip(P＜0.05).ROC curve analysis results showed that the sensitivity,specificity and the area under the curve(AUC)of serum miR-423-5p combined with ferritin were 0.786,0.892 and 0.818(95％CI:0.715-0.912),which were higher than the AUC predicted by the two alone and had higher predictive value(P＜0.05).Conclusion The combination of serum miR-423-5p and ferritin levels can predict the risk of hip fragility fracture in elderly OP patients.

Objective The aim of this study was to develop a method for the determination of nine vulcanizing agents and accelerators in pharmaceutical rubber stoppers by headspace gas chromatography with sulfur chemiluminescence detector(HS-GC-SCD).Methods A DB-1 capillary column(30 m×0.32 mm×0.25 μm)was used with He as the carrier gas.The injection port temperature was 220 ℃,the split ratio was 10∶1,and the carrier gas flow rate was 1.5 mL·min-1.The temperature program was as follows:the starting temperature was 40 ℃,and it was increased to 60 ℃ at a rate of 5 ℃ per minute,and then to 260 ℃ at a rate of 15℃per minute.SCD detector parameters:base temperature was 280℃,combustion chamber temperature was 800 ℃,air flow rate was 60 mL·min-1,and hydrogen flow rate was 40 mL·min-1.Results The sample pretreatment method was simple and convenient,and it effectively reduced the extraction loss.The methodological results showed that all sulfides showed good linear relationships within the concentration range(r2≥ 0.990).The RSD was less than 2％;and the average recovery rate was 86.4％-97.5％.From the analysis of the sample test results,free sulfur is commonly found in rubber stoppers.Among all the samples of the vulcanization system,the free sulfur detected in the sulfur vulcanization system is higher than the free sulfur produced by degradation of other vulcanization systems.Conclusions This method is simple to operate,compared with other existing detection methods.HS-GC-SCD has a smaller matrix effect,higher sensitivity and selectivity,and is appropriate for quantifying the concentrations of sulfide present in various rubber stoppers.

Objective To systematically evaluate the effect of inspiratory muscle training(IMT)on weaning outcomes in patients with weaning failure.Methods Literatures in Chinese and English were retrieved from databases such as PubMed,Cochrane Library,Web of Science,Embase,CNKI,VIP,Wanfang data and CBM for researches on the effect of IMT in mechanical ventila-tion weaning failure,from the inception of the databases to October 22,2024.The methodological quality of the researches was evaluated with PEDro scale,and data were extracted for a systematic review.Results Nine randomized controlled trials were included,published between 2011 and 2023,from Brazil,China,the United States,Iran and Australia,with a total of 499 patients.The scores of the PEDro scale ranged five to eight.The population included patients with prolonged weaning,difficult weaning and tracheostomy.The IMT methods included threshold load training and tapered flow resistance training.The training intensity was 30%to 80%of maximal inspiratory pressure(MIP),and some researches did not set the training intensity based on MIP.The pro-gression of intensity varied widely across researches.The intervention frequency ranged from five to 30 breaths per set,with at least one minute rest between sets,two to six sets per session,one to two sessions per day,and five to seven days per week.The duration of the intervention ranged from successful weaning,one week after weaning,extubation,or four days to eight weeks.Regarding the efficacy of the intervention,IMT was not benefi-cial for the duration of mechanical ventilation and intensive care unit(ICU)length of stay on weaning failure pa-tients.However,the effect of IMT on weaning successful rates,duration of weaning,MIP and mortality was in-consistent.Conclusion IMT can not improve the duration of mechanical ventilation and ICU length of stay for weaning failure pa-tients,and there is still debate regarding its effect on successful rate of weaning,duration of weaning,MIP and mortality.