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.

Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory disease around the world, and pharmacotherapy is the foremost treatment method currently. In recent decades, with the rapid development of bronchoscopic interventional therapy, endoscopic physical ablation technology presents a therapeutic effect in treating COPD, with few treatment-related side effects, showing excellent application prospects in treating COPD. Since ablation techniques in this field are emerging technologies with low patient acceptance, they are not widely used in the clinical treatment of COPD. This article reviews the development process of physical ablation techniques. Moreover, their current application status and the prospects in the field of COPD treatment are also summarized and analyzed. We hope to promote the application of physical ablation in the clinical treatment of COPD and provide practical references and a theoretical basis for the clinical treatment of COPD.

Digestive system malignant tumors （DT） are one of the leading causes of death globally and carry a heavy economic burden. Gut microbiota plays a critical role in maintaining host health， including providing nutrition， defending against pathogens， and promoting immune development. In recent years， more and more studies have shown that dysbiosis of gut microbiota is closely associated with DT such as gastric cancer， liver cancer， and colon cancer. Therefore， targeted regulation of gut microbiota plays a potential role in inhibiting the growth and metastasis of DT， while its specific regulatory mechanism remains unclear. As the studies about the anti-tumor effects of traditional Chinese medicine （TCM）， especially the basic and clinical studies on the regulation of gut microbiota by TCM in tumor treatment， have been growing， the therapeutic effects of TCM on DT have attracted much attention. This paper provides a systematic review of the relationship between gut microbiota and DT， as well as the related studies on the modulation of gut microbiota by TCM against DT， with the aim of providing a foundation and direction for future basic and clinical studies on DT. The literature review shows that gut microbiota influence the occurrence and development of DT through multiple pathways. These pathways include triggering chronic inflammation， producing oncogenic metabolites， inducing genomic instability， regulating the immune system， and altering the tumor microenvironment. TCM can exert anti-DT effects by regulating the composition of gut microbiota， modulating gut microbiota metabolites， repairing intestinal barrier function， and influencing immune functions. Therefore， understanding the relationship between gut microbiota and DT and the regulatory mechanisms of TCM may provide new strategies for future prevention and treatment of DT.

Objective To investigate the correlation between serum levels of long non-coding RNA(Ln-cRNA)-prostate androgen regulated transcript 1(PART1),LncRNA-nucleolar ribonucleic acid host gene 14(SNHG14)and disease stage,cognitive impairment and motor function in patients with Parkinson's disease(PD).Methods A total of 100 PD patients(PD group)who admitted to the Department of Neurology in the hospital from January 2021 to December 2023 and 100 healthy subjects(control group)who underwent the physical examination during the same period of time were selected.According to Hoehn-Yahr staging,PD pa-tients were divided into early stage group(grade 1.0-2.5,20 cases),middle stage group(grade 3.0,48 ca-ses)and late stage group(grade 4.0-5.0,32 cases).According to the Montreal Cognitive Assessment(Mo-CA)score,the patients were divided into normal cognitive group(MoCA score≥26 points,33 cases),PD-mild cognitive impairment group(MoCA score 21-＜26 points,46 cases)and PD dementia group(MoCA score＜21 points,21 cases).According to the Unified Parkinson's Disease Rating Scale(UPDRS)-Ⅲ score,the pa-tients were divided into mild dyskinesia group(0-15 points,29 cases),moderate dyskinesia group(＞15-40 points,46 cases)and severe dyskinesia group(＞40-56 points,25 cases).Real-time fluorescence quantitative PCR was used to detect serum LncRNA-PART1 and LncRNA-SNHG14 levels.Spearman method was used to analyze the correlation between serum LncRNA-PART1,LncRNA-SNHG14 levels and Hoehn-Yahr staging,MoCA score and UPDRS-Ⅲ score in PD patients.Results The level of serum LncRNA-PART1 in PD group was lower than that in control group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in control group(P＜0.05).The serum levels of LncRNA-PART1 in the middle stage group and late stage groups were lower than those in the early stage group(P＜0.05),and the levels of LncRNA-SNHG14 were higher than those in the early stage group(P＜0.05).In addition,the serum level of LncRNA-PART1 in the late stage group was lower than that in the middle stage group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in the middle stage group(P＜0.05).The serum LncRNA-PART1 levels in the PD-mild cognitive impairment group and PD dementia group were lower than those in the normal cognitive group(P＜0.05),while the LncRNA-SNHG14 levels were higher than those in the normal cognitive group(P＜0.05).Additionally,the serum LncRNA-PART1 level in the PD dementia group was lower than that in the PD-mild cognitive impairment(P＜0.05),while the LncRNA-SNHG14 level was higher than that in the PD-mild cog-nitive impairment group(P＜0.05).The serum levels of LncRNA-PART1 in the moderate dyskinesia group and severe dyskinesia group were lower than those in the mild dyskinesia group(P＜0.05),and the levels ofLncRNA-SNHG14 were higher than that in the mild dyskinesia group(P＜0.05).In addition,the serum level of LncRNA-PART1 in the severe dyskinesia group was lower than that in the moderate dyskinesia group(P＜0.05),and the level of LncRNA-SNHG14 was higher than that in the moderate dyskinesia group(P＜0.05).Spearman method results showed that serum LncRNA-PART1 level was negatively correlated with Hoehn-Yahr staging and UPDRS-Ⅲ score in PD patients,and positively correlated with MoCA score(P＜0.05).The level of serum LncRNA-SNHG14 was positively correlated with Hoehn-Yahr staging and UPDRS-Ⅲ score in PD patients,and negatively correlated with MoCA score(P＜0.05).Conclusion The level of ser-um LncRNA-PART1 in PD patients is decreased,and the level of LncRNA-SNHG14 is increased,both of them are related to the disease stage,cognitive impairment and motor function of PD patients,which may be-come evaluation indicators for PD progression.

Objective To investigate the application value of uterine artery Doppler parameters combined with cerebral placental ratio(CPR)in predicting late-onset fetal growth restriction(FGR).Methods A total of 82 pregnant women with singleton pregnancy of FGR who were admitted to Jiangyin Hospital of Traditional Chinese Medicine from May 2021 to May 2023 were enrolled.And 60 healthy pregnant women with singleton pregnancy who underwent physical examinations during the same period were enrolled as control.All participants underwent arterial ultrasound examination,and CPR was measured.The uterine artery Doppler parameters and CPR were compared between the FGR group and control group,and their correlation with the disease was analyzed.The predictive efficacy of combined detection was assessed through receiver operator characteristic(ROC)curve.Results The systolic peak velocity/end diastolic velocity(S/D),resistance index(RI),and pulsatility index(PI)of the uterine artery and umbilical artery(UA)in the FGR group were higher than those in the control group,whereas the S/D,RI,and PI of the middle cerabral artery(MCA)and CPR in the FGR group were lower than those in the control group(P<0.05).Spearman correlation analysis showed that the S/D,RI,and PI of the uterine artery and UA were positively correlated with late-onset FGR,and the S/D,RI,and PI of the MCA and CPR were negatively correlated with late-onset FGR(P<0.05).ROC curve analysis indicated that the AUC for predicting late-onset FGR by combining uterine artery Doppler parameters with CPR was 0.925,with a sensitivity of 79.3%and a specificity of 88.3%.Conclusion The uterine artery Doppler parameters combined with CPR can effectively predict late-onset FGR,providing significant clinical value in early identification of high-risk pregnant women and guiding clinical interventions.

This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

This study aims to reveal the effect and mechanism of Gentianella turkestanorum total extract(GTI) in ameliorating non-alcoholic steatohepatitis(NASH). UPLC-Q-TOF-MS was employed to identify the chemical components in GTI. SwissTarget-Prediction, GeneCards, OMIM, and TTD were utilized to screen the targets of GTI components and NASH. The common targets shared by GTI components and NASH were filtered through the STRING database and Cytoscape 3.9.0 to identify core targets, followed by GO and KEGG enrichment analysis. AutoDock was used for molecular docking of key components with core targets. A mouse model of NASH was established with a methionine-choline-deficient high-fat diet. A 4-week drug intervention was conducted, during which mouse weight was monitored, and the liver-to-brain ratio was measured at the end. Hematoxylin-eosin staining, Sirius red staining, and oil red O staining were employed to observe the pathological changes in the liver tissue. The levels of various biomarkers, including aspartate aminotransferase(AST), alanine aminotransferase(ALT), hydroxyproline(HYP), total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione(GSH), in the serum and liver tissue were determined. RT-qPCR was conducted to measure the mRNA levels of interleukin 1β(IL-1β), interleukin 6(IL-6), tumor necrosis factor α(TNF-α), collagen type I α1 chain(COL1A1), and α-smooth muscle actin(α-SMA). Western blotting was conducted to determine the protein levels of IL-1β, IL-6, TNF-α, and potential drug targets identified through network pharmacology. UPLC-Q-TOF/MS identified 581 chemical components of GTI, and 534 targets of GTI and 1 157 targets of NASH were screened out. The topological analysis of the common targets shared by GTI and NASH identified core targets such as IL-1β, IL-6, protein kinase B(AKT), TNF, and peroxisome proliferator activated receptor gamma(PPARG). GO and KEGG analyses indicated that the ameliorating effect of GTI on NASH was related to inflammatory responses and the phosphoinositide 3-kinase(PI3K)/AKT pathway. The staining results demonstrated that GTI ameliorated hepatocyte vacuolation, swelling, ballooning, and lipid accumulation in NASH mice. Compared with the model group, high doses of GTI reduced the AST, ALT, HYP, TC, and TG levels(P<0.01) while increasing the HDL-C, SOD, and GSH levels(P<0.01). RT-qPCR results showed that GTI down-regulated the mRNA levels of IL-1β, IL-6, TNF-α, COL1A1, and α-SMA(P<0.01). Western blot results indicated that GTI down-regulated the protein levels of IL-1β, IL-6, TNF-α, phosphorylated PI3K(p-PI3K), phosphorylated AKT(p-AKT), phosphorylated inhibitor of nuclear factor kappa B alpha(p-IκBα), and nuclear factor kappa B(NF-κB)(P<0.01). In summary, GTI ameliorates inflammation, dyslipidemia, and oxidative stress associated with NASH by regulating the PI3K/AKT/NF-κB signaling pathway.
Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Mice ; Network Pharmacology ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Chromatography, High Pressure Liquid ; Liver/metabolism* ; Mice, Inbred C57BL ; Humans ; Mass Spectrometry ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation

Cardiovascular disease (CVD) remains one of the leading causes of mortality among adults globally, with continuously rising morbidity and mortality rates. Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression, involving multifaceted mechanisms such as altered substrate utilization, mitochondrial structural and functional dysfunction, and impaired ATP synthesis and transport. In recent years, the potential role of peroxisome proliferator-activated receptors (PPARs) in cardiovascular diseases has garnered significant attention, particularly peroxisome proliferator-activated receptor alpha (PPARα), which is recognized as a highly promising therapeutic target for CVD. PPARα regulates cardiovascular physiological and pathological processes through fatty acid metabolism. As a ligand-activated receptor within the nuclear hormone receptor family, PPARα is highly expressed in multiple organs, including skeletal muscle, liver, intestine, kidney, and heart, where it governs the metabolism of diverse substrates. Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions, PPARα exerts its cardioprotective effects through multiple pathways: modulating lipid metabolism, participating in cardiac energy metabolism, enhancing insulin sensitivity, suppressing inflammatory responses, improving vascular endothelial function, and inhibiting smooth muscle cell proliferation and migration. These mechanisms collectively reduce the risk of cardiovascular disease development. Thus, PPARα plays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation, anti-inflammatory actions, and anti-apoptotic effects. PPARα is activated by binding to natural or synthetic lipophilic ligands, including endogenous fatty acids and their derivatives (e.g., linoleic acid, oleic acid, and arachidonic acid) as well as synthetic peroxisome proliferators. Upon ligand binding, PPARα activates the nuclear receptor retinoid X receptor (RXR), forming a PPARα-RXR heterodimer. This heterodimer, in conjunction with coactivators, undergoes further activation and subsequently binds to peroxisome proliferator response elements (PPREs), thereby regulating the transcription of target genes critical for lipid and glucose homeostasis. Key genes include fatty acid translocase (FAT/CD36), diacylglycerol acyltransferase (DGAT), carnitine palmitoyltransferase I (CPT1), and glucose transporter (GLUT), which are primarily involved in fatty acid uptake, storage, oxidation, and glucose utilization processes. Advancing research on PPARα as a therapeutic target for cardiovascular diseases has underscored its growing clinical significance. Currently, PPARα activators/agonists, such as fibrates (e.g., fenofibrate and bezafibrate) and thiazolidinediones, have been extensively studied in clinical trials for CVD prevention. Traditional PPARα agonists, including fenofibrate and bezafibrate, are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα, and their cardioprotective effects have been validated in numerous clinical studies. Recent research highlights that fibrates improve insulin resistance, regulate lipid metabolism, correct energy metabolism imbalances, and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells, thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure. Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications, activating PPARα may serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy, atherosclerosis, ischemic cardiomyopathy, myocardial infarction, diabetic cardiomyopathy, and heart failure. This review comprehensively examines the regulatory roles of PPARα in cardiovascular diseases and evaluates its clinical application value, aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.

ObjectiveTo investigate and analyze an outbreak of rotavirus infectious diarrhea in a prison in Chongqing Municipality, to provide a basis for adult rotavirus surveillance and prevention, and to explore the public health problems in special settings. MethodsA retrospective survey was conducted to collect and analyze data on individual cases with diarrheal disease on-site. The clinical characteristics, as well as the temporal, spatial and geographical distribution patterns of the epidemic were described. Multi-pathogen detection tests were conducted both on diarrhea cases and environmental samples, with viral genotyping performed on positive samples. A case-control analysis was performed to identify the causes of the outbreak, and an SEIR model was adopted to predict the outbreak trend and evaluate the effectiveness of interventions. ResultsA total of 65 cases were found among the inmates, with an attack rate of 2.03%. The predominant clinical manifestations included diarrhea (89.23%), watery stool (73.85%), and dehydration (18.46%). The epidemic curve indicated a “human-to-human” transmission pattern, with an average incubation period of 5‒6 days. The attack rates among chefs in the main canteen (80.00%, 8/10) and caterers (28.33%, 17/60) were significantly higher than those of other inmates （P<0.05）. Multi-pathogen polymerase chain reaction (PCR) testing detected positive for group A rotavirus, with the viral genotyping identified as G9P [8] strain. Factors such as unprotected "bare-handed" food distribution among cases with diarrhea (OR=9.512, 95%CI: 4.261‒21.234) and close contact with diarrhea cases (OR=3.656, 95%CI: 1.719‒7.778) were the possible cause of the outbreak. The SEIR model (r₀=5, α=0.3, β₁=0.08, β₂=0.04) was constructed using prison inmates as susceptible population, aiming at fitting the initial transmission trend of the outbreak, and the epidemic rate declined rapidly after intervention measures were implemented (r_t≈0). ConclusionThis rare rotavirus infection diarrhea outbreak among adults in confined settings suggests that the construction of public health prevention and control systems in prison may be overlooked. Cross infection during meal processing and distribution in the canteens of such settings is likely to be the cause of the outbreak. Given the potential neglect of public heath system construction in special settings, it is imperative to enhance the surveillance and monitoring of rotavirus and other intestinal multi-pathogens among adults, as well as the construction of public health prevention and control systems in these special settings.

Objective To explore the effect of competitive respiratory training in patients undergoing abdominal contrast-enhanced magnetic resonance imaging(MRI).Methods A total of 115 patients who un-derwent abdominal contrast-enhanced MRI in the hospital from October 2021 to April 2022 were randomly as-signed to the control group(n=64)and the experimental group(n=51).The control group received routine one-on-one respiratory training,while the experimental group received a competitive respiratory training,wherein the first of the two individuals to achieve qualified breath-holding would undergo scanning first.The duration of respiratory training and scanning,as well as abdominal MRI image quality,were compared between the two groups.Image quality was assessed based on respiratory motion artifact scores,anatomical detail scores,and the percentage of sequences affected by respiratory motion artifacts.Results The average duration of respiratory training in the experimental group was significantly shorter than that in the control group[(39.90±14.26)s vs.(71.31±20.96)s,P=0.001].The difference in total scan time of the abdomen and up-per abdomen was not statistically significant(P＞0.05).The respiratory motion artifact score was higher in the experimental group compared to the control group(P＜0.05).The anatomical detail scores for both the FIESTA and LAVA sequences were higher in the experimental group than in the control group(P＜0.05),while no significant difference was found for the T1 sequence score(P＜0.05).The percentage of sequences affected by respiratory motion artifacts was significantly lower in the experimental group than in the control group(P=0.006).Conclusion Competitive respiratory training can shorten the duration of respiratory train-ing,improve breath-hold quality and persistence,reduce respiratory motion artifacts,and consequently enhance image quality in abdominal contrast-enhanced MRI.