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.

Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

Objective To investigate the relationship between serum nesfatin-1(NSF-1)and soluble tumor necrosis factor receptor-Ⅰ(sTNFR-Ⅰ)with premature rupture of membrane(PROM)in patients with severe preeclampsia(SPE),and their effects on pregnancy outcomes.Methods A total of 84 patients diagnosed with SPE in the Obstetrics Department of The First Affiliated Hospital of Nanyang Medical College from April 2023 to April 2024 were selected and grouped into the PROM and non-PROM groups based on whether they had PROM.The pregnant women were separated into good and poor pregnancy groups based on their pregnancy outcomes.Logistic regres-sion analysis was performed to assess the factors influencing PROM in patients with SPE and adverse pregnancy outcomes in patients with PROM.Receiver operating characteristic(ROC)curves were plotted to analyze the value of serum NSF-1 and sTNFR-Ⅰ in the evaluation and prediction of PROM in patients with SPE,as well as adverse pregnancy outcomes in patients with PROM.Results Serum levels of NSF-1 and sTNFR-Ⅰ were significantly higher in the study group than in the control group(P＜0.05).In addition,serum levels of NSF-1 and sTNFR-Ⅰ were significantly higher in the PROM group than in the non-PROM group(P＜0.05).Logistic regression analysis showed that NSF-1 and sTNFR-Ⅰ were risk factors for PROM in patients with SPE(P＜0.05).Based on the ROC curve,the area under the ROC curve(AUC)of serum NSF-1 and sTNFR-Ⅰ levels combined to assess PROM in patients with SPE was 0.887,and the combination of the two was superior to their respective individual predictions(Z=2.601,Z=2.585,both P＜0.05).Serum levels of NSF-1 and sTNFR-Ⅰ in the poor pregnancy group were significantly higher than those in the good pregnancy group(P＜0.05).Logistic regression analysis showed that NSF-1 and sTNFR-Ⅰ levels were risk factors for adverse pregnancy outcomes in patients with PROM(P＜0.05).Based on the ROC curve,the AUC of the combination of serum NSF-1 and sTNFR-Ⅰ for predicting adverse pregnancy outcomes in patients with PROM was 0.908,and the combination of the two was better than their respective individual predictions(Z=2.534,Z=2.556,both P＜0.05).Conclusion Serum levels of NSF-1 and sTNFR-Ⅰ were significantly increased in patients with SPE,and both were related to PROM.Elevated levels of both proteins can increase the risk of adverse pregnancy outcomes.

Objective To investigate the effect of electrotherapy on liver and intestinal mucosal injury in hyperlipidemia rats.Methods Wistar rats were divided into control group,model group and electroacupuncture group,with 6 rats in each group.Both the model group and the electroacupuncture group were fed with high-fat diet,and the electroacupuncture group re-ceived electroacupuncture intervention.After treatment,HE staining was used to detect the pathological changes of liver and ile-al mucosa.The contents of TC,TG,LDL-C and HDL-C in serum of rats were detected by biochemical method.AB-PAS staining was used to detect ileum mucosa in rats.The protein expressions of FXR,FGF19,ZO-1,occludin and JAM-C in rat ileum were detected by Western blotting.Results Compared with the control group,the body weight was significantly increased in the model group(P＜0.05),and the liver and ileum tissues were seriously damaged.The levels of TC,TG and LDL-C in serum and the expression of JAM-C protein in ileum were increased(P＜0.01).HDL-C level in serum,FXR,FGF19,ZO-1 and occludin in ileum tissue were decreased(P＜0.01).Compared with model group,the weight gain of rats in electroacupuncture group was significantly reduced(P＜0.01),and the pathological injury of liver and ileum tissue was alleviated.The levels of TC,TG and LDL-C in serum and the expression of JAM-C protein in ileum were decreased(P＜0.01).HDL-C level in serum as well as FXR,FGF19,ZO-1 and occludin levels in ileum tissue were increased(P＜0.01).Conclusion Electroacupuncture stimulation can improve the damage of intestinal barrier by activating FXR/FGF19 pathway in rats,play a protective role in liver,and inhibit dyslipidemia.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To assess performance advantages of voxel-less optimization(VoLO)algorithm of CyberKnife-based S7 treatment plan system for the optimization of stereotactic body radiation therapy(SBRT)for liver cancer.Methods:The case data of 20 patients with hepatocellular carcinoma from Chinese PLA General Hospital during June 2022 and April 2023 were retrospectively selected,which included 10 patients with large hepatocellular carcinoma and 10 patients with small hepatocellular carcinoma.All patients adopted respectively sequential optimization(SO)and VoLO to conduct optimization for plan.The optimized quality of plan and execution efficiency of two kinds of algorithms were assessed,and the influences of different tumor volumes also were considered.The planed quality assessment included dosimetric parameters of the target region and organ at risk(OAR).The assessment parameters of execution efficiency included the numbers of monitor units(MUs),nodes and beams,and estimated treatment time.Paired t-test method was adopted to analyze quality of plan and treatment efficiency.Results:On the aspect of the dose of target region,for small hepatocellular carcinoma,the conformity index(CI)value(1.08±0.05)of target region of VoLO algorithm was significantly better than(1.17±0.06)of SO algorithm(t=4.631,P<0.05).The gradient index(GI),coverage rate and dose by 95%(D95%)of VoLO algorithm were better than those of SO algorithm,while the differences were not significant(P>0.05).According to the defined standards of liver surgery,for large hepatocellular carcinoma,the differences in CI,GI,coverage rate and D95%of target region between two kinds of algorithms were significant(t=3.337,4.238,-3.359,-3.311,P<0.05),respectively.On the aspect of dosimetry for OAR,for the target region of large hepatocellular carcinoma,the differences of liver Dmean and D700 cm3 between two kinds of algorithms were significant(t=4.114,3.415,P<0.05).However,for small hepatocellular carcinoma,there was no significant statistical difference in dosimetry parameters of OAR between two kinds of algorithms(P>0.05).The execution efficiency of the plan of VoLO group was obviously higher than that of SO group,and the differences of MU number,node number,beam number and estimated treatment time between two groups were significant(t=12.661,4.423,5.024,9.487,P<0.05).Conclusion:The quality of VoLO plan is significantly better than that of SO,which has a significant improvement in execution efficiency of treatment.For the cases of large hepatocellular carcinoma with more complexity,the VoLO optimization shows better advantages on the aspect of dose on target region,and protection for normal liver.

Aim To establish and evaluate an alternative meth-od for detecting skin sensitization of cosmetics based on local lymph node assay using bromodeoxyuridine(BrdU)with flow cytometry(FCM).Methods(1)25％hexyl cinnamic alde-hyde(HCA)was chosen as a positive control with an acetone:olive oil(4∶1,V/V,AOO)mixture as a vehicle control for the experiment.The dorsal sides of both ears of mice were treated with test solutions on day 1,day 2,and day 3.Brdu solution was injected inter-peritoneally on day 5.On day 6,the bilateral ears and mandibular lymph nodes were excised,and the number of Brdu positive cells was measured by flow cytometry.The stim-ulation index(SI)was calculated to identify whether it was ≥3,in order to establish the method of LLNA:Brdu-FCM.(2)BrdU-FCM test was conducted using a blind method with the fif-teen reference substances listed in OECD TG429 whose skin sensitization potentials were known.The test substances were dissolved in AOO,N,N-dimethylformamide(DMF)or dimeth-yl sulfoxide(DMSO)at three different concentrations.Tests were performed the same as above.SI and EC2.7 were calculat-ed to evaluate whether the test substance was categorized as a skin sensitizer.The reliability and accuracy of the method were validated by comparing the classification of test substances with that in OECD TG429.Results The SI for 25％HCA was 3.9,showing positive in the skin sensitization test.It demonstrated that the LLNA:Brdu-FCM test method was properly implemen-ted.Nine test substances(2,4-dinitrochlorobenzene,4-pheny-lenediamine,cobalt chloride,2-mercaptobenzothiazole,hexyl-cinnamaldehyde,eugenol,phenyl benzoate,cinnamic alcohol,imidazolidinyl urea)were positive,and six test substances(methyl methacrylate,chlorobenzene,isopropanol,lactic acid,methyl salicylate,salicylic acid)were negative.The method was evaluated with sensitivity of 90％,specificity of 100％,positive prediction rate of 100％,negative prediction rate of 83％,false positive rate of 0％,false negative rate of 17％and accuracy of 93％.The LLNA:BrdU-FCM assay could correctly categorize the test substances that were skin sensitizers or non-sensitizers.Conclusion The LLNA:BrdU-FCM assay appears to be a relia-ble predictor of skin sensitization protential of chemicals,and it is expected to an alternative method for identifying skin sensitization as a supplementary in safety evaluation of cosmetic ingredient.

Objective To explore the injury types,associated injuries,and correlations of the lateral meniscus posterior root(LMPR),and to improve the comprehensive understanding of LMPR and its associated injuries.Methods The patients with LMPR who underwent knee MRI examination were retrospectively selected.A total of 223 patients with LMPR injury were classified into 4 types.The integ-rity of the meniscofemoral ligament and the grading of the cartilage injuries in the lateral tibiofemoral compartment were recorded.The relationship between the types of LMPR injury and the lateral meniscus tear locations,as well as lateral meniscus extrusion were analyzed.The relationship between the integrity of the meniscofemoral ligament and lateral meniscus extrusion was analyzed.The correlation between the time to clinical presentation after injury and the grading of the cartilage injuries was analyzed in patients with anterior cruciate ligament(ACL)ruptures.Results The incidence of LMPR injury was 1.02％,with males affected 2.19 times more frequently than females.Among patients with ACL ruptures,the incidence was 13.17％.Both type Ⅰ and type Ⅱ LMPR inju-ries predominantly involved only the posterior root,while type Ⅲ injuries mainly affected the posterior root extending to the posterior horn and body.The incidence of the lateral meniscus extrusion was higher in type Ⅲ LMPR injury than in type Ⅱ.When the menis-cofemoral ligament was not intact,the incidence of the lateral meniscus extrusion increased.In patients with ACL ruptures,a longer time to clinical presentation after injury was associated with more severe cartilage injuries grading in the lateral tibiofemoral compart-ment.Conclusion Males are more susceptible to LMPR injuries than females.The classification of LMPR injuries is correlated with the location of the lateral meniscus tears and the incidence of the lateral meniscus extrusion.The integrity of the meniscofemoral lig-ament is related to the incidence of the lateral meniscus extrusion.The time to clinical presentation after injury is related to the sever-ity of cartilage injury in ACL rupture patients.