OBJECTIVE To prepare reactive oxygen species （ROS）-responsive methotrexate （MTX）-modified paclitaxel （PTX）/icariin （ICA） micelles （MTX-oxi-Ms@PTX/ICA）， and perform technology optimization and in vitro anti-tumor effect evaluation. METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test. The micelles were prepared by thin film hydration method， and their technology was optimized by response surface methodology. The fundamental characteristics of the micelles prepared by the optimal technology were evaluated. The micelles’ cytotoxicity， targeting ability to renal carcinoma RENCA cells of mice， and their inhibitory effects on invasion and migration were assessed. RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L. The optimal technology of MTX-oxi-Ms@PTX/ ICA was determined to include 80 mg Soluplus®， Soluplus® and TPGS1000 mass ratio of 4∶1 （mg/mg）， 2 mg DSPE-PEG2000-TK- PEG5000， 2 mg DSPE-PEG2000-MTX， 1 mg PTX， and 1.5 mg ICA， with a hydration temperature of 35 ℃ and a formulation volume of 5 mL. Under the optimal conditions， average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi- Ms@PTX/ICA reached 92.75%， the critical micelle concentration （CMC） was 0.007 9 mg/mL， the particle size was （62.09±1.68） nm， the polydispersity index （PDI） was 0.046±0.032， and the Zeta potential was （－2.47±0.15） mV. Within 30 days of placement， there was no significant change E-mail：yingqiang_1126@163.com in particle size and polydispersity index of micelle. In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments. The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was （5.170±0.036） μmol/L. In vitro cellular uptake experiments indicated that compared with unmodified micelles， MTX modified micelles had stronger targeting effects on cancer cells， and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells （P＜0.05）. CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared， which exhibit high encapsulation efficiency， low critical micelle concentration， and good stability. These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.

Objective To explore the effect mechanism of lipophagy in diabetic nephropathy model rats based on intervention of Dangui Hongqi ultrafiltration in diabetic nephropathy model rats.Methods Fifty male Wistar rats of SPF grade were randomly selected 7 rats as the blank group,and the other 43 rats were given a one-time high-dose intraperitoneal injection of streptozotocin combined with high-fat and high-sugar diet to prepare diabetes nephropathy model.The modeling rats were randomly divided into model group,irbesartan group(17.9 mg/kg),and TCM low-,medium-,and high-dosage groups(1.5,3,6 g/kg).The rats were continuously gavaged by corresponding drugs for 12 weeks.Randomized blood glucose,body mass,and 24 h urine protein content were detected;biochemical tests were used for GSP,SCr,BUN,TG,TC,HDL-C,LDL-C,FFA content;HE staining was used to observe morphology changes in renal tissue,Masson staining was used to observe fibrosis changes in renal tissue,renal tissue microstructure changes were observed under transmisson electron microscopy,RT-qPCR was used to detect the mRNA expressions of mTOR and LC3B in renal tissue,and Western blot was used to detect the protein expressions of mTOR,TFEB,p-TFEB,and LC3B in renal tissue.Results Compared with the blank group,the model group rats showed a significant increase in randomized blood glucose(P<0.01),a significant decrease in body mass(P<0.01),a significant increase in 24 h urine protein content(P<0.01),a significant increase in GSP,SCr,BUN,TG,TC,LDL-C,FFA content(P<0.01),and a significant decrease in HDL-C content(P<0.01);renal tubular epithelial cells underwent vacuolar degeneration,cytoplasmic vacuolization,and extensive infiltration of inflammatory cells,collagen fibers increased and were distributed randomly,the number of lipid droplets increased,and autophagosomes decreased;the mTOR mRNA expressions in renal tissue significantly increased(P<0.01),the LC3B mRNA expressions significantly decreased(P<0.01),the mTOR and p-TFEB protein expressions significantly increased(P<0.01),the expression of TFEB,LC3BⅡ protein significantly decreased(P<0.01).Compared with the model group,the randomized blood glucose and 24 h urine protein content of rats in each treatment group were significantly reduced,the body mass significantly increased,and the contents of GSP,SCr,BUN,TG,TC,LDL-C,FFA decreased at 12 week of treatment,while the content of HDL-C increased;the inflammatory cell infiltration,fibrosis,and lipid droplet deposition in renal tissue alleviated to varying degrees;the expressions of mTOR mRNA decreased,the expressions of LC3B mRNA increased,the expressions of mTOR and p-TFEB protein decreased,while the expression of TFEB and LC3BⅡ protein increased.There was a statistically significant difference in the irbesartan group and TCM high-dosage group(P<0.01,P<0.05).Conclusion Dangui Hongqi ultrafiltration can improve the disorder of glucose and lipid metabolism,antagonize heterotopic lipid deposition in the kidney,promote lipid phagocytosis,and delay the process of diabetic nephropathy in model rats.The mechanism may be related to mTOR/TFEB signaling pathway.

Objective To evaluate the molluscicidal effects and costs of spraying 20% suspension concentrate of pyricloben-zuron sulphate (SCPS) with drones against Pomacea canaliculata in paddy environments, so as to provide insights into the extensive applications of pyriclobenzuron against P. canaliculata. Methods On July 2022, a paddy field was selected from Nanchang City, Jiangxi Province as the study area, and 72 independent rectangular plots measuring 2 m × 1 m were allocated in the study area, with 1 m interval between each plot, and 20 P. canaliculata snails gently placed in each plot. The activity of 25% wettable powder of pyriclobenzuron sulphate (WPPS) by manual spraying at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m² against P. canaliculata was tested in 54 plots, and manual spraying of 50% wettable powder of niclosamide ethanolamine salt (WPNES) at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with 9 plots in each group. The activity of SCPS against P. canaliculata was tested in the remaining 18 plots. Based on the molluscicidal tests of WPPS, the molluscicidal effect of SCPS by manual spraying at doses of 0.20, 0.30, 0.40 g/m² and 0.50 g/m² against P. canaliculata was evaluated, and manual spraying of WPNES at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with three plots in each group. On July 2023, 14 paddy fields with a mean living P. canaliculata density of > 5 snails/m² were selected from Yujiang District, Yingtan City, Jiangxi Province for molluscicidal tests. Based on the molluscicidal effect of pyriclobenzuron against P. canaliculata in plots, the molluscicidal effects of WPPS by manual spraying at doses of 0.25, 0.50 g/m² and 1.00 g/m² and manual applications of WPPS at dose of 0.25, 0.50, 1.00 g/m² and 2.00 g/m² mixed with soil were tested, and manual spraying of 0.10 g/m² WPNES served as a chemical control group, while manual spraying of the same volume of clean water served as a blank control, with one paddy field in each group. Based on the effect of pyriclobenzuron against P. canaliculata in plots, the activity of SCPS sprayed with drones at doses of 0.25 g/m² and 0.50 g/m² mixed in water at 2 kg/667 m² and 4 kg/667 m² was tested against P. canaliculata, and spraying of the same volume of clean water with drones served as a blank control. All P. canaliculata snails were captured 3 days and 7 days following chemical treatment in plots and paddy fields and identified for survival, and the mortality and corrected mortality of P. canaliculata snails were estimated. In addition, the areas of chemical treatment, amount of molluscicide use and labor costs of chemical treatment were estimated in molluscicidal tests in paddy fields, and the costs of chemical treatment for an area covering 667 m² by drones and manual applications were calculated. Results The mortality of P. canaliculata snails was all 100% in plots 3 days and 7 days following spraying WPPS at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m², and the mortality rates of P. canaliculata snails were 66.67% to 100.00% 3 days post-treatment with SCPS at various doses (χ² = 277.897, P < 0.05) and 76.67% to 100.00% 7 days post-treatment (χ² = 274.206, P < 0.05). The mortality rates of P. canaliculata snails were 98.19% to 100.00% 3 days post-treatment with WPPS at various doses in paddy fields. There was a significant difference in the mortality of P. canaliculata snails among WPPS treatment groups and controls (χ² = 270.778, P < 0.05), and there were no significant differences between WPPS treatment groups and the chemical control group (all P values > 0.05), while there were significant differences in the mortality of P. canaliculata snails between WPPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 89.83% to 95.31% 3 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 132.892, P < 0.05). There were no significant differences in the mortality of P. canaliculata snails among SCPS treatment groups or water mixture groups (all P values > 0.05), and there were significant differences in the mortality of P. canaliculata snails between SCPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 94.62% to 100.00% 7 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 266.932, P < 0.05), with the highest mortality found following spraying 0.50 g/m² SCPS mixed in 2 kg/667 m² water with drones (P < 0.05). The costs of P. canaliculata snail control by drones and manually were 35.85 Yuan/667 m² and 43.33 Yuan/667 m²; however, the snail control efficiency was 6.67 times higher by drones than by manual applications. Conclusions SCPS sprayed with drones is highly active against P. canaliculata snails in paddy fields. SCPS sprayed with drones is highly efficient and low in cost for P. canaliculata snail control in paddy fields, beaches and river courses.

Objective·To explore the predictive capability of retinal vascular features in preeclampsia(PE)based on artificial intelligence(AI)models.Methods·This retrospective study enrolled 789 pregnant women who registered from June 2020 to January 2021 at Shanghai First Maternity and Infant Hospital of Tongji University in the first 16 weeks of gestation.These women underwent regular prenatal examinations,had retinal fundus images captured,and delivered singleton live births at the hospital.According to whether they developed hypertensive disorders of pregnancy(HDP),they were divided into unaffected group(n=685)and HDP group(n=104).Within the HDP group,pregnancies were further categorized into gestational hypertension(GH)group(n=36)and PE group(n=68)based on the occurrence of PE.Based on the gestational age at onset,the PE group was further divided into early-onset PE group(gestational age<34 weeks)and late-onset PE group(gestational age≥34 weeks).Fundus images of the pregnant women were obtained,and an AI algorithm was utilized to diagnose retinal lesions and quantify retinal vascular features.Comparative analyses were conducted on fundus features and retinal vascular features.Univariate Logistic regression model was employed to analyze the influencing factors of PE occurrence,and multivariate Logistic regression model was further utilized to assess the correlation between retinal vascular features and the occurrence of PE.The predictive capability of retinal vascular features for PE(both early-and late-onset PE)was analyzed by using area under the curve(AUC)of receiver operator characteristic curve(ROC curve).Results·The comparative analysis of fundus features and retinal vascular features demonstrated statistically significant differences between the unaffected group and PE group in terms of central retinal artery equivalent(CRAE),central retinal vein equivalent(CRVE),arteriole-to-venular ratio(AVR),retinal artery tortuosity and retinal artery fractal dimension(all P<0.05).Univariate Logistic regression analysis indicated that second-trimester mean arterial pressure(MAP),second-trimester estimated fetal weight(EFW),CRAE,CRVE,AVR,retinal artery tortuosity and retinal artery fractal dimension were the influencing factors for PE occurrence(all P<0.05).Multivariate Logistic regression analysis revealed that second-trimester EFW,CRAE,CRVE,AVR,retinal artery tortuosity and retinal artery fractal dimension were the protective factors for the occurrence of PE,while second-trimester MAP was the risk factor for PE(all P<0.05).The analysis of ROC curves revealed that maternal risk factors along with second-trimester prenatal examination data(including MAP and EFW)and retinal vascular features model had good predictive ability for PE[AUC(95%CI)=0.784(0.725-0.843),and this model exhibited better predictive capability for early-onset PE,with an AUC(95%CI)of 0.840(0.756-0.924).Conclusion·The integration of quantified retinal vascular features based on AI models with maternal risk factors and second-trimester prenatal examination data(including MAP and EFW)enables a more effective prediction of PE occurrence,particularly early-onset PE.

Traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of Coronavirus disease 2019 (COVID-19) epidemic in China. The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment. According to a series of evidence-based studies, TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups. For patients with mild and moderate forms of COVID-19, TCM can relieve the related signs and symptoms, shorten the period of nucleic-acid negative conversion, and reduce conversion rate to the severe form of the disease. For COVID-19 patients with severe and critical illnesses, TCM can improve inflammatory indicators and blood oxygen saturation, shorten the hospital stay, and reduce the mortality rate. During recovery, TCM can improve patients' symptoms, promote organ function recovery, boost the quality of patients' life, and reduce the nucleic-acid repositive conversion rate. A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects, immune regulation, and protection of organ function via a multicomponent, multitarget, and multipathway approach.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; SARS-CoV-2 ; Epidemics

With the rapid development of clinical trials, the relevant medical research and molecular detection based on biological samples are closely related to the progress of clinical trials, making the role of biological samples in clinical trials increasingly obvious. The standardized supervision mode of biological samples is an important prerequisite for carrying out high-quality clinical trials. Although the laws and regulations related to clinical trials are becoming more and more perfect, there are still a large number of adverse events related to biological samples, which seriously affects the progress and results of clinical trials, and is one of the important challenges currently facing. Therefore, it is urgent to enhance the supervision of biological samples and improve the management methods of biological samples in clinical trials at this stage. Through in-depth discussion of the current status of biological sample management in clinical trials at home and abroad, this paper analyzed the issues existed during the supervision of biological samples, and supplemented the biological sample management methods by further combing the existing relevant laws and regulations and the Guidelines for the Ethical Management of Biological Samples in Clinical Trials, with a view to providing suggestions and ideas for optimizing the management mode of biological samples in clinical trials.

Objective:To compare the clinical outcomes of endovascular therapy in acute stroke patients with anterior circulation tandem occlusions caused by atherosclerosis or dissection.Methods:A retrospective cohort study. A total of 98 patients with anterior circulation tandem lesions undergoing endovascular therapy in the Wuhan NO.1 Hospital (March 2016 to March 2022) were analyzed. Median age was 64(55,71) years old, and 82.7% (81/98 cases) were males. According to the lesion etiology, the patients were divided into atherosclerosis and dissection groups. The differences in clinical outcomes between the two groups were investigated, including favorable 90-day functional outcome (modified Rankin Scale score of 0-2), successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction score of 2b-3), symptomatic intracranial hemorrhage, stroke-associated pneumonia, 90-day all-cause mortality, and average hospitalization days. Logistic regression analysis was used to adjust for potential confounders affecting functional outcomes in both groups, and to determine odds ratios and 95% confidence intervals.Results:Seventy-one patients were grouped into the atherosclerotic cause and 27 into the dissection cause cohorts. The rate of favorable 90-day functional outcome was 43.7% (31/71 cases) in the atherosclerosis group versus 55.6% (15/27 cases) in the dissection group (adjusted odds ratio=1.339; 95% confidence interval, 0.374-4.798; P=0.654). No significant differences were found in other clinical outcomes between the two groups (all P>0.05). Conclusion:The clinical prognosis of patients with tandem lesions caused by atherosclerotic stenosis or artery dissection was similar after endovascular therapy. Future studies are still needed to verify our results.

Objective:To investigate the influencing factors of the survival in infants with congenital diaphragmatic hernia (CDH) and to develop a prediction model for CDH.Methods:Clinical data of 252 infants with a prenatal diagnosis of CDH in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2018 were retrospectively analyzed. Adverse outcomes were defined as neonatal death on discharge. Chi-square and t test were used for univariate analysis of 16 perinatal and five postnatal risk factors. Regression analysis was used to determine the independent predictors of survival. The receiver operating characteristics (ROC) curves of the risk factors for predicting the survival of CDH were drawn. A prediction model based on the combination of risk factors for predicting adverse outcomes of CDH was established using the cut-off value. ROC curves of the model were drawn and the area under curve (AUC), sensitivity, and specificity were calculated. Results:Out of the 252 patients, 173(68.7%) survived on discharge. Univariate analysis showed that lung-to-head ratio (LHR), polyhydramnios, right diaphragmatic hernia, liver herniation, intrathoracic stomach, premature birth, low birth weight, 5 min Apgar score <7, and amniotic fluid index (AFI) were significantly associated with the survival of CDH. Regression analysis showed that polyhydramnios ( OR=11.19,95% CI:2.83-45.33), liver herniation ( OR=2.81,95% CI:1.32-11.92), intrathoracic stomach ( OR=5.02, 95% CI:1.29-17.13), low birth weight ( OR=8.58,95% CI:1.59-45.01) and AFI ( OR=3.68, 95% CI:1.37-14.72) were independent risk factors for survival at discharge in children with CDH, while LHR ( OR=0.36, 95% CI:0.01-0.69) were protective factors. The predictive cut-off values of LHR, polyhydramnios, liver herniation, intrathoracic stomach, low birth weight, and AFI were 1.6, 1.0, 1.0, 1.0, 1.0, and 232.5 mm, respectively. The model based on the combination of the above indicators for predicting CDH adverse outcomes was shown with an AUC value of 0.904, predictive sensitivity of 0.747, and specificity of 0.896. Conclusions:In this study, LHR, liver herniation, intrathoracic stomach, polyhydramnios, low birth weight, and AFI are independent risk factors for CDH survival. The combination of prenatal and postnatal indicators is noted for a higher accuracy for predicting CDH survival.

Objective: To investigate the predictors of death after endovascular mechanical thrombectomy (EMT) in patients with acute vertebrobasilar occlusive stroke (VBOS). Methods: Patients with acute VBOS treated with EMT in Wuhan No. 1 Hospital were enrolled retrospectively. The demographic and clinical data were collected. According to whether the patients died at 90 d after procedure, they were divided into survival group and death group. The demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent risk factors for death at 90 d after EMT. Results: A total of 47 patients were enrolled. The median age was 62 years, 34 were males (72.3%), the median baseline National Institutes of Health Stroke Scale (NIHSS) score was 16, 42 patients (89.4%) had recanalization (modified Thrombolysis in Cerebral Infarction[mTICI] 2b/3 grade), and 12 (25.5%) died within 90 d after procedure. Univariate analysis showed that the baseline NIHSS score (26 [21-28]vs. 12 [5-23]; Z=-3.165, P=0.002), percentage of neutrophil (81.61% ±11.82% vs. 72.20% ±12.09%; t=-2.137, P=0.033), neutrophil/lymphocyte ratio (10.54±7.17 vs. 4.98±3.57; t=-2.393, P=0.017), and incidence of sICH (25.0% vs. 2.9%; χ²=5.627, P=0.018) in the death group were significantly higher than those in the survival group, while the percentage of lymphocyte (12.00%±9.04% vs. 20.67%±10.39%; t=-2.429, P=0.015) was significantly lower than that of the survival group. Multivariate logistic regression analysis showed that high baseline NIHSS score (odds ratio [OR] 1.243, 95% confidence interval [CI] 1.046-1.318; P=0.038), high neutrophil/lymphocyte ratio (OR 1.278, 95% CI 1.002-1.630; P=0.049) and symptomatic intracranial hemorrhage (OR 5.088, 95% CI 1.065-38.718; P=0.046) were the independent predictors for death. Conclusion High baseline NIHSS score, high neutrophil/lymphocyte ratio and symptomatic intracranial hemorrhage are the independent predictors for death within 90 d after EMT in patients with acute VBOS.

Objective To investigate the effect of home diabetes care platform based on internet and family fixed partner on the continuous care of diabetes patients outside the hospital.Methods A total of 150 out-patients with diabetes were collected from June 2016 to November 2016,divided into family fixed partner group(group A),smart phone APP home diabetes care platform group(group B),family fixed partner combination with smart phone APP home diabetes care platform group(group C)with 50 cases each by random digits table method.The three groups received the same health education during their stay in hospital,patients in group A and group C were required to have family fixed partners,patients in group B and group C were required to receive the home diabetes care platform for smart phones APP after they left the hospital,the intervention time was six months,and the indexes of blood glucose metabolism,self-management ability of diabetes were assessed at the end of six months after intervention and before intervention.Results Fasting blood glucose and postprandial blood glucose and glycosylated hemoglobin values of the three groups after intervention were lower than those before intervention.The postprandial blood glucose and glycosylated hemoglobin values was(9.96±4.23)mmol/L,(7.16±1.47)%in group C,(13.78±3.34),(11.46±4.85)mmol/L and(8.46±2.21)%,(8.07±2.45)%in group A and B,the difference was significant(F=10.57,3.92,P＜0.05).The scores of self-management ability of diabetes of the three groups after intervention were all higher than those before intervention.The score of self-management ability of diabetes of item 1-6 was(6.45±1.65),(4.87±2.23),(6.17±2.12),(5.24±1.65),(4.67±2.13),(6.27±2.02)points in group C,(5.78±1.96),(3.63±2.14),(5.25±2.34),(4.12±1.97),(3.65±1.34),(5.26±2.21)points in group B,(5.04±1.78),(3.37±1.64),(4.63±1.87),(4.03±2.17),(3.32±1.74),(5.30±1.97)points in group A,the difference was statistically significant(F=3.82-7.94,P＜0.05).Conclusions Home diabetes care platform based on internet,combined with family fixed partner education,are more conductive to patient blood sugar control,and enhance self-management ability and account ability.