Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Abstract: Objective To investigate the anti-human immunodeficiency virus-1 (HIV-1) activity of Euonymus fortunei extract and its mechanism, providing a theoretical basis for the research and development of traditional Chinese herbal resources in the treatment of acquired immunodeficiency syndrome (AIDS). Methods The peripheral blood mononuclear cells (PBMCs)-HIV-1bal cell model system was used as the experimental model, and the effect of Euonymus fortunei extract on the cell activity and anti-HIV-1 activity of PBMCs was investigated by CellTiter-Glo assay and HIV-1 p24 antigen assay. Additionally, the mechanism of anti-HIV-1 action of Euonymus fortunei extract was determined through the time-of-addition assay and HIV-1 enzymatic assays. Results In the PBMCs-HIV-1bal cell model, Euonymus fortunei extract showed no significant effect on cellular activity at the highest concentration, with a median cytotoxic concentration (CC50)>40 μg/mL. Within the non-cytotoxic concentration range, the level of HIV-1bal decreased with the increase of the extract concentration, with the IC50=0.084 μg/mL, and the SI>476.19. Time-of-addition assay revealed that Euonymus fortunei extract had the highest inhibitory activity on HIV-1IIIB when it was added to cells at the same time as the virus, and the inhibitory rate of HIV-1 activity decreased at 2 h and gradually lost its inhibitory effect on the virus at 18-24 h, similar to the known HIV entry inhibitor Enfuvirtid (T-20). Key HIV-1 enzyme activity experiments found that the extract had no significant inhibitory effect on reverse transcriptase activity but exhibited dose-dependent inhibition of integrase activity, with integrase activity decreasing with increasing extract concentration (IC50=0.18 μg/mL); The extract could inhibit the activity of HIV-1 protease in a certain concentration range (IC50=39.18 μg/mL). Conclusions In this study, it was found that Euonymus fortunei extract has a strong inhibitory activity against HIV-1 activity, which may exert anti-HIV-1 effects by acting on viral entry into cells and inhibiting integrase activity, and has a good application prospect in the research and development of multi-target new drugs against HIV-1.

Objective    To share the experience of treating special cardiac malformations by applying minimally invasive techniques. Methods    Eight children with special cardiac malformations admitted to our hospital from July 2014 to September 2020 were recruited, including 3 males and 5 females, aged 0.8-1.2 (1.1±0.4) years, and weighted 7.8-11.5 (9.6±2.9) kg. There were 2 patients of huge muscular ventricular septal defect (VSD), 3 perimembranous cribriform VSD, 1 right coronary-right atrial fistula, 1 right coronary-right ventricular fistula, and 1 young, low-weight child with large aortopulmonary. All were treated with minimally invasive techniques using transesophageal echocardiography (TEE) as a guiding tool. All children received intraoperative TEE immediately to evaluate the curative effect of the surgery, and all went to outpatient clinic for reexamination of echocardiography, electrocardiogram and chest X-ray after discharge. Results    Eight children underwent minimally invasive surgery successfully without any incision infection, intracardiac infection, arrhythmia or pericardial effusion. None of the 8 children were lost to follow-up, and the results of all reexaminations were satisfactory. Conclusion    The application of minimally invasive techniques is a bold and innovative attempt for the treatment of a few special types of cardiac malformations. It has significant advantages in reducing trauma and medical costs in some suitable patients, and has certain clinical reference values.

BACKGROUND: Understanding the association between floods and bacillary dysentery (BD) incidence is necessary for us to assess the health risk of extreme weather events. This study aims at exploring the association between floods and daily bacillary dysentery cases in main urban areas of Chongqing between 2005 and 2016 as well as evaluating the attributable risk from floods. METHODS: The association between floods and daily bacillary dysentery cases was evaluated by using distributed lag non-linear model, controlling for meteorological factors, long-term trend, seasonality, and day of week. The fraction and number of bacillary dysentery cases attributable to floods was calculated. Subgroup analyses were conducted to explore the association across age, gender, and occupation. RESULTS: After controlling the impact of temperature, precipitation, relative humidity, long-term trend, and seasonality, a significant lag effect of floods on bacillary dysentery cases was found at 0-day, 3-day, and 4-day lag, and the cumulative relative risk (CRR) over a 7-lag day period was 1.393 (95%CI 1.216-1.596). Male had higher risk than female. People under 5 years old and people aged 15-64 years old had significantly higher risk. Students, workers, and children had significantly higher risk. During the study period, based on 7-lag days, the attributable fraction of bacillary dysentery cases due to floods was 1.10% and the attributable number was 497 persons. CONCLUSIONS This study confirms that floods can increase the risk of bacillary dysentery incidence in main urban areas of Chongqing within an accurate time scale, the risk of bacillary dysentery caused by floods is still serious. The key population includes male, people under 5 years old, students, workers, and children. Considering the lag effect of floods on bacillary dysentery, the government and public health emergency departments should advance to the emergency health response in order to minimize the potential risk of floods on public.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China/epidemiology* ; Cities ; Dysentery, Bacillary/epidemiology* ; Female ; Floods ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective:To summarize the experience in diagnosis and treatment of primary cardiac tumors in pediatric patients.Methods:Retrospectively analyzing 7 pediatric patients who were suspected as primary cardiac tumors and diagnosed and treated in Department of Heart Center, Children′s Hospital of Dalian Medical University from August 2013 to February 2019.All patients underwent echocardiography and other examinations, so as to confirm the diagnosis and the treatment plan was chosen based on the size and location of the tumor.All patients were followed up after discharge.Results:A total of 7 patients were diagnosed as primary cardiac tumors by echocardiography, among which 5 cases underwent surgical treatment, and 2 cases were diagnosed with tuberous sclerosis without surgery.In children undergoing surgery, 1 patient underwent autologous heart transplantation to remove the tumor, 1 patient had arrhythmia, 1 patient had mitral regurgitation after surgery, and the mitral regurgitation was corrected again.The remaining children had no adverse complications and were discharged successfully.Histologic examination revealed rhabdomyoma in 4 patients, and fibroma in 1 patient.The patients were followed up for 2-66 months after discharge, and no tumor recurrence was observed in the children who performed surgery.There was a trend of spontaneously regress of cardiac tumor in 2 patients without surgery.Conclusions:Echocardiography is the first choice for the diagnosis of primary cardiac tumors in Pediatric patients.Rhabdomyoma is the most prevalent histologic type of primary cardiac tumors, and tuberous sclerosis should be excluded during the diagnosis process.Patients with tuberous sclerosis selected conservative treatment, and surgical treatment was selected for children with obvious symptoms.According to the location and size of lesion, therapy strategies should be chosen and autologous heart transplantation can be adopted to remove the tumor for children with large tumors.Autologous heart transplantation to remove the tumor is a good surgical treatment.

Clinical data of 23 children with atrial septal defect and pulmonary valvular stenosis admitted in Dalian Children′s Hospital during March 2015 to March 2018 were retrospectively analyzed. Twenty patients were treated with percutaneous closure of atrial septal defect through femoral vein first, then transthoracic echocardiography-guided balloon pulmonary valvuloplasty was performed; while 3 patients had no balloon pulmonary valvuloplasty after percutaneous closure of atrial septal defect. Patients were followed up by transthoracic echocardiography and all were doing well. The transvalvular pressure fell under 35 mmHg (1 mmHg=0.133 kPa) [(19.5±1.9)mmHg] in all patients, which was significantly lower than that before treatment [(62.0±7.8 mmHg)] (t=28.92, P<0.01). During follow-up, no residual shunt of atrial septal defect was found; and mild pulmonary regurgitation occurred in 3 cases. The study indicates that combined percutaneous treatment with transthoracic echocardiography guidance is effective and safe for children with atrial septal defect and pulmonary valvular stenosis. The pulmonary artery stenosis of some patients can be alleviated, after closuring of the atrial septal defect.

Objective To investigate the efficacy and safety of percutaneous patent ductus arteriosus (PDA) closure via femoral vein solely under transesophageal echocardiography guidance.Methods From May 2014 to May 2015,28 patients(13 boys,15 girls) were selected in Dalian Children's Hospital Affiliated to Dalian Medical University with PDA closure via the femoral vein under transesophageal echocardiography guidance,with mean age (3.5 ± 2.6)years and mean body weight (16.0 ± 6.5) kg.The mean diameter of PDA was (7.1 ± 3.9) mm.Patients were all treated by percutaneous PDA closure solely by transesophageal echocardiography via the femoral vein.The effect of the procedures was evaluated by echocardiography.The transthoracic echocardiography,chest X-ray film,cardiogram at 1 month,3 months and 6 months after procedure were followed up.Results Twenty-seven cases were successfully treated with percutaneous PDA closure via the femoral vein solely under transesophageal echocardiography guidance,while 1 patient was closed by surgical closure with on-pump beating-heart because PDA occluder strayed into the left pulmonary artery on 1-month follow-up.The procedural time was (48.5 ±8.7) min.The mean diameter of PDA occluder was (8.2 ± 4.1) mm.Twenty-seven patients survived without peripheral vascular injury or complications such as residual shunt,arrhythmia and cardiac perforation.One patient was transformed to surgical closure.Hospitalization time was (2.5 ± 0.5) days.At one month follow-up,no complications such as residual shunt or pericardial effusion occurred.Conclusion Transesophageal echocardiography guided percutaneous PDA closure via the femoral vein approach is safe and effective without the damage from radiation and contrast agents,and aviods the use of femoral artery puncture.

Objective To analyze the gonadal hormone and seminal plasma of patients with abnormal semen liquefaction and investigate the influence mechanism in order to provide guidance for the diagnosis and treatment. Methods 152 men of childbearing age were divided into two groups according to the liquefaction time (cut?off point: 60 minutes). Routine semen parameters,gonadal hormone and seminal plasma were tested and compared between the above groups. T?test was applied to compare individual gland function (pH value,neutralα?glycosidase,fructopyranose,seminal plasma zinc and citric acid) and gonadal hormone (FSH,LH,PRL,T and E2). Logistic regression analysis was adopted to probe the influencing factors for abnormal semen liquefaction. Results Seminal pH value (7.47 ± 0.13 vs. 7.32 ± 0.18),citric acid(51.12 ± 12.95 vs. 83.11 ± 33.46)and FSH (4.40 ± 1.03 vs. 4.85 ± 1.50)levels were significant different between the two groups (P < 0.05),but the other indexes showed no significant difference. Correlation regression analysis showed that semen liquefaction capacity has correlative relationship with seminal plasma fructose (OR=2.644),citric acid (OR=0.922),serum T (OR=1.029) and E2,while no correlative relationship with other indexes. Conclusions Correlation between two glands (seminal vesicle and prostate) and balance in the two hormones (T and E2) influence the liquefaction time. Specific causes should be distinguished before diagnosis.

Objective To compare the effect of kidney-tonifying blood-activating recipe (KBR) and Aescuven Forte Tablets ( AFT) in improving the sperm quality of varicocele-induced male sterility, thus to optimize the therapeutic therapy for varicocele-induced male sterility. Methods A total of 102 varicocele-induced male sterility with abnormal sperm parameters after conservative treatment were randomized into KBR group (N=53) and AFT group ( N=49) . KBR group was given KBR plus natural vitamin E and AFT group was given AFT plus natural vitamin E, and the treatment lasted for 8 continuous weeks. Before and after treatment, the quality of seminal fluid was analyzed, sperm quantization parameters such as total number of sperm (TNS) , total number of progressive motility sperm ( TNPS) , total number of normal form sperm ( TNNS) and total number of nor mal form and progressive motility sperm ( TNNPS) were observed, and the improvement rate of sperm quantization parameter was compared. Results (1) Before treatment, the differences of TNS, TNPS, TNNS and TNNPS were insignificant between the two groups ( P>0.05) . After treatment, TNNS was not improved in AFT group ( P>0.05) , but TNS, TNPS, TNNPS were much improved in both groups ( P<0.01 compared with those before treatment) . The improvement of KBR group was superior to that of AFT group ( P<0.05) . ( 2) The improvement rate for TNS, TNPS, TNNS, TNNPS was 90.57%, 79.25%, 67.92%, 77.36%in KBR group, and was 75.51%, 73.47%, 28.57%, 61.22% in AFT group respectively. The improvement rate for TNS and TNNS in KBR group was superior to that in AFT group ( P<0.05 or P<0.01) . Conclusion Varicocele-induced male sterility patients usually have the syndrome of kidney deficiency and blood stasis, so KBR, which has the function of tonifying kidney and activating blood, has synergistic action on the effect of AFT in improving sperm quality of varicocele-induced male sterility patients.