Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

Objective To analyze the treatment and follow-up of congenital coronary artery fistula (CAF) with giant coronary artery aneurysm (GCAA) in children.Methods The clinical data were analyzed retrospectively in 13 patients who were diagnosed as congenital CAF with GCAA between July 2009 and December 2016 in Guangzhou Women and Children's Medical Center.There were 8 boys and 5 girls.The median age was 18 months,ranging from 40 days to 12 years old.The body weight ranged from 3.8 kg to 29.0 kg with a median of 8.8 kg.Fistulas originated from right coronary artery accounted in 8 patients,with 5 from left coronary artery.Fistulas drained into right atrium in 3 patients,right ventricular in 8 patients and left ventricular in 2 patients.Single fistula occurred in 12 patients and multiple fistulas in 1 patient.The diameter of coronary artery aneurysm ranged from 8 mm to 16 mm with a median of 9.2 mm.Results One patient had tachypnea and growth retardation without heart murmur.The other 12 patients were asymptomatic with heart murmurs occasionally found in routine physical examination.One patient underwent fistula ligation without cardiopulmonary bypass (CPB).The remaining 12 cases received fistula correction with beating heart CPB.Direct suture was used in 10 patients and autologous pericardial patch in other 2 patients.Two patients were associated with atrial septal defect (ASD) and underwent repair of ASD concurrently.The coronary artery aneurysm remained original shape without any intervention during the operation.The mean hospital delay was (11.0 ± 2.5) days.Two patients had decreased ejection fraction as low as 38％ within 3 days after the operation,but went up to over 50％ in follow-up 1 month later.Transient T wave change occurred in 7 patients,and another 2 patients showed a residual shunt with size of 1 to 2 millimeters through the fistula without further intervention after the surgical closure.All 13 patients had antiplatelet therapy with 12 taking Aspirin and one taking Dipyridamole.The dosage was 3-5 mg/(kg · d) with duration ranging from 3 days to 13 months with a median of 1 month.During the perioperative period and the follow-up period (3 months to 8 years),all patients were asymptomatically alive.Transthoracic echocardiography showed normal cardiac function.Compared with preoperative status,the diameter of dilated coronary arteries was not changed after the operation.There was no formation of thrombus in the coronary arteries.Electrocardiography showed no ST-T changes or arrhythmia or myocardial ischemia.Conclusions GCAA can be combined with congenital CAF in children,so it needs early operation.The evidence-based intervention of coronary artery aneurysm and usage of anticoagulant and antiplatelet therapy in pediatric patients was still lacking,which needs long-term follow-up.

Objective Analyze the surgical and follow-up outcomes of congenital coronary artery fistula(CAF) in children and to discuss the treatment methods.Methods The clinical data were analyzed retrospectively in 22 patients who were diagnosed as congenital CAF and received surgical treatment between July 2008 and January 2017 in Guangzhou Women and Children's Medical Center.There were 14 boys and 8 girls.The median age was 17 months ranging from 14 days to 12 years old.The median weight was 8.8 kilograms ranging from 3.0 to 31.0 kilograms.Results Two patients had shortness of breath.Three had growth retardation with recurrent respiratory infection or tachypnea.The remaining 17 patients were asymptomatic.Twenty had heart murmurs.Fistulas originated from right coronary artery accounted for 11 patients,with 10 from left coronary artery,1 from both right and left coronary arteries.Fistulas drained into coronary sinus in 1 patient,right atrium in 6 patients,right ventricular in 13 patients and left ventricular in 2 patients.Single fistula occurred in 20 patients and multiple fistulas in 2 patients.The coronary arteries were obviously dilated in all patients with diameter from 4.0 to 12.0 millimeters.There were 8 cases with aneurysmal dilation of coronary arteries.Two patients underwent fistula ligation without cardiopulmonary bypass(CPB).The remaining 20 cases received fistula correction with beating heart CPB.Direct suture was used in 3 patients for closure of fistula inlet and 11 children for outlet.Both inlet and outlet were closed in 6 patients,and in 2 of them autologous pericardial patch was used for outlet.Other associated intra-cardiac anomalies in 7 children were corrected during the operation.The aneurysmal coronary arteries remained original shape without any intervention during the operation.The mean hospital delay was(12.3±3.2) days.Two patients appeared decreased heart function within 3 days after the operation,and recovered in return visit one month later.Another 2 patients showed a residual shunt with size of 1 to 2 millimeters through the fistula without further intervention after the surgical closure.During the perioperative period and the follow-up period(3 months to 8 years),all 22 patients were asymptomatically alive without regular anticoagulation management.Transthoracic echocardiography showed normal cardiac function.Compared with preoperative status,the diameter of dilated coronary arteries was reduced over 6 months follow up after the operation.There were no formation of thrombus in the coronary arteries.Electrocardiography showed no ST-T changes or arrhythmia or myocardial ischemia.Conclusion Clinical symptoms can be appeared in children with congenital CAF due to large shunt.Surgical correction is an effective method for the management of single CAF or CAF with coexisted intra-cardiac anomalies.The outcome was well.

Objective To determine the effect of apigenin on inducing apoptosis and inhibiting proliferation of non-small cell lung cancer cell line NCI-H1650. Methods NCI-H1650 cell line was cultured routinely in vitro, with blank control group and different concentrations of apigenin (10, 20, 40, 80 μmol?L-1). The blank control group was RPMI-1640 solution without apigenin. Cell proliferation was detected by MTT. Hoechst 33258 was applied to observe morphological changes of the apoptotic cells after treatment of different concentrations of apigenin. Flow cytometry AnnexinV-FITC/PI double staining method was used to determine cell apoptosis rate. The expression levels of apoptosis-related signaling molecules Bax and Bcl-2 protein were performed by Western blotting. Results MTT showed that apigenin inhibited proliferation of NCI-H1650 cell line in a concentration-and time-dependent manner (P<0.01).Hoechst 33258 nuclear staining showed typical characteristics of apoptosis in certain concentration-dependent manner, such as nuclear condensation and appearance of apoptotic bodies. In addition, the results of flow cytometry staining indicated that the apoptotic rate of NCI-H1650 cells cultured with blank control group and different concentrations of apigenin (10, 20, 40, 80 μmol?L-1) for 48 h was (5.00±0.33)%, (18.05±4.67)%, (21.48± 1.95)%, (43.24±1.11)%, (66.23±3.65)%, respectively (P<0.01).Western blotting results showed that the expression levels of Bax increased with increasing of the drug concentration, but Bcl-2 decreased with increasing of the drug concentration. Conclusion Apigenin can inhibit the proliferation and induce apoptosis of NCI-H1650 cells in non-small cell lung cancer. Mechanisms may be related to increase of the expression of apoptosis related protein Bax and decrease of the expression of anti apoptosis protein Bcl-2.

OBJECTIVETo study the effect of apigenin on the proliferation and apoptosis of human lung cancer cell line NCI-H460.

METHODSNCI-H460 cells were cultured with different concentrations of apigenin, and MTT assay was used to evaluate the cell inhibition rates. Apoptosis of NCI-H460 cells was observed under a fluorescence microscope with Hoechst 33258 staining and quantified by flow cytometry using annexin V-FITC/PI stain. The expressions of apoptosis-related proteins Bax, Bcl-2 and caspase-3 were analyzed by Western blotting.

RESULTSApigenin causes concentration- and time-dependent inhibition of the proliferation of the cells. NCI-H460 cells treated with apigenin showed significant morphological changes of apoptosis, and the cell apoptotic rates increased as apigenin concentration increased. Western blotting demonstrated that apigenin increased the protein levels of Bax and caspase-3 and reduced the protein expression of Bcl-2.

CONCLUSIONApigenin can inhibit the proliferation and induce apoptosis of NCI-H460 cells possibly by up-regulating expression of Bax and caspase-3 and down-regulating the expression of Bcl-2.

Apigenin ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Signal Transduction ; bcl-2-Associated X Protein ; metabolism

The curative efficacy of percutaneous transluminal angioplasty and stenting (PTAS) in the treatment of patients with ischemia cerebrovascular disease caused by artery stenosis was explored.The clinical data of 111 patients with ischemia cerebrovascular disease receiving PTAS in Guangdong Province General Hospital from Aug.2007 to Nov.2009 were retrospectively analyzed.In total 132 stents were implanted in the 111 patients.The mortality and rate of neural and non-neural complications were assessed perioperatively.Outcomes [including the frequency of transient ischemic attack (TIA),stroke,or death from vascular diseases) were assessed after operation.NIHSS rating was performed in all cases before and at first week,6th month and 12th month after the operation.The PTAS success rate was 100％.The degree of stenosis was reduced after PTAS.The total complication rate during perioperative period was 15.3％ (the rate of neural complications was 3.6％).Sixty-seven patients were followed up.Three patients (4.48％) developed cerebrovascular events within 1 month,containing one case of TIA,one case of ipsilateral mild stroke and one case of contralateral mild stroke.No severe stroke or death was observed.During a follow-up period of 12 months 7 patients had cerebrovascular events (10.44％),including 2 cases of ipsilateral TIA (2.99％),2 cases of ipsilateral mild stroke and 2 cases of contralateral mild stroke (2.99％),one case of severe stroke (1.49％).In 13 patients receiving DSA re-examination one year after PTAS,2 patients (15.38％) had in-stent restenosis.NIHSS scores were obviously decreased during a follow-up period as compared with those pre-operation (P＜0.05).It was concluded that PTAS could significantly alleviate the neural function deficit of the patients with ischemia cerebrovascular disease.The success rate of PTAS was high,and the rate of complications was lower and the clinical outcomes were satisfactory.PTAS is a safe and effective therapeutic method,though the long-term outcomes need further study.

Adipose tissue is a readily available source of adult stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications.Peptide hydrogel is a novel biomaterial which provides three-dimensional microenvironments for a variety of cells for tissue grafting.In this study,adipose-derived stem cells (ADSCs) were isolated from rats,seeded into the peptide hydrogel polymer scaffolds and cultured in Neurobasal (NB) media supplemented with B27,basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF).Ten days after the culture,some cells were expanded into clonal populations in which the expression of both Nestin and Brdu was detected but only Brdu expression was detected in the cells that were not expanded into clonal populations.Our results suggested that ADSCs in peptide hydrogel polymer scaffolds can be induced to differentiate into cells capable of expressing the neuron-associated markers,self-renewal and self-propagation.

Adipose tissue is a readily available source of adult stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications. Peptide hydrogel is a novel biomaterial which provides three-dimensional microenvironments for a variety of cells for tissue grafting. In this study, adipose-derived stem cells (ADSCs) were isolated from rats, seeded into the peptide hydrogel polymer scaffolds and cultured in Neurobasal (NB) media supplemented with B27, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Ten days after the culture, some cells were expanded into clonal populations in which the expression of both Nestin and Brdu was detected but only Brdu expression was detected in the cells that were not expanded into clonal populations. Our results suggested that ADSCs in peptide hydrogel polymer scaffolds can be induced to differentiate into cells capable of expressing the neuron-associated markers, self-renewal and self-propagation.

The curative efficacy of percutaneous transluminal angioplasty and stenting (PTAS) in the treatment of patients with ischemia cerebrovascular disease caused by artery stenosis was explored. The clinical data of 111 patients with ischemia cerebrovascular disease receiving PTAS in Guangdong Province General Hospital from Aug. 2007 to Nov. 2009 were retrospectively analyzed. In total 132 stents were implanted in the 111 patients. The mortality and rate of neural and non-neural complications were assessed perioperatively. Outcomes [including the frequency of transient ischemic attack (TIA), stroke, or death from vascular diseases) were assessed after operation. NIHSS rating was performed in all cases before and at first week, 6th month and 12th month after the operation. The PTAS success rate was 100%. The degree of stenosis was reduced after PTAS. The total complication rate during perioperative period was 15.3% (the rate of neural complications was 3.6%). Sixty-seven patients were followed up. Three patients (4.48%) developed cerebrovascular events within 1 month, containing one case of TIA, one case of ipsilateral mild stroke and one case of contralateral mild stroke. No severe stroke or death was observed. During a follow-up period of 12 months 7 patients had cerebrovascular events (10.44%), including 2 cases of ipsilateral TIA (2.99%), 2 cases of ipsilateral mild stroke and 2 cases of contralateral mild stroke (2.99%), one case of severe stroke (1.49%). In 13 patients receiving DSA re-examination one year after PTAS, 2 patients (15.38%) had in-stent restenosis. NIHSS scores were obviously decreased during a follow-up period as compared with those pre-operation (P<0.05). It was concluded that PTAS could significantly alleviate the neural function deficit of the patients with ischemia cerebrovascular disease. The success rate of PTAS was high, and the rate of complications was lower and the clinical outcomes were satisfactory. PTAS is a safe and effective therapeutic method, though the long-term outcomes need further study.

Objective To evaluate the effectiveness of constraint-induced movement therapy (CIMT),modified CIMT and forced use in the treatment of the upper limbs of adults after stroke. Methods Published ac-counts of trials of these techniques were located through electronic searches of the following databases: PubMed,EBSCO, Ovid, the Cochrane Central Register of Controlled Trails, EMbase, Science Citation Index (Expanded),HighWire Press, CBMDisc, CCTR, CNKI and VIP from the date of establishment of the databases to September 2009. The bibliographies of the articles thus retrieved were also checked. Results A total of 12 trials involving 648 patients were discovered. Meta-analysis showed that CIMT has been shown to increase movement efficiency, reduce normalized movement time, increase use of the more affected arm, improve the quality of use of the more affected arm and reduce the impact of the affected arm. C1MT showed no significant effect in improving independence in daily life compared with traditional rehabilitation. Conclusions To some extent, (modified) CIMT promotes arm rehabilita-tion after stroke effectively. However, these studies were small and their quality was poor. They had different follow-up points, assessed with different rating scales, and the course of stroke in the studies was also different. So more high-quality and large-scale randomized controlled trials are needed.