Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

ObjectivesTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. DesignMulticenter, open-label, randomized controlled trial. Setting16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. Participants150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. InterventionsHCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). Main outcome measuresThe primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention-to-treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. ResultsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70). The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. ConclusionsThe administration of HCQ did not result in a significantly higher negative conversion probability than SOC alone in patients mainly hospitalized with persistent mild to moderate COVID-19. Adverse events were higher in HCQ recipients than in HCQ non-recipients. Trial registrationChiCTR2000029868 What is already known on this topic-- The pandemic of coronavirus disease 2019 (COVID-19) imposes substantial burdens on individuals, communities, health-care facilities, markets, governments, etc. globally. -- There is no specific treatment approved for COVID-19 or vaccine to prevent infection with the novel coronavirus. -- During the urgent pandemic, media headlines the utility of drugs without solid evidence but buries the side-effects of these drugs. What this study adds-- In this randomized clinical trial of patients mainly with persistent mild to moderate COVID-19, exposure to hydroxychloroquine led to a similar probability of virus elimination comparing to the current standard-of-care. -- Adverse events, mostly gastrointestinal related, were significantly increased in patients who received hydroxychloroquine. -- Overall, the results from our trial do not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19. Print abstractO_ST_ABSStudy questionC_ST_ABSTo assess the efficacy and safety of hydroxychloroquine (HCQ) plus standard-of-care (SOC) compared with SOC alone in adult patients with COVID-19. MethodsThis is a multicenter, open-label, randomized controlled trial conducted in 16 government-designated COVID-19 treatment centers in China through 11 to 29 in February 2020. A total of 150 patients hospitalized with laboratory confirmed COVID-19 were included in the intention to treat analysis. Among them, 75 patients were assigned to HCQ plus SOC and 75 to SOC alone. HCQ was administrated with a loading dose of 1, 200 mg daily for three days followed by a maintained dose of 800 mg daily for the remaining days (total treatment duration: 2 or 3 weeks for mild/moderate or severe patients, respectively). The primary outcome was whether participants had a negative conversion of SARS-CoV-2 by 28 days, and was analyzed according to the intention to treat principle. Adverse events were analyzed in the safety population in which HCQ recipients were participants who actually received at least one dose of HCQ and HCQ non-recipients were those actually managed with SOC alone. Study answer and limitationsAmong 150 patients, 148 were with mild to moderate disease and 2 were with severe disease. The mean days ({+/-} standard deviation, min to max) from symptoms onset to randomization was 16.6 ({+/-}10.5 days, 3 to 41 days). The negative conversion probability by 28 days in SOC plus HCQ group was 85.4% (95% confidence interval (CI) 73.8% to 93.8%), similar to that in the SOC group 81.3% (95%CI 71.2% to 89.6%). Between-group difference was 4.1% (95%CI -10.3% to 18.5%). In the safety population, adverse events were recorded in 7 (8.8%) HCQ non-recipients (N=80) and in 21 (30%) HCQ recipients (N=70) with two serious adverse events. The most common adverse event in the HCQ recipients was diarrhea, reported in 7 (10%) patients. Two HCQ recipients reported serious adverse events. What this study addsOur trial does not support the use of hydroxychloroquine in patients with persistent mild to moderate COVID-19 due to limited effects on virus eliminating and significantly increased adverse events. Funding, competing interests, data sharingThis work was supported by the Emergent Projects of National Science and Technology (2020YFC0844500), National Natural Science Foundation of China (81970020, 81770025), National Key Research and Development Program of China (2016YFC0901104), Shanghai Municipal Key Clinical Specialty (shslczdzk02202, shslczdzk01103), National Innovative Research Team of High-level Local Universities in Shanghai, Shanghai Key Discipline for Respiratory Diseases (2017ZZ02014), National Major Scientific and Technological Special Project for Significant New Drugs Development (2017ZX09304007), Key Projects in the National Science and Technology Pillar Program during the Thirteenth Five-year Plan Period (2018ZX09206005-004, 2017ZX10202202-005-004, 2017ZX10203201-008). All authors declared no competing interests. Anonymized datasets can be made available on reasonable request after approval from the trial management committee. Study registrationChiCTR2000029868

Overexpression of CLPTM1L inhibits the sensitivity of 95-D lung cancer cells to gemcitabine / 实用肿瘤学杂志

Objective This study aimed to investigate the relationship between CLPTM1L gene and lung cancer 95-D cells sensitivity to gemcitabine,and to explore its potential mechanism of action. Methods Overexpression of lentivirus against CLPTM1L gene was constructed and infected with lung cancer 95-D cells;Cells were divided into the CLPTM1L overexpression group and con-trol group;The proliferation of cells in the overexpressing and control groups after gemcitabine treatment was detected by CCK-8;The changes of CLPTM1L gene and protein were detected by real-time PCR,Western blot and immunochemiluminescence;The changes of caspase-3/7 and caspase-9 activities were detected by bioluminescence;Western blot was used to detect the changes of p-4E-BP1 protein. Results The expression of CLPTM1L gene( P =0. 036) and its protein ( P <0. 01) was significantly increased after CLPTM1L overexpressed lentivirus-infected 95 -D cells;Compared with the control group,the proliferation of CLPTM1L overex-pressing group after gemcitabine treatment was increased(P <0. 01);The activity of caspase activity showed that the activities of caspase-3/7 and caspase-9 in the CLPTM1L overexpression group were significantly lower than those in the control group(P<0. 01);The phosphorylated level of 4E-BP1 protein in the CLPTM1L overexpression group was significantly higher than that in the control group. Conclusion Overexpression of CLPTM1L can reduce the sensitivity of lung cancer cells to gemcitabine. Its mechanism may be to increase the phosphorylation level of 4E-BP1.

Therapeutic and It's Mechanism of Qixiantang Decoction in Asthma Model Mice / 医药导报

Objective To observe the effect of qixiantang decoction on asthma model mice and to explore its mechanism of phosphatase gene ( PTEN)-up-regulation. Methods A total of 28 healthy female BALB/c mice were divided into 4 groups according to the random number table ( n=7 ): normal control group, model control group, qixiantang decoction group, and dexamethasone group. The mice were sensitized with ovalbumin ( OVA) for asthma model. Qixiantang decoction group was treated with drug after OVA sensitization. Hematoxylin-eosin ( H-E) staining was applied to observe the pulmonary inflammation in mice, and periodic acid Schiff ( PAS) staining was used to examine airway mucus secretion. ELISA was used to detect the concentration of serum IgE. Real-time quantitative PCR was used to examine IL-13 and IL-5 gene expression changes in lung tissues of mice. Western blotting was used to detect the expression of PTEN and SIRT1 protein in lung tissues. Results The lung tissue inflammatory infiltration and mucus secretion in model control group were higher than normal control group (P<0. 01), and that in the qixiantang decoction group. The level of serum IgE in model control group [(6. 67 ± 2. 59) pg·mL-1)] was significantly higher than normal control group [(0.27 ± 0.05) pg·mL-1, P <0.01] ,and that in the qixiantang decoction group [(3.52 ±1.44) pg·mL-1,P<0.05]. The expression of PTEN and SIRT1 in lung tissue of model control group were significantly lower than normal control group, and that of qixiantang decoction group. The expression of IL-5 and IL-13 mRNA of qixiantang decoction group was significantly lower (P<0. 05). Conclusion Qixiantang decoction could significantly ameliorate inflammation in asthmatic mice by regulate IgE、IL-5、IL-13 expression, and might up-regulate PTEN expression via SIRT1 signal.

Application experience of transumbilical abdominal wall within the three-channel single-incision laparoscopic combined cholecystectomy and appendectomy / 中国医师进修杂志

Objective To explore the clinical valuation and feasibility of transumbilical abdominal wall within the three-channel single-incision laparoscopic combined cholecystectomy and appendectomy.Methods The clinical data of 40 patients who underwent transumbilical abdominal wall within the three-channel single-incision laparoscopic combined cholecystectomy and appendectomy from January 2011 to March 2013 were retrospectively analyzed.Results Forty patients were successfully completed surgery,no transfer laparotomy and death cases,surgery time was 60-80 min,average 70 min,without postoperative incision infection,wound bleeding,bile duct injury,appendix stump fistula and abdominal residual abscess,neither postoperatively used analgesics,1 month after without incision scar,cosmetic effect was remarkable.Half a year's follow-up,the excellent operation evaluation.Conclusions The performer should have accomplish laparoscopic operation skills,and master the indications and the principle.The method of transumbilical abdominal wall within the three-channel single-incision laparoscopic combined cholecystectomy and appedectomy is safe,feasible and valid.The postoperative wound is more minimally invasive and aesthetic effect is obvious.

The clinical investigation of therapy of peptic ulcers combined with ulcer locally excision antrectomy and anti-helicobacter pylori drugs / 临床外科杂志

Objective To investigate the effect of therapy on the patients of gastric ulcer by antrectomy ulcer locally excision with anti-helicobacter pylori drugs.Methods According to the principal of vertical incision and parallel suture,the ulcer was locally existed by parallel axis.The area beyond the margin of ulcer one centimeter must be resected,26 cases have been performed the antrectomy retaining pylorus and gastroduoden-cstomy.After operating all of the patients had taken anti-helicobacter pylori drugs for 21 days.Results We follow up this group of patients for 5 years.Symptom that occurred preoparation disappeared in 24 cases and patients' weight increased.2 patients performed preservative therapy of posthepatitis cirrhosis.After 5 years all of them had been taken gastr ofiberscope reexamination and the result of no recurrence of ulcer and HP negative.Conclusions This method is a simple and safe procedure with quite small injury.It prevents recurrence and is fit for the physiology of human body with few postoperative complication and retain pylorus.

The differential expression of tumor associated antigen CA-X in vitro and in vivo / 第二军医大学学报

Objective: To explore the differential expression of tumor associated antigen CA X in tumor cells in vitro and in vivo . Methods: Tumor xenografts of the human lung adenocarcinoma cell line SpcA1 were grown in athymia mice. The antigen was measured before and after xenograft by Western blotting and flow cytometric analysis. Results: The antigen CA X was a glycoprotein with a molecular weight of 170 000 to 200 000 . Human lung adenocarcinoma cell lines regain expression of antigen CA X when xenografted into athymia mice. Conclusion: These data indicate that CA X synthesis in human lung adenocarcinoma cells SpcA1 is regulated by factors presented only in the xenograft.

The prevention and treatment of postoperative complications after portaazygous disconnection in patients with portal hypertension / 中国普通外科杂志

Objective To review our experiences in portaazygous disconnection for the treatment of portal hypertension and to analyze the causes of postoperative complications. Methods We reviewed the results of 236 patients with portal hypertension who were treated with disconnection from April 1994 to July 2002. Results Postoperative complications occurred in 65 of all the patients(the incidence rate was 27.5%). Twenty-four patients experienced postoperative infection(10.2%),12 patients suffered from intraabdominal massive bleeding(5.1%),12 from massive ascites (5.1%),8 patients suffered from recurrent upper gastrointestinal bleeding (3.4%),7 patients experienced acute thrombosis of portal venous system(3.0%). Two patients suffered from multiple organ dysfunction syndrome (1.0%). The operative mortality was 3.4%(8/236). The main causes of death included intraabdominal massive bleeding and severe infection with MODS. Conclusions The occurrence of postoperative complications was related with the selection of patients,thorough portaazygous disconnection and perioperative management.