Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19

BackgroundEffective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. MethodIn this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. ResultsA total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. ConclusionsAlthough randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating 102 the COVID-19 pandemic.

Application and optimization of RT-PCR in diagnosis of SARS-CoV-2 infection

BackgroundCoronavirus Disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat to public health. Aiming to construct an efficient screening pattern, we comprehensively evaluated the performances of RT-PCR and chest CT in diagnosing COVID-19. MethodsThe records including demographics, RT-PCR, and CT from 87 confirmed COVID-19 cases and 481 exclusion cases were collected. The diagnostic accuracy of the pharyngeal swab RT-PCR, CT, combination with the second pharyngeal swab RT-PCR or with CT were evaluated individually. Besides, all the stool RT-PCR results were plotted by time to explore the value of stool RT-PCR. FindingsCombination of RT-PCR and CT has the higher sensitivity (91.9%,79/86) than RT-PCR alone (78.2%,68/87) or CT alone (66.7%, 54 of 81) or combination of two RT-PCR tests (86.2%,75/87). There was good agreement between RT-PCR and CT (kappa-value, 0.430). In 34 COVID-19 cases with inconsistent results, 94.1% (n=32) are mild infection, 62.5% of which (20/32) showed positive RT-PCR. 46.7% (35/75) COVID-19 patients had at least one positive stool during the course. Two cases had positive stool earlier than the pharyngeal swabs. Importantly, one patient had consecutive positive stool but negative pharyngeal swabs. InterpretationCombination of RT-PCR and CT with the highest sensitivity is an optimal pattern to screen COVID-19. RT-PCR is superior to CT in diagnosing mild infections. Stool RT-PCR should be considered as an item for improving discovery rate and hospital discharge. This study shed light for optimizing scheme of screening and monitoring of SARS-CoV-2 infection. FundingThis work was supported by the National Natural Science Foundation of China (No. 81502104), National Program on Key Basic Research Project (No. 2018YFC0910600),the Nature Science Foundation of Guangdong Province, China (Grant No: 2017A030313771 and 2020A151501001) and the Young Teachers Nurturing Program of Sun Yat-Sen University (Grant No:17ykpy62)

Characterization analysis of gM, gL genes of varicella zoster virus in six provinces of China / 中华预防医学杂志

Objective@#To analyze the genetic characterization of glycoprotein M(gM.),glycoprotein L(gL) of varicella zoster virus.@*Methods@#According to the program of "Ministry of Science and Technology of China" , Based on the 12 suspected VZV patients monitored in Beijing (1 case), Shanghai (5 cases), Jilin (2 cases), Qinghai (1 case), Guangdong (2 case) and Sichuan (case) in 2007-2015. A total of 12 Vesicle fluid and throat swab samples were collected. Positive samples were identified by Agarose gel electrophoresis and two glycoprotein genes were amplified by polymerase chain reaction (PCR). Nucleotide sequences were determined and analyzed by PCR amplification of VZV positive specimens V-OKA-BK of the domestic varicella attenuated live vaccine and the Varilrix-1 of the imported attenuated live vaccine. Nucleotide sequences of VZV positive specimens, vaccine strains (V-OKA-BK, varilrix-1) and GenBank foreign wild strains (41 strains), parent strains (P-oka), vaccine strains (V-oka, Varilrix, Varivax) were compared using BioEdit and MEGA 5.0.@*Results@#12 specimens were VZV positive. Compared with the vaccine strains and the parent strains, the GM gene of 1 positive specimen had radical mutation at 86686 sites, which resulted in amino acid mutation, 5 positive specimens had base mutation at 87844 sites, and 30 strains of foreign wild strains had the same variation at 87 844 sites. 1 positive specimens of gL gene in 101245 sites had base mutation, and led to amino acid mutation, 6 positive specimens at 101624, 101625, 101626 sites had base of loss and the foreign wild strains in these 3 sites had the same variation. Compared with the vaccine strains, the nucleotide and amino acid homology of gM of 12 VZV positive specimens were 99.2%-100% and 98.2%-100%, respectively, and gL of those were 99.3%-100% and 98.6%-100%, respectively. Compared with 41 strains of foreign wild strains, homology of gM's nucleotides and amino acid were 99.3%-100% and 98.5%-100%, respectively; 99.1%-100% and 98.6%-100% for gL. The results of phylogenetic analysis showed that 7 VZV positive samples were on the same branch with 4 vaccine strains and p-oka strain. Based on gL, 12 VZV positive samples were on the same branch as the vaccine strains and p-oka strain.@*Conclusion@#This study demonstrates that the genes of gM, gL are highly conserved and remain stable immunogen, which may be involved in the attenuation of VZV and need to be further researched.

Monitoring of 4 patients with heparin-induced thrombocytopenia after complex congenital heart surgery / 中南大学学报(医学版)

From July 2013 to February 2015, 4 infant patients with complex congenital heart disease, who underwent open heart surgery in Xiangya Hospital of Central South University, were diagnosed as heparin-induced thrombocytopenia (HIT). After comprehensive treatments, such as intensive monitoring of the platelet count, close observation of thromboembolic skin lesions and close monitoring of argatroban therapy, 3 patients were cured and 1 died. HIT is rare but serious in patients who received heparin therapy. The incidence of mortality and thrombosis is very high. Early identification and diagnosis of high-risk groups can improve the prognosis.

Impact of isolated diastolic hypertension on new-onset cardiovascular and cerebro-vascular diseases / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the impact of isolated diastolic hypertension (IDH) on new-onset cardio-cerebral vascular diseases (CVD).</p><p><b>METHODS</b>This cohort study involved 101 510 participants who were employees of the Kailuan Group-a state-run coal mining company, in 2006 and 2007. Among them, 6 780 subjects were diagnosed with IDH, 35 448 subjects were diagnosed with high-normal blood pressure and 19 460 subjects were diagnosed with normal tension. However, none of them had the history of either cardio-cerebral vascular disease or malignant cancer. Cardio-cerebral vascular events including cerebral infarction, cerebral hemorrhage, acute myocardial infarction were recorded every 6 months during the follow-up (47.1 ± 4.8) period. Multivariable Cox proportional hazards regression models were used to analyze the risk factors of first-ever CVD events.</p><p><b>RESULTS</b>1) There were 675 CVD events occurred during the follow-up period. The incidence rates of CVD events (1.7% vs. 0.9%), cerebral infarction (1.0% vs. 0.6%) and cerebral hemorrhage (0.4% vs. 0.1%) were significantly higher in IDH group than that in the normal tension group (all P < 0.05). 2) After adjustment for other established CVD risk factors, the hazards ratios became 1.67 (95% CI: 1.28-2.17) for total CVD events and 1.59 (95% CI: 1.12-2.27) for cerebral infarction and 2.67 (95% CI: 1.54-4.65) for cerebral hemorrhage in the IDH group. 3). In stratified analysis on age, after adjustment for other established CVD risk factors, the hazards ratio was 2.22 (95% CI: 1.41-3.50) for cerebral infarction in lower 60 years old group, while the it was 7.27 (95% CI: 2.58-20.42) for cerebral hemorrhage in groups older than 60 years of age.</p><p><b>CONCLUSION</b>IDH was the independent risk factor for the total cardio-cerebral vascular events, on both cerebral infarction and cerebral hemorrhage. The predicted values of IDH for different CVD events were diverse on different age groups.</p>

Effect of precursor on growth and accumulation of alkaloids of Lycoris radiata suspension cells / 生物工程学报

In order to investigate the effects of phenylalanine, tyrosine and tyramine on the growth of Lycoris radiata suspension cells and the accumulation of alkaloids, the growth quantity of the cells as well as the content of alkaloids in cells were determined, which were treated with above three kinds of precursors alone and phenylalanine combined with tyrosine respectively. The results indicate that the addition of phenylalanine alone and addition of phenylalanine on the basis of tyrosine at high concentration (200 micromol/L) had no significant effect on the growth of Lycoris radiata suspension cells and the content of alkaloids in cells; whereas tyrosine and tyramine promoted the growth of the cells and alkaloids accumulation. Treated with tyrosine at high concentration (200 micromol/L), the content of alkaloids of the cells was 2.56-fold higher than that of the control group, the amounts of lycoramine (3.77 mg/g) and galanthamine (4.46 mg/g) were 6.61-fold and 6.97-fold higher than that of the control group, respectively. When treated with tyramine (200 micromol/L), the amount of alkaloids in Lycoris radiata suspension cells was 2.63-fold higher than that of the control group, and the amounts of lycoramine (4.45 mg/g) and galanthamine (5.14 mg/g) were 9.08-fold and 9.18-fold higher than that of the control group, respectively. The above results demonstrate that adding tyrosine and tyramine in the media significantly promoted the growth of the Lycoris radiata suspension cells and alkaloids accumulation in the cells.

Prevalence of isolated diastolic hypertension and associated cardiovascular risk: four years follow up results / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the prevalence of isolated diastolic hypertension and associated cardiovascular risk and blood pressure changes during follow up.</p><p><b>METHODS</b>This cohort study screened 101 510 participants who were employees of the Kailuan Group, a state-run coal mining company in 2006 and 2007. Among them, 6 778 subjects were diagnosed with isolated diastolic hypertension (IDH). IDH subjects without history of cardiovascular disease and not treated with antihypertensive drugs were included in this analysis. Participants without health examination between 2008 to 2009 or 2010 to 2011 were excluded. A total of 4 600 participants were included in the final analysis. At the end of the third health examination, the conversion rate of different blood pressure turnover was calculated after standardizing age and gender according to demographic data of China in 2006. Multivariate logistic regression analysis was applied to analyze the risk factors of blood pressure turnover in IDH population.</p><p><b>RESULTS</b>(1) Participants were followed up for (4.03 ± 0.26) years and the rates of turnover from IDH to normotension, isolated systolic hypertension (ISH) and systolic diastolic hypertension (SDH) were 51.4%, 3.5%, 18.3%, respectively (45.6%, 3.6%, 22.0% in male, 57.4%, 3.3%, 14.7% in female). (2) Multivariate logistic regression analysis showed that low baseline age, low diastolic pressure, low body mass index, low uric acid, physical exercise and low alcohol intake were associated with turnover from IDH to normotension; the risk factors of turnover from IDH to ISH were older age at baseline, higher systolic pressure and higher sensitivity C-reactive protein; the risk factors of turnover from IDH to SDH were older baseline age, high systolic pressure and excessive salt intake.</p><p><b>CONCLUSIONS</b>Untreated subjects with IDH can transform from IDH to normotension,ISH, SDH, and the rate of turnover from IDH to normotension is higher than others during follow up. Aging, higher systolic pressure, higher sensitivity C-reactive protein and excessive salt intake are risk factors for IDH subjects to suffer from ISH and SDH.</p>

REV procedure for complex congenital heart diseases / 中南大学学报(医学版)

OBJECTIVE@#To introduce REV procedure in patients with transposition of the great arteries (TGA) with a ventricular septal defect (VSD) and pulmonary stenosis (PS).@*METHODS@#From May 2012 to June 2012, 4 patients with TGA were admitted for surgery. Two patients with VSD underwent SWITCH operation. REV procedure was used for the other two patients with PS. The Senning procedure was also used for the patient with atrioventricular discordance.@*RESULTS@#There was no in-hospital mortality. Shortest cardiopulmonary bypass time and aortic crossclamp time were found in simple REV procedure patient. Postoperative echocardiography demonstrated physiologic hemodynamics in the left ventricular outflow tract and normal heart function. All the patients were in excellent clinical condition during follow-up.@*CONCLUSION@#REV procedure is a good choice for transposition of great arteries associated with ventricular septal defect and obstruction of the pulmonary outflow tract.

Illness severity and prognosis assessment with acute physiology and chronic health evaluation II for patients after cardiovascular surgery / 中南大学学报(医学版)

OBJECTIVE@#To evaluate illness severity and to assess the prognosis with acute physiology and chronic health evaluation II (APACHE II) for patients after cardiovascular surgery.@*METHODS@#APACHE II scores of 234 patients in the cardiac surgical intensive care unit (CSICU) were calculated, and the actual mortality and the predicted mortality were obtained based on the score.@*RESULTS@#The APACHE II score of the 234 patients was 14.22±6.77. The difference in the APACHE II score between the survivors, the patients with complications and the death group was significant; the difference in the APACHE II score between patients with different preoperative cardiac functions was significant; the detention time in the CSICU was positively related to APACHE II scores; and the ROC area under the curve of APACHE II was 0.991±0.006. With the predicted rate >30% as the standard for death, sensitivity of APACHE II score for mortality risk prediction was 80.00%, specificity was 99.12%, and the accuracy was 98.72%. According to the score, we divided the patients into 3 groups (20 points), forecast mortality in the >20 point group was in the 95% confidence interval of actual mortality.@*CONCLUSION@#APACHE II is a good index for illness severity and prognosis assessment for patients after cardiovascular surgery.

Expression and clinical significance of TIG1 gene in acute leukemia / 白血病·淋巴瘤

Objective To investigate correlation between the expression of TIG1 and the prognostic significance in acute leukemia (AL).Methods The TIG1 expression level of 75 AL and 20 normal control (NC) were measured by Real-Time Quantitative PCR(RT-QT-PCR).Results TIG1 gene expressed at a higher level in NC(0.0609±0.0281 ) than that in de novo AL(0.0057±0.0035)(U=-6.321,P=0.000).The expression of TIG1 in complete remission patients(AL-CR)(0.0409±0.0244)were lower than that in NC too(U=-2.582,P=0.01).The expression of TIG1 in AL-CR patients (83.3 ％) were higher than that in de novo AL (53.1％)(U=-6.366,P=0.000).In AL patients,the CR rate of high TIG1 level cases were higher than that in low level cases (x2=4.563,P=0.033).Conclusions Reduced expression of TIG1 may play an important role in the pathogenesis of AL.TIG1 can serve as a marker of poor prognosis in AL.

Protective effects of adenosine against lung ischemia-reperfusion injury in rabbit / 中国医师杂志

Objective To study the protective effects and mechanisms of adenosine on lung ischemia-reperfusion injury in rabbit. Methods The rabbit ltng model of ischemia-reperfusion was constructed.Thirty Chinese rabbits were random divided into three groups: Group A (no surgery), group B (ischemiareperfusion) and group C (Adenosine + ischemia-reperfusion). The MDA content,SOD content of the plasma, wet-dryrate (W/D) and the pathology of lung tissue and the index of quantitative assessment of histologic lung injury (IQA) were measured after 60 min reperfusion. Results After 60min reperfusion, the value of W/D, MDA and IQA in group B were significantly higher than those in group A (q = 7. 06,13.71,18. 62, P ＜0.01), while the concentration of SOD were lower than those in group A (q = 14. 33, P ＜0.01). In contrast with group B, W/D,MDA and IQA in group C was obviously lower (q =5.23 ,8. 51, 9.99,however, the concentration of SOD were higher than those in group B (q = 7.73, P ＜ 0. 01). In contrast with group A and C ,the expression of CD11b/CD 18 of group B was significantly increased after 60min reperfusion (q =8.59,9.56, P ＜0. 01). Conclusion Adenosine can prevent ischemia-reperfusion injury in rabbit lung in vivo by inhibiting the expression of CD-11b/CD18 on PMNs and dropping oxygen free radicals level.

The effect of levocarnitine and Vitamin-E on oxidative stress state and the function of endothelial cells in maintenance hemodialysts patients / 中国综合临床

Objective To study the treatment effects of intravenous levocarnitine in combinaton wlth vitamin-E in the oxidative stress state,endothelial cell function and nutritional status of patients with maintenance hemodialvsis (MHD).Methods 83 patients with MHD were randomized to the control group (Group A),and three treatment groups:with levocarnitine (Group B),with Vitamin-E (Group C),with levocarnitine and Vitamin-E(Gmup D).Intravenous 1.0 g levocarnitine were administered to Group B,oral vitamin-E(200 mg,two times each day) to group C,and vitamin-E and levocarnitine were coadministratered to group D at the end of dialysis.The blood biochemical indicators of each group were measured respectively.At the same time,malondialdehyde(MDA),glutathione peroxidase (GSHPx) and nitricoxide (NO) expression were mesured.Results MDA of group A increased compared with pre-dialysis at the end of the 3rd month[(4.81±0.08)nmoL/L vs(4.62±0.06)nmol/L(P<0.05)].and GSHPx declined at the end of the 3rd month[(72.02±2.05)μmol/L vs(74.62±1.46)μmol/L(P<0.01)] Hemoglobin(Hb),and blood albumin (Alb) reduced without statistical significan (P>0.05);In group B and C.MDA declined more compared with Group A[(3.86±0.06)nmol/L,(3.81±0.19)nmol/L vs (4.81±0.08)nmoL/L,(P<0.01)],while the GSHPx and NO increased significantly[(92.11±1.62)μmol/L,(92.14±1.37)μmol/L vs(72.02±2.05)μmol/L;(64.24±1.72)μmol/L,(64.35±1.67)μmol/L vs (49.91±1.19)μmol/L(P<0.05)].In the 3rd month,Hb and Alb level rised obviously(P<0.05);Group D was better than Group B and C(P<0.01).Conclusions Levocamitine and Vitamin-E effectively improve oxidative stress and nutrition status and the function of endotllelial cells of the MHD patients.It probably slows atherosclerosis progress.Furthermore,the combined medication is better.

Application of a Simple Method for Detection of Rubella Virus Genome by Loop-mediated Isothermal Amplification (LAMP) / 中国疫苗和免疫

Objective To use a new simple Reverse Transcription Loop-mediated isothermal amplification(RTLAMP) method was applied to detect rubella virus nucleic acid and compared with Reverse TranscriptionPolymerase Chain Reaction (RT-PCR).Method Comparing the detection rate of the RT-LAMP method with that of RT-PCR for detecting rubella virus nucleic acid from rubella virus.Results The nucleic acid positive rates of all 11 strains of rubella virus were 100% by the two methods,the positive rate was 55%.Conclusion RT-LAMP is more simple and convenient than RT-PCR.

Clinical application of dorsal carpometacarpal island flap with fascia vessel and nerve / 中国医师进修杂志

Objective To present the clinical effect of dorsal carpometacarpal island flap with fascia, vessel and nerve to repair soft tissue defected. Methods The island flap was designed with root of fascia, dorsal metalcarpals artery and nerve.The flap to soft tissue defected in the nearby area was applied, including 30 cases in the last segment of thumb, 4 cases in the first segment of thumb, 1 case in the IP articulation of thumb, 1 case in the first segment of middle finger, 1 case in the carpometacarpal dorsal area and 1 case in the back of index finger. Results Thirty-eight cases were survived. All cases obtained good appearance and sensory recovery approach normally with little affection in supply area. Conclusions This method has advantage of simple, practical, high survive rate, low impairment, sensible and good appearance.