Effects of angiotensin II receptor blocker usage on viral load, antibody dynamics, and transcriptional characteristics among COVID-19 patients with hypertension / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.

Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset

BackgroundTimely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. MethodA patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial plasma of COVID-19 patients and were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. ResultsThe seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. ConclusionsTypical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection. Take-Home MessageAntibody responses are induced after SARS-CoV-2 infection and complement diagnosis value of antibody test to RNA test was observed. Antibody tests are critical tools in clinical management and control of SARS-CoV-2 infection and COVID-19.

Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCoV, in the nasal tissue

A novel coronavirus (2019-nCoV) was first identified in Wuhan, Hubei Province, and then spreads to the other Provinces of China. WHO decides to determine a Public Health Emergency of International Concern (PHEIC) of 2019-nCoV. 2019-nCov was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-Cov. Here based on the public single-cell RNA-Seq datasets, we analyzed the ACE2 RNA expression profile in the tissues at different locations of the respiratory tract. The result indicates that the ACE2 expression appears in nasal epithelial cells. We found that the size of this population of ACE2-expressing nasal epithelial cells is comparable with the size of the population of ACE2-expression type II alveolar cells (AT2) in the Asian sample reported by Yu Zhao et al. We further detected 2019-nCoV by polymerase chain reaction (PCR) from the nasal-swab and throat-swab of seven suspected cases. We found that 2019-nCoV tends to have a higher concentration in the nasal-swab comparing to the throat-swab, which could attribute to the ACE2-expressing nasal epithelial cells. We hope this study could be informative for virus-prevention strategy development, especially the treatment of nasal mucus.

Rapid determination of paraquat in human plasma using liquid chromatography-tandem mass spectrometry / 临床检验杂志

Objective@#To establish a high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the detection of human plasma paraquat concentration. @*Methods@#The plasma samples were pretreated with methanol to precipitate plasma protein, and then were separated by a Waters XBridge BEH HILIC column (2.5 μm, 2.1 mm × 100 mm) with acetonitrile-water containing 200 mmol/L of ammonium formate and 0.1% of formic acid as mobile phase and 0.4 mL/min of flow rate. The paraquat was monitored by ESI positive ion mode, multi-reaction ion monitoring (MRM) scanning, and m/z 186.1-171.1 as quantitative transition ion-pair. The plasma paraquat concentrations in patients were determined by the established method, and the clinical values of plasma paraquat concentration and severity index of paraquat poisoning (SIPP) were evaluated by the receiver operating characteristic (ROC) curve. @*Results@#When the plasma paraquat concentration ranged from 50 to 10 000 ng/mL, the linearity was good (R 2 =0.997), and the lower limit of quantification was 50 ng/mL. The recovery rates and imprecisions of three quality control products at low (100 ng/mL), medium (2 000 ng/mL) and high (8 000 ng/mL) concentration levels all met the requirements, and no matrix effect was found. The pretreated samples were stable at room temperature for 6 hours, and the results were not affected by repeated freezing and thawing for 3 times. The SIPP of 31 poisoned patients was 17.76 (0.30-90.91) h·mg/L. The SIPP in dying patients was significantly higher than that in survival patients (P＜0.05). The area under the ROC curve of SIPP was 0.889, and the optimal cut-off value was 11.679 h·mg/L. @*Conclusion@#The established method is sensitive, accurate, rapid and specific, and suitable for the detection of plasma paraquat concentration in patients.

Molecular epidemiological analysis of norovirus in patients with acute gastroenteritis in Zhejiang province during 2016 / 临床检验杂志

Objective To explore the molecular epidemiological characteristics of norovirus isolated from the patients with acute gastroenteritis in Zhejiang province during 2016.Methods The stool samples and clinical data of 1 308 patients with acute gastroenteritis were collected from January to December in 2016.The type Ⅰ and Ⅱ of norovirus in stool samples were detected by one-step double real-time RT-PCR.Some of the positive specimens were selected by stratified sampling and amplified by conventional RT-PCR,and the PCR products were sequenced for genotype identification and phylogenetic analysis.Results Among the samples studied the positive rate of norovirus was 10.55％ (138/1 308) in which 12 cases were GⅠ genotype,118 cases were G Ⅱ genotype and 8 cases were mixed infection of G Ⅰ/G Ⅱ genotypes.The positive rate of norovirus in different age groups decreased with the increased age of patients,and became the lowest in the patient group of more than or equal to 60 years old.There was no significant difference for the positive rates of norovirus in different genders.Norovirus infection was distributed throughout all the year with the peak value of positive rate (37.50％) in December.The sequence analysis demonstrated that G Ⅱ.4 and G Ⅱ.17 genotypes were the prevalent strains of G Ⅱ genotypes with proportions of 40.91％ (18/44) and 34.09％ (15/44),while GⅠ.6 genotype was the prevalent strain of GⅠ genotypes.Conclusion Norovirus should be the important pathogen causing acute gastroenteritis in Zhejiang province during 2016.G Ⅱ.4 and G Ⅱ.17 of norovirus may be the predominant epidemic genotypes.

Research progress on drug-resistance of influenza virus to neuraminidase inhibitors / 中华临床感染病杂志

Influenza virus , the causative agent of influenza , has characteristics of fast transmission and strong infectivity, posing a major threat to public health .Currently, with widely use of the first-line antiviral neuraminidase inhibitors , drug-resistant strains have appeared and brought difficulties to the precaution and treatment of influenza .This article reviews influenza virus structural characteristics , drug-resistance mechanisms , resistance situation and detection methods of drug-resistant virus strains , aiming to provide a reference for future research on influenza virus drug-resistance and clinical medication .

Effect of butylphthalide injection on serum neuron specific enolase, C-reactive protein and fatty acid binding protein levels in patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage / 中国生化药物杂志

To investigate influence of butylphthalide injection on serum neuron specific enolase, C-reactive protein and fatty acid binding protein levels in patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage.Methods Ninety patients with cerebral vasospasm were admitted to The First Affiliated Hospital of Fujian Medical University, then the patients were divided into two groups: The control group (45 patients) was treated with nimodipine and triple-H therapy after surgery;in addition to nimodipine and triple-H therapy, butylphthalide injection was administered to the experimental group(45 patients).Transcranial doppler(TCD)was used for the evaluating cerebral artery blood flow velocity, and the serum neuron specific enolase(NSE), C-reactive protein(CRP) and fatty acid binding protein(FABP) levels in patients with cerebral vasospasm were measured. Results The experimental group improved significantly more than the control group, a significant decrease in cerebral blood flow velocity of the middle cerebral artery in the experimental group as measured by TCD (P<0.05).The serum levels of NSE, CRP and FABP in the patients in the experimental group decreased more significantly (P<0.05).And the incidence of cerebral infarction in experimental group was lower than that in control group (P<0.05).Conclusion The serum levels of NSE, CRP and FABP in the patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage could be significantly reduced by administration of butylphthalide injection, which also could improve cerebral blood supply.Therefore, administration of butylphthalide injection is an effective treatment for cerebral vasospasm.

Prevalence and trends of human papillomavirus infections in gynecology patients from 11 sentinel hospitals in Zhejiang province / 中华临床感染病杂志

Objective To investigate the prevalence and trends of human papillomavirus (HPV)infections in gynecology outpatients in Zhejiang province.Methods Samples of cervical exfoliated cells were collected from gynecology outpatients in 11 sentinel hospitals in Zhejiang Province from January 2011 to December 2013.Twenty one HPV subtypes were detected by flow-through hybridization technique.Chisquare test was performed to analyze the prevalence rates of HPV infections in different years and in different age groups.Results A total of 14 569 patients were enrolled in the study,among whom 3 552 (24.38％)were positive for HPV.HPV-16 (5.77％,840/14 569),HPV-52 (4.71％,686/14 569) and HPV-58 (4.52％,659/14 569) were the most prevalent subtypes.Among all patients,2 244 (15.40％) were infected with a single high-risk subtype,426 (2.92％) were infected with a single low-risk subtype,and 882 (6.05％) were infected with multiple subtypes.The rate of multiple infection was on the rise during 2011 and 2013 (x2 =23.65,P ＜0.01).The positive rates of HPV in patients with 15-24 y age group and ＞54 y age group were 27.91％ (211/756) and 27.73％ (439/1 583) respectively,which were higher than those in other age groups (x2 =18.664,P ＜ 0.01).Conclusion HPV infection is popular in gynecology outpatients in Zhejiang province,especially in patients aged 15-24 y and ＞ 54 y,and a certain proportion of patients are infected with multiple subtypes.

Retrospective analysis of hepatitis B virus serological markers in 70 582 inpatients / 中华检验医学杂志

Objective To analyze the detection rate of HBV serological makers in non-hepatic inpatients in the past six years. Methods Serum samples of 70 582 non-hepatic inpatients from three large hospitals were collected during 2003 to 2008. Serological markers of HBV ( HBsAg, anti-HBs, HBeAg, antiHBe and anti-HBc) were detected by the AxSYM MEIA system (Abbott Laboratories,Abbott Park,IL).Combining the test results of serological makers with other clinical data, several analysis models for this retrospective study were set up to evaluate the year-to-year changes in serological makers and the detection rates of each model. Results The order from high to low of detection rate of the 5 HBV serological markers was anti-HBc (55. 17% ), anti-HBs (49. 57% ), anti-HBe (28.42%), HBsAg ( 8. 92% ) and HBeAg (2. 12% ), and all of them had a downward trend in the past six years. The positive rate of HBsAg went down from 9. 30% (2003) to 8.70% (2008). The positive rate of HBsAg among people who were born after 1992 (2. 28% ) were significantly lower than that of the overall population (8. 92% ) and fell from 3.57%(2003) to 1.85% (2008). Each detection rate of all serological makers had male sexual side effect [HBsAg ( 12. 38%/7. 25% ), HBeAg ( 2. 72%/1.58% ), anti-HBc ( 56. 57%/53.43% ), anti-HBe (41.50%/28. 35% ) and anti-HBs (65.48%/50. 00% ), male/female]. The differences were statistically significant (Chi-square values of HBsAg, HBeAg, anti-HBc, anti-HBe and anti-HBs were 509.74,105.78, 69.66, 1 321.61 and 1 726.91, respectively; all P ＜ 0. 01).Twenty-six models of HBV serological makers from 70 582 inpatients were summed up, and 8 models had positive rates geater than or equal to 1%. The "All Negative" model ranked No. 1 and had no significant change from year to year. During the past six years, models representing "A11 Negative" and "anti-HBs Positive alone" were mainly in individuals younger than or equal to 20-year-old, while the models representing "anti-HBc and/or anti-HBe,anti-HBs Positive" were mostly in people older than 20-year-old. The distribution curve of models representing "HBsAg, HbeAg and anti-HBc Positive" and "HBsAg, anti-HBc, anti-HBe Positive"etc. showed a bell-shape, covering the population from 20-year-old to 70-year-old. Conclusions The slowlydescending tendency of the detection rates of HBV serological makers was observed during the past six years.The detection rates of HBV in the younger generation decreased significantly. However, the HBV infection rates of overall population is still high, so it is a high time that we made continuous improvement for the serum HBV screening technique in order to reduce the HBV infection ratess.