A 3-month-old neonatal rhesus macaque HFMD model caused by coxsackievirus B1 infection and viral tissue tropism.

Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.

Fucoidan sulfate from Sargassum fusiforme regulates the SARS-CoV-2 receptor AXL expression in human embryonic lung diploid fibroblast cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

新冠病毒感染疫情严重威胁着世界各国人民的生命健康。目前，对病毒感染的防治研究主要集中在抑制病毒与分子受体的结合上。AXL作为新发现的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）受体，在协助病毒感染人体呼吸系统中发挥着重要作用，是未来临床干预的潜在靶点。本研究对已发表的单细胞测序数据进行整理和分析，发现AXL在年轻人肺细胞中的表达水平明显高于老年人。人胚肺二倍体成纤维细胞（2BS）是衰老研究的公认细胞株。本文采用2BS细胞构建复制性细胞衰老模型，发现年轻细胞中AXL的蛋白水平明显高于衰老细胞，据此推测年轻人感染的风险可能更高，需要注意防护。我们发现一种羊栖菜褐藻多糖硫酸酯组分（SFW-3）可显著下调年轻2BS细胞中AXL的表达水平，表明SFW-3具有一定的抗SARS-CoV-2感染的研究价值，同时表明2BS细胞株也可作为潜在的SARS-CoV-2体外感染模型。

An Antioxidant Enzyme Therapeutic for COVID-19

The COVID-19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. We report herein a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS-CoV-2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID-19.

Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. Currently there is no vaccine, effective therapeutic or prophylactic. Like other betacoronaviruses, attachment and entry of SARS-CoV-2 is mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in anti-viral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH and 6-O-desulfated enoxaparin with an IC50 of 5.99 {micro}g/L, 1.08 mg/L, 1.77 {micro}g/L, and 5.86 mg/L respectively. The low serum bioavailability of intranasally administered UFH, along with data suggesting that the nasal epithelium is a portal for initial infection and transmission, suggest that intranasal administration of UFH may be an effective and safe prophylactic treatment.

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 M, 0.12 M, and 26.4 M, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development.

Correlation of platelet/lymphocyte ratio with short-term and long-term prognosis in patients with acute myocardial infarction / 中华全科医师杂志

Ninety-five patients with acute myocardial infarction (AMI) treated in our hospital from January 2015 to December 2017 were enrolled. According to thrombolysis in myocardial infarction (TIMI) risk score, 95 patients were divided into high group (TIMI>4, n=46) and low group (TIMI≤4, n=49) . According to platelet/lymphocyte ratio (PLR), 95 patients were divided into low PLR group (PLR≤170, n=60) and high PLR group (PLR>170, n=35) . The correlation of PLR with short-term and long-term prognosis in patients with acute myocardial infarction was analyzed. The results showed that there were no significant differences in red blood cell count (RBC), hemoglobin (HB), white blood cell count (WBC), neutrophil ratio (NEU), percentage of intermediate cells (MON), lymphocyte count (LYM), basophils (Bas), red blood cells distribution width (RDW), eosinophils (EO) between high and low TIMI groups ( P>0.05) . The platelet count (PLT) and PLR in high TIMI group was significantly higher than that in low TIMI group ( t=42.196, 10.053; P<0.05) . The in-hospital mortality and all-cause mortality of high PLR group were significantly higher than those of low PLR group [1.67%(1/60) vs. 14.28%(5/35), χ 2=5.949, P=0.02; 3.33%(2/60) vs. 17.14%(6/35), χ 2=5.466, P=0.04]; while there was no significant difference in 1-year re-hospitalization rate, interventional therapy and thrombolytic therapy between the two groups ( P>0.05) . Pearson correlation analysis showed that PLR was positively correlated with TIMI score ( r=0.563, P=0.024) . Logistic regression analysis showed that Killip grade, serum creatinine and PLR were independent risk factors of AMI ( OR=7.532,60.14,8.234; P<0.05). PLR may effectively evaluate the prognosis of acute myocardial infarction, suggesting that its clinical value should be condidered.

Study on improving the quality standard of Taohong Tongmai granule / 药学实践杂志

Objective To improve the quality standard of Taohong Tongmai granule.Methods TLC was used to make qualitative identification of Paeoniae Radix Rubra,Rehmanniae Radix,Glycyrrhizae Radix;The effective components of the main walnut kernel were identified by HPLC;and HPLC was used to do quantitative determination of Paeoniflorin,the determination was performed on Agilent HC-C18(250mm×4.6mm,5μm)column with mobile phase consisted of Acetonitrile-water(13:87) at the flow rate of 1.0 ml/min,the column temperature was 30 ℃ and the detection wavelength was set at 230 nm.Results These TLC spots were fairly clear,and the blank test showed no interference;The paeoniflorin at the range of 1·79-57.28 μg/ml was linear with peak area(r= 0.999 9),its average recovery rate was 99.99% and RSD was 2.05%(n= 9). Conclusion The quality standard of Taohong Tongmai granule had been improved,identification method was better reproduc-ibility,the determination method of paeoniflorin content had enhanced the controllability of product quality.

Qualitative identification and quantitative determination of Fufang Shenghua granules / 药学实践杂志

Objective To improve quality standard of Fufang Shenghua granules.Methods TLC was used to identify chief components in the preparation, Radix et Rhizoma Glycyrrhizae and Salvia Miltiorrhiza.HPLC was applied to identify Amarogentin and to determine the content of Salvianolic acid B.Salvianolic acid B assay was performed on Agilent HC-C18(4.6 mm×250 mm, 5 μm) column with Acetonitrile-0.1% phosphoric acid (23∶77)as mobile phase.The flow rate was 1.0 ml/min.The column temperature was 30 ℃.The detection wavelength was set at 286 nm.Results The spots on TLC were fairly clear with good separation.There was no interference from the negative control samples.However, HPLC was a more accurate, reliable and objective method for qualitative identification.Salvianolic acid B showed a good linear correlation in the range of 1.56~49.92 μg/ml (r=0.999 9).The average recovery was 100.07%, RSD 1.61% (n=9).Conclusion A simple, accurate and reliable method was developed for the quality control of Fufang Shenghua granules.

Study of CJ016 in treatment of lung cancer / 中国药理学通报

Aim Tostudythetherapeuticeffectof CJ016 on human lung cancer model and the mecha-nism.Methods Anexperimentalhumanlungadeno-carcinoma model of A549 was set up to investigate the anti-tumor effect of CJ016,while the effect of angio-genesis and apoptosis in tumor were detected.Results In vitro,the cell proliferation was inhibited signifi-cantly by CJ016,and the value of IC50 was 34. 22 nmol ·L-1 .In vivo,the tumor inhibition rate and T/C%value were 70. 08%and 27. 75%,respectively,at the dose of 20 mg·kg-1 .Meanwhile,CJ016 could reduce the expression of CD31 and promote the apoptosis of tumorcells.Conclusion CJ016caninhibitthegrowth of A549 cells,and the possible mechanism may be re-lated to the reduction of angiogenesis and inducing tumor cell apoptosis.

Study on quality standards of hospital preparation Ganmao granules / 药学实践杂志

Objective To establish a quality standard for Ganmao granules of hospital preparations .Methods Radix Scutellariae ,cortex phellodendri and radix bupleuri were identified by thin layer chromatography (TLC) qualitatively .High performance liquid chromatography (HPLC) was used for the content of baicalin .The determination was performed on Agilent HC-C18 column (250 mm × 4 .6 mm ,5 μm) at 30 ℃ with mobile phase composed of methanol-0 .2% phosphoric acid (43∶57) at the flow rate of 1 .0 ml/min .The detection wavelength was set at 280 nm .Results In TLC chromatograms ,the spectra of different test products had spots of the same color at corresponding sites ,with no interference from negative control .A good linearity range of baicalin was 1 .81~72 .40 μg/ml (r=0 .999 9) .The average recovery rate was 98 .55% (RSD=1 .91% ,n=9) .Conclusion The quality standard was established and the method of identification has good reproducibility .The method of determination of baicalin content improved the controllability of formulated quality of Ganmao granules .

Comparision two kinds of content determination method of mannatide for injec-tion / 药学实践杂志

Objective To compare two methods in the determination of mannatide for injection .Methods The contents were determined by spectrophotometry and HPLC method .Results In the samples determined by Spectrophotometric Determi‐nation ,soluble in phenol solution and sulfuric acid ,was detected at wavelength 490 nm ,D‐mannose derivatives linear concen‐tration range is 10 .2‐51 μg/ml (r=0 .999 1) ,the average content was 92 .14% ,the average RSD value was 1 .17% .In the HPLC determination , with color spectrum column : Gemini C18 (250 mm × 4 .6 mm , 5 μm ) , mobile phase acetonitrile -0 .02 mol/L ammonium acetate solution (20∶80) ,flow rate:1 ml/min ,the detection wavelength was at 250 nm , column temperature:30 ℃ ,sample size:10 μl detection .The average content ws 83 .47% ,the average RSD value was 0 .65% ,the content of two kinds of methods could effectively determine the D‐mannose .Conclusion The average content for spectrophotometry was higher ,but the phenol was used in detection of special odor ,poisonous ,corrosive ,would cause a cer‐tain risk .HPLC was exclusive ,chromatogram was more intuitive ,on the operator harmfulness and less irritating .A new meth‐od for the determination of D‐mannose was established at the same time .

The meta-analysis on the correlation between depression and interleukin-6 / 中国神经精神疾病杂志

Objective To investigate the association of interleukin-6 (IL-6) with depression using meta analysis. Methods A systematic literature search was conducted to examine depression and interleukin-6 in Chinese patients us-ing“depression”and“interleukin-6”in Databases including PubMed, CBM, VIP, CNKI and WanFang Data. A me-ta-analysis was performed to analyze correlation between depression and interleukin-6 using RevMan 5.2.8 software. Results A total of 9 studies were recruited, involving 432 depression patients and 277 healthy controls. The results of meta-analysis showed that concentration of IL-6 was higher in depression patients than in healthy controls(SMD=1.48, 95%CI:0.78~2.18,P<0.05). Subgroup analysis in the first-episode subgroup and the non first-episode subgroup showed that concentration of interleukin-6 was higher in depression patients than that in controls [the first-episode subgroup (SMD=1.94,95%CI:0.07~3.81,P<0.05), the non first-episode subgroup (SMD=1.26,95%CI:0.60~1.93,P<0.05)]. Conclusion There is a good correlation between depression and the serum IL-6 concentration. Due to the small number of studies and heterogeneity in different studies, the present meta-analysis has not yet confirmed the quantitative correla-tion between IL-6 and depression.

Comparative study of fractional lfow reserve measurement by intravenous ATP infusion through ;femoral veins and hand dosal veins / 中国介入心脏病学杂志

Objective To compare and evaluate fractional flow reserve (FFR) by intravenous infusion of adenosine 5’-triphosphate (ATP) through femoral veins and hand dosal veins. To find the feasibility of measuring FFR through ATP infusion at hand dosal veins. Methods A total of 27 patients receiving coronary angiography (CAG) were enrolled. FFR was measured by intravenous injection of ATP through femoral veins and hand dosal veins separately in 31 stenosed coronary arteries. Results A linear correlation between ATP infusion measuring FFR through femoral and hand dosal veins was observed. Heart rates, PR intervals and side effects were of no difference between the 2 routes of ATP infusion (P=0.79, P=0.56, P=0.85). It indicated that ATP infusion[160μg/(kg·min)]measuring FFR through hand dosal veins was compatable to which measuring FFR though femoral veins (y=0.945x+0.0043, R2=0.904, P=0.001). Compared with ATP infusion by femoral vein[from (53.7±15.8) s to (58.2±11.6) s], the time to FFR by infusion ATP measurement by hand dosal veins was longer[(48.7±17.9) s, P=0.015]. Conclusions The FFR measurement through ATP infusion at hand dosal veins has similar results with the FFR measured by femoral veins ATP infusion.

Evaluation of anticoagulant efficacy and safety for domestic bivalirudin during percutaneous coronary intervention in elderly patients with acute coronary syndrome / 中国介入心脏病学杂志

Objective To evaluate the safety and efficacy of bivalirudin during perioperation of percutaneous coronary intervention (PCI) in patients older than 80 years old with acute coronary syndrome. Methods A total of 64 patients were randomly divided into two groups, respectively received heparin(n=32), or bivalirudin (n=32). We compared the activated coagulation time (ACT), procedural success rate, bleeding rate between two groups. Results The two groups ACT, PCI success rates are not statistically different, No signiifcant difference in the incidence of mild hemorrhage which is 4 (12.5%) for heparin and 1(3.1%) for bivalirudin and severe bleeding which is 2 (6.2%) for heparin and 0 for bivalirudin. However there are signiifcant differences in the overall incidence of bleeding between the two groups with lower incidence of beeding in the bivalirudin group than the heparin group (P<0.05). Conclusions Bivalirudin has comparable anticoangulation effect as heparin during perioperation of percutaneous coronary intervention (PCI) among patients older than 80 years of age with acute coronary syndrome with lower bleeding incidence than heparin dose.

Soldiers participate in relief state of emergency under medication analysis / 药学实践杂志

Objective Through the analysis of the 5.12 earthquake relief soldiers medication , to provide a reference for future e-mergency treatment relief workers .Methods May 18, 2008 to August 19, the officers and men of our hospital free treatment for earth-quake relief prescription 161 analysis.Results The skin diseases and accessories were the most reported situations and it′s up to a total of 47 prescriptions ( accounting for 29.19%) , diagnosis of insect bite dermatitis and acute bronchitis prescription , 11 and 9, respective-ly, constitute more than 6.83%and 5.59%.The first factor is the environment in emergency rescue personnel .Conclusion during the emergency relief process , rescue workers targeted prevention is very important .

Study on Quality Standard for Tangzhixiao Capsules / 中国药师

Objective:To establish the quality standard for Tangzhixiao capsules. Methods: The qualitative identification of Salvia miltiorrhiza,Atractylodes and Hawthorn was detected by TLC, and the quantitative determination of salvianolic acid B was determined by HPLC. The HPLC determination was performed on a YMC-Triart C18 (250 mm × 4. 6 mm, 5μm ) column with the mobile phase consisted of acetonitrile-0. 1% phosphoric acid (24∶ 76) at the flow rate of 1. 0 ml·min-1 , the column temperature was 30℃ and the detection wavelength was set at 286 nm. Results: The TLC spots were fairly clear, and the negative samples showed no interference. The concentration of salvianolic acid B within the range of 0. 012-0. 120 mg·ml -1 was linear with peak area(r = 0. 999 5), the average recovery was 100. 06% and RSD was 0. 83%(n = 6). Conclusion: The method is accurate, reliable and reproducible, which can be used in the quality control of Tangzhixiao capsules.

Ultrasound imaging findings of anatomical relationship between femoral artery and vein in children of different ages / 中华麻醉学杂志

Objective To investigate the ultrasound imaging findings of anatomical relationship between femoral artery and vein in children of different ages.Methods Sixty-five children aged 4 months-7 years were enrolled in this study.The children were divided into 3 age groups: group Ⅰ＜ 1 yr;group Ⅱ 1-3 yr and group Ⅲ＞ 3,≤ 7 yr.A protable ultrasound machine was used.The probe was placed at the level of inguinal ligament and 2 and 4 cm below inguinal ligament.The children were placed in supine position.The legs were placed in 2 positions:(1)extended and in standard anatomical position and(2)flexed and 45° abducted and 45° laterally rotated.Results The examination showed that at the level of inguinal ligament,the femoral vein lay behind and lateral to femoral artery in 91% of children.At the level of 4 cm below inguinal ligament,the femoral vein lay posterior and lateral to the femoral artery in all children.When the leg was placed in abducted and laterally rotated,the depth of femoral vein was reduced and the vein was less overlapped by artery in all children,especially in preschool children.Conclusion At the level of 4 cm below inguinal ligament,the femoral vein lies posterior and lateral to the femoral artery in children.When the leg is placed in abducted and laterally rotated,the depth of femoral vein is reduced and the vein is less overlapped by artery.It is indicated that femoral vein puncture should be performed at the level of 4 cm below inguinal ligament with the leg flexed and abducted in all children,especially in preschool children.

Analysis on the Rationality of Clinical Medication According to the Treatment Guide / 中国药房

OBJECTIVE:To provide guidance for pharmacists to adopt a right method in participating in clinical drug treatment work.METHODS:In participating in clinical drug treatment work,pharmacists identified physicians’ drug treatment schemes by sticking to Guiding Principle of Clinical Use of Antibacterials and made remarks on the evaluation results.RES-ULTS & CONCLUSION:Through participating in clinical medical quality ward round,pharmacists can bring their professional advantages into full play,timely find out problems existed in the clinic drug treatment,guide clinical rational drug use,and play a key role in promoting drug treatment.

Effects of Interleukin-1 Receptor Antagonist Gene Polymorphism in Cardiovascular Events of Patients with Coronary Arterial Disease / 航天医学与医学工程

Objective To test the relationship between interleukin-1 receptor antagonist(IL-1Ra)gene polymorphisms and the incidence of coronary artery disease and the effect of IL-1Ra gene polymorphisms in prediction cardiovascular events.Methods Polymerase chain reaction was used in a series of 220 patients of coronary arterial disease(CAD)and a control group of 100 cases.A prospective 12 months follow-up was conducted in the CAD patients and cardiovascular events were recorded.Serum levels of total cholesterol,triglyceride,low density lipoprotein cholesterol,fibrinogen,hsCRP,and body mass index were measured.Results There was no significant difference between CAD patients and the control subjects in IL-1Ra gene polymorphisms.However,the IL-1Ra gene polymorphism was significantly higher among subjects in CAD patients without cardiovascular events than those with cardiovascular events.Conclusion It suggests that IL-1Ra gene polymorphisms can not predict the incident of coronary heart disease but might possess some protection for the patients of coronary arterial disease from cardiovascular events.

Computerized Data Management Pattern of Drug Storehouse in Our Hospital / 中国药房

OBJECTIVE:To improve the efficiency and accuracy in database management of drug storehouse.METH?ODS:The computerized database management pattern of drug storehouse in the hospital where the authors work was intro?duced as follows:the account books of storehouse in-and out-record as well as invoice payments were established in Excel by computers,and these drug storehouse data were managed with the support of‘Military Health No.1’system.RESULTS&CONCLUSION:The established pattern can fill in the gap in‘Military Health No.1’system and improve the database man?agement of drug storehouse in hospital.