Visceral leishmaniasis is a zoonotic parasitic disease caused by viscerotropic Leishmania species and transmitted by bites of infected phlebotomine sandflies, which is predominantly prevalent in the Indian subcontinent, eastern Africa and South America. Currently, visceral leishmaniasis is the second most fatal parasitic disease in the world. Because of climate changes, urban development and individual conditions, there are changes in the density of visceral leishmaniasis vector sandflies and the likelihood of contact with humans, resulting in a visceral leishmaniasis transmission risk. The review summarizes natural, social and biological factors affecting the transmission of visceral leishmaniasis, so as to provide insights into formulation of targeted control measures for visceral leishmaniasis.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective:To investigate whether adjuvant skin-marker positioning can decrease the set-up errors in overweight patients with thoracic and abdominal tumors.Methods:A total of 60 overweight patients with thoracic and abdominal tumors treated with radiotherapy in the First Affiliated of Fujian Medical University between January 2018 and December 2018 were randomly divided into two groups. In group A, conventional skin-marker positioning was adopted. In group B, conventional skin-marker positioning combined with adjuvant skin-marker position was employed. All patients were immobilized with thermoplastic positioning body membrane with head-body plate fixation. The set-up errors in the right-left, head-foot and dorsoventral directions were obtained from cone-beam CT (CBCT) scan system before radiation delivery. The set-up errors were statistically compared between two groups by using t-test. Results:In group A, the set-up errors in the right-left, head-foot and dorsoventral directions were (4.47±2.91) mm, (5.43±2.61) mm and (3.87±2.40) mm, significantly higher compared with (2.97±1.68) mm, (3.21±1.62) mm and (2.59±1.57) mm, respectively (all P<0.001). Conclusion:Adjuvant skin-marker positioning method can reduce the set-up errors and enhance the positioning repeatability in overweight patients with thoracic and abdominal tumors receiving radiotherapy.

Chuangxinmycin is an antibiotic isolated from CPCC 200056 in the 1970s with a novel indole-dihydrothiopyran heterocyclic skeleton. Chuangxinmycin showed antibacterial activity and efficacy in mouse infection models as well as preliminary clinical trials. But the biosynthetic pathway of chuangxinmycin has been obscure since its discovery. Herein, we report the identification of a stretch of DNA from the genome of CPCC 200056 that encodes genes for biosynthesis of chuangxinmycin by bioinformatics analysis. The designated cluster was then confirmed to be responsible for chuangxinmycin biosynthesis by direct cloning and heterologous expressing in M1146. The cytochrome P450 CxnD was verified to be involved in the dihydrothiopyran ring closure reaction by the identification of seco-chuangxinmycin in M1146 harboring the gene cluster with an inactivated . Based on these results, a plausible biosynthetic pathway for chuangxinmycin biosynthesis was proposed, by hijacking the primary sulfur transfer system for sulfur incorporation. The identification of the biosynthetic gene cluster of chuangxinmycin paves the way for elucidating the detail biochemical machinery for chuangxinmycin biosynthesis, and provides the basis for the generation of novel chuangxinmycin derivatives by means of combinatorial biosynthesis and synthetic biology.

Objective To explore the efficacy and safety of low dose dopamine combined with phentolamine in the treatment of primary nephrotic syndrome (PNS) with edema. Methods Retrospective control studies were performed in 155 patients of PNS with edema, who received comprehensive treatment with small dose dopamine combined with phentolamine (group A). Patients treated with furosemide infusion were recruited as control (group B). Results The urinary output, urinary sodium increased after therapy in group A, showing significant differences (P ＜ 0. 01). But urinary potassium excretion, serum sodium and potassium showed no significant difference after therapy in group A. The urinary output, urinary sodium and potassium excretion increased and the serum sodium and potassium decreased after therapy in group B, all showing significant differences between before and after treatment (P ＜0. 01). The edema relief rate,urinary output, urinary sodium excretion, serum sodium and potassium in group A was significantly higher whereas urinary potassium excretion were significantly lower than those of group B(P ＜0. 01). The rate of drug adverse reaction in group A was significantly lower than that of group B. Conclusion Low dose dopamine combined with phentolamine in PNS with edema is safe and effective,which may be a substitute of diuretic like furosemide in the treatment of edema of patients with different blood volume.

Objective To investigate the efficacy of laboratory tests in the renal damage early diagnosis of children with Henoch-Schoalein purpura (HSP) and clinical effect of early intervention.Methods For the 143 HSP patients with normal repeated urine routine test findings,renal function biomarkers including urinary proteins ( immunoglobulin G (IgG),micro-albumin ( MA ),transferrin (TRF),a1 -microglobulin ( α1 -MG),β2-Microglobulin (β2-MG) ) and urinary enzymes ( N-acetyl-beta-D-glucosaminidase ( NAG ),γ-glutamyltransferase (y-GT) ) were detected to investigate the details of renal function changes.One hundred and thirty-one HSP patients,who had abnormal laboratory test findings of renal function biomarkers mentioned above,were randomly divided into control group ( n =65 ) and intervention group ( n =66 ),and both groups received comprehensive treatment including cimetidine,loratadine and calcium agents.However,66 patients in intervention group received low-dose heparin via micropump-based continuous intravenous infusion and regular oral diammonium glycyrrhizinate treatment.Sixty-five patients were enrolled in control group,without further treatment.Results Among the 143 patients with normal urine routine examination,131 cases (91.61％ ) had abnormal findings of renal function biomarkers.After therapy either for 2 months or 4 months,urine protein and urine enzymes were lower than before treatment,and the difference was significant (P ＜ 0.01 ).In the control group only β2-MG,NAG,γ-GT3 indexes significantly lowered at the end of 2 months ( P ＜0.01 ),and all parameters were significantly decreased at the end of 4 months ( P ＜0.01 ).Furthermore,Intervention group had lower levels of renal function biomarkers at the end of 2 months or 4 months,as compared with the control group,showing significant difference ( P ＜0.05 or P ＜0.01 ).Urinary IgG,MA,TRF,NAG recovered rapidly in the intervention group after 4 months and almost returned to the normal,but urinary α1-MG,β2-MG,γ-GT recovered slowly and still remained abnormal after 4 months due to the varying severity.After treatment for 4 months,the rate of urine testing abnormalities was higher in the control group than in the intervention group (36.92％ vs 6.10％ ),and the difference was significant (P ＜0.05).Conclusion Combined detection of renal function biomarkers is helpful for early diagnosis of renal damage in HSP patients.Early intervention with heparin and diammonium glycyrrhizinate can prevent kidney damage,delay disease progress.Early diagnosis and early intervention should be emphasized for the treatment strategy of the renal damage of children with HSP.

Objective To explore the efficacy and safety of low-dose heparin in the treament of children with primary nephrotic syndrome (PNS). Methods It was an open and comparative trial. Eightyeight children with PNS in the hypercoagulable state,on the basis of administrating with glucocorticosteroid,were administrated with low-dose heparin that infused by micro pump oriented to time ( group A). Eighty patients only treated with glucocorticosteroid were chosen as control (group B). Results Serum-albumin and activated partial thromboplastin time (APTT) increased,but fibrinogen (Fib) decreased after therapy in the group A,and they all showed significant differences (P ＜ 0. 01 ). Serum-albumin increased after therapy in the group B and there was significant difference (P＜0. 01 ). However,APTT and Fib in the group B showed no significant difference( P ＞ 0. 05 ) between post-treatment and pretherapy. Post-treatment serum-albumin and APTT in the group A were significantly higher than those in group B, and Fib was significantly lower than that in group B ( P ＜ 0. 01 ). The rate of urine protein remission in group A (82/88) was significantly higher than that in group B (63/80). Urine protein remission time and edema disappearance time were significantly shorter in group A than group B ( P ＜ 0. 01 ). APTT of group A at the peak concentration of heparin after therapy was significantly higher than that of pretherapy ( P ＜ 0. 01 ), and the ratio was 2. 38. However, there was no significant difference in APTT at the valley concentration of heparin between post-treatment and pretherapy ( P ＞ 0.05 ). Conclusion Low dose-heparin infused by micro pump oriented to time in the treatment of children with PNS has an obvious anticoagulative effect. It can improve the rate of urine protein remission and shorten edema disappearance time. Meanwhile it is safety ,requires no laboratory monitor and has few drug side effects,thus it deserves further clinical application.

Cycloheximide (CHX) inhibits protein synthesis in most eukaryotic cells and it is a well-known tool commonly used in biochemical research. In this paper, the antiviral spectrum of CHX against several DNA and RNA viruses have been evaluated. CHX showed strong inhibitory activities against several RNA viruses such as HIV-1, influenza viruses, coxsackie B virus, enterovirus (EV71) and several DNA viruses such as HSV and HCMV. Especially the strong inhibitory activities of CHX against coxsackie B virus and enterovirus caught our attention, since effective drugs available in clinic are limited. The SAR of CHX derivatives also has been discussed in the paper. The hydroxyl group at C-2' and carbonyl group at C-2" of CHX are essential for its antiviral activity. And modification to these groups results its derivatives' antiviral activities reduced or lost.

Scavenger receptor CD36 could bind and endocytose oxLDL into macrophages which were then differentiated into foam cells that constitute the atherosclerotic lesion core, and was considered to be a potential target to treat atherosclerosis. In the establishment of the compound library of berberine (BBR, 1) analogues, we discovered that 13-hexylberberine (2) showed an antagonistic activity against CD36. Taking 2 as the lead compound, 21 derivatives were synthesized and their antagonistic activities were evaluated via an ELISA-like high-throughput screening (HTS) model. The primary structure-activity relationships were studied. It was indicated that the introduction of suitable groups at the 2- and 3-position of the aromatic ring A or at the 9-position of the aromatic ring D could enhance the activity. Among the 21 studied compounds, 7g bearing a benzyloxyl group at the 9-position provided a highest CD36 antagonistic activity with the IC50 value of 7.7 micromol L(-1). Besides, its antagonistic activity was further verified with Sf9 insect cell HTS model. So berberine analogues are a new family of CD36 receptor antagonists and worthy to be studied further.

Ten pharmacophore models of beta-tubulin inhibitors were established from the training set of seventeen beta-tubulin inhibitors (two categories) with comformer analysis by using the Catalyst software. The optimal pharmacophore model with two hydrophobic units and two hydrogen bond acceptor units were confirmed (RMS = 0.43, Correl = 0.98, Weight = 2.06, Config = 15.97). This pharmacophore model is able to predict the activity of known beta-tubulin inhibitors and can be further used to identify structurally diverse compounds with higher activity.