Acute Disease ; Adult ; Brain Diseases ; chemically induced ; Carbon Disulfide ; poisoning ; Humans ; Male ; Occupational Diseases ; chemically induced

Humans ; Postural Orthostatic Tachycardia Syndrome

Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Doxorubicin ; administration & dosage ; analogs & derivatives ; pharmacology ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; pathology ; Valproic Acid ; administration & dosage ; pharmacology

TTI gene coding for Tsetse thrombin inhibitor was modified with E.coli bias codon and expressed in Escherichia coli with high efficiency.Recombinant protein was purified to more than 98% purity.Assay for enzyme activity determination was set up.The result showed that the fusion protein exhibited inhibiting activity for thrombin.Inhibitory rate of purified TTI was 73% when concentration of thrombin and substrate was 10U/ml and 250?mol/L respectively.Inhibition pattern was determined as competitive with Ki at 35?mol/L.

?-lactamase inhibitor research is popular for its potential on ?-lactam antibiotics resistant strain.A ?-lactamase binding peptide SIPIS04-01 was obtained by the yeast two-hybid system.In vitro assay showed that it can inhibit the ?-lactamase activity.In order to improve the expression level of the recombinant peptide,a two-copy expression plasmid pYG563 was constructed by random orientation tandem repeat method after codon modification,the two-copy plasmid was successfully expressed and the product was increased by 48.4% than that of one-copy plasmid.Purified peptide showed inhibitory activity against TEM-1 ?-lactamase in vitro and the inhhibitory constant Ki was measured.

Background Intravitreal injection with triamcinolone acetonide (TA) may cause complications,including increase of intraoculapressure (IOP),cataracand endophthalmitis.Ketorolatromethamine (Ketorolac) inew,lesadverse reactionof non-steroidal anti-inflammatory drug.The action mechanism of Ketorolaisimilato TA.Therefore,Ketorolamay be completely opartly replace Tin the treatmenof retinal edema.Objective The purpose of thistudy wato investigate the effectof Tand Ketorolaon the expressionof aquaporin-4 (AQP4) and vasculaendothelial growth facto(VEGF) in hypoxiretinal Müllecellin vitro and to explore the mechanism of treating retinal edemwith Tand Ketorolac.MethodThe propose of research and use of the animalwere approved by Animal ExperimenResearch Review Committee of Hubei University of Medicine.Twenty eyeof New Zealand albino rabbitwere extracted and the retinal tissue waisolated.The Müllecellwere cultured and passaged using the enzymatidigestion method and Müllecellwere identified using glial fibrillary acidiprotein (GFAP),vimentin and α-smooth muscle actin (α-SMA) by immunofluorescence staining.The hypoxicell modelwere established by culturing the cellin DMEM with 500 μmol/L CoCl2 fo0,6,12,24 hours.The cellof hypoxifo24 hourwere divided into normal control group,hypoxicontrol group,hypoxia+50,100,200 mg/L To50,100,200 mg/L Ketorolagroups.Corresponding drugwere added into the medium in the differengroups.The expressionof AQP4 mRNand VEGF mRNin Müllecellwere detected by semi-quantitative reverse transcription PC(RT-PCR).ResultThe cellgrew well and reached 80％ confluence with the irregulashape and ovoid nuclei 14-15 dayaftecultured.More than 95％ primary cellshowed positive reaction to GFAP,vimentin and α-SMA.The expressing levelof AQP4 mRNand VEGF mRNin Müllecell(values) were significantly differenin varioutime point(AQP4 mRNA:F=18.70,P＜0.01 ; VEGF mRNA:F =53.20,P＜0.01),and those of 6,12 and 24 houraftecultured with CoCl2were increased than those withouCoCl2 (P＜0.05).The expressing levelof AQP4 mRNand VEGF mRNin Müllecell(values) were significandifferenamong the normal control group,hypoxicontrol group,hypoxia+50,100,200 mg/L ToKetorolagroup(AQP4 mRNA:F =27.98,P ＜ 0.01 ; VEGF mRNA:F =10.03,P ＜0.01).Compared with the hypoxicontrol group,the expressing levelof AQP4 mRNand VEGF mRNin the Müllecellwere declined in the hypoxia+ 100,200 mg/L Tgroup and the hypoxia+100,200 mg/L Ketorolagroup (P＜0.05).The expressing levelof AQP4 mRNand VEGF mRNwere found statistically insignificandifference between hypoxia+ 100 mg/L Tgroup and hypoxia+ 100 mg/L Ketorolagroup,obetween hypoxia+ 200 mg/L Tgroup and hypoxi+200 mg/L Ketorolagroup (P＞ 0.05).ConclusionTand Ketorolacan downregulate the expressionof AQP4 and VEGF in Müllecellundehypoxiconditions,inferring thathey have similamechanism in the impacon AQP4 function in retinal edematoueye.

This study aimed to investigate the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" (GX) on phlegm and blood stasis syndrome (PBSS) rats combining the methods of network pharmacology and experimental verification. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Anhui University of Chinese Medicine (grant number: AHUCM-rats-2021070). Based on the HPLC-Q-TOF-MS analysis and database, 69 chemical constituents of GX and 163 targets of GX for the treatment of phlegm and blood stasis-related cardiovascular diseases were obtained. Then, key targets such as serine/threonine kinase 1 (Akt1), tumor necrosis factor (TNF), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (Tp53) were screened. Pathway analysis showed that the targets of GX in the treatment of phlegm and blood stasis-relate cardiovascular diseases were mainly involved in PI3K/Akt signaling pathway, sphingolipid metabolism, platelet activation, hypoxia inducible factor-1 (HIF-1), ras-proximate-1 (rap1) and other signaling pathways. In addition, molecular docking analysis showed that apigenin, cucurbitacin D, linolenic acid and kaempferol and other key components had potential binding ability with Akt1, TNF, IL6, VEGFA and Tp53. In the animal experiments, compared to the phlegm and blood stasis syndrome group, GX could significantly improve the traditional Chinese medicine syndrome score, blood lipid, vascular endothelial structure disorders and reduce serum endothelin-1 (ET-1) level, increase serum nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) levels, which could restore aortic endothelial function. In addition, the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aorta could be significantly reduced, which could improve the vascular endothelial injury of aorta. Western blot revealed that GX could significantly decrease the phosphorylation levels of phosphoinositide 3-kinase (PI3K) and Akt in aorta. This study revealed the mechanism of GX in treatment of phlegm and blood stasis-relate cardiovascular diseases is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. In addition, this study also clarified that the reversal of pathological of phlegm and blood stasis syndrome rats may be related to GX inhibiting PI3K/Akt signaling pathway, which could improve vascular inflammation and vascular endothelial function injury.

Objective To discuss the clinical diagnostic method of postural orthostatic tachycarda syndrome(POTS) in children.Methods Thirty-six children with POTS were selected for the research.Among them 15 were boys,21 cases were girls.The age ranged from 5.9 to 16 years,average age 12.3 years.Among them 28 patients(78%) were in between 11-16 years.The age distribution,clinical courses and hemodynamic indexes were analyzed and also the incidence of clinical manifestations and investigation reports were observed.Results Among 81 patients of orthostatic regulation disturbance,36 patients were diagnosed POTS,which was 47% of total.The clinical courses ranged from 1 day to 5 years,average clinical course 10.2 months.The clinical courses of more than half of the total patients were within 6 months(56%).The common clinical features of POTS were chest tightness on standing,vertigo,fatigue,palpitation,syncope,orthostatic regulation disturbance.Ten patients were also associated with gastrointestinal symptoms like nausea,vomiting.The most common feature of POTS patients was tachycardia(HR increased by ≥30 times/min) within 10 min after head-up tilt test(HUT).Average HR increased by 38 times/min.In some patients HR increased up to ≥120 times/min.There were no significant changes in blood.In 23 cases(64%),the T waves were descended by ≥0.2 mV in 2 or more than 2 leads in ECG reading.Investigations reports showed that there were 12 cases whose urine specific gravity was increased.In 11 cases HCO_3~-decreased.Conclusions POTS is commonly seen in schooling female children.The common symptoms are vertigo,chest tightness,fatigue,palpitation.HUT is an important method for the diagnosis of POTS.

Objective To study the characteristics and clinical features of positive response during head - up tilt test (HUT) in children. Methods Forty- nine cases of syncope and aura of syncope were included in the study. All of them underwent HUT (tilt angle 60 degree,lasting 45 minutes). During the test,children' blood pressure,heart rate.electrocardiography and clinical symptoms and signs were dynamically observed. Results The common syncope aura symptoms were headache, dizziness, chest distress, difficulties in breathing, pale, perspiration, blurred vision, auditus depression and symptoms related to digestive symptoms. Among the 28 positive cases, 7 cases were of vaso - inhibitory pattern (25%), with a decrease in blood pressure and an increase in heart rate, 3 cases inhibitory pattern (11%), with a decrease in heart rate but withoilt'blood pressure changes, 4 cases mixed pattern (14 %), with decreases in heart rate and blood pressure obviously, 10 eases POTS (36%), with an increase in heart rate by 30 bpm or up to 120 bpm within 10 minutes while testing, and 4 cases orthostatic hypotension (14%), with a decrease in blood pressure within 3 minutes. Conclusion HUT can be regarded as the main tool in differential diagnosis of unexplained syncope in children.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.