Vancomycin-associated hemorrhagic occlusive retinal vasculitis masquerading as central retinal vein occlusion / Vasculite hemorrágica oclusiva da retina associada à vancomicina (HORV) mascarada como oclusão da veia central da retina

ABSTRACT A 69-year-old female was referred with sudden unilateral painless decreased vision that began 2 days after uncomplicated cataract surgery in the left eye. Visual acuity was hand motion and biomicroscopy showed a mild anterior chamber reaction, no hypopyon, and an intraocular lens that had been placed within the capsular bag. A dilated fundus examination revealed optic disk edema, widespread deep and superficial intraretinal hemorrhages, retinal ischemia, and macular edema. A cardiological evaluation was normal and thrombophilia tests were negative. After surgery, prophylactic vancomycin (1mg/0.1ml) had been injected intracamerally. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to vancomycin hypersensitivity. Recognition of this entity is important to ensure early treatment and the use of intracameral vancomycin in the fellow eye should be avoided after cataract surgery.

RESUMO Esse caso se refere a uma paciente de 69 anos, sexo feminino, com relato de baixa acuidade visual súbita e indolor no olho esquerdo, de início 2 dias após cirurgia de catarata sem complicações. A acuidade visual era de movimento de mãos e a biomicroscopia mostrou reação de câmara anterior moderada, sem hipópio, e lente intraocular posicionada dentro do saco capsular. A fundoscopia evidenciou edema de disco óptico, hemorragias difusas intrarretinianas superficiais e profundas, isquemia retiniana e edema macular. A avaliação cardiológica foi normal e os testes para trombofilia foram negativos. Ao final da cirurgia foi injetado antibioticoprofilaxia com vancomicina (1mg/0,1ml) na câmara anterior. A paciente foi diagnosticada com vasculite hemorrágica oclusiva da retina secundária à hipersensibilidade a vancomicina. O reconhecimento dessa entidade é importante para o tratamento precoce e para evitar o uso de vancomicina intracameral em caso de cirurgia de catarata no olho contralateral.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients / Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.

Myocardial protective effect of Yangxin dingji capsule on diabetic cardiomyopathy model golden hamsters / 中国药房

OBJECTIVE To explore t he protective mechanism of Yangxin dingji capsules on the cardiomyocytes of diabetic cardiomyopathy（DCM）model golden hamsters. METHODS In this study ，golden hamsters were divided into control group （n＝ 10，no modeling ，no drug administration ），model group （n＝9，modeling，no drug administration ），TCM high-dose group [ n＝8， modeling，Yangxin dingji capsules 2 g/（kg·d）]，TCM low-dose group [ n＝8，modeling，Yangxin dingji capsules 1 g/（kg·d）] and empagliflozin group [ n＝9，positive control ，modeling，10 mg/（kg·d）]. All the golden hamsters were gavaged continuously for 8 weeks. The general conditions of golden hamsters were observed during the experiment. Blood glucose ，total cholesterol （TC）and creatine kinase MB （CK-MB），ejection fraction （EF），fractional shortening （FS），interleukin 1β（IL-1β）and transforming growth factor β1（TGF-β1）were detected ；the histopathological changes of myocardium were observed. mRNA and protein expression of nucleotide-binding oligomerization domain-like receptor protein 3（NLRP3），caspase-1，aspirin D （GSDMD），nuclear factor κB （NF-κB）and IL- 1β were detected and observed；DNA damage in myocardial was detected. RESULTS Compared with control group，the blood glucose ，TC，CK-MB，serum IL- 1β，TGF-β1 levels，the mRNA expressions and positive protein expression of NLRP 3，caspase-1，GSDMD，NF-κ B and IL-1 β and protein expression of GSDMD in golden hamsters were significantly increased in model group （P＜0.05 or P＜0.01） EF and FS were significantly decreased （P＜0.01）；the fibers of myocardial cells was disordered ， and the blue-stained collagen fibers between the myocardium increased ； DNA damaged positive cells in myocardial tiss ue of gold hamsters increased significantly. Compared with model group，the above indexes of administration groups were reversed to varying degrees ；the gap of myocardial cells were clear ，and the fibers disorder was improved ；the DNA damaged positive cells in the myocardial tissue were reduced to varying degrees. CONCLUSIONS Yangxin dingji capsule can inhibit the cardiomyocyte pyroptosis and relieve the inflammatory injury of DCM in DCM model golden hamsters by regulating the NLRP 3/caspase-1/GSDMD signaling pathway ，so as to protect the cardiomyocytes.

Effects of Dexmedetomidine on Ventricular Arrhythmia in Myocardial Hypertrophy Model Rabbits and CaMK Ⅱ Expression in Cardiac Tissue / 中国药房

OBJECTIVE：To study th e effects of dexmedetomidine on ventricular arrhythmia in myocardial hypertrophy model rabbits and the expression of calcium ion /calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）in myocardial tissue of rabbits. METHODS： The rabbits were randomly divided into sham operation group ， model group ， dexmedetomidine low-dose ， medium-dose and high-dose groups （10，25，50 μ g/kg），CaMK Ⅱ inhibitor KN- 93 group （10 mg/kg），high-dose of dexmedetomidine+KN-93 group（50 μg/kg+10 mg/kg），with 10 rabbits in each group. Except for the sham operation group ，other groups received abdominal aortic coarctation to induce myocardial hypertrophy model. After surgery ，administration groups were given relevant dose of dexmedetomidine or/and intraperitoneal injection of KN- 93；sham operation group and model group were given constant volume of normal saline intravenously ，once every other day ，for consecutive 8 weeks. After last medication ， programmed stimulation was used to induce ventricular arrhythmia. The induction rate of early posterior depolarization （EAD）and tip torsion type ventricular tachycardia （Tdp）were recorded. Left ventricular ejection fraction （LVEF）and left ventricular shortener fraction（FS）were measured. QT interval ，transventricular wall repolarization dispersion （TDR）and transmembrane 90％ action potential duration （APD90）of endocardial and epicardial cardiomyocytes in wedge-shaped myocardium were recorded. The ratio of heart weight to body weight （HW/BW）and the thickness of left ventricular wall （LVT）were measured and calculated. The cross-sectional area of cardiomyocytes ，mRNA expression of ANP and BNP as well as protein expression of CaMK Ⅱ and p-CaMK Ⅱ in myocardial tissue was measured. RESULTS ：Compared with sham operation group ，the induction rate of EAD and Tdp ，HW/BM， LVT，mRNA expression of ANP and BNP and protein relative expression of CaMK Ⅱ and p-CaMK Ⅱ in cardiac tissue were all increased significantly ，while LVEF and FS were decreased significantly ；QT interval ，APD90 of endocardial and epicardial cardiomyocytes were all prolonged significantly ；TDR was increased significantly ，while cross-sectional area of cardiomyocytes was increased significantly in model group （P＜0.05）. Compared with model group ，induction rate of EAD and Tdp ，HW/BW （except for dexmedetomidine low-dose group ），LVT（except for dexmedetomidine low-dose group ），mRNA relative expression of ANP（except for dexmedetomidine low-dose group ）and BNP （except for dexmedetomidine low-dose group ）as well as protein relative expression of CaMK Ⅱ and p-CaMK Ⅱ were all decreased significantly in administration groups ；the levels of LVEF （except for dexmedetomidine low-dose group ） and FS （except for dexmedetomidine low-dose group ） were all increased significantly； QT interval ，APD90 of endocardial and epicardial cardiomyocytes were shortened significantly ； TDR and cross-sectional area of cardiomyocytes （except for dexmedetomidine low-dose group ）were decreased significantly （P＜0.05）；the improvement effects of dexmedetomidine high-dose group were significantly better than those of dexmedetomidine low-dose and medium-dose groups （P＜0.05）. Compared with dexmedetomidine high-dose group and KN- 93 group，the improvement of above indexes were all more significant in high-dose of dexmedetomidine+KN- 93 group（P＜0.05）. CONCLUSIONS ：Dexmedetomidine can reduce the induction rate of ventricular arrhythmia and improve myocardial hypertrophy in myocardial hypertrophy model rabbits，the mechanism of which may be associated with down-regulation of CaMK Ⅱ expression.

Construction of RHBDF2 gene over-expression lentivirus vector and establishment of RHBDF2 cell line stably expressing RHBDF2 / 吉林大学学报(医学版)

Objective: To construct the RHBDF2 gene over-expression lentivirus vector and to establish the KA. hy926 cells stably expressing RHBDF2, and to provide the evidence for the construction of RHBDF2 gene over-expression lentivirus vector and the establishment of RHBDF2 cells stably expressing RHBDF2. Methods: According to the sequence of RHBDF2 gene provided by NCBI, and the primers were designed and synthesized; the RHBDF2 gene was amplified by PCR method, and the target gene was cloned into the entry vector by Gateway cloning technology, and then subcloned into the lentivirus vector pLV [Exp]-EGFP to construct the recombinant lentivirus plasmid pLV I Exp]-EGFP-RHBDF2; the lentivirus expression vector plasmid pLV I Exp]-EGFP and the recombinant lentivirus plasmid pLV I Exp]-EGFP-RHBDF2 were co-transfected into the HEK293T cells with the virus-assisted packaging plasmids to package the lentivirus and the titer of the lentivirus was detected. The EA. hy926 cells infected with pLV [Exp]-EGFP-control were used as control group and the EA. hy926 cells infected with pLV [Exp]-EGFP-RHBDF2 were used as experiment group. The EA. hy926 cells stably expressing RHBDF2 were screened by puromycin. The fluorescent quantitative PCR (qPCR) and Western blotting methods were used to detect the expression levels of RHBDF2 mRNA and protein in the EA. hy926 cells in control group and experiment group. Results: The enzyme digestion electrophoresis and sequencing results showed that the gene sequence of the EA. hy926 cells over-expression lentivirus vector in experiment group was completely consistent with the designed and synthesized sequence. The lentivirus titer in control group was 1 X 10 TU • mL , and the lentivirus titer in experiment group was 3X 10 TU • mL . The EA. hy926 cells were successfully infected with the lentivirus under fluorescence microscope and the infection efficiency was above 95%. The qPCR detection results showed that the expression level of RHBDF2 mRNA in the EA. hy926 cells in experiment group was higher than that in control group (P'<0.01). The Western blotting results showed that the expression level of RHBDF2 protein in the EA. hy926 cells in experiment group was higher than that in control group ( P < 0. 05 ). Conclusion: The lentivirus vector over-expressing RHBDF2 is successfully constructed∗ and the EA. hy926 cell line stably up-regulating the expression of RHBDF2 is established by using pLV [Exp]-EGFP-RHBDF2 lentivirus.

Síndrome de Bartter: una tubulopatía infrecuente de inicio antenatal / Bartter syndrome: an infrequent tubulopathy of prenatal onset

INTRODUCCIÓN: Síndrome de Bartter (SB) es una tubulopatía hereditaria, poco frecuente que tiene dos formas de presentación, forma grave de inicio antenatal (Bartter neonatal) y forma de aparición más tardía (Bartter clásico). En su forma antenatal se manifiesta con poliuria fetal, polihidroamnios de inicio precoz y severo, parto prematuro secundario y restricción de crecimiento intrauterino. La etapa postnatal presenta episodios recurrentes de deshidratación y desbalance electrolítico que pue den comprometer la sobrevida del paciente. OBJETIVO: Comunicar un caso de SB neonatal y presentar una revisión de la literatura en esta patología. CASO CLÍNICO: Prematuro 35 semanas, con antecedente de severo polihidroamnios diagnosticado a las 27 semanas de gestación, sin causa aparente. Desde su nacimiento evolucionó con poliuria y alcalosis metabólica hipokalémica haciendo plantear, en primera semana de vida, diagnóstico de Síndrome de Bartter neonatal. El laboratorio confirmó per didas urinarias de electrólitos. Fue manejado con balance hídrico estricto y suplementación de sodio y potasio, logrando estabilizar peso y desbalance electrolítico. Se mantiene en control nefrológico, con suplementación de gluconato de potasio y cloruro de sodio. Se agregó ibuprofeno al cuarto mes como parte del tratamiento. Al séptimo mes de vida, ecografía renal demostró nefrocalcinosis. Al año de vida se evidenció hipoacusia sensorioneural profunda requiriendo implante coclear. CONCLUSIÓN: Presencia de polihidroamnios severo de aparición temprana sin causa identificada debe hacer sospechar SB, que aun siendo infrecuente determina graves alteraciones hidroelectrolíticas y debe ser iniciado su tratamiento precozmente.

INTRODUCTION: Bartter syndrome (BS) is a rare inherited tubulopathy that has two presentation forms, the first one is a severe form of antenatal onset (neonatal Bartter) and the second one is a later on set form during the first years of life (classic Bartter). In the antenatal form, it manifests with fetal polyuria, polyhydramnios of early and severe onset, premature delivery, and intrauterine growth restriction. In the postnatal stage, it presents recurrent episodes of dehydration and electrolyte im balance that can compromise the survival of the patient. OBJECTIVE: To report a clinical case of neo natal BS and a review of the literature. CLINICAL CASE: Premature newborn of 35 weeks of gestation with history of severe polyhydramnios diagnosed at 27 weeks of gestation, without apparent cause. From birth, the patient presented polyuria and hypokalemic metabolic alkalosis making a diagnosis of Neonatal Bartter Syndrome in the first week of life. Laboratory tests confirmed urinary electrolyte losses. The patient was treated with strict water balance and sodium and potassium supplementa tion, achieving weight and electrolyte imbalance stabilization. The patient remains in control in the nephrology unit, with potassium gluconate and sodium chloride supplementation. At the fourth month, ibuprofen was added as part of treatment. At the seventh month of life, renal ultrasound showed nephrocalcinosis. At one year of life, profound sensorineural hearing loss was observed re quiring a cochlear implant. CONCLUSION: The presence of severe polyhydramnios of early onset with no identified cause should lead to suspicion of neonatal BS which even when infrequent determines severe hydroelectrolytic alterations and should be treated early.

Inhibitory Effect of Cinnamaldehyde on Proliferation, Migration and Tube Formation of VEGF-induced Endothelial Cells via JAK2/STAT3 Pathway / 中国实验方剂学杂志

Objective: To investigate the effect and mechanism of cinnamaldehyde on the angiogenesis of diabetic retinopathy, and the effect of cinnamaldehyde on vascular endothelial growth factor (VEGF) induced proliferation, migration, tube formation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway of EA.hy 926 cells were observed. Method:EA.hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (60, 90, 120, 150 μmol·L-1). The methyl thiazolyl tetrazolium (MTT) assay and scratch test were used to observe the effect of cinnamaldehyde on the proliferation and migration of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), and VEGF+cinnamaldehyde group (90, 150 μmol·L-1). The tube formation experiment was used to observe the effect of cinnamaldehyde on the tube formation of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L-1 VEGF), VEGF+AG490 group (50 μmol·L-1), VEGF+cinnamaldehyde group (90 μmol·L-1), VEGF+cinnamaldehyde group (150 μmol·L-1), and VEGF+cinnamaldehyde group (150 μmol·L-1)+AG490 group (50 μmol·L-1). Western Blot method was used to explore the effect of cinnamaldehyde on the JAK2/STAT3 signaling pathway in EA.hy 926 cells induced by VEGF. Result:Compared with the control group, model group obviously promoted the proliferation and migration of EA.hy 926 cells(P-1) significantly suppressed VEGF-induced proliferation and migration of EA.hy 926 cells (P-1) showed an obvious inhibitory effect on the number of nodes, junctions and meshes of tubules (PPPP-1) significantly reduced the expressions of P-JAK2, P-STAT3, STAT3 proteins (P-1) obviously reduced the expressions of p-STAT3 and STAT3 proteins (PPConclusion:Cinnamaldehyde showed a significantly inhibitory effect on the proliferation, migration and tube formation of VEGF-induced EA.hy 926 cells, which was related to the inhibition of the activation of JAK2/STAT3 pathway.

Construction of miR-186 sponge vector and its expression in EA. Hy926 cells / 吉林大学学报(医学版)

Objective: To construct the sponge vector which can target microRNA-186 (miR-186), and to create a stable EA. hy926 cell line that can knockdown miR-186. Methods: The miR-186 sponge sequence was chemically synthesized and cloned into lentiviral vector FV040. Then the FV040-miR-186-sponge recombinant plasmid together with the helper plasmids were cotransfected into the HEK293T cells by using lipofectamine 2000 to package lentivirus and the viral titer was determined. The FV040-control lentivirus (designated as the control group), and the FV040-miR-186-sponge (designated as the experiment group) were used to infect EA. hy926 cells for establishing stable cell lines. The fluorescent quantitative PCR (qPCR) method was used to detect the relative expression levels of miR-186 in the EA. hy926 cells in blank group, FV040-control group and FV040-miR-186 sponge group, respectively. Results: The cloned target sequence was identical with the designed miR-186 sponge sequence. The green fluorescence protein (GFP) was observed in the infected EA. hy926 cells. The lentivirus titre of viruses in the FV040-control group was 2×108 TU middot; mL-1, and which was 6 × 108 TU middot; mL-1 in FV040-miR- 186 sponge group. The EA. hy926 cell line stably expressed miR-186-sponge was established successfully and the infection rate was as high as 95%. The qPCR results indicated that the relative expression level of miR-186 in the EA. hy926 cells in FV040-miR-186-sponge group was lower than those in blank control group and FV040-control group (P<0. 01). Conclusion: The miR-186-sponge vector is successfully constructed, and the EA. hy926-miR- 186-sponge cell line with the stably decreased expression of miR-186 is established successfully.

Estesioneuroblastoma Olfatorio: Presentacion De Un Caso / Oligatory Esthesioneuroblastoma: Presentation of a Case

Se presenta un caso de una paciente con pérdida de peso, congestión nasal epistaxis, aumento de volumen en cuello con disfagia a sólidos y líquidos de 1 mes de evolución. La tomografía de cuello muestra una masa de tejidos blandos en la base de cuello con erosión del esfenoides con extensión a la fosa craneal media, con erosión del clivus, el esfenoides y la si­lla turca. El diagnostico histopatológico es un estesioneuroblastoma.

We present a case of a patient with weight loss, nasal congestion, epistaxis, increase neck volu­ me with dysphagia to solids and liquids of 1 month of evolution. The neck tomography shows a soft tissue mass at the base of the neck with erosion of the sphe­ noid with extension to the middle cranial fossa, with erosion of the clivus, the sphenoid and the sella turcica. The histopathological diagnosis is an esthesioneuroblastoma.

Neuroprotective effects of estrogen on rat model of perimenopausal depression and possible mechanism / 国际药学研究杂志

Objective: To investigate the antidepressant roles of estrogen in the perimenopausal depression rat model and po- tential mechnisms. Methods: The perimenopausal depression rat model was performed by ovariectomized(OVX)rat following unpre- dictable chronic mild stress(UCMS). The rats were divided into 6 groups:the control group(CON),OVX group,model (OVX+UC- MS)group,estrogen(estradiol,E2)treatment group,escitalopram group(ESC),and OVX+E2 group. Open filed and sucrose prefer- ence tests were used to investigate depression-like behavior. Nissl staining was used to analyze neuron numbers in the dentate gyrus (DG)region of rat hippocampus,Levels of 5-HT,5-H1AA, norepinephrine(NE)and dopamine(DA)in the hippocampus were deter- mined by the HPLC method,while the levels of several markers associated with HPA axis were determined by ELISA. Results: OVX+ UCMS decreased the number of crosses and rearings in open field test and decreased sucrose preference in sucrose preference test in the perimenopausal depression rat model. E2 treatment could reverse the depression behavior. E2 treatment also reversed the de- creased neuron numbers of DG region in the rat hippocampus and decreased monamine transmitter and high hypothalamic-pituitary-ad- renal axis(HPA)activation. Conclusion: E2 plays antidepressant roles in perimenopausal depression rat model through protecting neuron,increasing monamine transmitter level and decreasing HPA axis activation.

Advances in differential roles of HIF-1αand HIF-2αin the pathogenesis of hypoxic pulmonary hypertension / 中国药理学通报

Hypoxia-induced factors(HIFs)are the main regula-tors for the response of hypoxic environment.They are involved in hypoxia-related lung tissue cell damage and abnormal cell pro-liferation,among which,HIF-1αand HIF-2αplay the most im-prominant roles.This paper reviews the current researches of HIF-1αand HIF-2α,focusing on their structural and functional similarities and diversities,as well as their roles in the patho-genesis of hypoxic pulmonary hypertension.

Premarketing Clinical Evaluation of Drug-induced Liver Injury / 世界科学技术-中医药现代化

The liver injury caused by drug and / or its metabolites is one of the most common reasons for drugs to be withdrawn or disapproved.Premarketing clinical evaluation of drug-induced liver injury (DILI) is extremely important to drug evaluation.Signals of DILI and Hyman's Law (Hy's Law),clinical evaluation and lessons of DILI were discussed to help developing new drugs.

Effects of penehychdine hydrochloride on severe acute pancreatitis associated acute lung injury in rats / 临床麻醉学杂志

Objective To investigate the effect of penehychdine hydrochloride (PHCD)on acute lung injury induced by acute severe acute pancreatitis and the expression of hypoxia inducible factor-1α(HIF-1α)in rats.Methods Forty healthy adult male SD rats were used and randomly divided into 3 groups, group S of sham operation,group ALI of pancreatitis-associated acute lung injury (PALI)and group P of PALI with PHCD.Rats of group ALI and group P were the model established of acute lung injury associated with SAP by retrograde injection of 4% sodium taurocholate into biliopancreatic duct.Rats of group P of acute lung injury with SAP were immediately given PHCD after SAP.Rats of group S and group ALI were injected the same amount of 0.9% sodium chloride solution.After modeling,the rats were sacri-ficed at 12 h.The wet/dry weight ratio (W/D)of lung tissue was calculated.Pathological changes of pan-creatic and lung tissues were scored.HIF-1α,IL-1β,IL-6 of lung tissues and serum amylase were detected by ELISA.The expression of TLR4,NF-κB p65 in lung tissue was detected by Western blot.Results Ex-tensive infiltration of neutrophils,alveolar hemorrhage and necrosis and fat necrosis with pancreatic tissue were observed in group PALI and group P.Pancreatic tissue injury score was significantly higher than that of group S (P <0.01).However,there was no statistically significant difference between the level of serum amylase in group P and group ALI.The W/D ratio of lung tissue in rats of group ALI and group P was sig-nificantly higher than those in group S (P <0.05).Compared with those of group ALI,the lung tissue pathological changes of group P were significantly improved,and the lung W/D value was significantly lower than that of group ALI (P <0.05).Compared with group S,the expression of TLR4,NF-κB p65,HIF-1αin lung tissue of group ALI and group P was significantly higher (P <0.01),and the expression of TLR4, NF-κB p65,HIF-1α,IL-1βand IL-6 in group P was significantly lower than that in group ALI (P <0.05).Conclusion PHCD could not alleviate the damage of pancreatic tissue of SAP.It suppressed the expression of HIF-1α,IL-1βand IL-6 and reduced the acute lung injury induced by SAP in rats,which might be depen-ded on suppressing the expression of inflammatory factors,such as HIF-1α.

The prospect of application with H-Y antigen in forensic science / 中国法医学杂志

As is known, H-Y antigens (male specific minor histompatibility antigens) are a group of minor histocompatibility antigens encoded on the Y-chromosome with homologous H-X antigens on the X-chromosome. H-Y antigens were originally discovered as transplant antigens, and they are only expressed in male individuals without specificity for different tissues and organs. A lot of research results show that H-Y antigens play an important role in the sex selection and identification. The paper reviews the above and discusses the application prospect of H-Y antigen in forensic science.

Study on the Effects of Astragalus Polysaccharides on Heart Function and Myocardial Fibrosis in Sponta-neously Hypertensive Rats and Corresponding Mechanism / 中国药房

OBJECTIVE:To investigate the effects of Astragalus polysaccharides on heart function and myocardial fibrosis in spontaneously hypertensive rats (SHR) and corresponding mechanism. METHODS:50 SHR were randomly divided into a model group,a captopril tablets group (positive drug,30 mg/kg) and the groups of high,medium and low-dose (100,50,25 mg/kg) Astragalus polysaccharides,with 10 SHR in each group. Another 10 Wistar Kyoto rats were included into the normal group. The rats in the drug administration groups were given corresponding drugs ip,while those in the normal group and the model group were given isometric distilled water ip,once a day,for 12 consecutive weeks. The left ventricular systolic pressure (LVSP),left ventricular end diastolic pressure (LVEDP),left ventricular pressure rise rate (+dp/dtmax) and left ventricular pressure decline rate (-dp/dtmax) of the rats were recorded. The heart mass index (HMI) and left ventricular mass index (LVMI) thereof were deter-mined. The level of hydroxyproline and the mRNA and protein expression of transforming growth factor-β1(TGF-β1)and peroxi-some proliferator-activated receptor-γ(PPAR-γ)in the cardiac muscle tissue thereof were detected. RESULTS:Compared to the nor-mal group,the rats in the model group had lower LVSP,+dp/dtmax and-dp/dtmax,higher LVEDP,HMI and LVMI,as well as high-er levels of hydroxyproline and the mRNA and protein expression of TGF-β1 and lower level of the mRNA and protein expression of PPAR-γ in the cardiac muscle tissue (P0.05) in all the above-mentioned indexes was shown between the model group and the group of low-dose Astragalus polysaccha-rides,except that the-dp/dtmax of the latter was significantly higher and the level of the mRNA expression of TGF-β1 was obvious-ly lower (P<0.05). CONCLUSIONS:Astragalus polysaccharide can improve heart function and myocardial fibrosis in SHR by a mechanism which may be related to downregulating the expression of TGF-β1 and upregulating the expression of PPAR-γin the car-diac muscle tissue.

Study on Inhibitory Effects of Berberine on Vascular Endothelial Cells Injury Induced by PM2.5 and Its p38 MAPK Signal Pathway Mechanism / 中国药房

OBJECTIVE:To study the inhibitory effects of berberine on EA.hy926 human umbilical vein endothelial cells (EA. hy926 cells) injury induced by particulates with no more than 2.5 μm air aerodynamic diameter in atmospheric (PM2.5),and its p38 mitogen-activated protein kinase(MAPK)signal pathway mechanism. METHODS:PM2.5 samples were collected and hatched EA.hy926 cells with concentrations of 0(blank control),20,200 and 400 mg/L for 24 h. The survival rate and apoptosis rate of cells,contents of IL-6,TNF-α and MDA,activities of SOD and LDH,protein levels of p-p38 MAPK,Bcl-2 and Bcl-2 associated X protein (Bax) were detected. The above indexes of EA.hy926 cells in blank control group,PM2.5 group (200 mg/L PM2.5), p38 MAPK pathway-specific blocker SB203580 group (20 μmol/L SB203580+200 mg/L PM2.5),berberine low-,medium- and high-concentrations groups(5,10,20 μmol/L berberine+200 mg/L PM2.5)were also determined. RESULTS:Compared with blank control,survival rate of cells,SOD activity and Bcl protein decreased after 200,400 mg/L PM2.5 hatched;apoptosis rate of cells, contents of IL-6,TNF-α and MDA,LDH activity,protein levels of p-p38 MAPK and Bax increased (P<0.05),in concentra-tion-dependent manner. Compared with PM2.5 group,survival rate of cells,SOD activity and Bcl-2 protein increased in berberine medium-,high-concentrations groups and SB203580 group;apoptosis rate of cells,contents of IL-6,TNF-α and MDA,LDH ac-tivity,protein levels of p-p38 MAPK and Bax decreased (P<0.05). CONCLUSIONS:Berberine attenuates PM2.5-induced EA. hy926 cells injury via the inhibition of p38 MAPK pathway.

Regulation of autophagy by store-operated calcium channel in arterial smooth muscle cells / 中国药理学通报

Aim To investigate the effect of store-oper-ated calcium channel( SOCC) on autophagy in rat arte-rial smooth muscle cells A7 R5 . Methods Lentiviruses containing STIM1 or Orai1 gene were packaged in 293 T cells and then were used to infect rat arterial smooth muscle cells A7 R5 . The expression levels of STIM1 , Orai1 and Beclin 1 , a critical autophagy-regu-lating protein, of lentivirus-infected A7R5 cells, were detected by Western-blot. Autophagy in lentivirus-in-fected A7 R5 cells was induced by starvation or rapamy-cin, an inhibitor of mammalian target of rapamycin ( mTOR ) . Autophagy marker LC3 of these cells was detected by Western-blot. Results The constructions of vector pLV-STIM1 and pLV-Orai1 were confirmed by restriction enzymes digestion analysis. Compared with the control group, expressions of STIM1 or Orai1 protein was significantly increased after lentivirusLV-STIM1 and LV-Orai1infection, whereas the expressions of autophagy related protein Beclin-1 were down-regu-lated. Starvation or rapamycin stimulated A7R5 auto-phagy but overexpression of STIM1 or Orai1 significant-ly inhibited starvation or rapamycin induced autoph-agy. Conclusion Overexpression of store-operated calcium channel components STIM1 and/or Orai1 in rat arterial smooth muscle cells A7 R5 inhibit autoph-agy. This mechanism might contribute to the develop-ment of pulmonary arterial hypertension.

R59022 promotes ET-1-induced cardiac hypertrophy in neonatal rat cardiomyocytes via regulating autophagy / 中国药理学通报

Aim To investigate the effects of DGK in-hibitor R59022 on ET-1-induced myocardial hypertro-phy and autophagy, and explore the possible mecha-nisms. Methods Myocardial hypertrophy was in-duced by ET-1 in cultured rat neonatal cardiomyo-cytes. Western blot was used to detect the expression of microtubule-associate protein 1 light chain 3 ( LC3 ) , beclin-1, p62, p-Akt and Akt. mRNA expression of brain natriuretic peptide ( BNP) and beta mysion heav-y chain (β-MHC) and the cell size of cardiomyocytes were detected by RT-PCR and immunofluorescence, respectively. Results Treatment cardiomyocytes with ET-1(10 -7 mol·L-1 ) for 24 h induced the myocardi-al hypertrophy in cultured neonatal rat cardiomyocytes with the activation of autophagy as evidenced by the in-creased expression of autophagy-related proteins LC3-II/I and beclin-1 , as well as the increased p62 degra-dation. While, myocardial hypertrophy induced by ET-1 , including the increased myocardial cell size and the mRNA expression of fetal gene BNP and β-MHC, could be reversed by autophagy inhibitor 3-methyl ade-nine (3-MA) and chloroquine ( CQ) ,but promoted by autophagy agonist rapamycin ( RAPA ) . Pretreatment cardiomyocytes with R59022, an inhibitor of DGK, en-hanced ET-1-induced myocardial hypertrophy by en-hancing autophagy in cardiomyocytes. Furthermore,ET-1 treatment inhibited the activation of Akt by the down-regulation of the Akt phosphorylation, and R59022 en-hanced the effect of ET-1 on the activation of Akt. Conclusions Enhanced autophagy contributes to car-diomyocyte hypertrophy. R59022 deteriorate ET-1-in-duced myocardial hypertrophy by activating autophagy. The possible mechanism may be related to the inhibi-tion of activation of mTOR signaling pathway by inhibi-ting the activation of Akt.

Allicin prevents EA. hy926 endothelial cell injury induced by PM2. 5 via inhibiting ERK1/2 pathway / 中国药理学通报

Aim To investigate the protective effect of allicin against EA. hy926 endothelial cell injury in-duced by PM2. 5 and the possible mechanism. Meth-ods The samples of fine particulate matter ( PM2. 5 ) were collected and made into suspension. Different concentrations of PM2. 5 ( 20 , 200 , 400 mg · L-1 ) were added to EA. hy926 cell. The viability and apop-tosis of EA. hy926 cell, the protein levels of p-ERK1/2, Bax and Bcl-2 in the EA. hy926 cell, the contents of tumor necrosis factor-α( TNF-α) , interleukin-6 ( IL-6 ) , and malonaldehyde ( MDA ) , the activities of su-peroxide dismutase ( SOD ) and lactic dehydrogenase ( LDH) in the EA. hy926 cell culture supernatant were measured by MTT assay, flow cytometry, Western blot, enzyme-linked immunosorbent assay ( ELISA ) and colorimetry, respectively. Allicin at different con-centrations(5,20,40 mg·L-1 ) or a specific inhibitor of ERK1/2 signaling pathway PD98059 ( 20 μmol · L-1 ) was added into the EA. hy926 cell to observe the effect of allicin. Results Compared with control group, PM2. 5 significantly increased the apoptosis, the contents of TNF-α, IL-6 and MDA, the activity of LDH, the protein levels of p-ERK1/2 and Bax/Bcl-2 ratio, but decreased the viability and SOD activity in the EA. hy926 cell(P<0. 05). Compared with PM2. 5 group, allicin significantly decreased the apoptosis, the contents of TNF-α, IL-6 and MDA, the activity of LDH, the protein levels of p-ERK1/2 and Bax/Bcl-2 ratio, but increased the viability and SOD activity in the EA. hy926 cell ( P <0. 05 ) . Conclusion Allicin displays a significant protective effect against EA. hy926 endothelial cell injury induced by PM2 . 5 and its mechanism may be related to the attenuations of in-flammation and oxidative stress via the inhibition of ERK1/2 pathway.

Role of Nrf2∕ARE signaling pathway in inhibition of LPS-induced inflammatory factor release from macrophages by hydrogen / 中华麻醉学杂志

Objective To evaluate the role of nuclear factor erythroid 2?related factor 2 ( Nrf2)∕antioxidant response element( ARE) signaling pathway in inhibition of lipopolysaccharide ( LPS)?induced inflammatory factor release from macrophages by hydrogen. Methods RAW264. 7 macrophages of mice were cultured in 6?well plates (2×106 cells∕well) and were divided into 4 groups (n=24 each) using a random number table: control group ( group C); LPS group; hydrogen?rich saline+LPS group ( group LPS+H2); Nrf2 small interference RNA (siRNA)+LPS+hydrogen?rich saline group (siRNA+LPS+H2 group) . LPS 1 μg∕ml was added in group LPS. In group LPS+H2 , LPS 1μg∕ml was added, and the cul?ture medium was then replaced with the culture medium containing 0. 6 mmol∕L hydrogen?rich saline. In group siRNA+LPS+H2 , after Nrf2?siRN was successfully transfected into the cells, the cells were continu?ously incubated for 24 h, and the culture medium was then replaced with the culture medium containing 0.6 mmol∕L hydrogen?rich saline after LPS 1 μg∕ml was added. At 24 h of incubation, the supernatant was sep?arated for determination of the lactic dehydrogenase (LDH) activity (using colorimetric method) and for detection of the concentrations of tumor necrosis factor?alpha ( TNF?α) , interleukin?1 beta ( IL?1β) , high mobility group box?1 (HMGB1) and IL?6 (by ELISA). The cells were collected for measurement of the proliferation of cells ( by methyl thiazolyl tetrazolium assay) and for determination of the expression of Nrf2 and heme oxygenase?1 ( HO?1) in cells ( by Western blot) . Results Compared with group C, the LDH activity and concentrations of TNF?α, IL?1β, IL?6 and HMGB1 in the supernatant were significantly in?creased, the proliferation of cells was significantly decreased, and the expression of HO?1 in cells was sig?nificantly up?regulated in LPS and siRNA+LPS+H2 groups, and the expression of Nrf2 in cells was signifi?cantly up?regulated in LPS and LPS+H2 groups (P<0.05). Compared with group LPS, the LDH activity and concentrations of TNF?α, IL?1β, IL?6 and HMGB1 in the supernatant were significantly decreased, the proliferation of cells was significantly increased, and the expression of Nrf2 and HO?1 in cells was sig?nificantly up?regulated in group LPS+H2 , and the expression of Nrf2 and HO?1 in cells was significantly down?regulated in group siRNA+LPS+H2 ( P<0.05) . Compared with group LPS+H2 , the LDH activity and concentrations of TNF?α, IL?1β, IL?6 and HMGB1 in the supernatant were significantly increased, the proliferation of cells was significantly decreased, and the expression of Nrf2 and HO?1 in cells was signifi?cantly down?regulated in group LPS+H2+siRNA ( P<0.05) . Conclusion The mechanism by which hydro?gen inhibits LPS?induced inflammatory factor release from macrophages is related to the activation of Nrf2∕ARE signaling pathway in mice.