Pulmonary arterial hypertension (PAH)is a disease of unknown etiology that leads to a progressive increase in pulmonary vascular resistance (PVR),if untreated,ultimately right heart failure and high mortality.It is concerted pulmonary vascular contraction and vascular remodeling are the 2 main courses of physiology and pathology leading to PAH,especially the significant role of proliferation of pulmonary arterial smooth muscle cells.A lot of relevant factors are revealed to take a participation into regulating the proliferation of pulmonary arterial smooth muscle cells and finally PAH.

Calcium-activated chloride channels(CaCCs) play an important role in cardiovascular system,including participating in a variety of physiological functions and being associated with the pathology progress of many cardiovascular diseases.With the development of research,transmembrane protein 16a (TMEM16A) has recently been identified as the molecular basis of CaCCs.Since the study of TMEM16A has got some achievement,especially in the section of cardiovascular system,its main research progress and key points from previous researches are summarized,in which the expression and physiological function of TMEM16A,as well as its clinical pathological correlations with some cardiovascular diseases are told about.Besides,the research prospect of TMEM16A in targeting therapy of cardiovascular disease is also discussed.

Objective:To investigate the different techniques and wave characteristic of applying non-invasive stimulation in blink reflex.Methods:Thirty volunteers participated in this study.Using the electrodiagnostic techniques,the orbital nerve and mental nerve were stimulated and the waves were respectively recorded at orbicularis oculi and levator labli superioris,then concluded the latency and amplitude of R1,R2,R2'.Results:The results of blink reflex were basically identical with the normative criteria.The wave of stimulating the orbital nerve and recording at levator labli superioris resembled BR.The images were steady and repeatable.The waves of stimulating mental nerve and recording at orbicularis oculi and levator labli superioris were unstable and partial R1 absent.Conclusion:The techniques of stimulating orbital nerve and recording at orbicularis oculi and levator labli superioris are valuable in the initial investigation of trigemino-facial reflex.The techniques of stimulating mental nerve and recording at orbicularis oculi and levator labli superioris can be used to examine assistantly.

AIM: To establish the Wistar rat model of furazolidone-induced dilated cardiomyopathy (Fz-DCM). METHODS: The Wistar rat model of Fz-DCM was established by feeding the animals with furazolidone. The left ventricular dimension and cardiac function were detected by echocardiogram. Aortic and right atrial pressure were measured by invasive catheter. Left ventricular interior diameter and the thickness of left ventricular free wall were measured after the rats were killed. Myocardial collagen network remodeling was observed and collagen volume fraction (CVF) was calculated by Van Gieson stain. RESULTS: ①The total incidence rate of DCM was 66.6% (20/30) in DCM group. ②Compared the corresponding subgroups to control group, the left ventricular end-diastolic diameter (LVED), left ventricular end-systolic diameter (LVES), the right atrial pressure, the left ventricular interior diameter and the ratio of left ventricle weight and body weight were increased significantly. The fraction shortening (FS), the left ventricular ejection fraction (LVEF) and the thickness of left ventricular free wall were decreased significantly. ③In FZ-DCM rat, the myocyte hypertrophy and degeneration, interistial fibrous tissue hyperplasia, the quantity of typeⅠand type Ⅲ collagen fibers and the collagen volume fraction (CVF%) were increased significantly. CONCLUSIONS: The rat model of DCM can be induced successfully by feeding the animals with furazolidone. In the rats with Fz-DCM, there are left ventricular dilation, the thinness of ventricular wall, the interistial fibrous tissue hyperplasia, and the decrease in left ventricular contractic function, indicating that the Fz-DCM rat model represents the pathophysiological characters of dilated cardiomyopathy.

Aim To investigate the effects of all-trans retinoic acid and benazepril on the expression of ?-smooth muscle actin in rats with glomerulosclerosis.Methods 80 Wistar male Rats were randomly assigned into the following groups: control group,model group,ATRA treatment group and benazepril treatment group,20 rats in each group.GS rats were uninephrectomized and injected with adriamycin(5mg?kg-1) after one week through the tail vein.All rats were sacrificed at the 12th week,GS was evaluated by glomerulosclerosis index(GSI) system.The expression of ?-SMA was assessed by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry.Results Comparing with control group,the expression of ?-SMA mRNA and protein were decreased significantly in ATRA treatment group and benazepril treatment group(P0.05).Conclusions The postponed effects of ATRA and benazepril on GS were evident and equivalent.

Objective To detect and investigate the expression and the effect of Prohibitin (PHB) in rats with renal interstitial fibrosis (RIF) induced by unilateral ureteral obstruction (UUO) .Methods Forty-eight Wistar male rats (6-weeks-old) were randomly assigned into 2 groups,sham-operated and model group.The model group rats were subjected to left ureteral ligation after anesthesia and the sham-operated group rats were subjected to sham operation.Six rats were killed 7,14,21,28 days after operation respectively.The renal tissues were collected.The index of RIF was calculated.The expressions of mRNA and protein of PHB were assayed by real time polymerase chain reaction and immunohistochemistry. Results Compared with sham-operation group,at each time point,the model group had significantly increased index of RIF (P < 0.01) and the obstruction for a longer period showed the higher index; the model group had significantly decreased expression of mRNA and protein of PHB (P < 0.01) and the obstruction for a longer period showed the lower expression; the model group had significantly increased expression of mRNA and protein of TGF-β1 (P < 0.01) and the obstruction for a longer period showed the higher expression.Correlation analysis showed that the index of RIF was negatively correlated with FHB (γ = -0.825) and positively correlated with TGF-β1 (γ = 0.995),while there was a positive correlation between PHB and TGF-β1 (γ = -0.786).Conclusions The lower expression of PHB in renal tissue of UUO rats might suggest that it play an important role in RIF.

Objective To study the effect of chloride channel blocker(niflumic acid,NFA) on pulmonary hypertension induced by high pulmonary blood flow in rats.Methods Fifty male or female Sprague-Dawley rats were randomly divided into 5 groups:normal group,sham group,model group,drug 1 group,and drug 2 group,with 10 rats in each group.After subjected to an abdominal aorta-inferior vena cava shunt,all the rats were reared under the same condition for 11 weeks.Then,mean pulmonary artery pressure(mPAP) and right ventricular hypertrophy index(RVHI) of each rat were measured.In addition,arterial wall area/vessel area (W/V) and arterial wall thickness/vessel external diameter(T/D) of each rat were also measured.Results 1.The mPAP of model group [(25.79 ± 4.03) mmHg,1 mmHg =0.133 kPa] was significantly higher than those of normal group [(16.48 ± 1.70) mmHg],sham group [(17.03 ± 2.01) mmHg],drug 1 group [(21.78 ± 2.77) mmHg] and drug 2 group [(20.31 ± 2.15) mmHg] (F =18.983,P ＜0.01).Although the mPAP of drug 1 group was a little higher than drug 2 group,there was no significant difference (P ＞ 0.05).Compared with normal group and sham group,the mPAP of drug 1 group and drug 2 group increased(P ＜0.01,respectively).2.The W/V and T/D of model group were significantly higher than those of normal group,sham group,drug 1 group and drug 2 group (F =26.135,15.527,all P ＜ 0.001).The W/V and T/D of two drug groups showed no significant difference,but they were higher than those of normal group and sham group (P ＜ 0.01,respectively).Conclusions Chloride channel blocker NFA partly decrease mPAP of pulmonary hypertension indnced by high pulmonary blood flow in rats,and inhibit proliferation of vascular smooth muscle cells.These results suggest that NFA had part of therapeutic effect to pulmonary hypertension induced by high pulmonary blood flow.

Objective To study the pulmonary interstitial changes in pulmonary hypertension induced by high pulmonary blood flow.Methods Sixty-five male or female Sprague-Dawley rats (180-230 g) were used and randomly divided into 3 groups:normal group (n =20) ; sham group (n =20),only exposing the abdominal aorta and inferior vena cava about 10-20 minutes;model group(n =25),rats in this group were subjected to an abdominal aorta-inferior vena cava shunt to create animal models of high pulmonary.After operation,all the rats were reared under the same conditions for 11 weeks.Then,the systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP) of every rat were determined by means of homemade right heart catheterization.After that,the right ventricle (RV) was separated from the left ventricle (LV) and septum (S),then weighed.And right ventricular hypertrophy index (RVHI) was measured by the ratio of RV to LV + S [RV/(LV + S)].In addition,the morphological changes of pulmonary interstitial of rats were observed under optical microscope by means of hematoxylin-eosin (HE) staining.In the end,single pulmonary artery smooth muscle cell (PASMC) was isolated through acute enzyme separation.Then membrane capacitance (Cm) was recorded through in the method of patch clamp technique.Results 1.Compared with sham group and normal group,the sPAP,mPAP and RVHI of model group increased significantly(F =17.293,16.259,12.878,all P ＜ 0.01).2.In contrast to sham group and normal group,arterial wall area/vessel area(W/V) and arterial wall thickness/vessel external diameter(T/D) in model group increased significantly(F =85.717,22.795,all P ＜0.01).3.The membrane capacitance of model group was bigger than that of sham group and normal group(F =8.704,P ＜ 0.01).4.mPAP was positively correlated with W/V,T/D and Cm (r =0.669,0.662,0.663,all P ＜ 0.01).Conclusions Shunts from abdominal aorta-inferior vena cava in SD rats caused high pulmonary blood flow-induced pulmonary hypertension,and these rats appeared with pulmonary smooth muscle cells hypertrophy,pulmonary vascular wall thickening and inflammatory cells infiltration.

OBJECTIVETo evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).

METHODSA total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.

RESULTSOver the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.

CONCLUSIONFor CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.

Adenine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Middle Aged ; Organophosphonates ; administration & dosage ; therapeutic use ; Retrospective Studies ; Tenofovir ; Young Adult

Improving the reproducibility of biomedical research results is a major challenge.Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at https://arriveguidelines.org). The fourth part of the article includes the items 1-5 of ARRIVE 2.0 Recommended 11 section, which covers "Abstract" "Background" "Objectives" "Ethical statement" and "Housing and husbandry". Its aim is to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhance the standardization of experimental animal research and reporting, and promote the high-quality development of experimental animal technology and comparative medicine research in China.