Aim To investigate the effects of the phos-phodiesterase 8(PDE8)inhibitor PF-04957325 on learning and memory,anxiety and depression in Alzhe-imer's disease(AD)mice induced by Okadaic acid(OA),and to explore its mechanism.Methods Twenty-one 2-month-old male C57BL/6J mice were se-lected for the experiment and randomly divided into the control group,AD model group,and PDE8 inhibitor group(0.1 mg·kg-1).AD model was induced by bi-lateral hippocampal localization injection of OA(50 ng on each side)in the model and PDE8 inhibitor groups of mice.Two days after the injection of OA,PDE8 in-hibitor group was given 0.1 mg·kg-1 drug,while the AD model groups and control group were given with the same volume of vehicle for 21 consecutive days.On day 13 of inhibitor administration,behavioral tests re-lated to learning and memory abilities,anxiety and de-pressive behaviors were performed in mice.HE stai-ning was used to observe the morphology of neuronal cells in the DG,CA1,and CA3 regions of the hippo-campus of mice,and Western blot was used to detect the levels of phosphorylated Tau proteins at different sites within the hippocampus of mice as well as the ex-pression of proteins related to the PDE8/cAMP/CREB pathway.Results Compared with the control group,the Y-maze Spontaneous alternation,Recognition index of NOR and Latency of PAT were significantly shorter(P＜0.01),and Entries times、Time in the target quadrant of MWM were reduced(P＜0.05)in the AD model group,which showed a decrease in the ability of learning and memory,whereas the administration of PF-04957325 significantly improved the ability of learning and memory in the AD mice;mice in the AD model group showed a significant decrease in the num-ber of entries into the central area of the OFT and the time spent in the central area(P＜0.05),and a sig-nificant increase in the Immobility time of TST(P＜0.01),suggesting that the mice had anxiety and de-pression,and the administration of PF-04957325 did not improve the anxious behavior of the mice,but im-proved the depressed behavior to a certain extent;the hippocampus of the AD model group mice showed ker-nel solidification in the DG,CA1 and CA3 regions,and neurons were not neatly arranged,and the admin-istration of PF-04957325 could alleviate the damage of hippocampal nerve cells in mice.Compared with the control group,the phosphorylation levels of Tau protein Ser1 99,Ser396 and Ser202 sites in the hippocampus of mice in the AD model group were significantly in-creased(P＜0.01),the expression of PDE8A and PDE8B proteins was significantly increased(P＜0.01),and the expression of p-PKA/PKA and BDNF proteins was decreased(P＜0.05),after administra-tion of PF-04957325,the phosphorylation levels of Tau protein Ser396 and Ser202 sites were significantly re-duced(P＜0.01),PDE8A and PDE8B protein ex-pression was significantly decreased(P＜0.01),and p-PKA/PKA,p-CREB/CREB and BDNF protein ex-pression was significantly increased(P＜0.01).Con-clusion PDE8 inhibitor PF-04957325 can improve learning memory ability,reduce cognitive dysfunction,restore Tau protein function,and attenuate neuronal cell damage in the hippocampus of AD mice with amel-iorative effects.The mechanism of action may be relat-ed to the activation of PDE8/cAMP/CREB pathway and inhibition of Tau protein phosphorylation.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To understand the incidence trend and epidemiological characteristics of COVID-19 in Shaanxi province.Methods:The incidence data of COVID-19 reported in Shaanxi as of 22 February, 2020 were collected for an epidemiological descriptive analysis.Results:A total of 245 confirmed cases of COVID-19 were reported in Shaanxi. Most cases were mild (87.76%). As time passed, the areas where confirmed cases were reported continued to increase. The case number in Xi’an was highest, accounting for nearly half of the total reported cases in the province. The epidemic pattern in Shaanxi had gradually shifted from imported case pattern to local case pattern, and the transmission of local cases was mainly based on family cluster transmission. The confirmed cases from different sources had caused the secondary transmission in Shaanxi. After February 7, the number of reported cases began to fluctuate and decrease stably, indicating a decrease-to-zero period.Conclusions:At present, the overall epidemic of COVID-19 in Shaanxi has gradually been mitigated. However, considering the approaching of return to work and study and the increasing of imported cases from other countries, the prevention and control of COVIS-19 in Shaanxi will face new challenges.

OBJECTIVETo research the bacteriostatic effects of Qingkailing Injection Extract (QKLIE) and combination therapy of Qingkailing Injection (QKLI) and antibiotics on bacteria carrying New Delhi metallo-3-lactamase 1 (NDM-1) blaNDM-1 resistance gene, and to determine their minimal inhibitory concentrations (MIC).

METHODSThe antimicrobial experiments of QKLIE (Radix Isatidis, baicalin, gardenia, honeysuckle) and combination therapy of QKLI and antibiotics were performed by using the agar dilution method and K-B method. The MIC was determined from each extract.

RESULTSThere were different degrees of inhibitory effects on resistant bacteria carrying blaNDM-1 by extracts from main components of QKLI. Of them, the inhibitory effect of baicalin was the best and the MIC of the resistant bacteria was 0.015 g/mL to WD, 0.020 g/mL to WX, 0. 005 g/mL to WJ, and more than 0.020 g/mL to pGEX-4T-NDM-1/DH5alpha (GST-NDM-1), respectively. The MIC value of each extract was sequenced from high to low as baicalin, honeysuckle, gardenia, and Radix Isatidis. Furthermore, combination therapy of QKLI and antibiotics greatly enhanced the antimicrobial activity of each antibiotics when used alone, showing very obvious antibacterial effects on multidrug resistant bacteria carrying blaNDM-1 gene. Of them, the optimal effects were obtained when combined with penicillins (penicillin G, mezlocillin, piperacillin/ tazobactam, ampicillin/sulbactam), with the antibacterial effects improved by 10 folds. The antibacterial effects of other kinds of antibiotics were improved to some extent. Conclusions QKLIE and combination therapy of QKLI and antibiotics showed better bacteriostatic effects on resistant bacteria carrying blaNDM-1 gene. This study provided theoretical bases for drug development, medication and treatment for super-resistant bacteria carrying blaNDM-1.

Anti-Bacterial Agents ; pharmacology ; Bacteria ; drug effects ; genetics ; Drug Resistance, Multiple, Bacterial ; drug effects ; genetics ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; pharmacology ; beta-Lactamases ; genetics

Myocardial ischemia and reperfusion (I/R) is a common problem in clinic and there is no satisfactory method for prevention or treatment of I/R injury so far. Chronic intermittent hypobaric hypoxia (CIHH), similar to the concept of ischemia preconditioning (IPC)or altitude hypoxia adaptation (AHA), has been recognized to confer a protective effect on heart against I/R injury with a longer protective effect than IPC and a less adverse effect than AHA. It has been proved that CIHH increases myocardial tolerance to ischemia or hypoxia, reserving cardiac function and preventing arrhythmia during I/R. Multiple mechanisms or pathway underlying the cardiac protection of CIHH have been proposed, such as induction of heat-shock protein, enhancement of myocardial antioxidation capacity, increase of coronary flow and myocardial capillary angiogenesis, activation of adenosine triphosphate (ATP)-sensitive potassium channels, inhibition of mitochondrial permeability transition pores, and activation of protein kinase C (PKC) and induced nitric oxide synthase (iNOS). In addition, CIHH has been found having many beneficial effects on the body, such as promotion of health, increase of oxygen utilization, and prevention or treatment for some diseases. The beneficial effects of CIHH and potential mechanisms are reviewed mainly based on the researches performed by our group.
Adenosine Triphosphate ; metabolism ; Antioxidants ; metabolism ; Heart ; physiopathology ; Heat-Shock Proteins ; metabolism ; Humans ; Hypoxia ; Myocardial Ischemia ; physiopathology ; Myocardium ; pathology ; Nitric Oxide Synthase Type II ; Potassium Channels ; metabolism ; Protein Kinase C ; metabolism ; Reperfusion Injury ; physiopathology