Effect of Clkl gene on level of Aβ-induced autophagy in Alzheimer's disease / 中国药理学通报

Aim To investigate the effect of siRNA transfection of silencing Clkl gene on autophagy levels in AD model cells. Methods The Clkl gene was silted using siRNA transfection techniques. MTT was used to observe the effects of Aβ

Correlation between Toxoplasma gondii infection and spontaneous abortion in pregnant women: a case-control study / 中国血吸虫病防治杂志

Objective To examine the correlation between Toxoplasma gondii infection and spontaneous abortion among pregnant women, so as to provide the evidence for the developmentofpreventivemeasuresforspontaneousabortion. Methods A total of 228 serum samples collected from women with spontaneous abortion for the first time from January 2018 to December 2019 were selected as the case group, while 228 serum samples collected from pregnant women with a normal delivery and without a history of abortion during the same period were selected as the control group. The serum IgG and IgM antibodies against T. gondii were detected and compared in both groups, and the correlation between T. gondii infection and spontaneous abortion was evaluated. Results There were no significant differences between the case and control groups in terms of age, education levels, occupation, residency and proportion of keeping cats (all P values > 0.05). The positive rate of anti-T. gondii IgM antibody was significantly higher in the case group than in the control group (adjusted χ2 = 4.08, P < 0.05; OR = 8.25), while no significant difference was seen between the case and control groups (χ2 = 0.42, P > 0.05). Conclusions Acute maternal T. gondii infection may remarkably increase the chance of spontaneous abortion. Progestational health education regarding toxoplasmosis prevention and control knowledge and detection of T. gondii infection during pregnancy should be strengthened.

Meta-analysis and trial sequential analysis of Qingjin Huatan Decoction for treating community-acquired pneumonia in elderly / 中国中药杂志

To systematically evaluate the clinical efficacy and safety of modified Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly, and provide evidence-based reference for the clinical application of this prescription. Randomized controlled trials of Qingjin Huatan Decoction in the treatment of community-acquired pneumonia in the elderly were collected by searching PubMed, EMbase, Cochrane Library, CNKI, China Biomedical Literature database, VIP database and WanFang database. Outcome indicators included clinical effective rate, inflammation index, symptom improvement time, chest radiograph improvement time, hospitalization time and adverse reactions. RevMan 5.3 and Stata/IC 15.1 software were used for Meta-analysis; TSA 0.9.5.10 Beta software was used for trial sequential analysis, and GRADE profiler 3.6 was used for grade evidence quality evaluation. Thirteen studies were included finally, including 1 058 patients, 536 patients in the experimental group and 522 patients in the control group.Meta-analysis showed that, the clinical effective rate of the experimental group was significantly higher than that of the control group(RR=1.16, 95%CI[1.10, 1.21], P<0.000 01); fever time(MD=-1.32, 95%CI[-1.93,-0.71], P<0.000 1), cough time(MD=-1.95, 95%CI[-2.69,-1.21), P<0.000 01), time to rale disappearance(MD=-1.55, 95%CI[-2.37,-0.73], P=0.000 2), time to chest radiograph improvement(MD=-1.72, 95%CI[-2.98,-0.46], P=0.007), and hospitalization time(MD=-3.16, 95%CI[-4.58,-1.74], P<0.000 01) in the experimental group were significantly shorter than those in the control group. The improvement in CRP(WMD=-3.44,95%CI[-4.50,-2.38],P<0.001), WBC(WMD=-2.04,95%CI[-3.31,-0.78],P<0.01), IL-6(WMD=-4.27,95%CI[-4.62,-3.92],P<0.001), and TNF-α(WMD=-0.47,95%CI[-0.55,-0.39], P<0.001) of the experimental group was significantly better than that of the control group. There was no significant difference in PCT improvement between the two groups(WMD=-0.63, 95%CI[-1.65, 0.40], P=0.23). No serious adverse reactions occurred in both groups. Sequential analysis of the trial showed that in the studies with cumulative inclusion of clinical effective rate, the data passed the traditional threshold and TSA threshold, further confirming its clinical efficacy. GRADE evaluation showed that the evidence level was low to extremely low. Western medicine treatment combined with Qingjin Huatan Decoction may improve clinical efficiency in the treatment of community-acquired pneumonia in the elderly, improve clinical symptoms faster, reduce CRP, WBC and other inflammatory indicators, and shorten hospital stay. The level of evidence obtained in this study is low, which needs to be further verified by high-quality multi-center, randomized controlled trials.

Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model: Critical Role of Immediate Early Genes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Etomidate (R-1-[1-ethylphenyl] imidazole-5-ethyl ester) is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurobiological mechanisms of cognitive impairments that caused by etomidate.</p><p><b>METHODS</b>A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection of etomidate or vehicle. Then, the rats' spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3',5'-monophosphate response element-binding (CREB) protein phosphorylation and immediate early gene (IEG, including Arc, c-fos, and Egr1) expression levels using Western blot analysis.</p><p><b>RESULTS</b>Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning (day 4: 27.26 ± 5.33 s vs. 35.52 ± 3.88 s, t = 2.988, P = 0.0068; day 5: 15.84 ± 4.02 s vs. 30.67 ± 4.23 s, t = 3.013, P = 0.0057; day 6: 9.47 ± 2.35 s vs. 25.66 ± 4.16 s, t = 3.567, P = 0.0036) and memory ability (crossing times: 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P = 0.0072; duration: 34.00 ± 4.24 s vs. 18.07 ± 4.79 s, t = 3.023, P = 0.0053; total swimming distance: 40.73 ± 3.45 cm vs. 27.40 ± 6.56 cm, t = 2.798, P = 0.0086) but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple IEGs (Arc: vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P = 0.0086; c-fos: Vehicle treated rats 100%, etomidate treated rats 72%, t = 2.996, P = 0.0076; Egr1: Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P = 0.0057) were significantly reduced in hippocampi of etomidate-treated rats.</p><p><b>CONCLUSION</b>Our data suggested that etomidate might induce memory impairment in rats via inhibition of IEG expression.</p>

Anti-proliferation effect of sorafenib in combination with 5-FU for hepatocellular carcinoma in vitro: antagonistic performance and mechanism / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the anti-cancer efficacy and mechanism of sorafenib and 5-fluorouracil (5-FU) therapy in vitro using the HCC cell line MHCCLM3.</p><p><b>METHODS</b>The effects of sorafenib and 5-FU, alone or in combination, on the proliferation of MHCCLM3 cells were evaluated by cell viability assays. Combined-effects analyses were conducted according to the median-effect principle established by Chou and Talalay. Effects on cell cycle distributions were tested by flow cytometry and expression of proteins related to the RAF/MEK/ERK and STAT3 signaling pathways and cyclinD1 were tested by western blotting.</p><p><b>RESULTS</b>Sorafenib and 5-FU alone or in combination displayed significant efficacy in inhibiting proliferation of the MHCCLM3 cells, with the following inhibition rates: sorafenib: 46.16% +/- 2.52%, 5-FU: 28.67% +/- 6.16%, and sorafenib + 5-FU: 22.59% +/- 6.89%. The sorafenib + 5-FU combination did not provide better results than treatment with either drug alone. The combination index values of the sorafenib and 5-FU treatments were mainly greater than 1, indicating that the two agents induced antagonistic, instead of synergistic, effects on the MHCCLM3 cells. In addition, the MHCCLM3 cells were less sensitive to 5-FU when administrated in combination with sorafenib, as evidenced by the half inhibitory concentration (IC50) significantly increasing from (102.86 +/- 27.84) mg/L to (178.61 +/- 20.73) mg/L (P = 0.003). Sorafenib alone induced G1 phase arrest (increasing from 44.73% +/- 1.63% to 65.80% +/- 0.56%; P less than 0.001) and significantly decreased the proportion of cells in S phase (decreasing from 46.63% +/- 0.65% to 22.83% +/- 1.75%; P less than 0.01), as well as down-regulated cyclinD1 expression (0.57 +/- 0.03-fold change vs. untreated control group; P less than 0.01). 5-FU alone up-regulated cyclinD1 expression (1.45 +/- 0.12-fold change vs. untreated control group; P less than 0.01). Moreover, sorafenib alone significantly inhibited the RAF/MEK/ERK and STAT3 pathways, with the fold-changes of p-C-RAF, p-ERK1/2 and p-STAT3 being 0.56 +/- 0.05, 0.54 +/- 0.02 and 0.36 +/- 0.02, respectively (all P less than 0.01); 5-FU alone produced no significant effects on these pathways.</p><p><b>CONCLUSION</b>Administered alone, both sorafenib and 5-FU exert anti-tumoral activity on in vitro cultured HCC cells. The sorafenib + 5-FU combination treatment produces antagonistic, rather than synergistic, effects. Sorafenib-inhibited RAF/MEK/ERK and STAT3 signaling and cyclinD1 expression may have induced the observed G1phase arrest and S phase reduction, thereby reducing the cells' sensitivity to 5-FU.</p>

Correlation between Serum Interleukin -4,12 and Cellular Immunity in Children with Asthma / 实用儿科临床杂志

Objective To study the changes of serum interleukin(IL)-4,IL-12 and correlation with cellular immunity in children with asthma of different stages.Methods Fifty asthmatic children were randomly selected, including 30 cases in attack stage (group A) and 20 cases in remission stage (group R). At the same time, 22 healthy children were studied as normal controls (group N).The levels of IL-12 and IL-4 ,T cells subgroups and erythrocyte immunity were detected.Results 1.Serum IL-12 levels were (24.44? 13.26 ),(42.30?12.65),(44.68?28.28) ng/L in group A, R and N,respectively. There was significant difference in three groups (F=8.92 P

The effects of interleukin-11 on high-dose methotrexate (HDMTX) induced mucositis in Wistar rats / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the therapeutic effect of interleukin-11 (IL-11) on high-dose methotrexate (HDMTX) induced mucositis in Wistar's rats, the proliferative effect on CEM leukemia cell line and the antitumor effect on HDMTX.</p><p><b>METHODS</b>Ninety-five 5-week old, 120 - 150 grams weight Wistar rats were randomly divided into five groups. Group A is normal control (n = 15), group B MTX control (n = 20), group C IL-11 pretreatment group before MTX injection (n = 20), group D (n = 20) the high dose IL-11 group (475 microg.kg(-1).d(-1)) after MTX injection, group E (n = 20) the low dose IL-11 group (150 microg.kg(-1).d(-1)) after MTX injection. All rats in group B approximately E were given 1 ml MTX intraperitoneally (100 mg/kg). Rats were killed at day 1, 3, 5, 7 after MTX injection. The mortality rates, changes of small intestine tissue morphology and ultra structure were observed. The proliferation of small intestine crypt cell was assayed by proliferating cell nuclear antigen (PCNA) immunohistochemical staining. MTT method was used to detect the proliferation of CEM cell line.</p><p><b>RESULT</b>IL-11 treatment resulted in a significant increase of survival of HDMTX treated rats, increased of small intestinal villus length and villus/crypt ratio. IL-11 administration was associated with enhancement of small intestine mucosa recovery after HDMTX therapy. Group C showed a greater effect than group B (P < 0.01). IL-11 had no effect on CEM cell proliferation.</p><p><b>CONCLUSION</b>IL-11 has a significant mitigating effect on high-dose MTX induced intestinal mucositis in rat, and significantly increase the survival of the rats. IL-11 could be safely used in the HDMTX treatment of childhood acute lymphocyte leukemia.</p>