Clinical value of new coagulation biomarkers in pediatric sepsis / 中华儿科杂志

Objective: To evaluate the clinical value of new coagulation biomarkers including soluble thrombomodulin (sTM) and tissue plasminogen activator inhibitor complex (t-PAI·C) for the diagnosis and prognosis of sepsis in children. Methods: The prospective observational study enrolled 59 children who were diagnosed with sepsis including severe sepsis and septic shock in the Department of Pediatric Critical Care Medicine of Shanghai Children's Medical Center affiliated to the Medical College of Shanghai Jiao Tong University from June 2019 to June 2021. The sTM, t-PAI·C and conventional coagulation tests were detected on illness day one of sepsis. Twenty healthy children were selected as the control group, and the above parameters were detected on the day of inclusion. Children with sepsis were divided into survival group and non-survival group according to prognosis at discharge. Baseline comparisons between groups were performed using Mann-Whitney U test. Multivariate Logistic regression analysis was used to evaluate the risk factors for the diagnosis and prognosis of sepsis in children. Receiver operating characteristic (ROC) curve was conducted to evaluate the predictive values of above variables for the diagnosis and prognosis of sepsis in children. Results: The sepsis group included 59 patients (39 boys and 20 girls), aged 61(22, 136)months. There were 44 patients in the survival group and 15 patients in the non-survival group, respectively. The control group consisted of 20 boys, aged 107 (94,122) months. Patients in the sepsis group had higher sTM and t-PAI·C ((12 (9, 17)×103 vs. 9(8, 10)×103 TU/L, 10(6, 22) vs. 2 (1, 3) μg/L, Z=-2.15, -6.05, both P<0.05) compared with children in the control group. The t-PAI·C was superior to sTM for the diagnosis of sepsis. The areas under the curve (AUC) of t-PAI·C and sTM for the diagnosis of sepsis were 0.95 and 0.66, respectively, and the optimal cut-off value were 3 μg/L and 12×103 TU/L, respectively. Patients in the survival group had lower sTM (10 (8, 14)×103 vs. 17 (11, 36)×103 TU/L, Z=-2.73, P=0.006) than those in the non-survival group. Logistic regression analysis showed that sTM was a risk factor for death at discharge (OR=1.14, 95%CI 1.04-1.27, P=0.006). The AUC of sTM and t-PAI·C for predicting death at discharge were 0.74 and 0.62, respectively, and the optimal cut-off values were 13×103 TU/L and 6 μg/L, respectively. The AUC of sTM combined with platelet counts for predicting death at discharge was 0.89, which was superior to sTM and t-PAI·C. Conclusion: The sTM and t-PAI·C had clinical application values in diagnosing and predicting prognosis in pediatric sepsis.

Wnt5a modulates vincristine resistance through PI3K/Akt/GSK3β signaling pathway in human ovarian carcinoma SKOV3/VCR cells / 生理学报

The aim of this study was to investigate the effect of Wnt5a on the vincristine (VCR) resistance in human ovarian carcinoma SKOV3 cells and its possible mechanism. The drug-resistant SKOV3/VCR cells were established by stepwise exposure to VCR, and then the SKOV3/VCR cells were stably transfected with specific shRNA interference plasmid vector targeting for Wnt5a. The mRNA expression level of Wnt5a was measured by RT-PCR. CCK-8 assay was used to detect the cell viability of SKOV3/VCR cells. The apoptosis was analyzed by flow cytometry. The protein expression levels of Wnt5a, MDR1, Survivin, β-catenin, Akt, p-Akt(S473), GSK3β and p-GSK3β(Ser9) were detected by Western blot. The result showed that SKOV3/VCR cells had significantly higher protein expression levels of Wnt5a, MDR1, Survivin and β-catenin, phosphorylation levels of Akt and GSK3β, and mRNA expression level of Wnt5a, compared with SKOV3 cells (P < 0.05). WNT5A gene silencing significantly increased the sensitivity of SKOV3/VCR cells to VCR, the IC of VCR being decreased from 38.412 to 9.283 mg/L (P < 0.05), synergistically enhanced VCR-induced apoptosis of SKOV3/VCR cells (P < 0.05), down-regulated the protein expression levels of MDR1, β-catenin and Survivin (P < 0.05), and inhibited phosphorylation of Akt and GSK3β (P < 0.05). Meanwhile, LY294002 (PI3K inhibitor) decreased the protein expression levels of MDR1, β-catenin and Survivin, as well as the phosphorylation levels of Akt and GSK3β in SKOV3/VCR cells (P < 0.05). These results suggest that WNT5A gene silencing reverses VCR resistance in SKOV3/VCR cells possibly through blocking the PI3K/Akt/GSK3β/β-catenin signaling pathway, and thus down-regulating the protein expression levels of MDR1 and Survivin.

Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism / 中国实验方剂学杂志

Objective:To assess the anxiolytic effect of Chaimu Anshen granules (CMASG) and investigate its bioactive mechanism. Method:ICR mice were randomly divided into normal group, diazepam group(0.002 g·kg-1),Jieyu Anshen granules group(0.001 4 g·kg-1), high, medium, and low-dose (0.001 98,0.000 99,0.000 495 g·kg-1)Chaimu Anshen granule groups, with 20 mice in each group. To detect the anxiolytic effect of CMASG, mice were intragastrically administered for 4 weeks in the morning, and light-dark box transition test and open field test were performed once the other day. After the behavior tests, blood samples were collected. Six mice of each group were perfused with formalin through heart, and then the brains were fixed for immunohistochemistry test. Hippocampus of the other mice in each group were collected and stored in liquid nitrogen. The content of γ-aminobutyric acid(GABA)and glutamic acid(Glu)in hippocampus and blood samples were detected by enzyme-linked immunosorbent assay (ELISA), and the ratio of GABA/Glu was calculated. The expression of GABAα1 receptor was evaluated by the immunohistochemistry method. To test the hypnosis effect of CMASG, mice were administered intragastrically for 7 days. The sub-threshold dose of pentobarbital sodium in the sleep experiment was tested. Result:Compared with normal group, the light-dark box transitions test demonstrated that low-dose and medium-dose CMASG groups significantly prolonged the duration in light box(PPPPPPPPPPα1 receptor protein in hippocampus showed that the medium-dose CMASG significantly increased the expression of GABAα1 protein. The sub-threshold dose of pentobarbital sodium on sleep experiments confirmed that the medium-dose CMASG significantly increased the rate of sleep in mice. Conclusion:CMASG showed an anxiolytic effect, and its bioactive mechanism was related with the increase of GABA content, and the decrease of Glu content in hippocampus. Furthermore, it increased the expression of GABAα1 protein in hippocampus. The changes in content of GABA and Glu in peripheral blood were positively correlated with the changes in hippocampal tissues, which provided reference for clinical diagnosis. CMASG also exhibited an effect in improvement of sleep.

Intensified Antiplatelet Treatment Reduces Major Cardiac Events in Patients with Clopidogrel Low Response: A Meta-analysis of Randomized Controlled Trials / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Clopidogrel low response (CLR) is an independent risk factor of adverse outcomes in patients undergoing percutaneous coronary intervention (PCI), and intensified antiplatelet treatments (IAT) guided by platelet function assays might overcome laboratory CLR. However, whether IAT improves clinical outcomes is controversial.</p><p><b>METHODS</b>Relevant trials were identified in PubMed, the Cochrane Library, and the Chinese Medical Journal Network databases from their establishment to September 9, 2014. Trials were screened using predefined inclusion criteria. Conventional meta-analysis and cumulative meta-analysis were performed using the Review Manager 5.0 and STATA 12.0 software programs.</p><p><b>RESULTS</b>Thirteen randomized controlled trials involving 5111 patients with CLR were recruited. During a follow-up period of 1-12 months, the incidences of cardiovascular (CV) death, nonfatal myocardial infarction (MI), and stent thrombosis were significantly lower in the IAT arm than in the conventional antiplatelet treatment arm (relative risk [RR] = 0.45, 95% confidence interval [CI]: 0.36-0.57, P < 0.000,01), whereas bleeding was similar between the two arms (RR = 1.05, 95% CI: 0.86-1.27, P = 0.65).</p><p><b>CONCLUSIONS</b>IAT guided by platelet function assays reduces the risk of CV death, nonfatal MI, and stent thrombosis (ST) without an increased risk of bleeding in patients undergoing PCI and with CLR.</p>

Androgen replacement therapy improves psychological distress and health-related quality of life in late onset hypogonadism patients in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Late onset hypogonadism negatively impacts on men's psychological well-being. This study was conducted to examine the interrelationship among symptoms of testosterone deficiency, psychological well-being, and quality of life.</p><p><b>METHODS</b>Eligible subjects were randomized into active treatment and control groups, and were asked to complete the following questionnaires at baseline and month 6: aging male's symptoms (AMS) rating scale, hospital anxiety and depression scale (HADS), perceived stress scale (PSS) and the short form health survey-12 (SF-12). In this study, men were treated and monitored for 6 months with oral testosterone undecanoate (TU) capsules or vitamin E/C capsules in a single-blinded fashion. All in the active treatment group were administered a total of 120 - 160 mg TU orally on a daily basis. Total and free T levels between baseline and month 6 were compared.</p><p><b>RESULTS</b>One hundred and sixty eligible subjects were recruited and followed up. In the active treatment group, total serum testosterone concentrations before and after intervention were (7.98 ± 0.73) nmol/L and (13.7 ± 1.18) nmol/L. The mean HADS anxiety subscale scores for the subjects at baseline and at month 6 were 3.47 ± 0.4 and 1.72 ± 0.2, respectively (t = 1.526, P < 0.05). Additionally, the mean HADS depression subscale scores were 4.91 ± 0.6 and 2.39 ± 0.3, respectively (t = 3.466, P < 0.05). The mean scores on PSS for the subjects at baseline and at month 6 were 12.88 ± 2.1 and 9.83 ± 1.7, respectively (t = 4.009, P < 0.05). Significantly improved SF-12 could be observed (t = 1.433 and 1.118, respectively; both P < 0.05). No significant changes were observed in the control group at month 6.</p><p><b>CONCLUSION</b>Androgen replacement not only improves androgen deficiency associated symptoms, but also enhances comprehensive improvement in psychological issues.</p>

Effects of combined surfactant and inhaled nitric oxide in ventilated rabbits with meconium aspiration-induced acute lung injury / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate dose response of inhaled nitric oxide (iNO) for surfactant-treated rabbits with meconium aspiration-induced acute lung injury (ALI) and hypoxemic respiratory failure (HRF), and variation of measured iNO by continuous NO delivery in pressure support ventilation (PSV).</p><p><b>METHODS</b>Adult rabbits (2.0 - 3.5 kg, n = 33) were randomized to receive intratracheal meconium instillation for 30 min and subjected to following treatment (n = 6 - 8). There were 4 groups: Control (C); NO, iNO at 1, 10, 20 and 40 x 10(-6) each for 60 min at 30 min interval of disconnection; Surf, intratracheal instillation of porcine lung surfactant phospholipids (100 mg/kg); SNO, both iNO and surfactant as in the NO and Surf groups; and a normal group (N), which did not undergo meconium aspiration but received sham deliveries of normal saline. All the animals were treated with PSV for 6 h. iNO levels at different input and sampling sites in the NO and SNO groups were detected by on-line chemiluminescent technique. The blood gas and lung mechanics were measured during the experiments every 2 h.</p><p><b>RESULTS</b>(1) Meconium aspiration induced ALI and severe HRF (PaO(2)/FiO(2) < 200 mmHg) and depressed dynamic compliance of respiratory system (Cdyn) and airway resistance (Raw). In both Surf and NO groups modestly improved oxygenation was observed. In the SNO, values for PaO(2)/FiO(2) were improved from (185 +/- 39) mmHg at baseline to (301 +/- 123) mmHg at 6 h, while moderate or transient improvement was observed in both Surf and NO groups. Cdyn and Raw were only improved for short time in the Surf, NO and SNO groups. iNO had a mild response at 1 x 10(-6) to good response at 10 and 20 x 10(-6), but no further improvement occurred at 40 x 10(-6). The response of iNO in NO group was relatively transient compared to the SNO group. (2) When iNO was connected to the ventilator circuit, the connected site should be placed before humidifier to minimize fluctuation of iNO concentration, and sampling site for iNO monitoring should be placed adequately to eliminate artifact.</p><p><b>CONCLUSIONS</b>iNO synergistically improved surfactant effects on oxygenation and lung mechanics. Continuous supply of iNO with non-continuous flow ventilator provided stable NO within accepted target range with least variation.</p>

Determination of tetrandrine and fangchinoline in Qingshenjianfei Tablets by RP-HPLC / 中成药

AIM: To determine the contents of tetrandrine and fangchinoline in Qingshenjianfei Tablets by RP-HPLC. METHODS:In this method Zorbax C 18 column was used, and methanol—0.3%diethylamine (75∶25) as a mobile phase , the detection wavelength was at 242 nm. RESULTS:The recovery of tetrandrine was 103.65% and RSD was 1.59% .The recovery of fangchinoline was 97.11% and RSD was 1.91% (n=6). CONCLUSION: This method is simple,quick,reproducible and can be used for the quantitative analysis。