A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA / 中华肝脏病杂志

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Molecular Mechanism of Shengxiantang in Treating Myasthenia Gravis： Based on Network Pharmacology and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo predict the pharmacodynamic basis and core target of Shengxiantang in the treatment of myasthenia gravis （MG） by network pharmacology and molecular docking and to further verify the molecular mechanism through animal experiment. MethodThe active components and potential targets of Shengxiantang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and the disease-related targets from GeneCards and other databases. Then the common targets of the decoction and the disease were screened out， followed by the construction of protein-protein interaction （PPI） network， and Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the common targets based on STRING database and Cytoscape 3.8.2. Afterward， Cytoscape 3.8.2 was employed to construct the disease-active component-target network. AutoDock and PyMOL were used for molecular docking of key components and hub genes. Finally， we used the Rα97-116 peptide to induce experimental autoimmune myasthenia gravis （EAMG） in rats and then verified the core target yielded in the docking with the model rats. ResultA total of 655 disease-related targets， 118 active components of the decoction， 21 common targets of the disease and the decoction， and 3 hub genes were screened out. The common targets were mainly involved in the GO terms of regulation of active oxygen metabolism， positive regulation of protein transport， and positive regulation of protein localization， and the KEGG pathways of toll-like receptor signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and T cell receptor signaling pathway. The results of molecular docking showed that quercetin and Akt1 had the lowest and stable binding energy and interacted with each other through the amino acid residue LYS-30. Western blot demonstrated that Shengxiantang significantly inhibited the expression of p-Akt protein in the spleen of EAMG rats. ConclusionThe pharmacological mechanism of Shengxiantang in the treatment of MG may be that the main chemical components regulate the expression of the core protein Akt， and then may participate in and affect PI3K/Akt signaling pathways， laying a theoretical and experimental basis for further research.

Mechanism of Xiao Qinglongtang Regulating Lung Water Transport-related Proteins Based on Theory of Lung Controlling Water Movement / 中国实验方剂学杂志

ObjectiveTo observe the regulatory effect of Xiao Qinglongtang and its ingredients on lung water transport-related proteins， and to explain the biological connotation of lung governing water movement， based on which the regulatory mechanism of Xiao Qinglongtang will be explored. MethodAccording to the composition rules of classical formula， Xiao Qinglongtang （11.22 g·kg-1）， Guizhi Gancao （2.70 g·kg-1）， Shaoyao Gancao （2.70 g·kg-1）， Jiangxinwei （3.90 g·kg-1）and Banxia Muahuang （0.032 7 g·kg-1） were prepared. The pathological model of syndrome of cold fluid accumulated in lung of rats was established by the "coldness of body + drinking cold + cold bath" method， and Xiao Qinglongtang and its ingredients were administrated to intervene with the model rats. Lung function parameters of forced vital capacity （FVC）， functional residual capacity （FRC）， mean mid-expiratory flow （MMEF）， inspiratory time （tI）， and inspiratory time （tE） were determined by lung function analyzer. Hematoxylin and eosin （HE） staining was used to observe the changes in pathological morphology. The expression of aquaporin （AQP）1， AQP5， epithelial sodium channel α subunit（α-ENaC） and Na+-K+-ATPase in lung tissues of rats， the content of tumor necrosis factor -α（TNF-α）， the mRNA expression of cyclic adenosine monophosphate （cAMP）， protein kinase A （PKA） and cAMP-response element binding protein （CREB）， and the protein expression of cAMP， PKA， CREB， and phosphorylated-CREB （p-CREB） were detected by immunohistochemistry （IHC）， enzyme-linked immunosorbent assay （ELISA）， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot， respectively. ResultCompared with normal group， functions of FVC， FRC and MMEF in model group were significantly decreased (P<0.01)， and the time of tI and tE was significantly prolonged （P<0.05，P<0.01）. The content of TNF-α in lung tissue was significantly increased （P<0.01）. The mRNA and protein expressions of cAMP， PKA and CREB in lung tissue were significantly decreased （P<0.01）. The expression of AQP5 and α-ENAC in lung tissue decreased significantly. The alveolar cavity of rats was filled with edema fluid， surrounding tissue hyperemia， inflammatory cell infiltration, bronchial mucosa epithelial adhesion. Compared with model group， Xiao Qinglongtang and its fangyuan group could significantly enhance the FVC, FRC and MMEF functions of model rats （P<0.05，P<0.01）， and tI and tE time were shortened （P<0.05，P<0.01）. The content of TNF-α in lung tissues of Xiao Qinglongtang group， Guizhi Gancao group and Banxia Mahuang group was significantly decreased （P<0.01）. The mRNA expressions of cAMP， PKA and CREB in Xiao Qinglongtang group were significantly up-regulated （P<0.01）， and the mRNA expressions of cAMP and PKA in Guizhi Gancao， Jiangxinwei and Banxia Mahuang groups were significantly up-regulated （P<0.01）. The protein expressions of cAMP， PKA and CREB in Xiao Qinglongtang group， Guizhi Gancao group， Jiangxinwei group and Banxia Mahuang group were significantly up-regulated （P<0.01）， and the protein expression of CREB in Shaoyao Gancao group was significantly up-regulated（P<0.05）. Xiao Qinglongtang could up-regulate the positive expression of AQP5 and α-ENAC， and Guizhi Gancao group could up-regulate the positive expression of α-ENAC. Xiao Qinglongtang and its fangyuan can reduce the lung edema， inflammatory cell infiltration and bronchial mucosal adhesion of model rats. ConclusionXiao Qinglongtang and its ingredients can reduce lung edema and inhibit inflammation by improving the expression of lung water transport-related proteins AQP1， AQP5， and α-ENaC through cAMP/PKA pathway， thereby restoring the lung functions in rats with syndrome of cold fluid accumulated in lung. Na+-K+-ATPase may play an auxiliary role in the regulation of lung water transport. This provides a certain objective basis for preliminarily elucidating the connotation of lung governing water movement from the perspective of lung water transport-related proteins.

Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Background@#Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. @*Methods@#Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. @*Results@#Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. @*Conclusion@#Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.

Analgesic effect of electroacupuncture on chronic pelvic pain in patients with sequelae of pelvic inflammatory disease / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on chronic pelvic pain in patients with sequelae of pelvic inflammatory disease.@*METHODS@#A total of 144 patients with chronic pelvic pain were randomly divided into an observation group (72 cases, 10 cases dropped off) and a control group (72 cases, 9 cases dropped off). The patients in the control group were treated with ibuprofen sustained-release capsules 10 days before menstruation, 0.3 g each time, once a day. On the basis of the treatment of the control group, the patients in the observation group were treated with EA at Guanyuan (CV 4), Shuidao (ST 28), Guilai (ST 29), Shenshu (BL 23) and Ciliao (BL 32), disperse-dense wave, 2 Hz/15 Hz of frequency, once a day. The patients in both groups were treated for 10 days per menstrual cycle for 3 menstrual cycles. The visual analogue scale (VAS) scores of lower abdomen and lumbosacral area, local sign score, quality of life scale score and pain disappearance rate were compared between the two groups before and after treatment.@*RESULTS@#The VAS scores of lower abdomen and lumbosacral area as well as each item score and total score of local signs in the observation group after treatment were significantly lower than those before treatment and those in the control group (@*CONCLUSION@#EA can relieve the pain symptoms in patients with chronic pelvic pain and improve their quality of life.

Acupuncture combined with western medication on chronic pelvic pain after pelvic inflammatory disease: a multi-center randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the therapeutic effect between acupuncture combined with ibuprofen sustained-release capsule and simple ibuprofen sustained-release capsule on chronic pelvic pain (CPP) after pelvic inflammatory disease (PID).@*METHODS@#A total of 144 patients were randomized into an observation group (72 cases, 10 cases dropped off) and a control group (72 cases, 9 cases dropped off). Ibuprofen sustained-release capsule was given orally in the control group, one capsule a time. On the basis of the treatment in the control group, acupuncture was applied at Guanyuan (CV 4), Shuidao (ST 28), Guilai (ST 29), Shenshu (BL 23) and Ciliao (BL 32), and Shuidao (ST 28), Guilai (ST 29), Shenshu (BL 23) and Ciliao (BL 32) were connected to electroacupuncture in the observation group. The treatment was given 10 days before menstruation, once a day for 3 menstrual cycles in both groups, and the follow-up was adopted 3 menstrual cycles after treatment. The visual analogue scale (VAS) scores of hypogastrium and lumbosacral region before treatment, after treatment, and at the follow-up, the score of local signs and the score of World Health Organization quality of life questionnaire-brief version (WHOQOL-BREF) before and after treatment were observed in the both groups.@*RESULTS@#After treatment and at the follow-up, the VAS scores of hypogastrium and lumbosacral region were decreased compared before treatment in both groups (@*CONCLUSION@#Acupuncture combined with ibuprofen sustained-release capsule can effectively improve the symptoms, signs and quality of life in patients with CPP after PID, the therapeutic effect is superior to simple ibuprofen sustained-release capsule.

Natural products as potent inhibitors of hypoxia-inducible factor-1α in cancer therapy / 中国天然药物

Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α (HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evidence has demonstrated that HIF-1α promotes tumor angiogenesis, metastasis, metabolism, and immune evasion. Natural products are an important source of antitumor drugs and numerous studies have highlighted the crucial role of these agents in modulating HIF-1α. The present review describes the role of HIF-1α in tumor progression, summarizes natural products used as HIF-1α inhibitors, and discusses the potential of developing natural products as HIF-1α inhibitors for the treatment of cancer.

Transforming growth factor-β-activated kinase 1 and pathological myocardial hypertrophy / 生理学报

The transforming growth factor-β-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family. TAK1 plays important roles in many biological functions. Cardiac hypertrophy can be identified as physiological or pathological myocardial hypertrophy. TAK1 not only participates in the development of normal myocardium, but also plays an important role in regulating the occurrence and development of pathological myocardial hypertrophy. Angiotensin II (Ang II) or pressure overload induces pathological cardiac hypertrophy through different ways, such as hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional expression of TAK1, or transforming growth factor-β1 (TGF-β1)-, thyroid hormone-, ubiquitin protease-mediated TAK1 phosphorylation or ubiquitination. This article reviews the role of TAK1 in the occurrence and development of pathological myocardial hypertrophy and discusses the potential of TAK1 as an important target for the prevention and treatment of clinical myocardial hypertrophy.

Four new corynanthe-type alkaloids from the roots of Alstonia scholaris / 中国天然药物

Four new corynanthe-type alkaloids, meloslines C-F (1-4), together with four known ones (5-8) were isolated from the roots of Alstonia scholaris. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation. Compounds 1 and 2 exhibited potent vasorelaxant activity on endothelium-intact renal arteries precontracted with KCl.

Protective effect of phellodendrine on bacterial vaginosis mice / 中草药

Objective To investigate the impact of phellodendrine on treating bacterial vaginosis (BV) mice. Methods BV model mice were induced by vaginal injecting with EPEC and MRSA. After the mice in control and model groups being administrated with phellodendrine (10, 20, and 40 mg/kg) for 7 d, the mice were sacrificed under deep anesthesia. The mice vaginal pathology changes were observed using HE staining method. IL-1β, IL-6, IL-8, and TNF-α secretion in vagina and PGE2, PGF2α levels in uterus were detected using ELISA assay. Uterine MMP-9, TLR4, and NF-κB expression levels were measured using western blotting. Results Vaginal pathology changes were improved by phellodendrine. Specifically, phellodendrine could reduce IL-1β, IL-6, IL-8, and TNF-α secretion in vagina, it could also reduce PGE2 and PGF2α content, and inhibit MMP-9, TLR4, and NF-κB expression levels in uterus tissue. Conclusion Phellodendrine could effectively treat BV and reduce the rise of pre-term birth by simultaneously inhibiting endovaginal inflammatory response and regulating intrauterine TLR4/NF-κB signal pathway in BV mice.

Effect of allogeneic adipose derived mesenchymal stem cells on regulatory T cells in peripheral blood of patients with premature ovarian failure / 解放军医学杂志

Objective To investigate the effect of allogeneic adipose derived mesenchymal stem cells (hADSCs) on regulatory T cells (Tregs) in peripheral blood of patients with premature ovarian failure (POF).Methods hADSCs were isolated from adipose tissue using 0.1％ type Ⅰ collagenase digestion.Adipogenic,osteogenic differentiation and surface molecular characterization were also performed.Peripheral blood mononuclear cells (PBMCs) of POF patients were isolated by density gradient centrifugation.PBMCs were co-cultured with 1 × 104,2 × 104 and 1 × 105 hADSCs for 72 hours under the stimulation of phytohemagglutinin (PHA).The proliferation rate of lymphocytes was measured by CCK-8 method,the proportion of CD4+ CD25+ Foxp3+ Treg cells was measured by flow cytometry.Real-time fluorescent quantitative PCR was used to detect the mRNA level of Foxp3+.Results hADSCs were positive for CD90,CD105 and negative for CD34,CD45,and has adipogenic and osteogenic differentiation ability.The results of CCK-8 showed that hADSCs could significantly inhibit the proliferation of lymphocytes compared with that in control group (P＜0.001).Flow cytometry showed that hADSCs could promote the proliferation of CD4+ CD25+ Foxp3+ Treg cells (P＜0.05).The results of qPCR showed that Foxp3+ mRNA expression was obviously up-regulated in all experimental groups compared with that in control group (P＜0.001).Conclusion hADSCs can play an immune regulatory role and promote the proliferation of Tregs in peripheral blood of patients with premature ovarian failure.

Perioperative Evaluation of Obstructive Sleep Apnea in Bariatric Surgery Population / 中国医学科学院学报

Objective To evaluate the prevalence and clinical characteristics of obstructive sleep apnea (OSA) in bariatric surgery population.Methods Consecutive patients undergoing preoperative evaluation for bariatric surgery and referred for sleep monitoring in Peking Union Medical College Hospital from January 2009 to December 2015 were retrospectively analyzed. Age,gender,symptoms of snoring,fatigue,apnea and somnolence,apnea hyponea index (AHI),arterial blood gas,pulmonary function,sleep respiratory monitoring,positive airway therapy of OSA,and postoperative complications were recorded. The clinical characteristics of OSA groups at different severity were compared using AHI≥5 events/hour and AHI≥15 events/hour as cut-off values. Correlation analysis was applied to identify the clinical factors associated with AHI.Results Of 42 patients with complete sleeping monitoring data before bariatric surgery,30(71.4%) were diagnosed as OSA,14 (33.3%) were moderate or severe and 11 (26.2%) were severe. Also,OSA was not detected before the bariatric surgery in 25 cases (83.3%). Compared with patients with AHI<5 events/hour,patients with AHI≥5 events/hour had significantly older age (t=2.869,P=0.007),higher proportion of observed apnea (P=0.035),higher AHI (z=-4.592,P=0.000),higher proportion of night pulse oxygen saturation(SpO) below 90% (z=-2.746,P=0.006),lower mean SpO (t=-2.071,P=0.046) and lower lowest SpO (t=-3.914,P=0.000). Compared with AHI<15 events/hour group,the AHI≥15 events/hour group had significantly higher BMI (t=2.281,P=0.043),male ratio (P=0.005),incidence of hypertension (P=0.011),proportion of observed apnea (P=0.001),percentage of smoking history (P=0.017),partial pressure of carbon dioxide(PaCO)(t=3.478,P=0.002),AHI (z=-4.592,P=0.000),and proportion of night SpO below 90% (z=-4.530,P=0.000); in addition,the forced expiratory volume in one second(FEV1)% predicted (t=-3.377,P=0.002),forced vital capacity(FVC)% predicted (t=-2.342,P=0.026),night time mean SpO (t=-3.392,P=0.007),lowest SpO (t=-5.535,P=0.000) were significantly decreased. Correlation analysis showed that,in populations with normal PaCO (n=36),AHI was positively correlated with age (r=0.450,P=0.006) and BMI (r=0.384,P=0.021) and negatively correlated with FEV1% predicted (r=-0.457,P=0.008) and FVC% predicted (r=-0.432,P=0.013). Partial correlation analysis showed that,after age and BMI were adjusted,AHI was not correlated with FEV1% predicted(r=-0.287,P=0.125)and FVC%predicted(r=-0.241,P=0.200).Conclusion The incidence and underdiagnosis rate of OSA are high in bariatric surgery population. OSA should be routinely screened in bariatric population to reduce the postoperative complication.

Mitochondrial Autophagy and NLRP3 Inflammasome in Pulmonary Tissues from Severe Combined Immunodeficient Mice after Cardiac Arrest and Cardiopulmonary Resuscitation / 中华医学杂志(英文版)

<p><b>Background</b>The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury.</p><p><b>Methods</b>A potassium chloride-induced cardiac arrest model was established in C57BL/6 and nonobese diabetic/SCID (NOD/SCID) mice. One hundred male C57BL/6 mice and 100 male NOD/SCID mice were randomly divided into five groups (control, 2 h post-CPR, 12 h post-CPR, 24 h post-CPR, and 48 h post-CPR). A temporal dynamic view of alveolar epithelial cells, macrophages, and neutrophils from bronchoalveolar lavage fluid (BALF) was obtained using Giemsa staining. Spatial characterization of phenotypic analysis of macrophages in the lung interstitial tissue was analyzed by flow cytometry. The morphological changes of mitochondria 48 h after CPR were studied by transmission electron microscopy and quantified according to the Flameng grading system. Western blotting analysis was used to detect the expression and activation of the markers of mitochondrial autophagy, NLRP3 inflammasome, and caspase-1.</p><p><b>Results</b>(1) In NOD/SCID mice, macrophages were disintegrated in BALF, and many alveolar epithelial cells were shed at 48 h after resuscitation. Compared with C57BL/6 mice, the ratio of macrophages/total cells peaked at 12 h and was significantly higher in NOD/SCID mice (31.17 ± 4.13 vs. 49.69 ± 2.43, t = 14.46, P = 0.001). After 24 h, the results showed a downward trend. Furthermore, a large number of macrophages were disintegrated in the BALF. (2) Mitochondrial autophagy was present in both C57BL/6 and NOD/SCID mice after CPR, but it began late in the NOD/SCID mice. Compared with C57BL/6 mice, phos-ULK1 (Ser) expression was significantly lower at 2 h and 12 h after CPR (2 h after CPR: 1.88 ± 0.36 vs. 1.12 ± 0.11, t = -1.36, P < 0.01 and 12 h after CPR: 1.52 ± 0.16 vs. 1.05 ± 0.12, t = -0.33, P < 0.01), whereas phos-ULK1 (Ser) expression was significantly higher at 2 h and 12 h after CPR in NOD/SCID mice (2 h after CPR: 1.28 ± 0.12 vs. 1.69 ± 0.14, t = 1.7, P < 0.01 and 12 h after CPR: 1.33 ± 0.10 vs. 1.94 ± 0.13, t = 2.75, P < 0.01). (3) Furthermore, NLRP3 inflammasome/caspase-1 activation in the pulmonary tissues occurred early and for only a short time in C57BL/6 mice, but this phenomenon was sustained in NOD/SCID mice. The expression of the NLRP3 inflammasome increased modestly in the C57 mice, but the increase was higher in the NOD/SCID mice than in the C57BL/6 mice, especially at 12, 24, 48 h after CPR (48 h after CPR: 1.46 ± 0.13 vs. 2.97 ± 0.19, t = 5.34, P = 0.001). The expression of caspase-1-20 generally followed the same pattern as the NLRP3 inflammasome.</p><p><b>Conclusions</b>There is a regulatory relationship between the NLRP3 inflammasome and mitochondrial autophagy after CPR in the healthy mice. This regulatory relationship was disturbed in the NOD/SCID mice because the signals for mitochondrial autophagy occurred late, and NLRP3 inflammasome- and caspase-1-dependent cell injury was sustained.</p>

Prognostic Analysis of Minimal Residual Disease from Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplant by Flow Cytometry / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the value of flow cytometry (FCM) detection in prognostic evaluation of minimal residual disease (MRD) of acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Eighty-two cases of AML (except M3) after allo-HSCT who accord to enrolled condition (no MRD positive after allo-HSCT confirmed by regular flow cytometry detection and followed-up for 2 years) from April 2012 to September 2016 in our department were selected. Among 82 cases males were 50 and females were 32 with average age of 27.27 (2-57) years old. According to FAB classification, 2 cases were classified as M0/M1, 51 cases as M2, 24 cases as M4/M5 and 5 cases as M6. The antibody panels were selected accordingly to the initial leukemia associated immunophentype(LAIP) of patients.</p><p><b>RESULTS</b>Twenty patients (24.39%) were identified as MRD(0.10%-4.91%, mean 1.64%) in 82 AML patients after allo-HSCT (all the patients were in complete remission phase based on bone marrow morphology). During follow-up, 16 cases relapsed (relapse rate 80%)in 20 MRDcases, including 1 case with extramedullary relapse; 4 out of 62 MRDcases relapsed (relapse rate 6.45%)in bone marrow, and 2 cases extramedullary relapsed. The average survival time of leukemia- free survival (LFS) in group MRDwas 15.19 ± 3.99 months, median LFS was 10± 3.84 months. The average LFS time was 53.50 ± 1.69 months in MRDgroup (P<0.001). The average overall survival (OS) of the MRDgroup was 22.52 ± 5.72 months, the median OS was 18 ± 3.27 months; the average OS time was 42.86 ± 2.83 months in MRDgroup(P=0.008).</p><p><b>CONCLUSION</b>For the patients with morphologically complete remission after allo-SCT, the FCM regular monitoring of bone marrow MRD closely relates with its relapse rate, LFS and OS. Compared with the MRDgroup, the relapse rate of MRDgroup is significantly increases, and the LFS and OS significantly decreases.</p>

Dynamic changes of pH2AX expression in the reversibility of mouse testicular reproductive function impaired by single heat stress / 中华男科学杂志

Objective@#To investigate the role of pH2AX in the reversibility of mouse testicular reproductive function impaired by single heat stress.@*METHODS@#Twenty-four C57 male mice were randomly divided into heat stress and control groups and immersed in water at 43℃ and 25℃, respectively, for 15 minutes. At 1, 7, and 14 days of heat exposure, all the mice were sacrificed and their testis tissues collected for determining the apoptosis of the germ cells by TUNEL and measuring the expression level of the pH2AX protein by immunohistochemistry and Western blot.@*RESULTS@#The highest percentage of apoptotic cells were found in the seminiferous tubules of the mice in the heat stress group on the 1st day of the exposure and almost no apoptosis was observed at 7 and 14 days. The pH2AX protein was expressed in the nuclei of the basement membrane of adjacent seminiferous tubules. Compared with the control group, the expression of pH2AX was significantly increased on the 1st day of exposure (0.47 ± 0.02 vs 1.61 ± 0.04, P <0.01), then decreased at 7 days (0.85 ± 0.03) in comparison with that on the 1st day (P <0.01), and again elevated at 14 days (1.72 ± 0.02) as compared with either those at 1 and 7 days (P <0.01) or that of the control (P <0.01).@*CONCLUSIONS@#Heat stress causes dynamic changes of the pH2AX expression in the testis of the mouse, which are associated with heat stress-induced proliferation and division of the testicular spermatogenic cells.

Secreted Frizzled-Related Protein 5 (SFRP5) in Patients with Obstructive Sleep Apnea / 中国医学科学杂志(英文版)

Objective Obstructive sleep apnea (OSA) is closely related to obesity, insulin resistance and inflammation. Secreted frizzled-related protein 5 (SFRP5) is a recently discovered adipokine. It is involved in insulin resistance and inflammation in obesity. This study aimed at evaluating the association between SFRP5 and sleeping characteristics as well as biochemical parameters of OSA patients. Methods This was a prospective case control study. Nondiabetic OSA patients and controls were consecutively recruited and divided into three groups: OSA group, apnea-hypopnea Index (AHI)≥5/h; healthy controls with normal body mass index (BMI); obese controls without OSA, and BMI > 24.0 kg/m. All participants underwent polysomnography (PSG). Plasma SFRP5 was examined using enzyme-linked immunosorbent assay (ELISA). Blood biochemical examinations, including fasting blood glucose (FBG), lipid profile, hypersensitive C-reactive protein (hsCRP), were performed early in the morning after PSG. Patients with severe OSA were treated with nasal continuous positive airway pressure (nCPAP), and plasma SFRP5 was repeatedly measured for comparison. Results Sixty-eight subjects were enrolled in the study, including 38 patients of OSA, whose medium AHI was 58.70 /h (36.63, 71.15), 20 obese controls, and 10 healthy controls. The plasma SFRP5 level of OSA patients was not significantly different from that of healthy controls or obese controls. In OSA patients, SFRP5 level correlated positively with triglyceride level (r=0.447, P=0.005) and negatively with LDL-cholesterol level and HDL- cholesterol level (r=-0.472 and P=0.003; r=-0.478 and P=0.002; respectively). SFRP5 level was not found correlating with FBG, AHI, or any of nocturnal hypoxia parameters. After overnight nCPAP treatment, plasma SFRP5 levels of OSA patients did not change significantly (t=1.557, P = 0.148) compared to that of pretreatment. Conclusions In nondiabetic OSA patients, plasma SFRP5 is associated with the lipid profile. However, no correlation was observed between SFRP5 and FBG or sleep parameters. The SFRP5 level of OSA patients did not differ from that of non-OSA individuals in our study.

Nano-LC-ESI MS/MS analysis of proteins in dried sea dragon Solenognathus hardwickii and bioinformatic analysis of its protein expression profiling / 中国天然药物

The sea dragon Solenognathus hardwickii has long been used as a traditional Chinese medicine for the treatment of various diseases, such as male impotency. To gain a comprehensive insight into the protein components of the sea dragon, shotgun proteomic analysis of its protein expression profiling was conducted in the present study. Proteins were extracted from dried sea dragon using a trichloroacetic acid/acetone precipitation method and then separated by SDS-PAGE. The protein bands were cut from the gel and digested by trypsin to generate peptide mixture. The peptide fragments were then analyzed using nano liquid chromatography tandem mass spectrometry (nano-LC-ESI MS/MS). 810 proteins and 1 577 peptides were identified in the dried sea dragon. The identified proteins exhibited molecular weight values ranging from 1 900 to 3 516 900 Da and pI values from 3.8 to 12.18. Bioinformatic analysis was conducted using the DAVID Bioinformatics Resources 6.7 Gene Ontology (GO) analysis tool to explore possible functions of the identified proteins. Ascribed functions of the proteins mainly included intracellular non-membrane-bound organelle, non-membrane-bounded organelle, cytoskeleton, structural molecule activity, calcium ion binding and etc. Furthermore, possible signal networks of the identified proteins were predicted using STRING (Search Tool for the Retrieval of Interacting Genes) database. Ribosomal protein synthesis was found to play an important role in the signal network. The results of this study, to best of our knowledge, were the first to provide a reference proteome profile for the sea dragon, and would aid in the understanding of the expression and functions of the identified proteins.

Effects of calycosin-7-O-β-D-glucoside on cell apoptosis in cervical cancer HeLa cells and expression of Bcl-2/Bax / 中草药

Objective: To explore the effect of calycosin-7-O-β-D-glucoside (CG) on apoptosis in cervical cancer HeLa cells and expression of Bcl-2/Bax. Methods: HeLa cells were cultured and divided into two groups, including control group and experimental group. Cell viabilities were determined by the MTT method; Apoptosis and cell cycle were analyzed by flow cytometry; The changes of protein expression of cleaved Caspase-3, Bcl-2, and Bax were detected by Western blotting. Results: From the data of MTT, the cell proliferation of human cervical cancer HeLa cells was inhibited by CG (2.5-100 μg/mL) in a dose- and time-dependent manner. Flow cytometry assays showed that EGCG significantly induced the apoptosis in HeLa cells. The apoptosis rate of the experimental group were increased gradually in 48 h after treated with CG (20, 40, and 80 μg/mL), they were 10.40%, 25.50%, and 39.40%, respectively, significantly higher than those in the control group. The data of Western blotting showed that CG down-regulated Bcl-2 and up-regulated cleaved Caspase-3 and Bax in a dose-dependent manner. Conclusion: CG could inhibit the the proliferation of HeLa cells and promote apoptosis, and the anticancer effect of CG may be associated with the down-regulation of Bcl-2 expression and up-regulation of Bax expression, as well as the increase of relative activity of Caspase-3. CG may be a promising antitumor agent for cancer treatment.

Gene melting curve spectratyping technique in analyzing polymorphism of t-cell receptor beta chain variable region in cd4+ t cells of tuberculosis patients / 第二军医大学学报

Objective To analyze the polymorphism of the T-cell receptor (TCR) beta chain variable region(BV) gene family spectratyping of peripheral blood CD4+T cells in tuberculosis patients by gene melting curve spectratyping (GMCS) technique combined 24 h fluorescence quantitative (FQ)-PCR. Methods The total RNA of peripheral blood mononuclear cells (PBMCs) from 15 healthy blood donors and 30 tuberculosis patients were used to obtain the cDNA. The cDNAs were amplified by FQ-PCRusing 26 different forward primers and the same reverse primer, and the spectratype was analyzed by DNA melting curve. Results The DNA melting curves of each TCR BV family in 15 healthy donors showed the same spectratype. However, the DNA melting curves of 26 TCR BV families showed different spectratypes in 30 tuberculosis patients comparedwith healthy blood donors, and the different rate was from 6. 7% to 33. 3%. The resutt indicated that the difference rate of 26 TCR BV families in tuberculosis patients was significantly different from that of healthy blood donors (P<0. 05, P<0. 01). In addition, the different rates of 13 TCR BV families (totally 26 families) in tuberculosis patients were more than 20%. Conclusion This study suggests that FQ-PCR combinedwithGMCS is a convenient and stable method for detecting the TCR beta gene repertoire in the peripheral blood of tuberculosis patients.

Socio-economic and psychosocial determinants of smoking and passive smoking in older adults / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To determine the associations of socio-economic and psychosocial factors with active and passive smoking in older adults.</p><p><b>METHODS</b>Using a standard interview method, we examined random samples of 6071 people aged⋝60 years in 5 provinces of China during 2007-2009.</p><p><b>RESULTS</b>World age-standardised prevalence for current and former smoking in men was 45.6% and 20.5%, and in women 11.1% and 4.5%. Current smoking reduced with older age but increased with men, low socioeconomic status (SES), alcohol drinking, being never-married, pessimistic and depressive syndromes. Former smoking was associated with men, secondary school education, a middle-high income, being a businessman, being widowed, less frequencies of visiting children/relatives and friends, and worrying about children. Among 3774 never-smokers, the prevalence of passive smoking was 31.5%, and the risk increased with women, low SES, alcohol drinking, being married, having a religious believe, and daily visiting children/relatives. There were sex differences in the associations, and an interaction effect of education and income on smoking and passive smoking.</p><p><b>CONCLUSION</b>Older Chinese had a higher level of smoking and passive smoking than those in high income countries, reflecting China's failures in controlling smoking. The associations with low SES and different psychosocial aspects and sex differences suggest preventative strategies for active and passive smoking.</p>