[Clinical and bioinformatics analysis of the relationship between LAMA3 DNA methylation expression and platinum resistance and prognosis in epithelial ovarian cancer].

Objective: To investigate the effect of DNA methylation of laminin α3 (LAMA3) on the prognosis of platinum-resistant epithelial ovarian cancer (EOC) and its possible mechanism. Methods: (1) The relationship between DNA methylation of LAMA3 and platinum resistance in EOC was evaluated by bioinformatics. (2) A total of 67 EOC patients treated at Guangxi Medical University Cancer Hospital from January 2000 to December 2012 were selected to detect the levels of LAMA3 DNA methylation in EOC tissues using pyrophosphate sequencing technology to explore its diagnostic efficacy for platinum resistance and prognosis in EOC patients. Furthermore, its impact on chemotherapy efficacy and prognosis of platinum resistant EOC patients were also analyzed. Results: (1) Ten proteins highly interacting with LAMA3 were screened from the Gene Interaction Retrieval Platform (STRING) database, including laminin ß (LAMB) 3, laminin γ (LAMC) 3, integrin α (ITGA) 6, intestine protein ß4 (ITGB4), ITGA3, LAMC1,LAMB2, dystrophin associated glycoprotein 1 (DAG1), LAMB1 and cytochrome P450c17α (COL17A1) protein; kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that LAMA3 and its related interacting proteins participate in the regulation of malignant tumor occurrence and development through signaling pathways such as apoptosis, cell cycle, DNA damage response, epithelial mesenchymal transition (EMT), androgen receptor (AR), estrogen receptor (ER), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt), RAS/mitogen activated protein kinase (MAPK), receptor tyrosine kinase (RTK), tuberous sclerosis protein complex (TSC)/mammalian target of rapamycin (mTOR), and their expression levels were related to the sensitivity of chemotherapy drugs such as cisplatin in EOC. (2) Our clinical data analysis found that the LAMA3 DNA methylation level in EOC tissue of the platinum-sensitive group (35 cases) was 71% (25/35), which was higher than 69% (22/32) in the platinum-resistant group (32 cases), with statistically insignificant difference (χ2=0.057, P=0.811). The area under the curve (AUC) of LAMA3 DNA methylation level for assessing platinum resistance in EOC was 0.601, and the AUC for predicting EOC patient prognosis was 0.686. The chemotherapy efficacy of EOC patients with high methylation of LAMA3 DNA was worse than that of patients with low methylation, 50% (12/24) vs 15/15, with statistically significant difference (χ2=10.833, P=0.001). The level of LAMA3 DNA methylation had a significant impact on the progression free survival and overall survival of EOC patients (both P<0.05). Conclusion: The level of LAMA3 DNA methylation has certain diagnostic and predictive value for platinum resistance and prognosis in EOC patients, which may be closely related to the regulatory mechanism, platinum resistance and prognosis of EOC.

[Application of acellular dermal matrix in periodontal soft tissue augmentation surgery].

The substitute materials of autologous tissue graft for periodontal soft tissue augmentation surgery develop rapidly. The use of substitute material can avoid the second operation area, shorten the operation time, reduce the postoperative reaction and pain, and is not limited by the quantity, suitable for a wide range of cases. In this paper, the characteristics, histological study, clinical application and therapeutic effect of acellular dermal matrix as a substitute material for autologous tissue transplantation were introduced to provide reference for clinical work.

[The correlation between metabolic parameters in (18)F-FDG PET-CT and solid and micropapillary histological subtypes in lung adenocarcinoma].

Objective: Solid and micropapillary pattern are highly invasive histologic subtypes in lung adenocarcinoma and are associated with poor prognosis while the biopsy sample is not enough for the accurate histological diagnosis. This study aims to assess the correlation and predictive efficacy between metabolic parameters in (18)F-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET-CT), including the maximum SUV (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and solid and micropapillary histological subtypes in lung adenocarcinoma. Methods: A total of 145 resected lung adenocarcinomas were included. The clinical data and preoperative (18)F-FDG PET-CT data were retrospectively analyzed. Mann-Whitney U test was used for the comparison of the metabolic parameters between solid and micropapillary subtype group and other subtypes group. Receiver operating characteristic (ROC) curve and areas under curve (AUC) were used for evaluating the prediction efficacy of metabolic parameters for solid or micropapillary patterns. Univariate and multivariate analyses were conducted to determine the prediction factors of the presence of solid or micropapillary subtypes. Results: Median SUV(max) and TLG in solid and papillary predominant subtypes group (15.07 and 34.98, respectively) were significantly higher than those in other subtypes predominant group (6.03 and 10.16, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for prediction of solid and micropapillary predominant subtypes [AUC=0.811(95% CI: 0.715~0.907) and 0.725(95% CI: 0.610~0.840), P<0.05]. Median SUV(max) and TLG in lung adenocarcinoma with the solid or micropapillary patterns (11.58 and 22.81, respectively) were significantly higher than those in tumors without solid and micropapillary patterns (4.27 and 6.33, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for predicting the presence of solid or micropapillary patterns [AUC=0.757(95% CI: 0.679~0.834) and 0.681(95% CI: 0.595~0.768), P<0.005]. Multivariate logistic analysis showed that the clinical stage (Stage Ⅲ-Ⅳ), SUV(max) ≥10.27 and TLG≥7.12 were the independent predictive factors of the presence of solid or micropapillary patterns (P<0.05). Conclusions: Preoperative SUV(max) and TLG of lung adenocarcinoma have good prediction efficacy for the presence of solid or micropapillary patterns, especially for the solid and micropapillary predominant subtypes and are independent factors of the presence of solid or micropapillary patterns.

Effect of menopausal symptom treatment options on palpitations: a systematic review.

This systematic review provides an overview of the effects of menopausal symptom treatment options on palpitations, defined as feelings of missed or exaggerated heart beats, reported by perimenopausal and postmenopausal women. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searches were conducted in PubMed, CINAHL and PsycINFO to identify articles meeting pre-specified inclusion criteria. Of 670 unique articles identified, 37 were included in the review. Treatments included drug therapies and non-drug therapies. Palpitations were studied as an outcome in 89% of articles and as an adverse effect in 11%. Articles provided mostly level II/III evidence due to their design and/or small sample sizes. Based on available evidence, no therapies can be fully recommended for clinical practice. Only some hormonal agents (e.g. estradiol) can be recommended with caution based on some positive evidence for reducing palpitation prevalence or severity. However, other drug therapies (e.g. moxonidine, atenolol), dietary supplementary treatments (e.g. isoflavones, Rheum rhaponticum, sage), cognitive-behavioral intervention and auricular acupressure cannot be recommended given the existing evidence. Additional well-designed randomized controlled treatment trials focusing on palpitations during the menopause transition as an inclusion criteria and outcome are needed to advance the field.

[Bioinformatics analysis of drug-resistant ceRNA in epithelial ovarian cancer].

Objective: To explore the possible biological function of long-chain non-coding RNA (lncRNA) on epithelial ovarian cancer (EOC) drug resistance and the value of new diagnostic markers through bioinformatics analysis, clinical testing and verification methods. Methods: (1) Mining the lncRNA related to EOC and constructing the competing endogenous RNA (ceRNA) regulatory network: comprehensively apply text mining, data prediction and network construction and other bioinformatics methods to establish a potential ceRNA regulatory network related to EOC drug resistance, namely lncRNA-microRNA (miRNA)-mRNA regulatory network. (2) Clinical verification: a total of 95 cancer tissue specimens were collected from EOC patients who underwent cytoreductive surgery at the Affiliated Tumor Hospital of Guangxi Medical University from June 2008 to October 2016, of which 54 were platinum-resistant patients (resistance group), 41 platinum-based drug-sensitive patients (sensitive group). Real-time fluorescent quantitative PCR was used to detect the expression of lncRNA in EOC tissues of the two groups, the effect of lncRNA expression on the prognosis of EOC patients, and the diagnostic efficacy of lncRNA expression on resistance to EOC were also analyzed. Results: (1) Text mining preliminarily screened out 25 differentially expressed lncRNA related to the occurrence and development of EOC, and further subcellular localization analysis found that 8 lncRNA exist in the cytoplasm. Through further data mining, collinear literature analysis and construction of ceRNA, the regulatory network predicts that the two lncRNA molecules, GAS5 and HOTAIR, could serve as key ceRNA molecules. (2) Through real-time fluoressent quantitative PCR verification, it was found that both GAS5 and HOTAIR were highly expressed in drug-resistant EOC tissues, which affects the progression-free survival (PFS) and overall survival (OS) time of patients with drug-resistant EOC independent risk factors (P<0.05). The receiver operating characteristic (ROC) area under the curve (AUC) of GAS5 alone was 0.678, the AUC of HOTAIR alone was 0.863, and the AUC of GAS5 combined with HOTAIR was 0.871, and there were statistically significant differences (all P<0.05). Conclusions: The high expression of GAS5 and HOTAIR is closely related to the drug resistance of EOC, which could be used as a potential predictor of response to chemotherapy. At the same time, the combined detection of GAS5 and HOTAIR has a certain diagnostic efficiency for patients with platinum-resistant EOC. This method of using the ceRNA regulatory network to predict key molecules will provide new ideas for the diagnosis and treatment of EOC.

Review and Prospect of Pathological Features of Corona Virus Disease.

ABSTRACT: Since 2003, coronavirus has caused multiple major public health events that resulted in global epidemics, such as severe acute respiratory syndrome （SARS）, Middle East respiratory syndrome （MERS） and corona virus disease 2019 （COVID-19）. Especially since COVID-19 outbroke in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people's health and lives. But so far, the pathological diagnosis of COVID-19 has been relatively deficient： it is still confined to the pathological findings of punctured organs, and the majority of medical workers have poor awareness of its pathological characteristics. The COVID-19, as same as SARS and MERS, is caused by coronaviruses and can cause viral pneumonia. They have certain similarities. This article comprehensively reviews the pathological features observed in the autopsies of the aforementioned three diseases, in order to provide reference to the analysis of pathological changes of COVID-19.

[Predictive value of serum glycosylated hemoglobin for the onset of nonalcoholic fatty liver disease].

Objective: To discuss the affect of glycosylated hemoglobin (HbA1c) level for the onset of nonalcoholic fatty liver disease (NAFLD) in cohort population. Methods: An epidemiological survey of the relationship between HbA1c and NAFLD conducted in 2012 was based at cohort baseline, and three follow-up sessions conducted in 2013, 2014 and 2015. In total 2 811 subjects were included in the study after exclusion of NAFLD patients at baseline and those who lost their lives due to relocation, and death. The Cox proportional hazard model was used to analyze the relationship between glycosylated hemoglobin and other risk factors of NAFLD. Continuous variables were compared using the t-test or the Mann-Whitney test. χ (2)-test was used for the measurement of categorical data. Results: A total of 2 811 subjects with mean age of 59 (58.2±9.8) years old, including 1 664 males and 1 147 females. Age, waist circumference, body mass index, systolic blood pressure, γ-glutamyltransferase and fasting blood glucose level of HbA1c abnormal group were higher than normal group. The incidence of NAFLD in the abnormal HbA1c level group (25.4%) was higher than normal group (14.9 %), and diastolic blood pressure, high-density lipoprotein cholesterol was lower than normal group and the differences were statistically significant. During the three follow-up intervals, there were 440 new cases of NAFLD, consisting 285 males and 155 females with cumulative incidence of 15.7% (440/2 811). Multivariate Cox regression analysis showed that patients with elevated HbA1c had a higher risk of developing NAFLD (HR 1.796; 95% CI 1.335~2.418; P < 0.01), and the increased HbA1c level after adjustment for gender, age, and metabolic syndrome-related factors remained an independent risk factors for NAFLD (HR 1.580; 95.0% CI 1.161-2.152; P < 0.01). Conclusion: An elevated HbA1c levels have a positive predictive value for the onset of NAFLD.

[Current epidemiological status of causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital within the past 20 years].

Objective: To investigate the causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in our hospital and the changes in such causes within the past 20 years. Methods: A retrospective analysis was performed for the clinical data of 7570 patients who were admitted to our hospital from January 1995 to December 2015. The chi-square test was used for the statistical analysis of constituent ratio. Results: Of all 7570 patients with liver disease, 4930 (65.13%) had viral hepatitis, 332 (4.39%) had immune disease, 215 (2.84%) had drug-induced liver injury, 192 (2.54%) had fatty liver disease, 88 (1.16%) had schistosome-induced liver disease, 160 (2.11%) had inherited metabolic diseases, and 20 (0.13%) had vascular disease; 689 (9.1%) still had no clear cause of disease at discharge. The proportion of patients with viral hepatitis was 77.61% in the first 10 years and 59.19% in the last 10 years (P < 0.01). As for liver disease caused by hepatotropic virus, there were significant increases in the proportion of patients with hepatitis C or hepatitis E from the first to the last 10 years (hepatitis C: 2.24% vs 15.56%, P < 0.01; hepatitis E: 18.61% vs 23.07%, P < 0.05), while there were significant reductions in the proportion of patients with hepatitis B (68.14% vs 60.01%, P < 0.05) or hepatitis A (10.7% vs 1.36%, P < 0.05). The proportion of patients with immune diseases was 0.82% in the first 10 years and 6.08% in the last 10 years (P < 0.01). There were also certain changes in the proportion of patients with liver disease caused by other reasons. Conclusion: There is a large proportion of patients with viral hepatitis among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital, especially hepatitis B and E caused by hepatotropic virus. There is a certain change in the epidemiology of liver disease within the past 20 years, with a reduction in the proportion of patients with viral hepatitis and an increase in the proportion of patients with non-infectious liver diseases. There is a large proportion of patients with unknown causes of liver disease.

Updated meta-analysis of controlled observational studies: proton-pump inhibitors and risk of Clostridium difficile infection.

Attention has recently been directed toward a plausible link between Clostridium difficile infection (CDI) and proton-pump inhibitors (PPIs). However, the results of studies on the association between CDI and PPI remain controversial. We searched the literature databases from their inception to December 2016, without restriction of language, including all controlled observational studies examining the association between acid-suppressive therapy and CDI. Pooled analysis of 50 studies showed a significant association between PPI use and risk of developing CDI (odds ratio: 1.26; 95% confidence interval: 1.12-1.39) as compared with non-users. When stratified by study patients, the relative risk of hospital-acquired CDI and community-associated CDI were 1.29 (1.14-1.44) and 1.17 (0.74-1.59). After restricting the studies according to hospital department, the relative risks of hospital-acquired CDI in ICUs and general wards were 1.43 (0.74-2.11) and 1.29 (1.13-1.45). By implementing cumulative meta-analysis, it was clear that earlier trials of CDI conducted in the early 2000s demonstrated a high degree of heterogeneity and a high percentage of negative results. Since 2011, the overall association between PPI use and risk of developing CDI has remained relatively stable within an effect size between OR 1.20 and 1.26. Our findings indicate a significant associated risk of incident CDI among PPI users, especially in general ward patients. The totality of evidence, when using cumulative meta-analysis, showed that further trials are unlikely to overturn this positive result. Therefore establishing a guideline for the use of PPIs may help in future with the control of CDI.

[Effect of neuroglobin on oxygen-glucose deprivation and reoxygenation induced autophagy in a human neuroblastoma cell line].

Objective: To investigate the effect of neuroglobin on oxygen-glucose deprivation and reoxygenation (OGD/R) induced autophagy in a human neuroblastoma cell line (SH-SY5Y). Methods: SH-SY5Y cells were transfected with plasmids (or vector) to establish a stable cell line of NGB overexpression (OE). After treated with OGD/R, cells were collected for the analyses of mRNA (Atg5, Atg7, BECN1 and FUNDC1) and protein levels of LC3. Furthermore, mitochondrial and cytosolic fractions were isolated for protein levels of PINK1 and Parkin. Results: Treatment of OGD/R significantly increased the levels of mRNA of Atg5, Atg7, BECN1 and FUNDC1 (peak levels were 4.90±0.71, 6.72±0.75, 2.71±0.39 and 3.96±0.78 fold, all P<0.05). The protein level of Parkin increased in mitochondria and decreased in cytoplasm after the treatment. Compared with the vector group, Ngb OE group showed a significant higher level of FUNDC1 mRNA (3.96±0.78 versus 6.86±0.63 fold, P<0.05), while Atg5, Atg7 and BECN1 mRNA levels showed no significant difference. Moreover, the mitochondrial or cytosolic protein levels of PINK1 or Parkin showed no significant difference between Ngb OE and vector group. Conclusions: Overexpression of Ngb can not affect autophagy or mitohpagy in OGD/R treated SH-SY5Y cells. Overexpression of Ngb can increase the mRNA level of FUNDC1 and the mechanism needs further study.

[The role of neuroglobin in oxygen-glucose deprivation and reoxygenation-induced mitochondrial depolarization and reactive oxygen species production in SH-SY5Y cells].

Objective: To investigate the role of neuroglobin (NGB) in oxygen-glucose deprivation and reoxygenation (OGD/R) induced mitochondrial depolarization and reactive oxygen species (ROS)production in a human neuroblastoma cell line (SH-SY5Y). Methods: SH-SY5Y cells were transfected with lentivirus to establish a stable cell line of NGB knockdown (KD). After treated with OGD/R, cells were collected at different time points to analyze NGB mRNA and protein levels. Furthermore, cells were stained with JC-1 and DCFH-DA to evaluate mitochondrial depolarization and ROS production by inverted fluorescence microscope. Also, to determine the neurotoxicity, we measured the lactate dehydrogenase(LDH)level in the cell culture medium. Results: After the treatment of OGD/R, the NGB mRNA and protein started to elevate and peak at 4 h and 8 h (2.04±0.35 fold, 1.69±0.18 fold). Compared with the vector group, NGB KD group had much more mitochondrial depolarization [JC-1 red/green (1.10±0.10) vs (1.46±0.11), P<0.05] and ROS production [DCFH-DA fluorescence (36.30±5.32) vs (16.26±2.97), P<0.05]. Furthermore, NGB KD groups had a higher level of LDH release [(63.42±6.14)%vs (49.65±5.09)%, P<0.05]. Conclusions: NGB plays an important role in the homeostasis of mitochondria. Knockdown of NGB results in increased mitochondrial depolarization, ROS production and neurotoxicity under hypoxia circumstances.

[Influences of DNA methylation upon neuroglobin sustained expression in oxygen- glucose deprivation model].

Objective: To investigate the influences of genomic DNA methylation upon neuroglobin sustained expression in oxygen- glucose deprivation model. Methods: With A549 cell strain as the research object, the control group were cultivated in the complete medium containing 10 µmol/L of 5-azacytidine for 4 days, and the control group was cultivated in the complete medium for 4 days.Then carried out oxygen glucose deprivation treatment for 4 h.Detecting neuroglobin expression, DNA methyltransferase expression, cell inhibition ratio and DNA methylation level at different time points. Results: DNA methylation level of the experimental group declined apparently[6 h : (1.0±0.0) vs (2.1±0.3); 12 h: ( 0.9±0.0) vs (1.4±0.0); 24 h: (0.9±0.0) vs (2.6±0.2); 36 h: (0.9±0.0) vs (2.9±0.1)], neuroglobin expression of the experimental group continued and was obviously higher than that of the control group at the same time point[NGB-PCR: 6 h: (3.3±1.1) vs (0.4±0.1); 12 h: (3.2±0.8) vs (0.1±0.1); 24 h: (4.6±0.6) vs (0.2±0.0); 36 h : (5.1±0.3) vs (0.1±0.1)], while the Cell inhibition ratio of the experimental group was obviously lower than that of the control group at the same time point[(6 h: (10.4±0.5) vs (14.1±0.7); 12 h: (22.0±1.3) vs (35.1±0.5); 24 h: (25.7±1.0) vs (40.6±1.3); 36 h: (30.0±0.8) vs (44.4±0.7)], differences had statistical significance (P<0.05).mRNA expression of three methyltransferases of the experimental group was higher than that of the control group at different time points, where, DNMT1 and DNMT3B showed great differences (P<0.05), while differences in DNMT3A of two groups had no statistical significance (P>0.05). Conclusions: In the OGD/R model of A549 cell strain, genomic DNA methylation resulted in unsustained expression of neuroglobin, but neuroglobin expression increased after demethylation inhibitor was used.

Association between polymorphisms in the promoter region of pri-miR-34b/c and risk of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. MicroRNA-34 (miR-34) gene plays a key role in altering the apoptotic cycle and pathways of downstream cells, and therefore influences carcinogenesis. In this case-control study, we assessed the role of the pri-miR-34b/c rs4938723 polymorphism in HCC risk. The pri-miR-34b/c polymorphic genotype was determined in 286 patients with HCC and 572 controls using polymerase chain reaction-restriction fragment length polymorphism. The male gender (X2 = 12.95, P < 0.001), regular alcohol consumption (X2 = 16.81, P < 0.001), and a family history of cancer (X2 = 11.88, P = 0.001) were associated with HCC risk. However, the age (t = 1.19, P = 0.12) and tobacco smoking habit (X2 = 0.64, P = 0.42) of HCC patients were comparable to those of the controls. The TC (adjusted OR = 1.46, 95%CI = 1.06-2.01) and CC (adjusted OR = 3.07, 95%CI = 1.77-5.34) genotypes of pri-miR-34b/c rs4938723 were correlated with a higher risk of HCC compared to the TT genotype. Moreover, the TC+CC genotype was correlated with an increased risk of HCC compared to the TT genotype (adjusted OR = 1.64, 95%CI = 1.21-2.22). In the recessive model, the CC genotype of pri-miR-34b/c rs4938723 was significantly correlated with an elevated risk of HCC compared to the TT+TC genotype (adjusted OR = 2.50, 95%CI = 1.49-4.22). Further large-scale and multi-center studies are required to confirm these results.

[Expression of mTOR/autophagy pathway in the hippocampus following cerebral ischemia/reperfusion injure in intermittent hypoxia rats].

Objective: To compare the changes in the expression of mTOR and beclin1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion, so as to explore the roles of mTOR/autophagy pathway in global cerebral ischemia/reperfusion injure aggravated by intermittent hypoxia. Methods: One hundred healthy male Wistar rats were randomly divided into: sham operation group(SO group, n=20), intermittent hypoxia group(IH group, n=20), merely ischemia/reperfusion group(I/R group, n=20), intermittent hypoxia ischemia/reperfusion group(IH+ I/R group, n=20), intermittent hypoxia ischemia/reperfusion+ mTOR inhibitor group(Inhibitor group, n=20). IH group, IH+ I/R group and inhibitor group were respectively given intermittent hypoxia for 21 days before ischemia/reperfusion. Ischemia animals were prepared cerebral ischemia-reperfusion model by improved pulsinelli four vessels block (4-VO), the morphological changes of hippocampus nerve cells of rat brain were detected with HE respectively 6, 24 h after ischemia, and the expressions of mTOR protein and beclin1 protein in hippocampus of rat brain was detected with immunohistochemistry and RT-PCR respectively 6, 24 h after ischemia.SPSS 17.0 software was used to analyze the data. Results: Compared with the SO group, the IH group increased the never cells morphology damages and the empression of mTOR and beclin1 (q value was 32.94, 47.31, 63.68, 78.45, all P<0.05); the I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (mTOR in I/R group: 22.38±0.46, 24.16±0.60; mTOR in SO group: 14.65±0.48, 15.40±0.58; beclin1 in I/R group: 8.58±0.58, 10.58±0.49; beclin1 in SO group: 2.06±0.23, 2.10±0.30; the differences were significant, q value was 90.59, 106.83, 95.88, 119.44, all P<0.05). Compared with the IH group, IH+ I/R group increased the never cells morphology damages and the empression of mTOR and beclin1 (q value was 152.23, 165.61, 135.01, 156.48, all P<0.05). Compared with the I/R group, IH+ I/R group increased the never cells morphology damages and the empression of mTOR and beclin1(q value was 94.35, 106.99, 102.79, 115.49, all P<0.05). Compared with the IH+ I/R group, the inhibitor group decreased the never cells morphology damages and the expression of mTOR, increased the expression of beclin1(mTOR in IH+ I/R group: 30.40±0.43, 32.86±0.50; mTOR in inhibitor group: 26.60±0.37, 28.51±0.52; beclin1 in IH+ I/R group: 15.57±0.57, 18.78±0.43; beclin1 in inhibitor group: 21.74±0.51, 24.32±0.49; the differences were significant, q value was 44.71, 53.05, 90.74, 78.03, all P<0.05). Conclusion: Intermittent hypoxia can aggravate the damage on nerve cells by activating mTOR/autophagy pathway after ischemia.

Breaking through the strength-ductility trade-off dilemma in an Al-Si-based casting alloy.

Al-Si-based casting alloys have a great potential in various industrial applications. Common strengthening strategies on these alloys are accompanied inevitably by sacrifice of ductility, known as strength-ductility trade-off dilemma. Here, we report a simple route by combining rapid solidification (RS) with a post-solidification heat treatment (PHT), i.e. a RS + PHT route, to break through this dilemma using a commercial Al-Si-based casting alloy (A356 alloy) as an example. It is shown that yield strength and elongation to failure of the RS + PHT processed alloy are elevated simultaneously by increasing the cooling rate upon RS, which are not influenced by subsequent T6 heat treatment. Breaking through the dilemma is attributed to the hierarchical microstructure formed by the RS + PHT route, i.e. highly dispersed nanoscale Si particles in Al dendrites and nanoscale Al particles decorated in eutectic Si. Simplicity of the RS + PHT route makes it being suitable for industrial scaling production. The strategy of engineering microstructures offers a general pathway in tailoring mechanical properties of other Al-Si-based alloys. Moreover, the remarkably enhanced ductility of A356 alloy not only permits strengthening further the material by work hardening but also enables possibly conventional solid-state forming of the material, thus extending the applications of such an alloy.

[Effect of obstructive sleep apnea hypoxia on learning memory capacity after cerebral ischemia-reperfusion in rats].

OBJECTIVE: To investigate the effect of obstructive sleep apnea hypoxia on learning memory capacity in rat after ischemia. METHODS: Eighty healthy male wister rats were randomly divided into: sham operation group (SO group, n=20), merely ischemia group (I/R group, n=20), and obstructive sleep apnea hypoxia for 7 days ischemia group (IH7+ I/R group, n=20), obstructive sleep apnea hypoxia for 21 days ischemia group (IH21+ I/R group, n=20). Obstructive sleep apnea hypoxia ischemia groups were respectively given obstructive sleep apnea hypoxia for 7 days and 21 days. Ischemia animals were prepared cerebral ischemia-reperfusion model by improved pulsinelli four vessels block (4-VO), the morphological changes of hippocampus nerve cells of rat brain were detected with HE, neuron pathology in hippocampal regin was observed using electron microscope, and learning memory capacity of rats were assessed by the Morris water maze test. RESULTS: Compared with the SO group, the I/R group demonstrated shortened escaping latency, increased frequency of crossing the platform in the water maze test, decreased survival rate of neurons, and increased apoptotic cells and ultrastructure damages(P<0.05). Compared with the I/R group, obstructive sleep apnea hypoxia ischemia groups showed shortened escaping latency, increased frequency of crossing the platform, decreased survival rate of neurons, and increased apoptotic cells and ultrastructure damages(P<0.05), especially in the IH21+ I/R group(P<0.05). CONCLUSIONS: Obstructive sleep apnea hypoxia can increase the damage of learning memory capacity. This damage is related to hippocampus nerve loss and ultrastructure injury from obstructive sleep apnea hypoxia.

[Clinical characteristics and prognosis in 12 patients with adult T cell leukemia/lymphoma confirmed by HTLV-1 provirus gene detection].

Objective: To analyze the clinical characteristics and prognosis of adult T cell leukemia/lymphoma (ATLL). Methods: Peripheral blood samples from patients who were suspected as ATLL from March, 2013 to July, 2015, were collected for HTLV-1 provirus genes detection in genomic DNA extraction by PCR. Cases showing positive results were confirmed as ATLL. Clinical and laboratory characteristics, therapeutic outcomes and survival evaluation were collected. Results: 12 out of 23 suspected patients were confirmedly diagnosed as ATLL through HTLV-1 provirus genes detection by PCR. Eight patients were male and four patients were female. Median age was 51 (range 28-66) years old. All of those patients came from coastal cities of Fujian province where a HTLV-1 epidemic area locates. In the subtype classification of these 12 ATLL, 11 patients were classified as acute type and one case as lymphoma type ATLL. As one of the clinical characteristics of ATLL, ' flower cells ', with typical or atypical morphology had been observed in a high rate (81.8%). Clinical symptom such as hepatomegaly, splenomegaly and lymphadenectasis were detected in most of patients, and hypercalcemia and elevated LDH were also noted commonly. The ATLL cells immunophenotype were typical, and the major subtype was CD4+ CD8- type. Confection of hepatitis B virus was detected in a high rate (54.5%). Ten patients received chemotherapy, and 2 cases in complete remission after chemotherapy received allogeneic hematopoietic stem cell transplantation. At the end of the follow-up, 7 cases died, 4 cases survived, 1 case was lost, and the median survival was 2.8 (0.9-10.8) months. We found a case had HTLV-1 provirus negative after transplantation. Conclusion: In the coastal area of Fujian Province, ATLL is not rare. Characteristics of those ATLL are typical. But prognosis is still unsatisfactory.

[Effect of umbilical cord mesenchymal stem cell transplantation on immune function and prognosis of patients with decompensated hepatitis B cirrhosis].

Objective: To investigate the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on the immune function and prognosis of patients with decompensated hepatitis B cirrhosis. Methods: A total of 65 patients with decompensated hepatitis B cirrhosis were divided into observation group and control group. The patients in the observation group were given intervention (via the proper hepatic artery or the portal vein) and intravenous infusion of 4×108 hUCMSCs in two doses, as well as the same basic treatment as in the control group. The patients in the control group were given conventional medical treatment. ELISA as used to measure the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), interleukin-10 (IL-10), and transforming growth factor-ß (TGFß) in the observation group before surgery and at 1 week after surgery, as well as the serum levels of IL-6, TNFα, IL-10, and TGFß in the control group on admission and at 1 week after admission. Flow cytometry was used to measure the percentage of lymphocyte subsets in the observation group before surgery and at 1 week after surgery, as well as that in the control group on admission and at 1 week after admission. In addition, the patients' prognosis and major complications during hospitalization were observed in both groups, and the patients were followed up for 24 weeks to record the number of deaths. The t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data which were expressed as percentages. Results: At 1 week after the transplantation of hUCMSCs, compared with the control group, the observation group had significant reductions in the serum levels of IL-6 and TNFα and significant increases in the serum levels of IL-10 and TGFß (all P < 0.001), as well as significant increases in the percentages of T4 cells and Treg cells and significant reductions in the percentages of T8 cells and B cells (all P < 0.05). There were no significant differences in the changes in T3 cells and natural killer cells between the two groups (P > 0.05). Compared with the control group, the observation group had a significantly lower probability of progression to liver failure (6.45% vs 14.71%, P = 0.017). Conclusion: In the treatment of patients with decompensated hepatitis B cirrhosis, transplantation of UCMSCs can inhibit the proliferation of T cells and B cells and the differentiation of T8 cells, upregulate Treg cells, promote the secretion of immunosuppressive cytokines, and reduce the production of inflammatory cytokines. Therefore, it can alleviate liver inflammatory response and liver cell damage and reduce the probability of hepatic failure.

Hypertension-mediated enhancement of JNK activation in association with endoplasmic reticulum stress in rat model hippocampus with cerebral ischemia-reperfusion.

Acute brain ischemia can induce the activation of c-Jun N-terminal kinases (JNKs). Hypertension is a critical etiology for brain ischemia. We identified the effects of hypertension on the activation of JNK as well as its impact on SP600125, a JNK inhibitor, during endoplasmic reticulum stress (ERS) in the hippocampus using a rat model. Transient whole-brain ischemia was induced by 4-vessel occlusion (bilateral vertebral and bilateral common carotid arteries) in normal and spontaneous hypertensive rats. SP600125 (0.05 mg/kg, iv) was administered 30 min before ischemia. Morphological changes in hippocampal nerve cells were observed by cresyl violet staining. Phosphorylation of JNK, and expression levels of CHOP and GPR78, markers for ERS, were detected by western blot at 1, 6, 24, and 48 h, and neurological outcomes were measured using an eight-arm radial maze 48 h after ischemia. Hypertension apparently aggravated impairment of memory function, decreased the density of surviving neurons, increased phosphorylation of JNK, and enhanced CHOP expression, but reduced GPR78 levels in hippocampal tissues following brain ischemia. SP600125 alleviated neurological dysfunction, improved neuron survival, decreased phosphorylation of JNK and levels of CHOP, but increased expression of GPR78 in rats with hypertension during cerebral ischemia by inhibition of ERS.