DNMT3A governs tyrosine kinase inhibitors responses through IAPs and in a cell senescence-dependent manner in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis. Using NSCLC organoid models, we observed that high DNMT3A levels reduced TKI susceptibility of NSCLC cells via upregulating inhibitor of apoptosis proteins (IAPs). Simultaneously, the DNMT3Ahigh subset, which escaped apoptosis, underwent an early senescent-like state in a CDKN1A-dependent manner. Furthermore, the cellular senescence induced by TKIs was observed to be reversible, whereas DNMT3Ahigh cells reacquired their proliferative characteristics in the absence of TKIs, resulting in subsequent tumour recurrence and growth. Notably, the blockade of DNMT3A/IAPs signals enhanced the efficacy of TKIs in DNMT3Ahigh tumour-bearing mice, which represented a promising strategy for the effective treatment of NSCLC.

Correlation between Serum Osteoprotegerin/Soluble Receptor Activator of Nuclear Factor-κβ Ligand Levels and the Left Ventricular Diastolic Dysfunction in Type 2 Diabetes / 中山大学学报(医学科学版)

ObjectiveTo study the possible correlation between serum osteoprotegerin （OPG）/soluble receptor activator of the nuclear factor κB ligand （sRANKL） levels and the left ventricular diastolic dysfunction （LADD） in patients with type 2 diabetes mellitus （T2DM）. MethodsTotally 68 T2DM patients and 37 healthy controls were selected. Serum OPG and sRANKL were determined by solid-phase enzyme-linked immunosorbent assay （ELISA）. The left ventricular diastolic function of T2DM patients was measured by transthoracic echocardiography， where E/A < 1 were regarded as LVDD. T2DM patients were further divided into two subgroups according to E/A ratio （E/A≥1.0 and E/A<1）. Spearman correlation analysis， logistic regression and ROC curves were used to assess the possible correlation between serum OPG/sRANKL and LADD in T2DM patients. ResultsCompared with the healthy controls， serum OPG level in T2DM patients was higher with statistically significant difference （P <0.01）， while serum sRANKL level was lower without statistically significant difference （P =0.32）. T2DM patients with E/A<1 had significantly higher OPG level and lower sRANKL level than those with E/A≥1（P <0.01） in subgroup analysis. Spearman correlation analysis showed serum OPG level was negatively correlated with E/A ratio， while sRANKL was positively related with E/A ratio. In single factor logistic regression analyses， serum OPG ［OR （95% CI）=1.068 （1.031， 1.106）， P<0.001］ and sRANKL ［OR （95% CI）=0.976 （0.959， 0.992）， P=0.003］ were significant correlation with LVDD in T2DM patients. ROC curve analysis showed that the sensitivity and specificity of combined OPG and sRANKL in diagnosing T2DM patients LADD were 78.13% and 88.3%， respectively （area under the curve： 0.857； 95% CI=（0.768， 0.946）； P<0.001）. ConclusionsThe elevated OPG and decreased sRANKL levels may be associated with LADD in T2DM patients.

Gene Analysis for the Sebaceous Carcinoma of Scalp by Whole Exome Sequencing / 中山大学学报(医学科学版)

ObjectiveTo reveal the differences of the related pathogenicity gene mutations between sebaceous adenocarcinoma （SC） of scalp and sebaceous adenoma （SA） of scalp on whole exome level. MethodsWhole exome sequencing was performed on a SC sample and a SA sample by Illumina Hiseq 2500 platform. Suspicious single nucleotide variation sites were selected for mutation conservation and functional analysis. SciClone was used to track subclone evolution and clonal map information was obtained for each tumor sample. The high-frequency significant gene mutations in the tumor sample were screened by MutSigCV software， and compared with the known driver genes. ResultsTwo driver genes TFDP1 and ACVR1B harboring mutations in scalp SC compared to SA were found. ConclusionsThe finding of mutation in driver genes TFDP1 and ACVR1B should be confirmed in a large cohort， which might reveal the mechanism of scalp SC development and find a therapeutic target for SC.

Mechanisms of PiT2-loop7 Missense Mutations Induced Pi Dyshomeostasis / 神经科学通报·英文版

PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.

Efficacy of the No. 10 lymphadenectomy with spleen preservation on patients with gastric cancer and/or esophagogastric junction adenocarcinoma who underwent total gastrectomy: a systematic review and meta-analysis.

Background: Surgery with total gastrectomy and D2 lymph node dissection (LND) has been recommended as the standard treatment for patients with advanced upper and middle gastric carcinoma and/or Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). However, whether the No. 10 lymph node (No. 10 LN, also known as splenic hilar LN) should be dissected in total gastrectomy remains controversial. We aimed to evaluate whether the No. 10 LND with spleen preservation has survival benefit for patients with gastric cancer and/or AEG who underwent the total gastrectomy. Methods: The PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and American Society of Clinical Oncology.org (ASCO.org) were electronically searched to identify eligible studies. The primary outcome was the survival rate, and secondary outcomes included the disease-free survival (DFS) rate and side effects. The Review Manager 5.3.5 software was used for the meta-analysis. The odds ratio (OR) and mean difference with 95% confidence interval (CI) were calculated. The statistical heterogeneity was assessed using chi-square (χ2) and I2 tests. Results: Eight studies enrolling a total of 4,131 patients were eligible for our review. The meta-analysis results demonstrated that the No. 10 LND group was significantly better than the non-No. 10 LND group in terms of the 3- (OR =0.71, 95% CI: 0.62-0.81, P<0.00001) and the 5-year (OR =0.66, 95% CI: 0.58-0.75, P<0.00001) survival rates but not in the 1-year survival rate (OR =0.91, 95% CI: 0.75-1.11, P=0.36). The DFS rates in the No. 10 LND group were significantly increased after 1 (OR =0.76, 95% CI: 0.61-0.93, P=0.008), 3 (OR =0.69, 95% CI: 0.60-0.81, P<0.00001), and 5 (OR =0.66, 95% CI: 0.56-0.76, P<0.00001) years compared with those in the non-No. 10 LND group. Discussion: Evidence shows that the No. 10 LND with spleen preservation can improve the survival and the DFS rates for patients with gastric cancer and/or Siewert type II/III AEG who underwent the total gastrectomy. High-quality prospective trials are expected.

Technical aspects and early results of uniportal video-assisted thoracoscopic complex segmentectomy: a 30 case-series study.

BACKGROUND: With the advantages of better cosmetic incision and faster recovery, uniportal video-assisted thoracoscopic surgery (UP-VATS) has developed rapidly worldwide in recent decades, and indications for UP-VATS have been further expanded to those for conventional VATS. Complex segmentectomy that makes several or intricate intersegmental planes, with more complex procedures, continues to be difficult in minimally invasive techniques. However, there are few reports on UP-VATS complex segmentectomy. In this report, we describe the perioperative clinical data and operative techniques and present our early results of UP-VATS complex segmentectomy in our hospital. METHODS: The records of a total of 30 patients who underwent UP-VATS complex segmentectomy by a single surgeon between January 2021 and June 2021 were retrospectively reviewed. We defined cases as complex segmentectomy if they required resection of segments 9 and 10, combined segmentectomy, segmentectomy + subsegmentectomy, subsegmentectomy, or combined subsegmentectomy. RESULTS: The mean age was 52.8 ± 9.9 years old; the mean nodule size was 0.84 ± 0.36 cm; the mean margin width was 2.307 ± 0.309 cm; the median operative time was 229.0 ± 58.06 min; the mean operative hemorrhage was 56.60 ± 17.95 mL; 5.58 ± 1.74 lymph nodes dissected had not metastasized; the mean duration of postoperative chest tube drainage was 4.7 ± 1.4 days; and the mean postoperative hospital stay was 6.5 ± 3.0 days. Although 1 patient experienced a prolonged air leak, the other 29 recovered uneventfully. Another patient failed to reach the 2-cm safe margins and subsequently underwent completion lobectomy. CONCLUSIONS: UP-VATS complex segmentectomy is a safe and effective procedure in the treatment of lung cancers, sparing more pulmonary parenchyma and ensuring safe margins, with the disadvantage being the lengthy operative times during early skill acquisition.

Free blood use among voluntary blood donors in Shiyan city / 中国输血杂志

【Objective】 To analyze the situation of free blood use and direct reimbursement of blood expenses in Shiyan city, so as to provide basis for more effective service of free blood use and direct reimbursement of blood expense after blood donation, and recruitment and retain of blood donors. 【Methods】 The data of free blood use from 1999 to 2019 in Shiyan city were collected for statistical analysis. Measurement data were described by mean±SD, and enumeration data were described by rate or construction ratio. Chi-square test was used for comparison of construction ratio or rate of stratified groups. 【Results】 In the past 21 years, free blood use has developed from the overall increasing stage (1999~2014) to the overall stable stage (2014~2019). Free blood use accounted for 3.52%(40 722.11/1 156 307.85)of the blood donation. Among the blood recipients, blood donors themselves accounted for only 18.83%(2 240/11 898), far lower than the proportion of their direct relatives. Since 2013, Shiyan has carried out the direct reimbursement of clinical blood expenses of voluntary blood donors according to the unified requirements of Hubei Province. The direct reimbursement rate over the past 7 years was 76.49%(5 397/7 056), and the proportion of people from other cities who applied for reimbursement was 4.02%(284/7 056). 【Conclusion】 The policy of free blood use and blood expense direct reimbursement has promoted the development of blood donation. It can also be further improved by relaxing the reimbursement scope of free blood use, strengthening publicity, optimizing services, strengthening supervision, using WeChat public service platform to carry out remote free blood, and strengthening national network construction.

Preventive effect of trace insulin on cognitive dysfunction induced by sevoflurane inhalation anesthesia in newborn rats and its possible mechanism / 解剖学报

Objective To study the preventive effect of microinsulin on cognitive dysfunction induced by sevoflurane inhalation anesthesia in rats and its possible mechanism. Methods Sixty newborn rats were randomly divided into control group (CON), insulin prevention low dose group (LIP), insulin prevention hihg dose group (HIP), and sevoflurane model group (MOD). The prevention group and the model group were induced by sevoflurane to construct rat cognitive dysfunction model. Morris water maze directional sailing test and space exploration test were used to evaluate the learning and memory function of rats; HE staining was used to observe the pathological morphological changes of hippocampus in rats; Flow cytometry was used to detect the hippocampus of rats cell apoptosis; Detection of rapamycin target protein (mTOR) and eukaryotic peptide chain elongation factor 2 (eEF-2) mRNA levels in hippocampus by RT-PCR; The expression levels of brain-derived neurotrophic factor (BDNF), post-synaptic dense protein-95 (PSD-95), synapsin- I, and calmodulin kinase II α (CaMK II α), mTOR and eEF-2 protein were detected by Western blotting. Results The result of the Morris water maze experiment showed that insulin significantly reduced the escape latency and swimming distance of rats, and increased the number of crossing platforms; Flow cytometry result showed that the insulin prevention group significantly inhibited the apoptosis of rat brain neurons, and the inhibition effect of high-dose insulin prevention group was more obvious; RT-PCR and Western blotting analysis found that the expression levels of mTOR and eEF-2 mRNA and proteins in the hippocampus of the model group increased significantly, while the expression levels of BDNF, PSD-95, synapsin- I, and CaMK II α proteins reduced significantly. The expression levels of mTOR and eEF-2 mRNA and proteins in the hippocampus of rats in the insulin prevention group decreased significantly, while the expression levels of BDNF, PSD-95, synapsin- I, and CaMK II α protein increased significantly. The difference was statistically significant (P < 0.05). Conclusion Trace insulin can increase the expression of synapse-related proteins in the hippocampus of cognitive dysfunction rats, reduce their mTOR and eEF-2 mRNA expression levels, and prevent sevoflurane-induced cognitive impairment in rats. The mechanism may be related to the regulation of mTOR-eEF-2 approach.

Efficacy and Safety of Sacubitril-valsartan in the Treatment of Heart Failure without Reduced Ejection Fraction ： A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and saf ety of sacubitril-valsartan in the treatment of heart failure without reduced ejection fraction （non-HFrEF）patients，and to provide evidence-based reference for its clinical treatment. METHODS：Retrieved from Cochrane Library ，PubMed，Embase，CNKI，VIP and Wanfang data ，during the inception to Feb. 29th，2020，randomized controlled trials （RCTs）about sacubitril-valsartan （trial group ）versus routine medicine as renin- angio- tensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists （control group ） in the treatment of non-HFrEF were collected. After literature screening and data extraction ，the quality of included literatures were evaluated with Cochrane bias risk evaluation tool 5.3.0. Meta-analysis was conducted with Stata 14.0 software，and the publication bias analysis and sensitivity analysis were performed. RESULTS ：Totally 6 RCTs were included ，involving 5 502 patients. Results of Meta-analysis showed that the HF re-hospitalization rate [RR ＝0.84，95％CI（0.77，0.91），P＜0.001] and the serum creatinine elevation rate [RR ＝0.78，95％ CI（0.67，0.91），P＝0.001] in trial group were significantly lower than control group. NYHA classification improvement rate [RR ＝ 1.25，95％CI（1.10，1.43），P＝0.001] and the hypotension rate [RR ＝1.43，95％CI（1.24，1.65），P＜0.001] were significantly higher than control group. There was no statistical significance in the cardiovascular mortality [RR ＝0.94，95％CI（0.79，1.12）， P＝0.481]，all-cause mortality [RR ＝0.95，95％CI（0.83，1.08），P＝0.417]，the levels of NT-proBNP [WMD ＝－301.16，95％CI （－602.77，0.44），P＝0.050] and LVEF [WMD ＝1.49，95％CI（－1.33，4.32），P＝0.300] after treatment ，and the hyperkalaemia rate [RR ＝0.88，95％CI（0.77，1.01），P＝0.070] between 2 groups. The results of publication bias analysis and sensitivity analysis showed there was a high possibility of publication bias ，and the results of several indexes were not stable. CONCLUSIONS ： Sacubitril-valsartan may effectively reduce HF re-hospitalization rate and the risk of elevated serum creatinine in non-HFrEFpatients，improve the heart function but the risk of hypotension is high. The results should be interpreted carefully.

Study on the Optimization of the Extraction Technology of Shengmaiyin Polysaccharide and Its Regulation Effects on Intest- inal Function of Spleen Deficiency Model Rats / 中国药房

OBJECTIVE： To optimize the extraction technology of Shengmaiyin polysaccharide， and to investigate the regulation effects of Shengmaiyin and its polysaccharide on intestinal function of spleen deficiency model rats. METHODS： The contents of polysaccharide were determined by phenol-sulfuric acid method， and the extraction rate of polysaccharide was calculated. Using extraction rate of Shengmaiyin polysaccharide as investigation index， singel factor and orthogonal tests were used to optimize material-liquid ratio， extraction time， extraction temperature and extraction times of Shengmaiyin polysaccharide. Validation test was also conducted. Totally 80 male SD rats were randomly divided into blank group， model group， Shengmaiyin low-dose， medium-dose and high-dose groups （350， 700， 1 400 g/L， by crude drug）， Shengmaiyin polysaccharide low-dose， medium-dose and high-dose groups （24.5， 49， 98 g/L， by crude drug）， with 10 rats in each group. Except for blank group， other groups were given Rheum palmatum water decoction 10 mL/kg to induce spleen deficiency model， once a day， for consecutive 15 d. Since the 16th day， blank group and model group were given isovolumic water intragastrically， while other groups were given corresponding drugs， once a day， for consecutive 10 d. The general status of rats and body weights were recorded in each group. The serum contents of D-xylose， gastrin （GAS） and vasoactive intestinal peptide （VIP） were detected by phloroglucinol method or ELISA. RESULTS： The optimal extraction technology of Shengmaiyin polysaccharide was material-liquid ratio 1 ∶ 10（g/mL）， extraction time 45 min， extraction temperature 80 ℃， extracting for 1 time. Results of validation test showed that extraction rates of the polysaccharide in 3 times were 7.43％， 7.64％， 7.80％ （RSD＝1.01％， n＝3）. After modeling， except for blank group， other groups suffered from loose stools， thin body and reduced food intake， and the body weight and serum level of D-xylose were decreased significantly compared with blank group （P＜0.01）. After last medication， above symptoms of administration groups were improved to different extents. Except for model group， body weight and serum contents of D-xylose in other groups were increased significantly than those before modeling or before medication （P＜0.05 or P＜0.01）. Compared with blank group， body weight and serum content of GAS were decreased significantly in model group， while serum content of VIP was increased significantly （P＜0.01）. Compared with model group， body weight of Shengmaiyin medium-dose group and Shengmaiyin polysaccharide low-dose and high-dose groups， serum contents of D-xylose and GAS in Shengmaiyin medium-dose and high-dose groups and Shengmaiyin polysaccharide low-dose and medium-dose groups were increased significantly， while serum contents of VIP in Shengmaiyin groups and Shengmaiyin polysaccharide low-dose and medium-dose groups were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： The optimized extraction technology of Shengmaiyin polysaccharide is stable and feasible. Shengmaiyin and its polysaccharide contribute to the recovery of intestinal function of spleen deficiency model rat， the effects of which may be associated with the secretion regulation of GAS and VIP.

New progress in the treatment for gastrointestinal stromal tumors / 医学研究生学报

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors. Surgery remains to be the primary treatment for patients with localized GISTs, but there are still many patients suffering from tumor metastasis and recurrence after surgery. Imatinib adjuvant therapy plays an important role in the prevention and treatment of tumor metastasis and recurrence, but there are still many controversies in terms of dosage and time of administration. For initial unresectable GISTs with large volume, neoadjuvant therapy may considered to be an option. Sunitinib and regorafenib have played an important role in the second and the third line treatments. BLU-285 has brought hope to patients with mutation of PDGFRA D842. The emerging immunotherapy is still in the exploration stage of gastrointestinal stromal tumors in recent years. This article reviews the research progress of surgical treatment, neoadjuvant therapy, postoperative adjuvant therapy and other treatments for GISTs.

Effects of dexmedetomidine on expression of c-fos in hippocampus and dentate gyrus in a rat model of endotoxic shock / 中华麻醉学杂志

Objective To evaluate the effects of dexmedetomidine on the expression of c-fos in hippocampus and dentate gyrus in a rat model of endotoxic shock.Methods Thirty-five pathogen-free healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-300 g,were divided into 5 groups (n =7 each) using a random number table:normal saline group (group NS),dexmedetomidine group (group D),endotoxic shock group (group ES),low-dose dexmedetomidine plus lipopolysaccharide (LPS) group (group LD) and high-dose dexmedetomidine plus LPS group (group HD).Dexmedetomidine 0.5 μg/kg was injected via the tail vein in D and LD groups,and dexmedetomidine 4.5 μg/kg was given in group HD.Normal saline 0.5 ml/kg was injected in NS and ES groups,5 min later normal saline 0.5 ml/kg was injected in NS and D groups and LPS 5 mg/kg was injected in the other groups,and the injection time was 10 min in all groups.Rats were sacrificed at 6 h after LPS injection,brains were removed,and the hippocampus and dentate gyrus were isolated for detection of the expression of c-fos by immunohistochemistry.Results Compared with group NS or group D,the expression of c-fos in the hippocampus and dentate gyrus was significantly up-regulated in group ES (P＜0.05).Compared with group LPS,the expression of c-fos in the hippocampus and dentate gyrus was significantly down-regulated in LD and HD groups (P＜0.05).Compared with group LD,the expression of c-fos in hippocampal CA1 and CA3 areas was significantly down-regulated in group HD (P＜0.05).Conclusion The neuroprotective mechanism of dexmedetomidine is related to inhibiting the up-regulated expression of c-fos in the hippocampus and dentate gyrus in a rat model of endotoxic shock.

Blocking programmed death-ligand 1 attenuates maturation inhibition of dendritic cells by co-cultured breast cancer cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study if programmed death-ligand 1 (PL-L1) expression in breast cancer cell activates PD-L1/PD-1 pathway in dendritic cells to inhibit dendritic cell maturation.</p><p><b>METHODS</b>Human monocytes were induced to differentiate into immature dendritic cells using GM-CSF and IL-4, and further to mature dendritic cells using TNF-α. PD-L1-expressing breast cancer cell line MDA-MB-231 was co-cultured in contact with the dendritic cells to observe the effects of the breast cancer cells on the maturation of the dendritic cells. A PD-L1 blocking antibody was applied to the co-culture, and the changes in the inhibitory effect of the MDA-MB-231 cells on dendritic cell maturation was observed. TNF-α-induced dendritic cells were treated with a recombinant human PD-L1 protein to study the effect of PD-L1/PD-1 pathway activation on the maturation of dendritic cells. The expression of PD-L1 in MDA-MB-231 cells and the dendritic cell maturation marker HLA-DR and CD83 were analyzed using flow cytometry.</p><p><b>RESULTS</b>MDA-MB-231 cell line showed PD-L1 positivity on the cell membrane cells at a rate as high as (99.7∓0.15)%. In mature dendritic cells, the positivity rates for HLA-DR and CD83 were (88.8∓6.96)% and (18.36∓3.07)%, respectively, but in the co-culture system, the positivity rates of the dendritic cells were significantly decreased to (42.76∓10.52)% (P<0.01) and (9.93∓2.74)% (P<0.05), respectively, indicating that MDA-MB-231 cells inhibited the maturation of dendritic cells. Following treatment with a PD-L1 antibody isotype control, the percentages of HLA-DR- and CD83-positive cells in the co-culture were (45.17∓10.19)% and (10.15∓2.54)%, which were significantly increased to (63.46∓1.72)% and (16.46∓2.58)% after treatment with PD-L1 antibody, respectively (both P<0.05). Compared with the mature dendritic cell controls, the cells treated with the recombinant human PD-L1 protein exhibited significantly lowered percentages of HLA-DR-positive [from (84.23∓4.18)% to (2.56∓2.39)%, P<0.05] and CD83-positive cells [(87.26∓1.54)% to (60.67∓1.63)%, P<0.05].</p><p><b>CONCLUSION</b>The effect of PD-L1 antibody therapy on triple negative breast cancer can be partially mediated by blocking PD-L1 expression on breast cancer cell membrane, which attenuates the inhibition of dendritic cell maturation in the cancer microenvironment.</p>

Efficiency and safety of drug-eluting stents and bare metal stents in elderly coronary artery disease： Meta-analysis / 中国介入影像与治疗学

Objective To evaluate the efficiency and safety of drug-eluting stents (DES) and bare metal stents (BMS) in elderly with coronary artery disease (CAD).Methods PubMed,Embase,Cochrane Library,CNKI and Wanfang databases were searched before October 28,2017.The pertinent randomized controlled trials (RCTs) and cohort studies (CS) were included.The outcomes were all-cause mortality (ACM),myocardial infarction (MI),target vessel revascularization (TVR),cardiac death (CD),stent thrombosis (ST) and bleeding.Relative risk (RR) with 95％ confidence interval (95％CI) was analyzed.Results A total of 17 studies with 10 813 patients were included.Overall and in CS group,there were significant lower risks of ACM (RR＝0.71,0.68,both P＜0.001),MI (RR＝0.66,P＜0.001;RR＝0.60,P＝0.008),TVR (RR＝0.50,0.54,both P＜0.001),CD (RR＝0.73,0.72,P＝0.003,0.020) and ST (RR＝0.68,0.59,P＝ 0.02,0.01) in DES patients compared with BMS patients,but the risk of bleeding was not significantly different (RR ＝ 1.00,1.00,P ＝ 0.96,0.97).In RCT group,DES (compared with BMS) was only associated with significantly lower risks of MI (RR＝0.68,P＝0.003) and TVR (RR＝0.43,P＜0.001),no difference was detected in other indexes.Conclusion DES is more efficacious and safer than BMS for elderly patients with CAD.

Comparative Proteomic Analysis of Posterior Silk Glands of Wild and Domesticated Silkworms Reveals Functional Evolution during Domestication.

The wild silkworm Bombyx mandarina was domesticated to produce silk in China approximately 5000 years ago. Silk production is greatly improved in the domesticated silkworm B. mori, but the molecular basis of the functional evolution of silk gland remains elusive. We performed shotgun proteomics with label-free quantification analysis and identified 1012 and 822 proteins from the posterior silk glands (PSGs) of wild silkworms on the third and fifth days of the fifth instar, respectively, with 128 of these differentially expressed. Bioinformatics analysis revealed that, with the development of the PSG, the up-regulated proteins were mainly involved in the ribosome pathway, similar to what we previously reported for B. mori. Additionally, we screened 50 proteins with differential expression between wild and domesticated silkworms that might be involved in domestication at the two stages. Interestingly, the up-regulated proteins in domesticated compared to wild silkworms were enriched in the ribosome pathway, which is closely related to cell size and translation capacity. Together, these results suggest that functional evolution of the PSG during domestication was driven by reinforcing the advantageous pathways to increase the synthesis efficiency of silk proteins in each cell and thereby improve silk yield.

Genetic analysis of three families affected with split-hand/split-foot malformation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic etiology of three families affected with split-hand/split-foot malformation (SHFM).</p><p><b>METHODS</b>Peripheral venous blood samples from 21 members of pedigree 1, 2 members of pedigree 2, and 2 members of pedigree 3 were collected. PCR-Sanger sequencing, microarray chip, fluorescence in situ hybridization (FISH), real-time PCR, and next-generation sequencing were employed to screen the mutations in the 3 families. The effect of the identified mutations on the finger (toe) abnormality were also explored.</p><p><b>RESULTS</b>Microarray and real-time PCR analysis has identified a duplication in all patients from pedigrees 1 and 3, which have spanned FKSG40, TLX1, LBX1, BTRC, POLL and FBXW4 (exons 6-9) and LBX1, BTRC, POLL and FBXW4 (exons 6-9) genes, respectively. A missense mutation of the TP63 gene, namely c.692A>G (p.Tyr231Cys), was found in two patients from pedigree 2. FISH analysis of chromosome 10 showed that the rearrangement could fita tandem duplication model. However, next-generation sequencing did not identify the breakpoint.</p><p><b>CONCLUSION</b>The genetic etiology for three families affected with SHFM have been identified, which has provideda basis for genetic counseling and guidance for reproduction.</p>

System practice, experience and trends on the long-term care insurance of China: Based on a comparative study of Qingdao model and Nantong model / 中国卫生政策研究

The system of long-term care insurance,which is one supportive system for the increasing long-term care needs of the elderly in China will be the highlight for the construction of social security system during the 13th Five-Year Plan period.This paper focuses on the current background,models feature and system design of regional practice of long-term care insurance in Qingdao and Nantong,and makes a comparison between them.On the basis of the summarized experience and inspiration,and the existing problems as well as the experience in advanced countries,the author puts forward the corresponding suggestions,in the hope of providing valuable references for the toplevel design of the long-term care insurance system.

System practice, experience and trends on the long-term care insurance of China: Based on a comparative study of Qingdao model and Nantong model / 中国卫生政策研究

The system of long-term care insurance,which is one supportive system for the increasing long-term care needs of the elderly in China will be the highlight for the construction of social security system during the 13th Five-Year Plan period.This paper focuses on the current background,models feature and system design of regional practice of long-term care insurance in Qingdao and Nantong,and makes a comparison between them.On the basis of the summarized experience and inspiration,and the existing problems as well as the experience in advanced countries,the author puts forward the corresponding suggestions,in the hope of providing valuable references for the toplevel design of the long-term care insurance system.

Reference range of left ventricular strain measured by three-dimensional speckle-tracking imaging:Meta analysis / 中国介入影像与治疗学

Objective To obtain the normal reference ranges of global longitudinal strain (GLS),global circumferential strain (GCS),global area strain (GAS) and global radial strain (GRS) of left ventricular in normal adults by three-dimensional speckle tracking imaging (3D-STI) using Meta analysis.Methods Eligible trials which detected global strain of left ventricular in normal subject through 3D-STI were searched in Embase,Pubmed,Cochrane Library database.According to the heterogeneity,parameters of contained studies were analyzed the weighted mean difference (WMD) and 95％ confidence interval (CI).The statistical software was STATA 12.0.Results Totally 1 552 healthy adults from 27 articles were included.Based on the Meta-analysis,theWMDand 95％CIofGLSwere 17.80 and (16.27,19.33),of GCS were 24.73 and (22.50,26.95),of GRS were 47.86 and (39.52,56.19),of GAS were 36.17 and (34.08,38.26).Conclusion The Meta analysis defines reference range of strains obtained by 3D-STI in healthy adults.Using these parameters of 3D globe strains,a guidance of reference for patienfs management and therapy selection may be provided.