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Evidence suggests that abnormal DNA methylation patterns play a crucial role in the etiology and pathogenesis of colon adenocarcinoma (COAD). In this study, we identified a total of 97 methylation-driven genes (MDGs) through a comprehensive analysis of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression analysis identified four MDGs (CBLN2, RBM47, SLCO4C1, and TMEM220) associated with overall survival (OS) in COAD patients. A risk prediction model was then developed based on these four MDGs to predict the prognosis of COAD patients. We also created a nomogram that incorporated risk scores, age, and TNM stage to promote a personalized prediction of OS in COAD patients. Compared with the traditional TNM staging system, our new nomogram was better at predicting the OS of COAD patients. In cell experiments, we confirmed that the mRNA expression levels of CLBN2 and TMEM220 were regulated by the methylation of their promoter regions. Moreover, immunohistochemistry showed that CBLN2 and TMEM220 were potential prognostic biomarkers for COAD patients. In summary, we have established a risk prediction model and nomogram that might be effectively utilized to promote the prediction of OS in COAD patients.

Objective To investigate the protective effect and mechanism of placental-derived mesenchymal stem cells (P-MSCs) on lung injury in rats with severe acute pancreatitis. Methods A total of 36 healthy adult male SD rats were randomly divided into control group (n=12), SAP group (n=12) and P-MSCs group (n=12). SAP rat model was established by retrograde injection of 4% sodium taurocholate into biliopancreatic duct. P-MSCs (1×10⁶ cells/100 g) were delivered through the tail vein of the rats at 6 h after the induction of SAP. The rats were sacrificed 12 and 24 h after P-MSCs infusion. The ratio of wet to dry weight of lung tissue and the number of neutrophils, leukocytes and macrophages in bronchoalveolar lavage fluid (BALF) was calculated. The degree of pancreatic and lung injury was evaluated by HE staining. The concentration of amylase, lipase and inflammatory factors in serum was measured by ELISA. The MPO activity in pancreas and lung tissue was measured by MPO assay kit, and the mRNA expression levels of TNF-α, IL-1β in lung tissue were detected by RT-qPCR. The ratio of M1 and M2 in lung tissue was detected by immunofluorescence stain. Results Compared with SAP group, the ratio of wet to dry weight of lung tissue in P-MSCs group significantly decreased, the number of neutrophils, leukocytes and macrophages in BALF were significantly reduced (P

Objective To investigate the potential mechanism of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP) through regulating Toll-like receptor 4 (TLR4) expression in rat intestine. Methods Male SD rats were randomized into the Sham group, SAP group, and APD group, with 15 rats in each group. Rats were treated with a retrograde injection of 5% sodium taurocholate into the pancreatic bile duct to induce SAP, followed by ADP treatment through placing a drainage tube in the right lower abdomen of rats. Rats without ADP treatment were used as controls: SAP group included rats without ADP surgical procedure; while Sham group included rats with ADP surgical procedure but without placing a drainage tube. About 24 hours after ADP treatment, pathological changes of small intestine and pancreas were observed by HE staining; serum amylase and lipase activities were detected by the automatic biochemical analyzer; serum endotoxin levels were detected by limulus amebocyte lysate method; serum DAO activity was detected by ultraviolet colorimetry; TNF-α, IL-6 and D-lactic acid levels were detected by ELISA; apoptosis of intestinal mucosal epithelial cells was detected by TUNEL assay; mRNA expression of TLR4 was detected by real-time PCR; the expression of TLR4 signaling pathway and apoptosis-related proteins were detected by immunohistochemistry and Western blotting. Results Compared with SAP rats, the pathological damage of small intestine and pancreas of APD rats was significantly reduced; the pathological score was decreased (P

Objective To investigate the effect of abdominal paracentesis drainage (APD) on pancreatic cell apoptosis in severe acute pancreatitis. Methods Male adult SD rats were randomized into the sham operation (SO) group, SAP group, and APD group, with 18 rats in each group. In the SAP group, 5% sodium sulfonate was pumped into the retrograde pancreatic bile duct to prepare the SAP model. On this basis, a gastric tube was introduced into the right lower abdomen for drainage, namely the APD group. Blood from the abdominal aorta and pancreatic tissues were collected at 6, 12, and 24 h time points in each group. The changes of serum amylase, inflammatory factor, and endotoxin were detected by ELISA. The HE staining was used to evaluate the pancreatic tissue injury. The apoptosis of pancreatic tissue was detected by TUNEL. Western blot and immunohistochemistry were used to detect the expression of apoptosis-related proteins and PI3K/AKT signaling pathway. Results Pancreatic tissue necrosis and edema were significantly lower in the APD group than in the SAP group, and the pathological score was decreased (P

Objective To observe the inflammatory response and peritoneal macrophage polarization phenotype of hypertriglyceridemic acute pancreatitis (HTG-AP) mice, and to record HTG-AP disease progression. Methods Adult male C57/BL6 mice were randomly divided into the control group, HTG group, AP group, and HTG-AP group, with 8 mice in each group. Mice in HTG and HTG-AP groups were intraperitoneally injected with Poloxamer 407 every other day for 28 days to construct the hyperlipidemia animal model. All animals anesthetized and sampled after caerulein treatment in the AP group and the HTG-AP group 12h later. Blood was collected to detect serum lipid and cytokine levels. HE staining was performed on the pancreatic tissues and pathological scores were obtained. The abdominal cavity was lavage with PBS to collect peritoneal macrophages, which were labeled by F4/80, CD11c, and CD206 and then detected by flow cytometry. Results The HTG-AP model of mice was constructed. Compared with AP group, pancreatic tissue pathology score, serum pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels, as well as the percentage of M1 polarization of peritoneal macrophages, were significantly increased (P

Objective To study the timing and mechanism of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in the treatment of acute biliary pancreatitis (ABP). Methods The data of 101 patients with ABP in General Hospital of Western Theater Command between January 2012 to June 2018 were retrospectively analyzed. Receiver operating characteristic (ROC) curve was used to calculate the optimal cut-off time of ERCP in the treatment of ABP. The patients were divided into early ERCP group (within 66 hours after onset) and late ERCP group (over 66 hours after onset), and the patients in the early ERCP groups were subdivided into 3 subgroups according to the result of the ROC curve: 0-24 h group (n=10), 24-48 h group (n=27) and 48-66 h group (n=18). Primary endpoints (main outcome measures or main observation indexes) were exacerbation rate, incidence of new onset of organ failure (NOF) and mortality. Secondary endpoints were infection rate, severity scores (APACHE Ⅱ, RANSON, Marshall, GCSI), serological variables (C-reactive protein, IL-6, IL-10, TNF-α, triglyceride) and incidence of ERCPrelated complications. Logistic regression was used to explore the risk factors for the exacerbation of ABP. Results The ROC curve analysis showed that 66 hours after the onset of ABP was the best cut-off time of ERCP. Exacerbation rate, incidence of NOF and infection rate were significantly lower in the early ERCP group than in the late ERCP group (P0.05). There was no significant difference between the early ERCP subgroups in primary and secondary (P>0.05). Logistic regression showed that elevated serum triglyceride and GCSI scores were risk factors for the exacerbation of ABP, while early ERCP treatment was a protective factor. Conclusions Early ERCP treatment (within 66 hours after the onset) could reduce the risk of exacerbation, and improve the prognosis of patients with ABP. The potential mechanism is to improve the gastrointestinal function and reduce serum triglyceride. DOI: 10.11855/j.issn.0577-7402.2020.06.06

Short tandem repeat (STR) markers have been widely used in forensic paternity testing and individual identification, but the STR mutation might impact on the forensic result interpretation. Importantly, the STR mutation rate was underestimated due to ignoring the "hidden" mutation phenomenon in most similar studies. Considering this, we use Slooten and Ricciardi's restricted mutation model based on big data to obtain more accurate mutation rates for each marker. In this paper, the mutations of 20 autosomal STRs loci (D3S1358, D1S1656, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D6S1043, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, and FGA; The restricted model does not include the correction factor of D6S1043, this paper calculates remaining 19 STR loci mutation rates) were investigated in 28,313 (Total: 78,739 individuals) confirmed parentage-testing cases in Chinese Han population. As a result, total 1665 mutations were found in all loci, including 1614 one-steps, 34 two-steps, 8 three-steps, and 9 nonintegral mutations. The loci-specific average mutation rates ranged from 0.00007700 (TPOX) to 0.00459050 (FGA) in trio's and 0.00000000 (TPOX) to 0.00344850 (FGA) in duo's. We analyzed the relationship between mutation rates of the apparent and actual, the trio's and duo's, the paternal and maternal, respectively. The results demonstrated that the actual mutation rates are more than the apparent mostly, and the values of μ1"/μ2"(apparent) are also greater than μ1/μ2 (actual) commonly (μ1", μ1; μ2", μ2 are the mutation rates of one-step and two-step). Therefore, the "hidden" mutations are identified. In addition, the mutations rates of trio's and duo's, the paternal and maternal, exhibit significant difference. Next, those mutation data are used to do a comparison with the studies of other Han populations in China, which present the temporal and regional disparities. Due to the large sample size, some rare mutation events, such as monozygotic (MZ) mutation and "fake four-step mutation", are also reported in this study. In conclusion, the estimation values of actual mutations are obtained based on big data, they can not only provide basic data for the Chinese forensic DNA and population genetics databases, but also have important significance for the development of forensic individual identification, paternity testing and genetics research.短串联重复序列(short tandem repeat, STR)已广泛用于法医学亲子鉴定和个体识别中,但STR的突变可能会影响其结果的解释。在大多数类似研究中,由于忽略“隐性”突变现象,STR的突变率被低估。鉴于此,为获得更加准确的STR实际突变率,本研究使用Slooten与Ricciardi提出的有限突变模型和大规模数据,对28,313例(78,739个体)中国北京汉族已确认亲生关系的亲子鉴定案的20个常染色体STR基因座(D3S1358、D1S1656、D13S317、Penta E、D16S539、D18S51、D2S1338、CSF1PO、Penta D、TH01、vWA、D21S11、D6S1043、D7S820、D5S818、TPOX、D8S1179、D12S391、D19S433和FGA;由于有限突变模型中未包含D6S1043的矫正参数,因此本文实际计算其余19个STR基因座的突变率)进行了调查。结果发现,所有基因座均存在突变现象,总计发生1665个突变事件,包括1614个一步突变,34个两步突变,8个三步突变和9个非整步突变。基因座特异性的平均实际突变率在三联体中为0.00007700 (TPOX)~0.00459050 (FGA),在二联体中为0.00000000 (TPOX)~0.00344850(FGA)。此外,本研究还分析了表面和实际突变率、三联体和二联体突变率、父源和母源的突变率之间的关系。研究表明,实际突变率多大于表面突变率,而且μ1”/μ2” (表面突变率)的比值通常也大于μ1/μ2 (实际突变率) (μ1”,μ1; μ2”, μ2分别是一步和两步的突变率),即更多的“隐性”突变被释放出来。而且父源和母源的三联体和二联体的突变率也有存在差异。随后,将这些突变率数据与已发表的中国其他汉族人口的相关研究进行比较,展现出了STR突变率的时间与区域差异。由于样本量大,本研究中还报告了一些少见的突变事件,例如同卵双胞胎突变和“假四步突变”等。综上所述,本研究通过大量数据获得了接近真实的STR突变率的估计值,不仅可为中国法医DNA数据库和群体遗传学数据库提供重要的基础数据,也对开展法医学个体识别、亲权鉴定和遗传学研究具有重要的意义。.

Forensic genetics mainly uses human biological samples as the objects, solves the identification of biological materials related to law by detecting genetic information, provides clues for investigation and evidences for trial, thus facing many ethical issues. This paper put forward the ethical principles in forensic genetics research and practice, and discussed the ethical issues in sample collection, forensic DNA phenotyping, forensic genetic genealogy analysis, forensic DNA database development, paternity and kinship testing, and research data sharing. We suggest that specific ethical requirements should be formulated, the ethical review system should be established for forensic genetics and ethical training for practitioners should be strengthened.法医遗传学主要以人体生物检材为对象,通过检测遗传信息解决与法律相关的生物检材鉴识问题,为侦查提供线索,为审判提供证据,往往涉及到众多伦理问题。本文提出伦理学在法医遗传学研究和鉴定中的应用基本原则,并对检材/样本收集、法医DNA表型分析、法医遗传系谱学分析、法医DNA数据库建设和应用、亲子鉴定和亲缘鉴定、法医遗传学科研数据交流和共享等方面涉及的伦理问题进行了分析,提示法医遗传学从业人员在研究和鉴定中要充分考虑伦理问题,建议有关部门制定法医遗传学具体的伦理要求,建立伦理审查制度,加强从业人员伦理学培训。.

IgG4-related sclerosing cholangitis is a biliary tract manifestation of IgG4-related diseases, characterized by biliary strictures, neoplastic hyperplasia of bile duct and its surrounding tissues, an increased serum level of immunoglobulin G4 (IgG4). The pathogenesis has not been fully elucidated and histopathological features include infiltration of lympho-plasmcytes, storiform fibrosis and obliterative phlebitis. Response to corticosteroids is prompt and multi-organ involvement is common. As a result of mimicking primary sclerosing cholangitis and cholangiocarcinoma in image, misdiagnose and missed treatment are not rare. Incorporating literature involved, we will review the pathogenesis, clinical manifestations, diagnostic criteria, treatment and prognosis of IgG4-related sclerosing cholangitis. DOI: 10.11855/j.issn.0577-7402.2019.10.13

Acute pancreatitis (AP) is a systemic inflammatory disease with complex pathogenesis. Acinar cell injury is the earliest pathological change of AP. Elucidating its pathological mechanism is of great significance for the development of new therapeutic strategies for AP. Studies have shown that activation of PI3K/Akt signaling pathways plays an important role in the progression of acute pancreatitis. It can not only contribute to acinar cell necrosis by inhibiting apoptosis, but also regulate the autophagy, oxidative stress and inflammation of acinar cells. Here, we reviews the advances about the PI3K/Akt signaling pathway and its significance in modulation of acinar cells in acute pancreatitis. DOI: 10.11855/j.issn.0577-7402.2019.09.13

Objective To investigate the expression of miR-345-5p in peripheral blood of patients with hyperlipidemic acute pancreatitis (HAP) and its clinical significance. Methods From December 2017 to September 2018, 40 patients with HAP (group A) and 75 patients with non-HAP (group B) admitted to the general surgery center of the General Hospital of Western Theater Command were enrolled. 25 patiens with hyperlipidemic non-acute pancreatitis patients (group C) and 30 healthy volunteers (group D) were selected as the control group. Group A was subdivided into H-MAP group and H-SAP group. All the patients were examined for serum triacylglycerol and amylase biochemical levels, and scored on the APACHE Ⅱ. The expression level of miR-345-5p in serum was detected by real-time fluorescent quantitative PCR. The relationship between miR- 345-5p expression level and clinical indicators of HAP was analyzed and the role of miR-345-5p in predicting the severity of acute pancreatitis evaluated. Results The expression level of miR-345-5p in serum of group A (2.28±0.23) was significantly higher than that of groups B (0.35±0.21), C (0.29±0.23) and D (0.25±0.33). The difference was statistically significant (P0.05). The ROC curve analysis showed that the area under the curve of miR-345-5p detection H-SAP was 0.785(0.634~0.935). The expression of miR-345-5p in the HAP severe group (2.95±0.46) was significantly higher than that in the mild HAP group (0.69±0.23), the difference was statistically significant (P0.05). Conclusion The serum miR-345-5p is significantly up-regulated in HAP, and it increases with the severity of the disease, which may provide a new way for the clinical diagnosis and severity assessment of HAP. DOI: 10.11855/j.issn.0577-7402.2019.04.08

Effective therapeutic system to periodontitis was designed using cross-linked cyclodextrin metal-organic framework (COF) as carrier for iodine and further suspended in hydroxyethyl cellulose gel as I2@COF-HEC hydrogel. Inclusion of iodine within the COF was demonstrated by SR-FTIR spectral and characteristic DSC and TGA changes. Molecular modelling identified the interaction of iodine with both COF central cavity and individual cyclodextrin moieties of COF. In vitro results of study demonstrated that iodine release in artificial saliva from I2@COF-HEC hydrogel could be extended up to 5 days, which was slower than I2@COF particles. Using an in vivo rat model of periodontitis, micro-computed tomography of alveolar bone morphology demonstrated that I2@COF-HEC hydrogel showed similar effects in decreasing periodontal pocket depth and alveolar bone resorption to minocycline ointment, a periodontitis antibiotic. The I2@COF-HEC hydrogel is a novel local delivery device of iodine as a broad spectrum antimicrobial use for treatment of periodontitis.

Objective To investigate the effect of early stage abdominal paracentesis drainage (APD) on phenotype transition of peritoneal macrophage in rats with severe acute pancreatitis (SAP). Methods A total of 36 adult male Sprague Dawley (SD) rats were randomized into SAP, APD, and sham-operated (Sham) groups (n=12). Pancreatitis in SAP and APD groups were induced by 5% sodium taurocholate retrograde injection. In the APD group, a drainage tube was placed in the lower right abdomen of rats with pancreatitis before closure. In the Sham group, rats didn't receive the injection procedure, and a segment of the drainage tube was placed in the abdomen. The rats were sacrificed 12 hours after model established. The histopathological injury was evaluated by HE staining and scored using a previously described scoring system. The level of amylase and lipase, pro/ anti-inflammatory mediators in serum, were determined by ELISA. The polarization of peritoneal macrophage was analyzed by flow cytometry. The mRNA expression of M1-associated protein tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), CD163 and CD206 in peritoneal cells were detected by qPCR. Results The histopathological injury and its score of the pancreas in APD group decreased as well as the serum level of amylase, lipase, TNF-α, interleukin-1β (IL-1β) compared with SAP group, however, the level of anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in plasma increased significantly (P0.05). Conclusion APD ameliorates SAP by enhancing the M2 polarization of peritoneal macrophage and inhibiting systematic inflammation. DOI: 10.11855/j.issn.0577-7402.2018.10.05

Objective To prepare and evaluate the biocompatibility of acellular liver matrix hydrogel in order to provide the experimental basis for clinical therapy application. Methods Rat liver acellular matrix was prepared by Triton X-100 and SDS method and stained by hematoxylin-eosin (HE) staining, and the DNA content was determined. The liver acellular matrix was then dissolved to prepare the hydrogel, which was observed by general morphology and scanning electron microscopy (SEM). Finally, BRL-3A cells were cultured on the surface of hydrogel and used by Live/Dead staining, AlamarBlue and cells skeleton staining to study the cytotoxicity, proliferation and adhesion behavior. Results Histology and DNA content test showed that the ideal liver acellular matrix materials were obtained. After being dissolved, the materials could be prepared into a thermosensitive hydrogel which had net-like porous structure by SEM. Furthermore, the hydrogel was favorable to the survival of BRL-3A cells, and could promote the adhesion and proliferation of BRL-3A cells. Conclusion The liver matrix hydrogel has been successfully prepared with good biocompatibility, which is expected to be used as an injectable hydrogel in the treatment of end-stage liver disease. DOI: 10.11855/j.issn.0577-7402.2018.05.09

Acute and chronic pancreatitis are most common gastrointestinal diseases. Recently, there are emerging evidences that immune cell play important roles in the pathogenesis of acute and chronic pancreatitis. Studies have shown that macrophages, high mobility group protein 1 (HMGB1) and interleukin-33 (IL-33) play an important role in the pathological process of pancreatitis, and are regulated by multiple levels. For example, immune cells are critical in the development and progression of pancreatitis, which not only have the ability to induce microenvironment, but also respond to danger signals derived from endogenous and exogenous molecules. Therefore, further understanding of relevant immune signaling will provide new idea and potential therapeutic targets that can prevent disease progression. Here, we review recent data from animal and human clinical studies that focus on immune responses. DOI: 10.11855/j.issn.0577-7402.2018.01.15

Objective To study the protective effects of human umbilical cord-derived mesenchymal stem cells (ucMSCs) against severe acute pancreatitis (SAP) in rats. Methods A total of 135 Sprague-Dawley male rats were randomly divided into Sham group, SAP group and SAP+ucMSCs group (45 each). SAP+ucMSCs group: Severe acute pancreatitis was induced by injecting 5% sodium taurocholate (0.1ml/100g) into the common biliopancreatic duct and then CM-DiI-labeled ucMSCs at 1×107cells/kg were injected via the tail vein. All the rats were sacrificed 12, 24 and 72 hours after SAP. The 72h death rate was counted. Pathological changes in the pancrease were detected by HE staining and pathological score was graded. ucMSCs colonization was observed by fluorescence microscopy. The serum levels of amylase, lipase, TNF-α, IL-1β, IL-4 and IL-10 were determined by ELISA. Results ucMSCs colonize the injured area of pancreatic tissue, the 72h death rate was reduced, and the serum amylase and lipase were also reduced significantly. Moreover, ucMSCs significantly reduced the pathological score of the pancrea and the level of proinflammatory cytokines (TNF-α and IL-1β), but the levels of anti-inflammatory cytokines were increased (IL-4 and IL-10). Conclusion Transplantation of ucMSCs can reduce the severity of pancreatic injury and inflammation in SAP rats. DOI: 10.11855/j.issn.0577-7402.2017.05.03

To describe the knowledge and attitude of Chinese patients with advanced cancer towards advanced care planning (ACP), a convenience sample of 275 patients with advanced cancer was recruited from a tertiary cancer hospital in Beijing, China, between February and December 2017. The multi-item questionnaire focused on patients' demographics, disease characteristics and knowledge about and attitude towards ACP and was administered to eligible patients. Descriptive statistics were performed. Most patients had never heard about ACP (82.2%) and had never talked about ACP (83.0%), but only a few (18.3%) were not willing to talk about ACP. A total of 67.8% patients chose to refuse resuscitation attempts or life-sustaining medical interventions, and 70.8% of patients hoped to have surrogate decision makers when they became unconscious. By binary logistic regression analysis, patients who were of greater age, female and living in urban areas preferred to refuse resuscitation attempts or life-sustaining medical interventions (OR = 1.023, P = 0.042; OR = 2.011, P = 0.020; OR = 0.254, P 0.01); patients who had very rich or rich family economic status preferred to involve surrogate decision makers compared with patients of very poor family economic status (OR = 0.250, P = 0.011). There is a large gap between the knowledge about ACP and the expectation of implementing ACP in Chinese patients with advanced cancer. To develop culturally appropriate and individualized programmes to promote knowledge and implementation in practice of ACP among Chinese patients with advanced cancer and their relatives is still a significant challenge.

Apoptosis is associated with various cardiovascular diseases. CGRP exerts a variety of effects within the cardiovascular system, and protects against the onset and development of angiotensin (Ang) II-induced vascular dysfunction and remodelling. However, it is not known whether CGRP has a direct effect on Ang II-induced apoptosis in vascular smooth muscle cells (VSMCs), and the mechanism underlying the anti-apoptotic role remains unclear. In this study, CGRP significantly suppressed reactive oxygen species (ROS) and apoptosis in Ang II-induced VSMCs. In VSMCs pre-treated with a CGRP receptor antagonist (CGRP8-37), the CGRP-mediated inhibition of Ang II-induced ROS and apoptosis was completely abolished. Moreover, pre-treatment with N-acetyl-L cysteine (NAC), an ROS scavenger, blocked the effects of CGRP on Ang II-induced apoptosis. In addition, the activation of CaMKII and the downstream transcription factor CREB stimulated by Ang II was abrogated by CGRP. Importantly, in both CGRP and NAC-treated VSMCs, CGRP failed to further attenuate CaMKII and CREB activation. The results demonstrate that CGRP attenuated Ang II-induced ROS-dependent apoptosis in VSMCs by inhibiting the CaMKII/CREB signalling pathway.

We had previously demonstrated that the calcitonin gene‐related peptide (CGRP) suppresses the oxidative stress and vascular smooth muscle cell (VSMC) proliferation induced by vascular injury. A recent study also indicated that CGRP protects against the onset and development of angiotensin II (Ang II)‐induced hypertension, vascular hypertrophy and oxidative stress. However, the mechanism behind the effects of CGRP on Ang II‐induced oxidative stress is unclear. CGRP significantly suppressed the level of reactive oxygen species (ROS) generated by NADPH oxidase in Ang II‐induced VSMCs. The Ang II‐stimulated activation of both Src and the downstream transcription factor, STAT3, was abrogated by CGRP. However, the antioxidative effect of CGRP was lost following the expression of constitutively activated Src or STAT3. Pre‐treatment with H‐89 or CGRP8–37 also blocked the CGRP inhibitory effects against Ang II‐induced oxidative stress. Additionally, both in vitro and in vivo analyses show that CGRP treatment inhibited Ang II‐induced VSMC proliferation and hypertrophy, accompanied by a reduction in ROS generation. Collectively, these results demonstrate that CGRP exhibits its antioxidative effect by blocking the Src/STAT3 signalling pathway that is associated with Ang II‐induced VSMC hypertrophy and hyperplasia.

We investigate the Andreev reflection in the heterostructure formed by the indirect coupling between the metallic lead and Majorana zero mode (MZM) via one quantum dot which suffers from the electron-phonon interaction. Our calculation results show that at the zero-temperature limit, the MZM-governed zero-bias conductance value is independent of the electron-phonon interaction. However at finite temperature, the electron-phonon interaction exacerbates the suppression of the magnitude of zero-bias conductance. We believe that the results in this work can help to further differentiate the signature of the MZM in the Andreev reflection process.

Progression of acute pancreatitis (AP) into a severe form usually results in a life-threatening condition with multiple organ dysfunction, and in particular acute lung injury (ALI), often contributes to the majority of AP-associated deaths. Increasing evidence has shown that uncontrolled activation of the immune system with rapid production of inflammatory cytokines play a dominant role in this process. As an intracellular inflammatory signaling platform, the NOD-like receptor protein 3 (NLRP3) inflammasome, is recently reported to be involved in the pathogenesis of AP progression, however, the relationship between NLRP3 inflammasome activation and AP-associated lung injury remains unclear yet. Here, we show that NLRP3 inflammasome activation and subsequent pyroptosis in alveolar macrophages (AMs) is responsible for the lung injury secondary to AP. In addition, plasma-derived exosomes from AP mice is capable of triggering NLRP3-dependent pyroptosis in AMs. Inhibition of exosome release or uptake in vivo by inhibitors substantially suppresses AMs pyroptosis and thereby alleviates AP-induced pulmonary lesion. Collectively, the current work reveals for the first time the involvement of NLRP3-dependent pyroptosis induced by plasma exosomes in the pathogenesis of AP-induced ALI, suggesting that the exosome-mediated NLRP3 inflammatory pathway is a potential therapeutic target for the treatment of lung injury during AP.

The study aims to investigate the changes and regulation of androgen receptor and insulin-like growth factor-1 in the PC3 prostate cells treated with 5α-dihydrotestosterone, estrone, and flutamide. The PC3 cells were cultured and treated with 5α-dihydrotestosterone, estrone, and flutamide. Immunocytochemistry and Western blot were used to detect the expression of androgen receptor and insulin-like growth factor-1. The androgen receptor expression was analyzed by Western blot and optic density scan in the presence or absence of various kinase inhibitors. The statistical calculations were performed with the statistics-analyzing software package SPSS 13.0. A P

Recent studies suggest that endoplasmic reticulum stress (ERS) is the key process in ischemic brain injury. The JNK pathway is also involved in the process of ischemic brain injury.We established a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats; detected the changes in c-Jun N-terminal kinase (JNK), GADD153 and caspase-12 at different reperfusion time points by immunohistochemistry, Western blot and double-label immunofluorescence; and observed the effect of JNK inhibitor SP600125 on the expression of JNK, GADD153 and caspase-12 to explore the relationship between the endoplasmic reticulum road and JNK pathway.The expression of the two hallmarks of ERS-GADD153 and caspase-12-significantly increased, and the activation of JNK also obviously increased. After interference by SP600125, the expression of p-JNk and caspase-12 obviously decreased, whereas the decrease of GADD153 occurred only after 24 h reperfusion.Both ERS and JNK pathways are involved in the pathological process of ischemic brain injury. The JNK pathway may be involved in the process of ERS, but perhaps has more effect on the caspase-12 pathway.

The current prospective randomized study was designed to evaluate the safety and efficacy of combined intrapleural cisplatin and OK-432 (picibanil) plus hyperthermotherapy in patients with malignant pleural effusion (MPE).A total of 358 patients with MPE due to end-stage malignancies were enrolled and randomly divided into two groups, A and B: the intrapleural combination of cisplatin and OK-432 with hyperthermotherapy (n = 179) or without hyperthermotherapy (n = 179), respectively. Mild toxicities such as nausea, vomiting or anorexia, bone marrow depression, and pyrexia were similar in both groups.Patients in Group A (with hyperthermotherapy) showed a significantly higher overall response (93.4%) compared to those in Group B (79.8%, χ(2) = 43.11, p.05). The median survival time for patients in Group A and Group B were 8.9 and 6.2 months, respectively (p.05). After treatment, the quality of life scores were significantly increased in both groups as compared to prior treatment (p.05).In conclusion, our study suggests that combined intrapleural cisplatin and OK-432 followed by hyperthermotherapy are more effective in the control of MPE and improve patients' quality of life.

Knowledge of allele and genotype frequencies is an essential prerequisite to the use of any human polymorphism in forensic work.To study the genetic polymorphism and evaluate the application value of nine STR loci.Genotyping of nine STR loci, including D11S2368, D12S391, D13S325, D18S1364, D22-GATA198B05, D6S1043, D2S1772, D7S3048 and D8S1132, of 1050 unrelated individuals was performed with the STR_Typer_10_v1 kit and Genetic Analyzer 3100 and analyzed with PowerState V12.xls and Arlequin ver 3.11 analyzing software.Allele frequency distribution was statistically analyzed and Hardy-Weinberg equilibrium determined. Several common parameters used in forensic sciences were found: the heterozygosity (H) ranged from 0.827 to 0.892; the matching probability (MP) ranged from 0.029 to 0.074; the power of discrimination (PD) ranged from 0.926 to 0.971; the power of exclusion (PE) ranged from 0.649 to 0.779; the polymorphic information content (PIC) ranged from 0.77 to 0.86; and the typical paternity index (TPI) ranged from 2.88 to 4.62.The results indicate that nine STR loci are high polymorphic among the Han population in Southern China. This set of polymorphic STR loci is a useful tool in forensic paternity testing and anthropological study.

To explore the mutation of Y-STR loci in meiotic allelic transmission in a large pedigree.The oral swabs of 163 male individuals were collected from a Lin pedigree. Twenty-two Y-STR genetic markers were typed with AGCU Y24 fluorescent detection kit (AGCU Y24 system), which also contained 16 Y-STR markers included in Yfiler multiple amplification kit (Yfiler system). The genotyping results of Y-STR loci were compared between each two males in the pedigree.There were 20 and 30 kinds of haplotypes obtained with Yfiler and AGCU Y24 systems in 163 male individuals from the Lin pedigree, respectively. The rates referred to haplotype differences (RRHD) of these two typing systems between male pairs were 0.910 5 and 0.922 7, respectively. The average number of marker differences were 6.582 1 and 9.824 8, respectively. The RRHD increased along with the incidents of meiosis.Y-STR mutation leads to different Y-STR haplotypes among the male members in a paternal pedigree and the rate of difference increases along with the incidents of meiosis.

A passive oscillating hydrofoil energy extracting technology that imitates the tail swinging of aquatic organisms to extract energy from flow field is presented in this paper, as an alternative to conventional rotating blades turbine. On the basis of analysis of the relationship between the movement characteristics of oscillating hydrofoil and the parameters including power coefficient, efficiency and reduced frequency, the device based on passive oscillating hydrofoil to extract tidal current energy is designed. The investigation is undertaken over a wide range of kinematic parameters including pitching amplitudes, heaving amplitudes and reduced frequency. The results reveal that the power extracted from the oncoming flow mainly comes from the heaving motion and the energy contribution from pitching motion is quite limited. Detailed examination of the motion parameters indicates that when the heaving amplitude reaches one chord length, the pitching amplitude reaches 70° and the reduced frequency reaches 0.11, the highest power extraction efficiency can reach 34.7%.

To investigate genetic diversity in Chinese populations, 706 unrelated male individuals from five ethnic groups (Han, Korean, Hui, Mongolian, and Tibetan, respectively) were analyzed with 17 Y-chromosomal STRs. The haplotype diversity was 0.99985 in the combined data. A total of 675 distinct haplotypes were observed, of which 649 were unique. Y-chromosome haplogroups in the five groups were also predicted with Y-STR haplotypes. Genetic distance between the five studied ethnic groups and other published groups was analyzed by analysis of molecular variance and visualized in a multidimensional scaling plot. In conclusion, the 17 Y-STR loci are highly polymorphic markers in the five groups and hence are very useful in forensic application, population genetics, and human evolution studies.

In order to detect weld defects in steel tube, a real-time imaging and detecting system is setup. In the extracted weld seam, based on spatial characteristics near defects—variance and contrast, defects such as slags, blowholes and incomplete penetration are automatically detected using the method of fuzzy pattern recognition, and the system will automatically alarm if the defect exceeds the national standard. Compared with other methods, it is simple and fast, and has fewer misinterpretations. It can detect weld defects in real-time.

This study aimed to identify potential miRNAs highly associated with the response to brain ischemic stroke. The miRNAs microarray expression profiles data were downloaded from Gene Expression Omnibus database under accession number GSE51586, including three ischemia and three ipsilateral normal samples from mouse brain tissues. Limma package was used to identify differentially expressed miRNAs between ischemia and ipsilateral normal samples. The common target genes of miRNA predicted from TargetScan, PicTar, miRanda and DIANA-microT databases were used as the candidate subset in which functional modules were identified by performing gene ontology enrichment analysis using ClusterProfile. Finally, the miRNA functional synergistic network was constructed by assembling all miRNA synergistic pairs. Fifty-one differentially expressed miRNAs were identified between ischemia and ipsilateral normal samples, including 32 up- and 19 down-regulated miRNAs. Among them, 24 miRNAs can commonly regulate at least one target gene and thus were used to construct a network, which included 274 pairs of co-regulating miRNAs. Further, 242 pairs of miRNAs interaction involving 23 miRNAs were shown to be synergetic in function. Sixteen miRNAs forming 20 miRNAs interaction pairs participated in inflammatory response, such as mir-185 and mir-674-3p. The 16 miRNAs related to inflammatory response during ischemic stroke may provide underlying targets for prevention and treatment of stroke.

To identify potential mutation in a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome (ATR-X).Based on clinical symptoms and inheritance pattern, linkage analysis of X chromosome short tandem repeats (X-STR) loci was carried out to locate the candidate gene. Subsequently, sequences of exons and exon-intron boundaries of the candidate gene were amplified with polymerase chain reaction (PCR). Potential mutations were detected by direct DNA sequencing. All patients were also analyzed for the trait of thalassemia.Linkage analysis indicated the candidate gene to be ATRX. Subsequently, a homozygous missense mutation c.736CT (p.R246C) was found in exon 9 of ATRX in all of the 3 patients. And a heterozygous mutation c.736CT (p.R246C) was also identified in the patient's mother and grandmother. Similar mutations were not detected in other members of the family. Alpha thalassemia was detected in the proband and another patient, whose genotypes were determined as -α(3.7)/αα and --(sea)/αα, respectively.Missense mutation of c.736CT in ATRX gene is a mutation hotspot, and p.R246C may disturb the function of ATRX-DNMT3-DNMT3L domain (ADD), which may be responsible for the disease in this family.

Y chromosome is a male-specific paternal inherited chromosome. The STR markers on Y chromosome have been widely used in forensic practices. This article summarizes the characteristics of Y-STR and some factors are considered of selecting appropriate Y-STR markers for Chinese population. The prospects of existing and potential forensic applications of Y-STR profiles are discussed including familial excluding, familial searching, crowd source deducing, mixture sample testing, and kinship identifying. The research, development, verification of Y-STR kit, Y-STR mutation rate, and search software are explored and some suggestions are given.

To deduce the calculation formulae of likelihood ratio for kinship testing with X-short tandem repeat (X-STR) typing.With the identity by decent coefficient of different relationships, the joint genotypic probability of two individuals with specific genotypes was calculated as X value, and then the joint genotypic probability of two unrelated individuals was calculated as Y value; therefore, the likelihood ratio value (X/Y) was obtained.The calculation formulae of the likelihood ratio for different genotype combinations of the female-female, female-male and male-male genetic relationships were derived and verified by real cases.The calculation formulae are simple and accurate to evaluate the likelihood ratio for two individuals' genetic relationship with X-STR typing. The formulae provide the basic potential value for the difficult kinship testing with X-STR loci.

Excessive K(+) efflux promotes central neuronal apoptosis; however, the type of potassium channel that mediates K(+) efflux in response to different apoptosis-inducing stimuli is still unknown. It is hypothesized that the activation of large-conductance Ca(2+)-activated K(+) channels (BKCa) mediates hypoxia/reoxygenation (H/R)- and ischemia/reperfusion (I/R)-induced neuronal apoptosis. Rat hippocampal neuronal cultures underwent apoptosis after reoxygenation, as assessed by morphologic observation, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and caspase-3 activation. Single-channel recordings revealed upregulation of BKCa channel activity 6 h after reoxygenation, which might be caused by elevated cytosolic Ca(2+). The K(+) ionophore valinomycin and the BKCa channel opener NS1619 induced neuronal apoptosis. Transfection of the BKCa channel α subunit into Chinese hamster ovary (CHO-K1) cells, which do not express endogenous K(+) channels, or into neurons will induce cell apoptosis, indicating that the opening of the BKCa channel serves as a pivotal event in mediating cell apoptosis. The specific BKCa channel blockers charybdotoxin and iberiotoxin and the nonselective K(+) channel blocker tetraethylammonium at concentrations more specific to the BKCa channel were neuroprotective. The A-type potassium channel blocker 4-aminopyridine and apamin, a small-conductance Ca(2+)-activated K(+) channel blocker, were not protective. This result suggests the involvement of the BKCa channel in H/R-induced apoptosis. Similarly, specific BKCa channel blockers also showed neuroprotection in neurons subjected to oxygen-glucose deprivation/reoxygenation or animals subjected to forebrain ischemia-reperfusion. These results demonstrate that the over-activity of BKCa channels mediates hippocampal neuronal damage induced by H/R in vitro and I/R in vivo.

To explore the HERVWE1 gene expression in the placentas of discordant monozygotic twins and identify its regulation by methylation.Fetuses from 21 pairs of monozygotic discordant twins were marked as "smaller" or "larger" according to birth weight. Placental HERVWE1 mRNA and protein expression profiles were analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) stain. Methylation profiles of the HERVWE1 promoter region were analyzed by COBRA, MSP-PCR and pyrosequencing assay.In discordant twins group, the mean methylation level of the HERVWE1 promoter region decreased in smaller fetuses (P0.05). And there were increased mRNA and protein levels of HERVWE1 in smaller fetuses versus larger counterparts (P0.05).In discordant monozygotic twins, the HERVWE1 expression is higher in smaller fetuses and lower in larger counterparts. Methylation of HERVWE1 gene promoter region may participate in the regulation of HERVWE1 gene expression in twins.

To study the roles of βIII-tubulin and survivin in the development of gastric cancer, and see for any relationship between the expression levels of these two genes and docetaxel chemoresistance in advanced gastric cancer.Patients with advanced gastric cancer treated with docetaxel-based chemotherapy were enrolled and their tumor samples were collected retrospectively for analysis (study group). The control group consisted of patients with benign gastric mucosa lesions. Expression levels of βIII-tubulin and survivin were evaluated with immunohistochemistry.The expression levels of βIII-tubulin and survivin in the study group were significantly higher compared with those in the control group (p0.01). Spearman's correlation analysis suggested that the expression of βIII-tubulin was also correlated with that of survivin (p0.05), but no correlation existed between the expression levels of βIII-tubulin and survivin with age, gender and pathological tumor type. The complete response (CR) + partial response (PR) rates were 54.10%. Patients with βIII-tubulin and/or survivin overexpression were less responsive to docetaxel-based therapy (p0.05) and also had shorter median time to progression and 1- and 2-year survival rates (p0.05).Overexpression of βIII-tubulin and survivin in gastric cancer cells was associated with resistance to docetaxel-based chemotherapy in patients with advanced gastric cancer.

To explore the cause for allelic drop-out at short tandem repeat (STR) loci upon paternity testing with a PowerPlex® 16 kit.A total of 10 642 DNA confirmed paternity testing cases (18 314 parent/child allelic transfers) were analyzed with the PowerPlex® 16 kit. Samples suspected for having allelic drop-out were verified with an Identifiler™ kit and/or locus-specific singleplex amplification systems. PCR products of null alleles were separated and directly sequenced.Eight cases of allelic drop-out were found. The overall rate of null allele in the PowerPlex® 16 system was 0.437 × 10(-3). DNA sequencing has confirmed single base variations within the binding region of published primers, in which 4 cases involved the D18S51 locus (2 cases with GA transitions at 79 bp upstream of the repeats, 1 case with GT transversion at 162 bp downstream of the repeats and 1 case with GC transversion at 74 bp upstream of the repeats), 2 cases involved the D21S11 locus (1 case with CA transversion at 17 bp upstream of the repeats and 1 case with AG transition at 12 bp upstream of the repeats). One case involved the FGA locus (1 case with GA transition at 142 bp downstream of the repeats) and 1 case involved TPOX locus (1 case with GA transition at 198 bp downstream of the repeats).Base variation in the primer binding region may cause failed PCR and result in null allele reports. Alternative primer sets should be used to verify the suspected allelic drop-out. Attention should be paid to this during paternity testing and data exchange for personal identification.