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Objective. To investigate a rapid and effective method for the examination of coronary CTA in emergency patients requiring coronary CTA examination, who have faster heart rate (≧80 bpm) or cannot cooperate with the examination due to the inability of breath holding at poor physical conditions. Methods. Before coronary CTA examination, with the ECG monitoring, intravenous injection of esmolol was given to achieve rapid heart rate reduction. Without the patient’s cooperation, coronary CTA examination was then performed in a quick and effective manner using the 640-slice high-speed CT. The diagnosis report was obtained through the subsequent reconstruction analysis using artificial intelligence software. Conclusion. Esmolol injection can rapidly reduce the heart rate of normal people during exercise and at rest, and the steady blood concentration can be reached in 2 minutes. The half-life is about 5 minutes, with short duration and fewer side effects on patients. The diagnostic rate of coronary artery segment using (excellent + good) CTA image of the patients with esmolol and artificial intelligence analysis in the experimental group was 95.4%, while the diagnostic rate was 91.1% in the control group, and there was no significant statistical difference between the two groups ( P > 0.05 ). Esmolol injection can rapidly reduce heart rate in patients with high heart rate, without holding breath or long-term preoperative preparation; the combination with the analysis of subsequent artificial intelligence reconstruction is a new method for rapid and effective coronary CTA examination in all patients.

Some previous researches raised the possibility of a novel acute myeloid leukemia (AML) entity presenting cup-like cytomorphology with mutations of both FLT3 and NPM1 or one of them. However, the clinical implications of this subtype remain unknown. We describe a 63-year-old patient belonging to this distinct AML subtype, who presented similar features of acute promyelocytic leukemia (APL) including nuclear morphology, negative for CD34 and HLA-DR, and abnormal coagulation. He had no response to both arsenic trioxide and CAG regimen (cytarabine, aclarubicin, and G-CSF). Given that the patient carried the FLT3-ITD mutation, we switched to a pilot treatment of FLT3 inhibitor sorafenib combined with low-dose cytarabine (LDAC). To date, the patient achieved durable complete remission over 58 months. These findings suggest that AML with cup-like blasts and FLT3-ITD and NPM1 mutations mimic APL, and the prognosis of this subtype may be improved by sorafenib combined with LDAC.

Background: The purpose of this study was to investigate the relationship between folic acid and iron nutrition during pregnancy and congenital heart disease (CHD) in the offspring. Methods: Conditional logistic regression models and nonlinear mixed-effects models were used to analyze the effects of folic acid and iron nutrition during pregnancy on CHD in offspring. Results: After adjusting for confounders, folic acid or iron supplementation during pregnancy reduced the risk for fetal CHD (OR = 0.60 (0.45, 0.82) or 0.36 (0.27, 0.48)). Similarly, dietary iron intake during pregnancy (≥29 mg/d) was associated with a reduced risk of fetal CHD (OR = 0.64 (0.46, 0.88)). Additionally, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or iron (OR = 0.32 (0.16, 0.60)), women who supplemented both folic acid and iron had lower risk for newborns with CHD (OR = 0.22 (0.15, 0.34)). Similarly, compared with women who only supplemented folic acid (OR = 0.59 (0.41, 0.84)) or higher dietary iron intake (≥29 mg/d) (OR = 0.60 (0.33, 1.09)), women who supplemented both folic acid and higher dietary iron intake (≥29 mg/d) had lower risk for the newborn with CHD (OR = 0.41 (0.28, 0.62)). The combined effects were significant in the multiplication model (OR = 0.35 (0.26, 0.48) or 0.66 (0.50, 0.85)) but not in the additive model. Conclusions: Our study found that folic acid and iron nutrition during pregnancy were associated with a reduced risk of CHD in the offspring and confirmed a statistically significant multiplicative interaction between folic acid and iron nutrition on the reduced risk of CHD in offspring.

The major risk factor for kidney stone disease is idiopathic hypercalciuria. Recent evidence implicates a role for defective calcium reabsorption in the renal proximal tubule. We hypothesized that claudin-2, a paracellular cation channel protein, mediates proximal tubule calcium reabsorption. We found that claudin-2–null mice have hypercalciuria due to a primary defect in renal tubule calcium transport and papillary nephrocalcinosis that resembles the intratubular plugs in kidney stone formers. Our findings suggest that a proximal tubule defect in calcium reabsorption predisposes to papillary calcification, providing support for the vas washdown hypothesis. Claudin-2–null mice were also found to have increased net intestinal calcium absorption, but reduced paracellular calcium permeability in the colon, suggesting that this was due to reduced intestinal calcium secretion. Common genetic variants in the claudin-2 gene were associated with decreased tissue expression of claudin-2 and increased risk of kidney stones in 2 large population-based studies. Finally, we describe a family in which males with a rare missense variant in claudin-2 have marked hypercalciuria and kidney stone disease. Our findings indicate that claudin-2 is a key regulator of calcium excretion and a potential target for therapies to prevent kidney stones.

Background Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not. Methods This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied. Results A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery. Conclusion For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

Fetal growth has been demonstrated to be an important predictor of perinatal and postnatal health. Although the effects of maternal exposure to air pollution during pregnancy on fetal growth have been investigated using ultrasound in many previous studies, the results were inconsistent and disputable. We aimed to qualitatively and quantitatively investigate the associations of air pollution exposure during different periods of pregnancy with fetal growth and anthropometric measurements at birth. We searched for all studies investigating the associations of air pollution exposure during pregnancy with fetal growth and birth anthropometric measurements in English and Chinese databases published before July 31, 2017. A random-effects model was employed in the meta-analysis to estimate the pooled effects of each 10 μg/m3 increment in air pollutant exposure. The ACROBAT-NRSI tool was applied to assess the quality of each included study, and the GRADE tool was employed to assess the overall quality of the meta-analysis. Maternal PM2.5 exposure (10 μg/m3) during the entire pregnancy was negatively associated with head circumference at birth (β = − 0.30 cm, 95% CI − 0.49, − 0.10), and NO2 exposure during the entire pregnancy was significantly linked to shorter length at birth (β = − 0.03 cm, 95% CI − 0.05, − 0.02). Maternal exposure to higher NO2 and PM2.5 during pregnancy may impair neonatal head circumference and length development, respectively. More studies are needed to confirm the effects of NO2 and PM2.5 and to identify the sources and major toxic components of PMs.

Background/Aims: Some adipokines, such as adiponectin and leptin, have been reported to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), while the association of adipsin and visfatin with NAFLD still remains unclear. This study aimed to examine the association of circulating adipsin, visfatin, and adiponectin with NAFLD in Chinese adults. Methods: We recruited a total of 211 eligible subjects, including 100 NAFLD cases and 111 age and sex frequency-matched controls. Circulating adipsin, visfatin, and adiponection concentrations were measured by enzymatic immunoassay. Unconditional logistic regression was conducted to assess the associations between quartiles of adipokines and NAFLD. Results: Compared with the controls, NAFLD cases had higher levels of adipsin and lower levels of visfatin and adiponectin. By multivariate logistic analysis, adjusting for potential confounders, circulating adipsin levels were found to be positively associated with NAFLD risk, and circulating levels of visfatin and adiponectin were inversely associated with the risk of NAFLD (all p-trend < 0.05). The ORs were 3.76 (95% CI 1.27–11.08) for adipsin, 0.30 (95% CI 0.10–0.91) for visfatin, and 0.30 (95% CI 0.10–0.88) for adiponectin comparing subjects in the highest quartile with those in the lowest. After stratified by obesity status, the association of higher adipsin with increased risk of NAFLD was only observed in nonobese group. Additionally, the inverse association between adiponectin and NAFLD was found in both groups. Conclusions: These results indicated that increased circulating levels of adipsin and decreased circulating levels of visfatin and adiponectin were independently associated with the increased risk of NAFLD.

Background Chemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear. Methods We compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA. Results We demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway. Conclusions Our studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.

INTRODUCTION: The treatment effects of antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin are controversial in patients with coronavirus disease 2019 (COVID­19). OBJECTIVES: This study aimed to evaluate the impact of drug therapy on the risk of death in patients with COVID­19. PATIENTS AND METHODS: The PubMed, Embase, Web of Science, Cochrane Library, and major preprint platforms were searched to retrieve articles published until April 7, 2020. Subsequently, the effects of specific drug interventions on mortality of patients with COVID­19 were assessed. Odds ratios (ORs) and relative risks (RRs) with corresponding 95% CIs were pooled using random effects models. RESULTS: Of 3421 references, 6 studies were included. Pooled results from retrospective studies revealed that antiviral agents may contribute to survival benefit (OR, 0.42; 95% CI, 0.17-0.99; P = 0.048; I2 = 82.8%), whereas a single randomized controlled trial found no effects of an antiviral agent on mortality (RR, 0.77; 95% CI, 0.45-1.3; P = 0.33). Glucocorticoid use led to an increased risk of death (OR, 2.43; 95% CI, 1.44-4.1; P = 0.001; I2 = 61.9%). Antibiotics did not significantly affect mortality (OR, 1.13; 95% CI, 0.67-1.89; P = 0.64; I2 = 0%). Similarly, intravenous immunoglobulin had a nonsignificant effect on mortality (OR, 2.66; 95% CI, 0.72-9.89; P = 0.14; I2 = 93.1%). CONCLUSIONS: With the varied heterogeneities across interventions, the current evidence indicated a probable survival benefit from antiviral agent use and a harmful effect of glucocorticoids in patients with COVID­19. Neither any of antibiotics nor intravenous immunoglobulin were associated with survival benefit in this population.

Welding fumes vary in composition depending on the materials and processes used, and while health outcomes in full-time welders have been widely studied, limited research on apprentices exists. Besides, few data are available for metals such as vanadium and antimony. This study aimed to look at individual metals present in welding fumes in the learning environment of apprentice welders. Forty-three welders and 41 controls were chosen from trade programmes at the Northern Alberta Institute of Technology. Ambient and personal air samples were collected at days 0, 1, 7, and 50 of their training and analysed for mass and metal concentrations using Inductively Coupled Plasma Mass Spectrometry. Results showed increases in particle and metal concentrations as apprentices progressed throughout their education and that concentrations at day 50 were similar to levels found in the literature for professional welders. Variable concentrations indicate that some individuals may not properly use the local exhaust ventilation system. Other possible explanation for variations are the position of the sampler on the shoulder, the time spent welding and in each welding position, and the skills of the welders. Strong relationships were observed between particle and metal concentrations, suggesting that these relationships could be used to estimate metal exposure in welders from particle exposure. Welding processes were the most important determinant of exposure in apprentice welders, with Metal Core Arc Welding producing the largest particle concentrations followed by oxyacetylene cutting, and Gas Metal Arc Welding. Health risk assessment showed that welder apprentices are at risk for overexposure to manganese, which suggests that professional welders should be monitored for manganese as they are exposed more than apprentices. Training in proper positioning of local exhaust ventilation system and proper use of respirators are recommended in training facilities.

BACKGROUND Percutaneous transforaminal endoscopic surgery has been used as a surgical measure for lumbar lateral recess stenosis. However, the necessary decompressive range has never been clearly documented in detail. Here, we discuss the effectiveness of a percutaneous transforaminal endoscopic procedure with clearly defined decompressive range. MATERIAL AND METHODS The relevant data were retrospectively collected from a series of degenerative lateral recess stenosis patients who acquired a prospectively designed percutaneous transforaminal endoscopic procedure in our department. The decompressive procedure mainly included undercutting of superior articular process and intervertebral disk annuloplasty. Leg pain and back pain was evaluated using visual analogue scale (VAS). The functional status was assessed using Oswestry disability index (ODI). The clinical results were also evaluated using MacNab criteria. RESULTS From May 2014 to October 2018, a total of 33 patients who met our inclusion criteria were included for analysis. There were no perioperative complications. Leg pain VAS decreased from preoperative score of 6.18±2.38 to final follow-up score of 0.45±1.00 (P

Background Grade V thoracic spondylolisthesis secondary to neurofibromatosis type 1 (NF-1), especially combined with vertebral fusion, is rare. We reported a case of a 26-year-old female diagnosed with grade V T2spondylolisthesis and T2-T5 autofusion secondary to NF-1, which caused severe kyphotic deformity and neurologic deficits, and she was treated with posterior decompression, internal fixation, and fusion. Case Description The right-handed patient admitted to the clinic due to weakness of her legs. An eye examination documented a sign of Lisch nodules in the iris. Cafe-au-lait macules, dermal neurofibroma of multiple forms, and rubbery bumps of varying sizes could be observed on her skin. Paresis with muscle strength of 2/5 in both lower extremities with increased muscle tone and decreased muscle mass could be observed. Radiographic results indicated grade V thoracic spondylolisthesis with vertebral fusion from T2-T5 level. To alleviate neurologic dysfunction, posterior decompression, internal fixation, and fusion were performed. She reported marked improvement in lower limb motor and sensory functions during the follow-up, and her muscle strength recovered to 5/5. Conclusions Grade V thoracic spondylolisthesis combined with vertebral fusion on T2-T5 level in NF-1 is rare. Early surgical intervention of posterior spinal decompression with internal fixation and fusion yielded satisfactory clinical outcomes.

Background Concerns about breast cancer had become the most dangerous cancer to women over the world, more and more anti‐cancer agents are developed to treat this malignancy. Pharmorubicin is a cytotoxic drug, widely used in the treatment of breast cancer, but its role is limited because of chemoresistance produced by cells. This study focused on exploring the influence of autophagy on the resistance of pharmorubicin in breast cancer cells. Methods The cell survival of breast cancer cells was detected by MTT. The mRNA expression of heme oxygenase‐1 (HO‐1) was tested by qRT‐PCR. The protein expression of HO‐1, autophagic proteins (LC3‐I,LC3‐II and Beclin‐1), PI3K and Akt was detected by Western blot. Cell autophagy was examined by Cyto‐ID Autophagy Detection Kit. Results After being treated with pharmorubicin, the expression of HO‐1 and autophagy related proteins was significantly enhanced, but the cell survival ratio in the two cell lines decreased. After autophagy was inhibited, HO‐1 expression in two cells was down‐regulated. When pharmorubicin‐resistant cells were transfected with si‐HO‐1, the cell survival decreased and the protein expression of HO‐1, autophagic proteins (LC3‐II/LC3‐I and Beclin‐1) as well as autophagy were all down‐regulated, while in pharmorubicin‐resistant cells transfected with pcDNA3.1‐HO‐1, the results were reverse. When the PI3K or Akt was inhibited, PI3K, p‐Akt, HO‐1, autophagic proteins and autophagy were decreased remarkably. Conclusion It was proved that HO‐1 induction mediated chemoresistance of pharmorubicin in breast cancer cells by promoting autophagy via PI3K/Akt pathway.

Aim Cyanidin-3-O-β-glucoside (Cy-3-G) the most abundant monomer of anthocyanins has multiple protective effects on many diseases. To date, whether Cy-3-G could regulate the function of brown adipose tissue (BAT) is still unclear and whether this regulation could influence the secretion of adipokines from BAT to prevent non-alcoholic fatty liver disease (NAFLD) indirectly remains to be explored. In this study we investigated the effect of Cy-3-G on BAT and the potential role of Cy-3-G to prevent fatty liver through regulating the secretion of BAT. Methods Male C57BL/6 J mice were fed with a high fat high cholesterol (HFC) diet with or without 200 mg/kg B.W Cy-3-G for 8 weeks. In in vitro experiments, the differentiated brown adipocytes (BAC) and C3H10T1/2 clone8 cells were treated with 0.2 mM palmitate with or without Cy-3-G for 72 or 96 h. Then the culture media of C3H10T1/2 clone8 cells were collected for measuring the adipokines secretion by immunoblot assay and were applied to culture HepG2 cells or LO2 cells for 24 h. Lipid accumulation in HepG2 cells or LO2 cells were evaluated by oil red O staining. Results Here we found that Cy-3-G regulated the activation of BAT and the expression of adipokines in BAT which were disrupted by HFC diet and alleviated diet induced fatty liver in mice. In in vitro experiments, Cy-3-G inhibited the release of adipokines including extracellular nicotinamide phosphoribosyltransferase (eNAMPT) and fibroblast growth factor 21 (FGF21) from differentiated C3H10T1/2 clone8 cells induced by palmitate, which was accompanied by a reduction of lipid accumulation in HepG2 cells and LO2 cells cultured by the corresponding collected media of C3H10T1/2 clone8 cells. Conclusions These results indicate that Cy-3-G can regulate the thermogenic and secretory functions of BAT. Furthermore, our data suggest that the protective effect of Cy-3-G on hepatic lipid accumulation is probably via regulating the secretion of adipokines from BAT.

Choline acetyltransferase neurons in the vertical diagonal band of Broca (vChATs) degenerate in the early stage of Alzheimer’s disease (AD). Here, we report that vChATs directly innervate newly generated immature neurons (NGIs) in the dorsal hippocampus (dNGIs) of adult mice and regulate both the dNGIs survival and spatial pattern separation. In a mouse model that exhibits amyloid-β plaques similar to AD patients, cholinergic synaptic transmission, dNGI survival and spatial pattern separation are impaired. Activation of vChATs with theta burst stimulation (TBS) that alleviates the decay in cholinergic synaptic transmission effectively protects against spatial pattern separation impairments in the AD mice and this protection was completely abolished by inhibiting the dNGIs survival. Thus, the impairments of pattern separation-associated spatial memory in AD mice are in part caused by degeneration of cholinergic synaptic transmission that modulates the dNGIs survival., Cholinergic neurons in the diagonal band of Broca degenerate early in Alzheimer’s disease. Here the authors show that in healthy mice, these cholinergic inputs innervate newborn neurons in the hippocampus, and that loss of this innervation in an Alzheimer’s disease model leads to impairments in spatial memory.

Objective Histone deacetylase 3 (HDAC3) has been reported to repress the expression of various genes by eliminating acetyl group from histone. The objective of this study was to discuss the effect of HDAC3/microRNA-130a-3p (miR-130a-3p)/high-mobility group box 3 (HMGB3) on immune escape of breast cancer. Methods HDAC3, miR-130a-3p and HMGB3 expression in breast cancer tissues and cells were tested, and the correlation between HDAC3, miR-130a-3p and HMGB3 was analyzed. CD8, CD69 and programmed cell death protein 1 (PD-1) expression was detected. MDA-MB-231 cells were treated with relative plasmid of HDAC3 or miR-130a-3p to test cell viability, migration, epithelial-mesenchymal transition (EMT) and apoptosis in MDA-MB-231 cells. The cytotoxicity of CD8+/CD69+/PD-1+T cells in MDA-MB-231 cells was tested, and CD8+/CD69+/PD-1+T cell proliferation and apoptosis before and after co-culture with MDA-MB-231 cells were detected. Results HDAC3 and HMGB3 expression were raised and miR-130a-3p expression was diminished in breast cancer tissues and cells. HDAC3 was negatively correlated with miR-130a-3p while miR-130a-3p was negatively correlated with HMGB3. Down-regulating HDAC3 or up-regulating miR-130a-3p restrained cell viability, migration, EMT and anti-CD8+/CD69+/PD-1+T cytotoxicity and facilitated apoptosis of breast cancer cells. HDAC3 regulated HMGB3 by mediating miR-130a-3p expression. Down-regulating miR-130a-3p reversed the role of HDAC3 reduction on breast cancer cells. HDAC3 regulated CD8+/CD69+/PD-1+T cell proliferation and apoptosis by mediating miR-130a-3p. Conclusion This study provides evidence that HDAC3 increases HMGB3 expression to promote the immune escape of breast cancer cells via down-regulating miR-130a-3p.

Raf-1 kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor in cancer cells. MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. In this study, we found the expression of RKIP and miR-185 in breast cancer tissues was significantly lower than that of in normal breast tissues. Over-expression of RKIP up-regulated miR-185 expression, inhibited breast cancer cell growth and invasion, and inhibited miR-185 target gene High-mobility group AT-hook 2 (HMGA2). HMGA2 is encoded by HMGA2 gene, which encodes a protein that belongs to the non-histone chromosomal high-mobility group (HMG) protein family. Moreover, RKIP knockdown attenuated the inhibition of breast cancer cell invasion and the expression of HMGA2 by miR-185. Forced HMGA2 overexpression could partly restore the inhibitory effect of miR-185 on breast cancer cell growth and invasion. Our findings newly described RKIP/miR-185 to HMGA2 link and provided a potential mechanism for breast cancer cell growth and invasion. It may illustrate the potential therapeutic utility of signaling pathway signatures.

Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1PV) and undergo selective degeneration in the early stages of Alzheimer's disease (AD). Here, we show that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPNof AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PVsynaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECIIPNcontributes to a memory loss in AD and hence warrants a promising target for the treatment of AD.SIGNIFICANCE STATEMENTOur recent study reported that excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) target to CA1 parvalbumin-type inhibitory neurons (CA1PV) at a direct pathway and are one of the most vulnerable brain cells that are selectively degenerated in the early stage of Alzheimer's disease (AD). Our present study shows that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPNof AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PVsynaptic loss and improves spatial learning and memory in the early stage of AD. These data not only demonstrate a crucial molecular event for synaptic degeneration but also provide a therapeutic target for the treatment of AD.

// Rui-Min Chang 1 , Lei Pei 1 , Feng Fang 1 , Jiang-Feng Xu 1 , Hao Yang 1 , Chao-Hui Zuo 4 , Jian-Hua Zhou 2 , Geng-Qiu Luo 2 , Lian-Yue Yang 1, 3 1 Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, China 2 Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China 3 Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, China 4 Department of Abdominal Surgical Oncology, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China Correspondence to: Lian-Yue Yang, email: lianyueyang@hotmail.com Keywords: YMO1, RhoC, PAX5, hepatocellular carcinoma, metastasis Received: November 21, 2015 Accepted: June 29, 2016 Published: July 27, 2016 ABSTRACT Previous studies have shown that 4.1 proteins, which are deregulated in many cancers, contribute to cell adhesion and motility. Yurt/Mosaic eyes-like 1 (YMO1) is a member of 4.1 protein family but it is unclear whether YMO1 plays a role in tumor invasion. This study aimed to investigate the effects of YMO1 on hepatocellular carcinoma (HCC) and attempted to elucidate the underlying molecular mechanisms. YMO1 expression in HCC tissues and its correlation with clinicopathological features and postoperative prognosis was analyzed. The results showed that YMO1 was down-regulated in the highly metastatic HCC cell line and in human tumor tissues. Underexpression of YMO1 indicated poor prognosis of HCC patients. Restoration of YMO1 expression caused a significant decrease in cell migration and invasiveness in vitro . In vivo study showed that YMO1 reduced liver tumor invasion and metastasis in xenograft mice. YMO1 directly inhibited RhoC activation. YMO1 expression in HCC was regulated by PAX5. Analysis of YMO1 expression levels in human HCC patients revealed a significant correlation of YMO1 expression with PAX5 and RhoC. Our findings revealed that YMO1 predicts favorable prognosis and the data suggest that YMO1 suppresses tumor invasion and metastasis by inhibiting RhoC activity.

Death-associated protein kinase 1 (DAPK1), a Ca2+/calmodulin (CaM)-dependent serine/threonine protein kinase, plays important roles in diverse apoptosis pathways not only in tumor suppression but also in neuronal cell death. The requirement of DAPK1 catalytic activity for its proposed cell functions and the elevation of catalytic activity of DAPK1 in injured neurons in models of neurological diseases, such as ischemia and epilepsy, validate that DAPK1 can be taken as a potential therapeutic target in these diseases. Recent studies show that DAPK1-NR2B, DAPK1-DANGER, DAPK1-p53, and DAPK1-Tau are currently known pathways in stroke-induced cell death, and blocking these cascades in an acute treatment effectively reduces neuronal loss. In this review, we focus on the role of DAPK1 in neuronal cell death after stroke. We hope to provide exhaustive summaries of relevant studies on DAPK1 signals involved in stroke damage. Therefore, disrupting DAPK1-relevant cell death pathway could be considered as a promising therapeutic approach in stroke.

The emergence of pathogens resistant to existing antimicrobial drugs is a growing worldwide health crisis that threatens a return to the pre-antibiotic era. To decrease the overuse of antibiotics, molecular diagnostics systems are needed that can rapidly identify pathogens in a clinical sample and determine the presence of mutations that confer drug resistance at the point of care. We developed a fully integrated, miniaturized semiconductor biochip and closed-tube detection chemistry that performs multiplex nucleic acid amplification and sequence analysis. The approach had a high dynamic range of quantification of microbial load and was able to perform comprehensive mutation analysis on up to 1,000 sequences or strands simultaneously in

Nonalcoholic fatty liver disease has become a social health challenge of global concern. The term nonalcoholic steatohepatitis (NASH) is a more severe condition than simple steatosis and distinguishing NASH from nonalcoholic fatty liver disease is particularly important. Liver biopsy remains a gold standard in diagnosing NASH. Meanwhile, radiological techniques such as ultrasonography and MRI are also applied widely. However, the invasive and expensive examination is not suitable for screening, and there is a great need for reliable and appropriate biomarkers to screen patients for NASH. Based on the current studies of blood-based novel biomarkers, we attempt to summarize the latest findings on biomarkers for NASH, including blood biomarkers encompassing proteins, lipids and miRNAs; the correlation between extracellular vesicles and NASH; and treatment strategies for NASH.

To explore the correlation between the number of previous gadolinium-based contrast agent administrations and high signal intensity (SI) in the cerebrum nucleus on unenhanced TThirty-nine patients who previously underwent at least three contrast-enhanced brain MRI examinations were enrolled in the study. The right globus pallidus, right thalamus, right dentate nucleus, pons and white matter of right frontal lobe were selected as region of interests (ROI). The mean SIs of the ROI were measured on unenhanced TThe dentate nucleus-to-white matter SI ratios of the last and first MRI scan were 1.113±0.136 and 1.014±0.096(High SI in the dentate nucleus on unenhanced T

Study design A retrospective study. Objective The aim of this study was to compare the clinical outcomes of continuous irrigation suction systems (CISS) or vacuum-assisted closure system (VACS) in early deep wound infection (DWI) after thoracolumbar instrumentation. Summary of background data DWI after thoracolumbar instrumentation is challenging and debridement followed by either CISS or VACS has been proven to be effective. So far, which one of the system has more advantages over the other remains unclear. Methods Patients after thoracolumbar instrumentation were evaluated at our spine surgery center from 2005 to 2015. Patients who were diagnosed with early deep DWI after spinal instrumentation and treated by meticulous debridement in the operating room followed by either CISS or VACS were included. Detailed information was obtained from the medical records, including clinical features, results of laboratory examinations, medical therapies, and outcomes. A follow-up was conducted to observe whether recurrent spinal infection or other complications happened. Results We identified 11 patients in the CISS group and 12 patients in the VACS group. There were no significant differences in terms of age, gender, follow-up duration, symptoms of infection, laboratory examinations, etc. The number of CISS or VACS replacement was 1.3 and 1.6, respectively, before wound healing (P > 0.05). And there were significant differences in terms of hospital stay and extra cost of infection treatment between the two groups. In the follow-up period, we observed sinus tract formation and low back pain in both groups and one patient in the VACS group died of pulmonary infection 4 years after the initial surgery. Conclusion Thorough debridement followed by CISS or VACS are comparable in treating early DWI after thoracolumbar instrumentation. The CISS treatment was statistically significant in comparison to the VACS treatment in terms of hospital stay and cost. Level of evidence 4.

Objective. We aim to determine the efficiency of CT in identification of cystic echinococcosis in sheep. Methods. Fifty-three sheep with liver cysts confirmed by ultrasonography were subject to CT scan to evaluate the number, size, and type of the cysts in liver and lung, confirmed using necropsy. The correlation of numbers between liver cysts and lung cysts was calculated using Pearson analysis. Results. Necropsy indicated a 98% consensus on size, location, number, and activity compared with CT scan. The viable cysts were 53.1% and 50.6% in the liver and lung, respectively. Among the cysts in liver, 35.5%, 9.5%, 5.7%, 10.2%, and 39.1% were Types CE1, CE2, CE3, CE4, and CE5, respectively. The cysts in the lungs, 17.4%, 26.9%, 12.1%, 11.6%, and 32.1%, were Types CE1, CE2, CE3, CE4, and CE5, respectively. A significant correlation was noticed between the number of cysts in liver and those in lung (R=0.770, P<0.001). Conclusions. CT scan is a suitable tool in determining the size and type of cystic hydatid cysts in both liver and lung of sheep. A significant correlation was noticed between the numbers in liver and lung, indicating that lung infection was likely due to the expansion of liver cyst burden pressure.

Tau hyperphosphorylation is a critical event in Alzheimer's disease, in which the neuronal Golgi fragmentation occurs earlier than tau hyperphosphorylation. However, the intrinsic link between Golgi impairment and tau pathology is missing. By electron microscopy and western blotting, we observed in the present study that the neuronal Golgi fragmentation was increased age-dependently with a correlated tau hyperphosphorylation in the brains of C57BL/6 mice aged from 4 to 16 months. Simultaneously, golgin-84 and Golgi reassembly stacking protein 65, 2 important Golgi matrix proteins, were decreased in the brains of elder mice. Further studies in HEK293/tau cells showed that Golgi-disturbing agents, brefeldin A and nocodazole induced tau hyperphosphorylation. Knockdown of golgin-84, not Golgi reassembly stacking protein 65, by small interfering RNA was sufficient to induce tau hyperphosphorylation, while over-expressing golgin-84 arrested the brefeldin A-induced Golgi fragmentation and tau hyperphosphorylation. Finally, we demonstrated that cyclin-dependent kinase-5 and extracellular signal-regulated kinase were activated after golgin-84 knockdown, and simultaneous inhibition of these kinases abolished the golgin-84 deficit-induced tau hyperphosphorylation. These data suggest Golgi fragmentation could be an upstream event triggering tau hyperphosphorylation through golgin-84 deficit-induced activation of cyclin-dependent kinase-5 and extracellular signal-regulated kinase.

The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer's disease (AD). Here, we report that the synaptic terminals of pyramidal neurons in the EC layer II (ECIIPN) directly innervate CA1 parvalbumin (PV) neurons (CA1PV) and are selectively degenerated in AD mice, which exhibit amyloid-β plaques similar to those observed in AD patients. A loss of ECIIPN-CA1PV synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECIIPN using a theta burst paradigm rescues ECIIPN-CA1PV synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECIIPN-CA1PV pathway.

We analysed the decisions of major European public funding organisations to fund or not to fund synthetic biology (SB) and related ethical, legal and social implication (ELSI) studies. We investigated the reaction of public organisations in six countries (Austria, France, Germany, the Netherlands, Switzerland and the UK) towards SB that may influence SB’s further development in Europe. We examined R&D and ELSI communities and their particular funding situation. Our results show that the funding situation for SB varies considerably among the analysed countries, with the UK as the only country with an established funding scheme for R&D and ELSI that successfully integrates these research communities. Elsewhere, we determined a general lack of funding (France), difficulties in funding ELSI work (Switzerland), lack of an R&D community (Austria), too small ELSI communities (France, Switzerland, Netherlands), or difficulties in linking existing communities with available funding sources (Germany), partly due to an unclear SB definition.

Synthetic biology is considered as an emerging research field that will bring new opportunities to biotechnology. There is an expectation that synthetic biology will not only enhance knowledge in basic science, but will also have great potential for practical applications. Synthetic biology is still in an early developmental stage in China. We provide here a review of current Chinese research activities in synthetic biology and its different subfields, such as research on genetic circuits, minimal genomes, chemical synthetic biology, protocells and DNA synthesis, using literature reviews and personal communications with Chinese researchers. To meet the increasing demand for a sustainable development, research on genetic circuits to harness biomass is the most pursed research within Chinese researchers. The environmental concerns are driven force of research on the genetic circuits for bioremediation. The research on minimal genomes is carried on identifying the smallest number of genomes needed for engineering minimal cell factories and research on chemical synthetic biology is focused on artificial proteins and expanded genetic code. The research on protocells is more in combination with the research on molecular-scale motors. The research on DNA synthesis and its commercialisation are also reviewed. As for the perspective on potential future Chinese R&D activities, it will be discussed based on the research capacity and governmental policy.

Background NLRP3 inflammasome plays a prominent role in the pathogenesis and progression of many diseases, such as type 2 diabetes mellitus, obesity, atherosclerosis, and Alzheimer's disease. However, little knowledge is known about the role of NLRP3 inflammasome in central post-stroke pain (CPSP). Methods We selected relevant studies by searching PubMed, Embase, and Medline from inception through February, 2018. We systematically reviewed available publications according to the terms "NLRP3 inflammasome" and "stroke" or "central post-stroke pain" in the title/abstract field. Results We reviewed the articles and put forward two possible ways for NLRP3 inflammasome in CPSP. One way is that NLRP3 activation causes cerebral cortex injure, decreasing descending projection fiber to thalamus. Such condition may let GABAergic releases reduce, making the ventral basal (VB) neurons excitability increased. Finally, CPSP occur. Another way is that NLRP3 inflammasome leads to thalamic lesion and strengthens inflammatory response of microglia at the same time. Persistent inflammation causes GABAergic alteration in thalamus reticular neurons (TRN) to restrain VB interneurons functions, contributing to CPSP. Conclusions These possible mechanisms will help become knowledgeable about the occurrence CPSP and provide potential therapy for CPSP.

Two approaches have been developed to construct plasmids that mediate RNA interference to inhibit the replication and expression of HBV in 2.2.15 cell. The overlapping PCR extension and restriction enzyme-digestion were used to generate DNA fragments encoding designed shRNA based on sequences of ORF C of HBV genome. The pU6 derived vectors were constructed to develop plasmid based shRNA delivery systems termed pU6/HBVi. There were significant reductions in the expression of HBsAg and HBeAg between cells transfected with pU6/HBVi and control groups (as to HBsAg: P < 0. 01; and HBeAg: P < 0. 01). Consistently, the HBV DNA copies were reduced from 2.71 x 10(7) to

Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney. We found that claudin-2-null mice conserve sodium to the same extent as WT mice, even during profound dietary sodium depletion, as a result of the upregulation of transcellular Na-K-2Cl transport activity in the thick ascending limb of Henle. We hypothesized that shifting sodium transport to transcellular pathways would lead to increased whole-kidney oxygen consumption. Indeed, compared with control animals, oxygen consumption in the kidneys of claudin-2-null mice was markedly increased, resulting in medullary hypoxia. Furthermore, tubular injury in kidneys subjected to bilateral renal ischemia-reperfusion injury was more severe in the absence of claudin-2. Our results indicate that paracellular transport in the PT is required for efficient utilization of oxygen in the service of sodium transport. We speculate that paracellular permeability may have evolved as a general strategy in epithelial tissues to maximize energy efficiency.

To investigate the expressions and prognostic value of stem cell markers, EpCAM and CD133, in benign and malignant lesions of gallbladder.Expression of EpCAM and CD133 was assessed in gallbladder adenocarcinoma (n = 100), peritumoral tissues (n = 46), adenoma (n = 30), polyp (n = 15), and chronic cholecystitis (n = 35) by using immunohistochemistry.The positive rates of EpCAM and CD133 expression were significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues (χ2(EpCAM7) = 15.36, χ2(CD133) =16.05; Ps0.01), adenoma (χ2 (EpCAM) =10.92, χ2(CD133) = 11.09; Ps0.01), polyp (χ2(EpCAM) = 8.88, χ2(CD133) = 10.43; Ps0.01) and chronic cholecystitism (χ2(EpCAM) = 28.58, χ2(CD133) =25.57; Ps0.01). In adenocarcinoma, the positive expression of EpCAM and CD133 was significanctly associated with differentiation, tumor mass, lymph node metastasis, invasion and overall survival. Notably, the benign lesions with positive EpCAM or /and CD133 expression showed moderately or severely atypical hyperplasia in gallbladder epithelium. The high consistence was found between the expressive levels of EpCAM and CD133 in gallbladder adenocarcinoma (χ2 = 10.02, P0.01). Unitivariate Kaplan-Meier analysis showed that high level of EpCAM (P = 0.004) and CD133 (P = 0.012) were associated with poor overall survival.The elevated expression of EpCAM and/or CD133 is closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

Background: Prognosis of locally advanced esophageal squamous cell carcinoma (ESCC) remains dismal even after curative resection and adjuvant radiotherapy. New biomarkers for predicting prognosis and treatment outcomes are needed for improved treatment stratification of patients with locally advanced ESCC. The prognostic and treatment predictive significance of perineural invasion (PNI) in the locally advanced ESCC remains unclear. This study aimed to examine the effect of PNI on the outcomes of locally advanced ESCC patients after curative resection with or without postoperative radiotherapy (PORT). Patients and methods: We retrospectively reviewed 262 consecutive locally advanced ESCC patients who underwent curative resection. Tumors sections were re-evaluated for PNI by an independent pathologist blinded to the patients’ outcomes. Overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method; univariate log-rank test and multivariate Cox proportional hazard model were used to evaluate the prognostic value of PNI. Results: Finally, 243 patients were analyzed and enrolled into this study, of which 132 received PORT. PNI was identified in 22.2% (54/243) of the pathologic sections. The 5-year DFS was favorable for PNI-negative patients versus PNI-positive patients (21.3% vs. 36.7%, respectively; P = 0.005). The 5-year OS was 40.3% for PNI-negative patients versus 21.7% for PNI-positive patients (P < 0.001). On multivariate analysis, PNI was an independent prognostic factor. In a subset analysis for patients received PORT, PNI was evaluated as a prognostic predictor as well (P < 0.05). In contrast to patients without PORT, PORT couldn’t improve the disease recurrence and survival in locally advanced ESCC patients with PNI-positive (P > 0.05). Conclusions: PNI could serve as an independent prognostic factor and prognosticate treatment outcomes in locally advanced ESCC patients. The PNI status should be considered when stratifying high-risk locally advanced ESCC patients for adjuvant radiotherapy. Future prospective study is warranted to confirm our results.

MicroRNAs (miRNAs) have been considered to be potent biomarkers for early disease diagnosis and for cancer therapy. The rapid and selective detection of miRNAs without reverse transcription and labelling is highly desired. Herein, we report a simple and label-free miRNA detection method that is based on the Duplex-Specific Nuclease (DSN)-Assisted simple target miRNA recycling procedure. The interaction of the G-quadruplex DNA structure with N-methyl mesoporphyrin IX (NMM) led to a label-free signal output. Under the optimised conditions, this method allowed for simple, rapid, and sequence-specific detection of miR-141 over a dynamic range from 1 fM to 100 nM with a linear range from 1 pM to 100 nM. Moreover, our method offered an excellent capacity to discriminate between miRNA family members with just one mismatched nucleotide. This simple and label-free strategy holds great potential in applications in biomedical research and in early clinical diagnostics.

To construct a new human chemotactic cytokine PSMP eukaryotic expression vector to express PSMP in Chinese hamster ovary (CHO) cells and to obtain the purified recombinant PSMP protein for its functional mechanism study.PSMP-myc/His fragment, cut from pcDNA3.1-PSMP-myc/His, was inserted into pMH3 expression vector. This expression vector was transfected into CHO cells by electroporation. Stable clone strains were selected by Geneticin resistance screening. The expressions of PSMP protein in the cell culture supernatant were measured by Dot blot and Western blot analysis. The monoclone was prepared from resistance screening polyclone by limiting dilution method. A large number of the engineering cells were cultured with serum-free medium and the protein in the cell culture supernatant was purified by nickel affinity chromatography. The purity of the PSMP protein was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The functional activity of the protein was analyzed in vitro by Boyden chamber chemotaxis assay.The eukaryotic expression vector pMH3-PSMP was successfully constructed by inserting PSMP-myc/His gene into pMH3 vector. After transfection of CHO cells, a stable expression of the PSMP gene engineering cell strain was obtained through twice cloning. The purity of the recombinant PSMP protein was 95% higher with bioactivity.The eukaryotic expression vector of PSMP protein is successfully constructed. The stable expression of PSMP is first obtained in CHO cell strain. The recombinant PSMP protein has higher purity and bioactivity, which provides a useful tool for further study of the functions and mechanisms of PSMP.

To explore the clinical characteristics and prognostic value of monosomal karyotype (MK) patients in adult acute myeloid leukemia (AML).We retrospectively studied 45 patients of MK⁺ in newly-diagnosed adult AML in our center from Oct 2000 to Dec 2012. Clinical characteristics, cytogenetic data and prognostic features were analyzed in the cohort of MK⁺ patients.MK was found in 45 patients (19.0%) of 237 newly-diagnosed adult AML with cytogenetic data available at diagnoses. Among these 45 cases, there were 28 male (62.2%) and 17 female (37.8%). Median age of MK⁺ patients at diagnose was 58(18-91) years old. The presence of -5(31.1%) and -7(17.8%) were the most common chromatid among MK⁺ AML patients. MK was much more prevalent among elderly patients. Among AML patients, the proportions of MK⁺ patients younger than 30, 30 to 59 and older than 60 years old groups were 11.5%, 17.7% and 22.4%, respectively. There was no difference between MK⁺ and MK⁻ patients in gender distribution (P=0.545). There was also no difference between MK⁺ and MK⁻ patients in the distribution of FAB castigation (P=0.239). Median survival of MK⁺ AML patients was 6.5 months. Cumulative 5-year overall survival (OS) of was 5.2%. Forty-three MK⁺ patients (43/45, 95.6%) also had a complex karyotype (CK). Two cases that did not meet the CK had not achieved complete remission (CR), and died within 6 months. There were 12 patients who were CK⁺ in 192 MK⁻ patients. The differences of OS and CR rates between MK⁺CK⁺ patients and MK⁻CK⁺ were statistically significant (P0.05).The increased detection rate of MK with age was associated with lower CR and OS in AML patients.

In contrast to cardiomyocytes, autophagy in cardiac microvascular endothelial cells (CMECs) during ischemia/reperfusion (I/R) injury has not been fully investigated. Tongxinluo (TXL), a traditional Chinese medicine, was shown to be vascular protective. We aimed to elucidate the role of autophagy and its regulatory mechanisms by TXL in CMECs subjected to I/R injury. CMECs were exposed to different treatments for 30 minutes and subjected to hypoxia/reoxygenation each for 2 hours. The results indicated that hypoxia/reoxygenation significantly induced autophagy, as identified by an increased number of monodansylcadaverine-positive CMECs, increased autophagosome formation, and a higher type II/type I of light chain 3 ratio, but not Beclin-1 expression. Autophagy inhibition using 3-methyladenine was proapoptotic, but rapamycin-induced autophagy was antiapoptotic. TXL enhanced autophagy and decreased apoptosis in a dose-dependent manner, reaching its largest effect at 800 μg/mL. 3-methyladenine attenuated the TXL-promoted autophagy and antiapoptotic effects, whereas rapamycin had no additional effects compared with TXL alone. TXL upregulated mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) phosphorylation; however, PD98059 abrogated ERK phosphorylation and decreased autophagy and increased apoptosis compared with TXL alone. These results suggest that autophagy is a protective mechanism in CMECs subjected to I/R injury and that TXL can promote autophagy through activation of the mitogen-activated protein kinase/ERK pathway.

The highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype infect poultry and have also been spreading to humans. Although new antiviral drugs and vaccinations can be effective, rapid detection would be more efficient to control the outbreak of infections. In this study, a phage-display library was applied to select antibody fragments for HPAI strain A/Hubei/1/2010. As a result, three clones were selected and sequenced. A hemagglutinin inhibition assay of the three scFvs revealed that none exhibited hemagglutination inhibition activity towards the H5N1 virus, yet they showed a higher binding affinity for several HPAI H5N1 strains compared with other influenza viruses. An ELISA confirmed that the HA protein was the target of the scFvs, and the results of a protein structure simulation showed that all the selected scFvs bound to the HA2 subunit of the HA protein. In conclusion, the three selected scFVs could be useful for developing a specific detection tool for the surveillance of HPAI epidemic strains.

Using infant and child feeding index (ICFI) to evaluate the relationship between infant feeding and physical development indicators in rural areas of Lhasa.In July and August 2010 in the rural areas of Lhasa, the multi-stage cluster random sampling method was adopted to select 540 Tibetan children who were between 6 to 35 months of age. There were 70, 79 and 391 cases in 6 to 8, 9 to 11 and 12 to 35-month-old group respectively. The basic status of infants, information about breastfeeding and complementary feeding were collected by using designed questionnaires. Their height and weight were measured to calculate the children's weight for age Z-score (WAZ), height for age Z-score (HAZ) and weight for height Z-score (WHZ) and assess feeding index score (out of 17 scores) and analyze the relationship between feeding index and HAZ, WAZ and WHZ.The mean ICFI score of 540 cases was 8.90 ± 2.82.It was 6.84 ± 3.16, 8.16 ± 2.78 and 9.41 ± 2.55 for 6 to 8, 9 to 11 and 12 to 35-month-old infants respectively. There was significant difference between the different month group (F = 30.99, P0.05).For the three month groups, the scores of WAZ were 0.10 ± 1.18, -0.09 ± 1.20 and -0.38 ± 0.96; HAZ were -0.60 ± 1.68, -1.02 ± 1.72 and -1.30 ± 1.30; WHZ were 0.62 ± 1.23, 0.69 ± 0.96 and 0.43 ± 0.95 respectively. The ICFI scores of 9 to 11, 12 to 35 and 6 to 35-month-old infants were positively correlated with HAZ (correlation coefficients were 0.25,0.12 and 0.09 respectively, all P values0.05). There was no correlation with WAZ (correlation coefficients were 0.15,0.08 and 0.03 respectively, all P values0.05) and WHZ (correlation coefficients were -0.08, -0.02, and -0.07 respectively, all P values0.05). There were no correlation between ICFI score with HAZ, WAZ and WHZ for 6 to 8 month-old infants (correlation coefficient were 0.06,0.16 and -0.07 respectively, all P values0.05).To some extent, the feeding index can effectively reflect the growth status of these infants and can serve as a comprehensive assessment of feeding situations among Tibetan children in rural areas of Lhasa.

In tight junctions, both claudin-2 and claudin-10b form paracellular cation-selective pores by the interaction of the first ECL 1 with permeating ions. We hypothesized that a highly conserved aromatic residue near the pore selectivity filter of claudins contributes to cation selectivity by cation-π interaction with the permeating cation. To test this, we generated MDCK I Tet-off cells stably transfected with claudin-2 Tyr67 mutants. The Y67L mutant showed reduced cation selectivity compared with wild-type claudin-2 due to a decrease in Na+ permeability, without affecting the Cl− permeability. The Y67A mutant enlarged the pore size and further decreased the charge selectivity due to an increase in Cl− permeability. The Y67F mutant restored the Na+ permeability, Cl− permeability, and pore size back to wild-type. The accessibility of Y67C to methanethiosulfonate modification indicated that its side chain faces the lumen of the pore. In claudin-10b, the F66L mutant reduced cation selectivity, and the F66A mutant lost pore conductance. We conclude that the conserved aromatic residue near the cation pore domain of claudins contributes to cation selectivity by a dual role of cation-π interaction and a luminal steric effect. Our findings provide new insight into how ion selectivity is achieved in the paracellular pore. Background: Claudin pore domain contains a highly conserved aromatic residue. Results: Cation selectivity of claudin-2 and claudin-10b was impaired by substitution of residues lacking an aromatic group. Conclusion: The aromatic residue confers cation selectivity by cation-π interaction and restricting the pore diameter. Significance: This advances our understanding of the paracellular ion selectivity mechanism.

EPAC (Exchange Proteins Activated by cAMP) regulates glutamate transmitter release in the central neurons, but a role underlying this regulation has yet to be identified. Here we show that EPAC binds directly to the intracellular loop of an ATP-sensitive potassium (KATP) channel type-1 sulfonylurea receptor (SUR1) receptor consisting of amino acids 859–881 (SUR1859–881). Ablation of EPAC or expression of SUR1859–881, which intercepts EPAC-SUR1 binding, increases the open probability of KATPchannels consisting of the Kir6.1 subunit and SUR1. Opening of KATPchannels inhibits glutamate release and reduces seizure vulnerability in adult mice. Therefore, EPAC interaction with SUR1 controls seizure susceptibility and possibly acts via regulation of glutamate release.

To investigate the prevalences of overweight and obesity in the rural communities in Hanzhong, Shaanxi Province.A total of 3030 residents in the rural areas of Hanzhong city were selected by stratified random sampling method to take questionnaire-based survey and physical examinations.The data of 3017 valid subjects (1048 men and 1969 women) entered the final analysis. The average body mass index was (22.9±4.2) kg/m(2) [(23.0±5.5) kg/m(2) in men and (22.9±3.2) kg/m(2) in women]. The prevalence rates of overweight and obesity were 27.9% and 5.9% respectively, and the standardized rates were 23.4% and 5.4%, respectively. More specifically, prevalence rates of overweight and obesity were 28.3% and 6.1% in men (standardized rates were 24.7% and 7.5%, respectively) and 27.6% and 5.8% (standardized rate were 22.8% and 4.5% respectively) in women. The overweight/obesity was more often in young and mid-aged married men with higher education and socioeconomic status and in middle-aged and older women with less education from wealthier households.The prevalences of overweight and obesity are relatively high in the rural areas of Hanzhong, and therefore effective interventions are warranted.

To understand the growth and malnutrition status of Tibetan children aged 0 to 35 months in rural Lhasa in 2010.Cross-sectional study and multistage sampling design were used to randomly select sampling units. A total of 640 children were studied. Height and weight were measured and nutritional status was evaluated with WHO reference in 2006 using Z-scores. Z-scores of weight-for-age (WAZ), Z-scores of height-for-age (HAZ) and Z-scores of weight-for-height (WHZ) were analyzed.At the age of 18 - 35 months, the children in rural Lhasa were 3.0 cm shorter as compared to the China national length reference. At the age of 6 - 11, 12 - 17 months, weight ((8.84 ± 1.23) and (10.20 ± 1.08) kg) and length ((70.45 ± 4.46) and (76.73 ± 4.78) cm) of boys were significantly higher than girls (weight: (8.42 ± 1.30) and (9.59 ± 1.26) kg; length: (67.61 ± 3.98) and (74.25 ± 4.50) cm) (all P values0.05). WAZ and HAZ were -0.17 ± 1.11 and -1.11 ± 1.46, respectively. The HAZ of 18 - 23 months children (-1.51 ± 1.24) was significantly different from the HAZ of 0 - 5, 6 - 11, 12 - 17 months children (HAZ: -0.75 ± 1.50, -0.83 ± 1.72, -1.07 ± 1.55, respectively) (all P values0.05), comparison with the HAZ of 24 - 29, 30 - 35 months children (HAZ: -1.41 ± 1.25, -1.24 ± 1.05), the results showed that there were no significant difference (all P values0.05), HAZ of 18 - 23 months children was the lowest. The prevalence of stunting, underweight, and wasting were 24.6% (155/630), 5.4% (33/616) and 1.0% (6/608), respectively. The malnutrition of boys was more serious than that of girls, the stunting of 18 - 23 and 24 - 29 months children had reached 35.0% (36/103) and 29.1% (25/86), respectively.The growth and development status of children in rural Lhasa under 3 years old was poor, and the malnutrition of local children should not be ignored with variations by gender and months of age.

To examine the relationship between cigarette smoking and body mass index (BMI) as well as waist circumference (WC) of men from 9 rural districts of Hanzhong, Shaanxi province.Cross-sectional data was analyzed from Hanzhong Health Survey on rural residents in 2010. Quantile regression mode was used to compare the results using the BMI (WC) and smoking status (degree) as the dependent variables and independent variable and confounding factors were also controlled.1039 male residents of rural areas of Hanzhong city were investigated. The prevalence rates on overweight and obesity among the males were 28.0% and 5.9%, with central obesity as 35.0% and the rate of current cigarette smoking was 63.6% in the areas.from the quantile regression showed that the relationship between smoking status and BMI beyond 80 percentile in men (BMI = 24.4) which was not significantly different BMI among the heavy smokers, was much higher than those mild smokers beyond 90 percentile (BMI = 24.9). WC of the current smokers was significantly higher than those ex-smokers beyond the 95 percentile (WC = 96.7 cm). WCs of the moderate and heavy smokers had an increase along with the increase of WCs beyond the 85 percentiles (WC = 89.9 cm).The effect of smoking status and BMI (WC) were inconsistent, however, with BMI and WC increased among the subjects whose BMI or WC were at the high extreme end of the distribution. Thus, we should advise the obese subjects to quit smoking.

Several genome-wide association studies on breast cancer have reported similar findings of a new cancer susceptibility locus, 8q24 rsl3281615. Subsequent case-control studies have rapidly investigated the association between the single nucleotide polymorphism of rsl3281615 at chromosome 8q24 and breast cancer risk, but the effect of 8q24 rsl3281615 polymorphism on breast cancer is still unclear due to the inconsistence among those studies. Given the contradictory findings, a meta-analysis was performed to determine the association between 8q24 rsl3281615 polymorphism and breast cancer risk. 12 eligible case-control studies with a total of 42,508 cases and 53,928 controls were finally included into this meta-analysis by searching the PubMed, Embase, and China Biology Medicine (CBM) databases. We estimated the summary odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) to assess this association. Meta-analyses of total 12 studies showed 8q24 rsl3281615 polymorphism was significantly associated with an increased risk of breast cancer in all contrast models (OR(G vs. A) = 1.10, 95 % CI 1.05-1.14, P (OR) 0.001; OR(GG vs. AA) = 1.20, 95 % CI 1.11-1.29, P (OR) 0.001; OR(AG vs. AA) = 1.08, 95 % CI 1.05-1.12, P (OR) 0.001; OR(GG vs. AA +AG) = 1.13, 95 % CI 1.07-1.19, P (OR) 0.001; OR(GG+AG vs. AA) = 1.13, 95 % CI 1.07-1.19, P (OR) 0.001). Meta-analyses of studies with high quality showed that 8q24 rsl3281615 polymorphism was still significantly associated with an increased risk of breast cancer under the five genetic contrast models. Sensitivity analyses by sequential omission of any individual studies and subgroup analyses by ethnicity further identified the significant association between 8q24 rsl3281615 polymorphism and breast cancer risk. Conclusively, this meta-analysis shows a significant association between 8q24 rsl3281615 polymorphism and breast cancer risk.

The objective of this study was to investigate the prevalence rate of abdominal obesity and to explore the associated risk factors in rural communities from Hanzhong area, Shaanxi province, and to provide baseline data for further targeted intervention programs.A cross-sectional study was conducted among all the participants with questionnaires, interview and physical examination. Nine townships were selected in Hanzhong area, followed by one village randomly chosen from the selected township, using the stratified random sampling method.There were 3030 participants in this survey, among which 3021 samples were valid, including 1048 males and 1973 females. The overall prevalence rate of abdominal obesity was 38.9% (standardized rate as 33.4%) in rural communities of Hanzhong, and the prevalence rate on males abdominal obesity (35.0%) was significantly lower than that of females (40.9%). It was found that following factors as: being male, married, having more household wealth, frequent consumption of fried food, non-engagement of agricultural labor work, being nonsmoker or ex-smoker, spending longer time on watching-TV etc. were positively associated with the bigger odds of having abdominal obesity when using the logistic regression analysis. Meanwhile, data from this study indicated that factors as: at younger age, frequent participation in agricultural labor, under artificial feeding, with more years of education, less frequency of pregnancy etc. were negatively related to the prevalence of female abdominal obesity.The prevalence rate of abdominal obesity in Hanzhong area, Shaanxi province was significantly higher than the national average level which called for the development of related intervention programs to prevent chronic diseases associated with gender related-obesity in Hanzhong.

To explore the cytogenetic characteristics of multiple myeloma (MM) patients, to evaluate the effect of a long-term culture stimulated by cytokines on cytogenetic study of MM, and to investigate the clinical detection value of RB1 and P53 deletion in interphase plasma cells by using fluorescence in situ hybridization (FISH).Karyotype analysis was performed in 81 MM patients by using the short-term culture of bone marrow cell and G-banding technique. Among the 81 MM patients, 28 patients used two culture methods: one was the short-term culture and the other was to culture cells for 6 days with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) (40 µg/L) and IL-6 (10 µg/L). RB1 and P53 deletion were detected on interphase plasma cells by using FISH in 31 patients.Among the 81 patients, 75 had enough metaphases for analysis. Among the 75 patients, 31 (41.3%) had clonal karyotypic abnormalities including 4 numeric abnormalities, 11 structural abnormalities and 16 both abnormalities. Among the 28 patients using two culture methods, the clonal karyotypic abnormalities were detected in 6 patients (25.0%) in the group of cultured for 24 hours, and 14 patients (51.9%) in 6-day culture group with a significant difference (P = 0.026). RB1 deletion and P53 deletion were detected in 10 patients (32.3%) and 11 patients (35.5%), respectively, with both RB1 and P53 deletions be detected in 5 patients (16.1%).More than half of the tested MM patients have both numeric and structural chromosome abnormalities. The karyotype analysis using banding technique is basic cytogenetic study. Extended culture in the presence of IL-6 and GM-CSF could improve the efficiency of cytogenetic analysis to MM. Interphase FISH is a sensitive method of clinical application significance to detect the gene deletion of MM.

Context: Rodent data show that altered hypothalamic signaling contributes to the development of obesity and insulin resistance. Objective: To determine differences in hypothalamic expression levels of neuropeptide Y (NPY), agouti-related peptide (AgRP), and alpha MSH in the infundibular nucleus, the human equivalent of the arcuate nucleus, in relation to body mass index (BMI). In addition, the expression in the infundibular nucleus of eight subjects diagnosed with type 2 diabetes was measured to determine possible interference of type 2 diabetes with the association observed between neuropeptides and BMI. Design: We studied AgRP, NPY, and alpha MSH expression by means of quantitative immunocytochemistry in postmortem hypothalami of 30 subjects with known BMI. In separate experiments, we compared neuropeptide expression in eight subjects with type 2 diabetes with eight matched controls. Results: We found that AgRP immunoreactivity showed a U-shaped correlation with BMI. No evidence was found for possible influences of corticosteroid treatment. NPY immunoreactivity was significantly lower in overweight and obese subjects. alpha MSH did not correlate with BMI but was significantly lower in subjects with type 2 diabetes compared with controls. By contrast, NPY and AgRP expression was not affected in type 2 diabetes. Conclusion: Our results indicate that the expression of AgRP and NPY are correlated with body weight changes, rather than the presence of type 2 diabetes, whereas changes in alpha MSH immunoreactivity are related to the presence of type 2 diabetes, indicating separate hypothalamic mechanisms. (J Clin Endocrinol Metab 97: E925-E933, 2012)

To explore the cytogenetic characteristics of acute myeloid leukemia (AML) patients.The karyotype analysis was performed in 178 AML using the short-term culture of bone marrow cell and G-banding technique.Among the 178 patients, 171 had enough metaphases for analysis and 128 (74.9%) had clonal karyotypic abnormalities. Twenty-seven patients were secondary to myelodysplastic syndrome (MDS-AML), with 25 (92.6%) patients carrying clonal karyotypic abnormalities. Among the remaining 144 patients of de novo AML, 103 (71.5%) had clonal karyotypic abnormalities. The rate of abnormal clonal karyotype was higher in MDS-AML than that of de novo AML (P = 0.021). Among the 171 patients, 41 (24.0%) were in favorable risk group, 80(46.8%) in intermediate risk group and 50 (29.2%) in adverse risk group. t(15;17) was the most common chromosomal aberration. The majority intermediate risk chromosomal aberration was normal karyotype. The most common cytogenetic abnormality among adverse group was a complex karyotype. Adverse cytogenetic aberrations, such as -5/5q-, -7/7q-, frequently occurred in conjunction with one another as part of a complex karyotype. Totally 75 patients were 60 years or older, among them, 16.0% were in favorable risk group, 48.0% in intermediate risk group and 36.0% in adverse risk group. Among 96 younger patients, 30.2% were in favorable risk group, 45.8% in intermediate risk group and 24.0% in adverse risk group. The rate of favorable risk chromosomal aberration was lower in elder patients than in younger (P = 0.031). The rate of adverse risk chromosomal aberration and the rate of monosomal karyotype were higher in MDS-AML than in de novo AML patients (P0.001).The most common favorable, intermediate and adverse chromosomal aberrations were t(15;17), normal karyotype and complex karyotype respectively. The karyotype was poor in MDS-AML and elder AML patients.