Calf Circumference and All-Cause Mortality: A Systematic Review and Meta-Analysis Based on Trend Estimation Approaches.

OBJECTIVES: To perform a systematic review and meta-analysis and quantify the associations of total mortality with calf circumference (CC) in adults 18 years and older via combining various analyses based on empirical dichotomic CC, continuous CC, and dose-response CC. METHODS: We conducted a systematic search of relevant studies in PubMed, EMBASE, Cochrane Library, and Web of Science published through April 12, 2022. This systematic review includes longitudinal observational studies reporting the relationships of total mortality with CC. We calculated the pooled relative risk (RR) and 95% confidence interval (CI) of total mortality with CC per 1 cm for each study and combined the values using standard meta-analysis approaches. Newcastle-Ottawa scale (NOS), Grading of Recommendations, Assessment, Development and Evaluations approach (GRADE), and the Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN) were assessed for meta-analyses. RESULTS: Our analysis included a total of 37 cohort studies involving 62,736 participants, across which moderate heterogeneity was observed (I2=75.7%, P<0.001), but no publication bias was found. Study quality scores ranged from 6 to 9 (mean 7.7), with only three studies awarded a score of 6 (fair quality). We observed an inverse trend between total death risk and CC per 1 cm increase (RR, 0.95, 95% CI, 0.94-0.96; P<0.001; GRADE quality=high). Only a very slight difference was found among residents of nursing homes (6.9% mortality risk reduction per one cm CC increase), community-dwellers (5.4%), and those living in hospitals (4.8%), respectively (P for meta-regression=0.617). Low credible subgroup difference was found based on the ICEMAN tool. CONCLUSIONS: Calf circumference is a valid anthropometric measure for mortality risk prediction in a community, nursing home, or hospital.

[Integration of clinical significance and statistical significance on clinical study results categorization: a Meta-epidemiology study].

Objective: Statistical significance plays an important role in the interpretation of clinical trial results. However, on the basis of obtaining statistical significance, the assessment of clinical significance is often neglected. This study attempted to propose a simple and unambiguous new classification method for study results, focusing on studies with statistical positive findings to evaluate whether the results have clinical significance. Methods: Our study subjects were the clinical studies in 2019 ACC and ESC annual meetings. Meta-epidemiology methods were used to extract the characteristic variable from each study. The primary evaluation indicators included target effect-size and observed effect-size. Based on the difference between the two indicators, the studies that had statistical significance were subdivided to identify studies with possible insufficient clinical significance; Furthermore, the theoretical threshold based on power analysis was proposed, which was used as the basis for the interpretation of study results. Results: There were 12 clinical studies included in the final analysis. All of them were published on top journals. Those studies had relative high quality on both study design and reporting. The correlation coefficient between the observed and target effect-size was 0.892. Among the 7 studies with statistical significance, two of them were classified as insufficient clinical significance. The counts was 1 (1/3) and 1 (1/4) for the studies reported in ACC and ESC respectively. Conclusions: The achievement of clinical significance is critical even in the study with positive results. This paper proposes a new classification standard that combines clinical significance with statistical significance and further suggests a method to evaluate the reliability of clinical study results in order to assist researchers in identifying potential risks caused by insufficient clinical significance, and provide some reference and help for the reasonable interpretation of clinical study results.

Growth performance, nutrient digestibility, blood parameters, and carcass characteristics by lambs fed an oregano and cobalt blend.

Shifting ruminal fermentation via feeding a blend of oregano (Organum vulgare L.) essential oils and Co-lactate (EOC; Rum-A-Fresh, Ralco, Inc. Marshall, MN) could improve lamb growth and carcass performance. Eighteen Suffolk × Little Han Tail F1 male lambs (20.3 ± 0.23 kg BW and approximately 3 months old) were randomly assigned using a completely random design to one of three treatments. Treatments were (1) EOC0: basal ration without EOC, (2) EOC4: basal ration plus 4 g/d EOC, and (3) EOC7: basal ration plus 7 g/d EOC. Initial and 24 d BW was similar (P > 0.10), but at 48 and 72 d, lambs fed EOC7 demonstrated greater (P = 0.01) BW compared with EOC0 fed lambs, while lambs fed EOC4 were intermediate and similar (P > 0.05). Average daily gains (ADGs) for 0-24 and 0-72 d were greater (P < 0.05) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0, while DM intake was similar (P > 0.10). Feed conversions for 0-24 d were improved (P < 0.02) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. However, 0-72-d feed conversions were greater (P < 0.01) for lambs fed EOC7 compared to lambs fed EOC0, with lambs fed EOC4 being intermediate and similar (P > 0.05). DM, NDF, and ADF digestibilities were similar (P > 0.10) among treatments, while CP digestibility was greater (P < 0.01) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. Carcass weight and dressing percentages were improved (P < 0.01) for lambs fed EOC7 compared with lambs fed EOC0 and EOC4. Head width was greater (P > 0.01) for lambs fed EOC7 compared with lambs fed EOC0 and EOC4, while rump width was greater (P > 0.01) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. Plasma triglyceride and cholesterol concentrations were lower (P < 0.05) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0, while albumin, total serum protein, and glucose concentrations were greater (P < 0.05) for lambs fed EOC4 and EOC7 compared with lambs fed EOC0. Feeding an EOC blend as an alternative antibiotic growth promoter at 4 and 7 g/d linearly improved lamb growth performance, feed conversions, frame growth, carcass weights, dressing percentages, and immunity.

Long noncoding RNA XIST regulates cardiomyocyte apoptosis by targeting miR-873-5p/MCL1 axis.

OBJECTIVE: The purpose of this study was to investigate the expression of miR-873-5p and long non-coding RNA X-inactive specific transcript (lncRNA-XIST) in myocardial infarction (MI), the interaction mechanism and the effect of target gene MCL1 on apoptosis in H9c2 cells. MATERIALS AND METHODS: quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect and compare the expressions of miR-873-5p and lncRNA XIST in 8 myocardial infarction rats and 8 normal rats tissues, respectively, and the correlation between the expressions of miR-873-5p and lncRNA XIST in the myocardial tissues was explored. Next, qRT-PCR and Western blot were used to detect the effects of upregulation of miR-873-5p and downregulation of lncRNA XIST, as well as the impacts of their interactions on the expression level of MCL1 in H9c2 cells and the apoptosis of cells. RESULTS: It was found that the downregulation of miR-873-5p protected the heart against apoptosis after AMI, and lncRNA XIST inhibited apoptosis in H9c2 cells after hypoxia. Besides, inhibiting lncRNA XIST could upregulate miR-873-5p and downregulate MCL1, thus increasing apoptosis in the H9c2 cells after hypoxia. CONCLUSIONS: LncRNA XIST can regulate cardiomyocyte apoptosis by targeting miR-873-5p.

Ghrelin inhibits inflammatory response and apoptosis of myocardial injury in septic rats through JAK/STAT signaling pathway.

OBJECTIVE: The purpose of this study was to explore the influence of Ghrelin on myocardial injury of septic rats through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into normal group (n=12), model group (n=12), and Ghrelin group (n=12). The rats in the normal group were fed normally, while those in the model group were intraperitoneally injected with endotoxin to establish the sepsis model. The rats in the Ghrelin group were given intraperitoneal injection of Ghrelin solution to prepare the sepsis model. 9 h later, the specimens were obtained. Then, the expressions of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were detected via immunohistochemistry, and the protein expressions of phosphorylated JAK (p-JAK) and STAT3 were determined by Western blotting (WB). Next, enzyme-linked immunosorbent assay (ELISA) was performed to measure the content of IL-6 and TNF-α, and quantitative Polymerase Chain Reaction (qPCR) was applied to examine the messenger ribonucleic acid (mRNA) expressions of JAK and STAT3. Finally, the cell apoptosis was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The results of immunohistochemistry showed that compared with those in the normal group, the positive expression levels of IL-6 and TNF-α were markedly increased in other groups (p<0.05), while in comparison with those in the model group, the positive expression levels of IL-6 and TNF-α were decreased significantly in the Ghrelin group (p<0.05). The WB results indicated that the model group and Ghrelin group had remarkably higher protein expression levels of p-JAK and STAT3 than the normal group (p<0.05), and Ghrelin group exhibited notably lower protein expression levels of p-JAK and STAT3 than the model group (p<0.05). According to the results of qPCR, the relative mRNA expression levels of JAK and STAT3 were distinctly raised in the model group and Ghrelin group in comparison with those in the normal group (p<0.05), while they were reduced evidently in the Ghrelin group compared with those in the model group (p<0.05). Furthermore, it was manifested in the results of ELISA that the model group and Ghrelin group had prominently elevated content of TNF-α and IL-6 compared with normal group (p<0.05), and Ghrelin group displayed significantly lowered content of TNF-α and IL-6 in comparison with the model group (p<0.05). Moreover, the TUNEL results revealed that the apoptosis rate was remarkably higher in the other two groups than that in the normal group (p<0.05), while it was evidently lower in the Ghrelin group than that in the model group (p<0.05). CONCLUSIONS: Ghrelin can inhibit inflammatory response and apoptosis in the process of myocardial injury in septic rats by repressing the JAK/STAT signaling pathway.

MNX1-AS1 accelerates the epithelial-mesenchymal transition in osteosarcoma cells by activating MNX1 as a functional oncogene.

OBJECTIVE: To investigate whether MNX1-AS1 can accelerate epithelial-mesenchymal transition (EMT) of osteosarcoma cells via activating MNX1. PATIENTS AND METHODS: The expression pattern of MNX1-AS1 in osteosarcoma tissues and cell lines was examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, the cytoplasmic and nuclear levels of MNX1-AS1 in osteosarcoma cells were also determined. The regulatory effects of MNX1-AS1 on viability, clonality, migratory, and invasive abilities of the osteosarcoma cells were evaluated. The relative levels of MNX1 and EMT-related genes influenced by MNX1-AS1 were detected. The methylation ability in the promoter of the osteosarcoma cells transfected with si-MNX1-AS1 or MNX1-AS1 vector was determined by the whole genome bisulfite sequencing. RESULTS: MNX1-AS1 was upregulated in osteosarcoma tissues and cell lines, which was mainly expressed in the nucleus. The knockdown of MNX1-AS1 markedly attenuated viability, clonality, migratory, and the invasive abilities of the osteosarcoma cells. Besides, the transfection of si-MNX1-AS1 in U2OS and MG63 cells downregulated MNX1 and Snail, and upregulated E-cadherin. The methylation ability increased after the knockdown of MNX1-AS1, while the overexpression of MNX1-AS1 obtained the opposite trends. CONCLUSIONS: MNX1-AS1 mediates EMT of the osteosarcoma cells via activating MNX1, thereafter accelerating the progression of the osteosarcoma.

Strain tuned InSe/MoS2 bilayer van der Waals heterostructures for photovoltaics or photocatalysis.

The isolation of different two-dimensional materials and the possibility to combine them in vertical stacks have led to new material systems, namely heterostructures based on two-dimensional crystals. By using density functional theory, we found that the InSe/MoS2 bilayer shows an indirect band gap of 0.65 eV with optical absorption over a wide range (300-800 nm) and a preferable separation of photogenerated electron-hole pairs. Moreover, the band gap can be readily tuned by external strain engineering, leading to a transition from the indirect band gap to a direct band gap of 1.55 eV under 7% compressive strain, where there is an enhanced and continuous spectrum. In addition, under a tensile strain of 9%, the bilayer is metallic. All of these properties enable the development of excellent photoelectric devices from the heterostructures with strain engineering.

The effect of energy restriction on fatty acid profiles of longissimus dorsi and tissue adipose depots in sheep.

Sheep production systems in northwest China depend mostly on natural grasslands. Seasonal growth and maturity fluctuations can cause periodical restrictions in food quality and quantity. These fluctuations, in turn, result in variability in fat deposition and fatty acid profiles in different fat depots. Consequently, the study objective was to compare fat deposition, intramuscular fat (IMF) percentage and fatty acid profiles of the longissimus dorsi (LD), kidney fat (KF), tail fat (TF), and subcutaneous fat (SF) in lambs under ME restrictions similar to seasonal changes observed in the natural grasslands of northwest China. Nineteen male Dorper × Small Tailed Han lambs were assigned to 2 treatments, a control (CON) fed at 1.0 MJ / W × d and restricted (RES) by restricting ME sequentially every 30 d (0.56 MJ / W × d, 0.84 / W × d, 1.0 MJ / W × d, 0.84 MJ / W × d, 0.56 MJ / W × d, 0.28 MJ / W × d). All lambs were harvested at the end of the 180 d experimental period. Compared to CON fed lambs, restricting ME resulted in lesser IMF, fat deposition indexes ( < 0.05) except testicular and heart fat and greater ( < 0.05) SFA in LD, KF, and TF depots. The RES fed lambs had greater ( < 0.05) -3 PUFA, eicosatrienoic acid (C20:3n3), eicosapentaenoic acid (C20:5n3, EPA), and trans-linolelaidic acid (C18:2n6t) in LD muscle. The conjugated linoleic acids (CLA) content was greater in the SF depots of the CON fed lambs compared to the RES fed lambs. Fatty acid ratios (unsaturated fatty acid; USFA:SFA, MUFA:SFA, PUFA:SFA), and percentage USFA in RES fed lambs were lesser in muscle and adipose tissue compared to CON fed lambs ( < 0.05), except SF depots. In RES fed lambs, EFA were less ( < 0.05) in LD and KF depots and the ratios of functional fatty acids were lesser in LD and some adipose tissues ( < 0.05), including lesser n-6:n-3 in KF and SF ( < 0.05) depots, lesser USFA, SFA, MUFA, SFA in LD, KF, and TF ( < 0.05) depots, and lesser PUFA and SFA in LD and TF ( < 0.05) depots. Results from this research demonstrate that sequential energy restriction, as might be experience during seasonal forage quality and quantity changes in natural grasslands, result in lesser intramuscular fat with associated lesser quality, as well as, changes in fatty acid composition in different fat depots, which has implications for both meat quality and animal physiological functions.

Development of small intestinal enzyme activities and their relationship with some gut regulatory peptides in grazing sheep.

Growth depends on an animal's capacity to digest and assimilate ingested nutrients, and insufficient supply and impairment will constrain lamb growth. Eight groups of Alpine Finewool lambs were harvested on 0, 3, 7, 14, 21, 28, 42, and 56 d to measure pH and enzymatic activities in the duodenum, proximal jejunum, middle jejunum, distal jejunum, and ileum mucosa or digesta. From the duodenum to the ileum the pH of intestinal mucosa and digesta increased, whereas pH changed very little with age. The trypsin, chymotrypsin, lipase, lactase, and α-amylase activities observed at birth decreased by d 3, followed by a nonuniform enzymatic response in the small intestine. The trypsin activity increased from d 3 to peak, at d 21, followed by a decline. Chymotrypsin activity followed the same general trend but with smaller responses in activities. Trypsin demonstrated greater enzymatic activity than chymotrypsin at the same age. The lipase activity of small intestinal mucosa and digesta changed little with age. The lactase activity was high at birth, decreased by d 3, and then increased, followed by a decrease as lambs approached weaning. α-Amylase activity was similar in the small intestinal mucosa and digesta at birth but increased with age for the duodenum and proximal jejunum. Plasma concentrations of cholecystokinin (CCK), secretin, and gastrin were positively correlated ( < 0.05) with ileal mucosa lipase activity. Plasma concentration of CCK, secretin, gastrin, and gastric inhibitory polypeptide (GIP) were positively correlated ( < 0.05) with ileal mucosa lactase activity. Plasma concentration of pancreatic polypeptide (PP) was negatively correlated ( < 0.05) with lactase activity in the middle jejunum and ileal mucosa. Plasma concentrations of CCK, secretin, gastrin, and GIP were positively correlated ( < 0.05) with α-amylase activity in the ileal mucosa but negatively correlated ( < 0.05) with duodenum, prejejunum, and middle jejunum. Plasma PP concentrations were positively correlated ( < 0.01) with α-amylase activity of duodenum, middle jejunum, and postjejunum mucosa but not with the enzyme activity of postjejunum and ileal mucosa ( > 0.05). Small intestinal enzymatic activities exist and may be sufficient to enhance lamb growth via appropriate nutrient supplementation.

Developmental changes in fatty acid-binding protein (H-FABP) mRNA expression and intramuscular fat (IMF) content in Oula sheep.

Increasing meat consumption by Chinese people has created a focus for improving meat quality for increasing quality of life. Twenty-five Male Oula sheep were selected at 2, 21, 56, 84, and 112 d to investigate the developmental changes associated with age on the intramuscular fat (IMF) content of heart fatty acid-binding protein (H-FABP) mRNA expression in muscle. Longissimus dorsal muscle and biceps femoris muscle were sampled to measure IMF concentrations and total mRNA was extracted to measure H-FABP mRNA expression using real-time polymerase chain reaction (PCR). Growing male Oula sheep demonstrated that the IMF concentrations continuously increased with age and significant differences (P < 0.05) were detected among the age groups; 2. The IMF concentrations among tissues were different; 3. The development changes in H-FABP mRNA expression in longissimus dorsal muscle and biceps femoris muscle were similar with a decrease from 2 to 21 d, followed by continuously increasing concentrations being significant different (P < 0.05) among age groups; 4. The H-FABP mRNA expression in the longissimus dorsal muscle tissue was significantly (P < 0.05) higher compared to the biceps femoris muscle; 5. The muscle H-FABP mRNA expression concentration was positively correlated with IMF concentrations from d 21 to 112; 6. The correlation coefficients were significantly (P < 0.01)different between H-FABP gene mRNA expression in the longissimus dorsal muscle and IMF concentration of 0.815 compared to the biceps femoris muscle and IMF concentration of 0.787,which indicated that the H-FABP gene may be affecting the IMF concentrations in the early developmental stages of Oula sheep. These results support the hypothesis that H-FABP gene and its expression in muscle tissue is related to the IMF concentration of meat.

P2X3 receptor-mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD-like stress in the dorsal root ganglia of rats.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) often share co-morbidity with chronic pain conditions. Recent studies suggest a role of P2X3 receptors and ATP signaling in pain conditions. However, the underlying mechanisms of visceral hyperalgesia following exposure to PTSD-like stress conditions remain unclarified. METHODS: The behavior and hormones relevant for PTSD were studied. Visceromotor responses (VMR) and the abdominal withdrawal reflexes (AWR) to colorectal distention (CRD) were recorded to determine P2X3-receptor-mediated alteration of hyperalgesia following single-prolonged stress (SPS) exposure. Immunofluorescence, Western blotting, and patch-clamp were used. KEY RESULTS: The escape latency, adrenocorticotropic hormone and cortisol were increased on days 7-14. Visceromotor responses and AWR was reduced at day 1 in SPS rats but increased to higher levels than in controls after exposure to day 7. Intrathecal administration of the P2X3-receptor antagonist TNP-ATP abolished the CRD response. Based on immunofluorescence and Western blotting analysis, SPS-treated rats exhibited reduced P2X3 expression in dorsal root ganglia (DRG) after day 1 compared with controls. P2X3 expression in DRG was enhanced on day 7 after SPS and the increase of the P2X3 expression was maintained on day 14 and 21 compared with controls. The P2X3-receptor agonist α,ß-me ATP (10 µM) induced a fast desensitizing inward current in DRG neurons of both control and SPS-treated rats. The average peak current densities in SPS-treated group were increased 3.6-fold. TNP-ATP (100 nM) markedly blocked all fast α,ß-me ATP-induced inward currents in the DRG neurons both in control and SPS-treated rats. CONCLUSIONS & INFERENCES: The data indicate an important role of P2X3 signaling in visceral hyperalgesia following PTSD-like stress.

[Clinical amalysis of left subclavian artery revascularization by stented trunk fenestration for acute Stanford type A aortic dissection].

OBJECTIVE: To summarize the results and methods of left subclavian artery revascularization by stented trunk fenestration for acute Stanford type A aortic dissection. METHODS: Clinical data of 67 patients (54 male and 13 female, mean age of (50±10) years) underwent surgical treatment of left subclavian artery fenestration for acute Stanford A aortic dissection in Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical College between September 2008 and December 2014 were analyzed retrospectively. The origin of the left subclavian artery was in the true lumen and no dissection existed near the artery's starting. There were 18 cases of Marfan's syndrome. Preoperative echocardiography showed moderate to severe aortic regurgitation in 10 cases, and mitral regurgitation in 3 cases. Electrocardiogram showed myocardial ischemia in 5 cases. Three patients had acute impaired renal function. All the patients received total arch replacement combined with stented elephant trunk implantation. Left subclavian artery revascularization was performed by stented trunk fenestration as follows: firstly, stented elephant trunk was implanted to completely cover the left subclavian artery, then part of stented trunk's polyester lining was removed which is located at the origin of left subclavian artery. Aortic root procedures included aortic valve replacement in 2 cases, Bentall procedure in 21 cases and aortic valve sparing in 44 cases. Three patients received mitral valve repair and 6 patients received coronary artery bypass grafting. RESULTS: The cardiopulmonary bypass time, cross-clamp time, and circulatory arrest time were (179±32) minutes, (112±25) minutes, and (26±10) minutes, respectively. The in-hospital mortality was 7.5% (5/67): 2 patients died of multiple organ failure, 1 patient died of acute renal failure and another 2 patients died of severe infection shock. Two patients required reexploration for root bleeding. Transient neurology dysfunction developed in 6 patients. Six patients received tracheotomy and prolonged ventilation due to pulmonary infection. All patients discharged from the hospital were followed up for 1 to 5 years. During long-term follow-up, the survival rate was 100% and 89.8% at 1 and 5 years, respectively. CT angiography was performed once per year after discharged. The left subclavian artery perfusion was good. No dissection or anastomosis leakage was identified in any case. Stroke and left limb ischemia did not develope. CONCLUSION: For acute Stanford type A aortic dissection whose origin of the left subclavian artery is in the true lumen and no dissection existed near the artery's starting, the left subclavian artery revascularization by stented trunk fenestration technique during total arch replacement combined with stented elephant trunk implantation is reliable and effective.

Correlation Between MMP-7 and bFGF Expressions in Non-small Cell Lung Cancer Tissue and Clinicopathologic Features.

The present study intends to investigate the correlation between clinicopathologic features of non-small cell lung cancer and matrix metalloproteinase-7 (MMP-7) and basic fibroblast growth factor (bFGF) and to investigate the roles of MMP-7 and bFGF in detecting the course of disease of non-small cell lung cancer. Ninety cases of paraffin-embedded tissue samples from patient with primary non-small cell lung cancer and fifty cases of lung tissue samples from normal subjects were included in the present study. Immunohistochemical S-P method was used to detect proteins MMP-7 and bFGF. (1) The positive rate of MMP-7 protein was 14 % in normal lung tissue section and 68.89 % in non-small cell lung cancer tissue section, and the difference was statistically significant (χ (2) = 38.774, P = 0.000 < 0.05). There were 43 cases (43/56) with positive expression in patients with squamous cell carcinoma and 22 cases (22/34) with positive expression in patients with adenocarcinoma, and the difference was not statistically significant (χ (2) = 1.539, P = 0.215 > 0.05). There were 14 cases (14/51) with positive expression in patients with moderate- and well-differentiated lung carcinoma and 36 cases (36/39) with positive expression in patients with poor-differentiated lung carcinoma, and the difference was statistically significant (χ (2) = 35.068, P = 0.000 < 0.05). There were 37 cases (37/42) with positive expression in patients with lymphatic metastasis and 26 cases (26/48) with positive expression in patients without lymphatic metastasis, and the difference was statistically significant (χ (2)  = 12.279, P = 0.000 < 0.05). (2) The mean intratumoral microvessel density (iMVD) was 46.2 ± 6.77 in the field of lung cancer tissue at high magnification under MMP-7-positive condition and 30.8 ± 7.54 in the field of lung cancer tissue at high magnification under MMP-7-negative condition, and the difference was statistically significant (t = 9.641, P = 0.000 < 0.05). (3) The positive rate of bFGF was 12 % in normal tissue section and 63.3 % in non-small cell lung cancer tissue section, and the difference was statistically significant (χ (2) = 34.222, P = 0.000 < 0.05). There were 41 cases (41/56) with positive expression in patients with squamous cell carcinoma and 20 cases (20/34) with positive expression in patients with adenocarcinoma, and the difference was not statistically significant (χ(2) = 2.006, P = 0.157 > 0.05). There were 29 cases (29/51) with positive expression in patients with moderate- and well-differentiated lung carcinoma and 35 cases (35/39) with positive expression in patients with poor-differentiated lung carcinoma, and the difference was statistically significant (χ (2) = 10.085, P = 0.001 < 0.05). There were 37 cases (37/42) with positive expression in patients with lymphatic metastasis and 25 cases (25/48) with positive expression in patients without lymphatic metastasis, and the difference was statistically significant (χ (2)  = 13.554, P = 0.001 < 0.05). (4) The (iMVD) was 45.8 ± 7.16 in the field at high magnification under bFGF-positive condition and 31.2 ± 6.46 in the field at high magnification under bFGF-negative condition, and the difference was statistically significant (t = 9.654, P = 0.001 < 0.05). (5) A correlation was demonstrated between MMP-7 and bFGF in non-small cell lung cancer (r = 0.353, P = 0.000 < 0.05). Both MMP-7 and bFGF are participated in the progression of non-small cell lung cancer and exert a synergistic effect during physiological processes including pathogenesis, invasion, and metastasis of non-small cell lung cancer. Therefore, a combined detection of MMP-7 and bFGF for non-small cell lung cancer contributes to predict the progression and prognosis of non-small cell lung cancer, with significant clinical value.

AGER genetic polymorphisms increase risks of breast and lung cancers.

We evaluated the associations between three common polymorphisms in the AGER gene and the risks of breast (BC) and lung (LC) cancer using meta-analysis. A systematic electronic search of the literature was conducted to identify all potential correlation studies in Embase, Web of Science, Cochrane Library, CINAHL, PubMed, CISCOM, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Five case-control studies that investigated the correlation of AGER gene polymorphisms with BC and LC were included in the meta-analysis, representing 4337 subjects. An increased frequency of the AGER rs1800625 T>C polymorphism was observed in patients with either BC or LC. We found that the frequencies of AGER rs1800624 T>A and rs2070600 G>A variants were positively related to the risks of BC and LC under allelic models, but that these relationships were not detected under dominant models. Disease-stratified results under allelic models demonstrated that the frequencies of the AGER rs1800625 T>C and rs2070600 G>A polymorphisms were positively correlated with the susceptibility to LC, while the same correlations were not found in BC. Further subgroup analysis by genotyping method indicated that the rs1800624 T>A variant was associated with increased risks of BC and LC under a dominant model in both non-polymerase chain reaction-restriction fragment length polymorphism (non-PCR-RFLP) and PCR-RFLP subgroups. In conclusion, these data indicated that common polymorphisms in the AGER gene might increase the risks of BC and LC.

Analysis of geographic and pairwise distances among sheep populations.

This study investigated geographic and pairwise distances among seven Chinese local and four introduced sheep populations via analysis of 26 microsatellite DNA markers. Genetic polymorphism was rich, and the following was discovered: 348 alleles in total were detected, the average allele number was 13.38, the polymorphism information content (PIC) of loci ranged from 0.717 to 0.788, the number of effective alleles ranged from 7.046 to 7.489, and the observed heterozygosity ranged from 0.700 to 0.768 for the practical sample, and from 0.712 to 0.794 for expected heterozygosity. The Wright's F-statistic of subpopulations within the total (FST) was 0.128, the genetic differentiation coefficient (GST) was 0.115, and the average gene flow (Nm) was 1.703. The phylogenetic trees based on the neighbor-joining method by Nei's genetic distance (DA) and Nei's standard genetic distance (DS) were similar. Sheep populations clustered into group 1 (Ta, M, L, H, O, G, and Q breeds) and group 2 (PD, WS, B, and T breeds). These results will have an important value applied and directive significance for sheep breeding in the future.

Al13@Pt42 core-shell cluster for oxygen reduction reaction.

To increase Pt utilization for oxygen reduction reaction (ORR) in fuel cells, reducing particle sizes of Pt is a valid way. However, poisoning or surface oxidation limits the smallest size of Pt particles at 2.6 nm with a low utility of 20%. Here, using density functional theory calculations, we develop a core-shell Al13@Pt42 cluster as a catalyst for ORR. Benefit from alloying with Al in this cluster, the covalent Pt-Al bonding effectively activates the Pt atoms at the edge sites, enabling its high utility up to 70%. Valuably, the adsorption energy of O is located at the optimal range with 0.0-0.4 eV weaker than Pt(111), while OH-poisoning does not observed. Moreover, ORR comes from O2 dissociation mechanism where the rate-limiting step is located at OH formation from O and H with a barrier of 0.59 eV, comparable with 0.50 eV of OH formation from O and H2O on Pt(111).

Combination of cetuximab and rapamycin enhances the therapeutic efficacy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide. It is well known that the activation of PI3K/AKT/mTOR and the Ras/MAPK signaling pathway plays a critical role in cellular metabolism, growth and proliferation, and its inhibitors have been used as therapeutic drugs for hepatocellular carcinoma. Cetuximab, a chimerical monoclonal EGFR IgG1 antibody, can block the binding of EGF or other ligands to EGFR and thus inhibit ligands-induced receptor phosphorylation. In the present study, we found that rapamycin could enhance the antiproliferation effect of cetuximab in both HepG2 cells and Huh-7 cells and arrest the cell cycle. Cetuximab in combination with rapamycin had synergistic effects on inhibiting the phosphrylation of proteins in PI3K/AKT/mTOR and Ras/MAPK signaling pathway. Combination of cetuximab with rapamycin treatment significantly suppressed the HCC development in HepG2 cells-xenografted mice and improved the survival. Cetuximab and rapamycin inhibited the growth of HCC both in vitro and in vivo. These results suggest that the combination therapy using the inhibitors for both EGFR and PI3K/AKT/mTOR signaling pathways may be a novel therapeutic approach for HCC.

Phylogeography and genetic effects of habitat fragmentation on endangered Taxus yunnanensis in southwest China as revealed by microsatellite data.

It is not known how the profoundly complex topography and habitat heterogeneity generated by the uplift of the Qinghai-Tibetan Plateau (QTP) during the late Tertiary affected population genetic structure of endangered Taxus yunnanensis. In addition, the effects of habitat fragmentation due to anthropogenic disturbance on genetic diversity and population differentiation of this species have not been studied. T. yunnanensis is an ancient tree/shrub mainly distributed in southwest China. Recently, the species has suffered a sharp decline due to excessive logging for its famous anticancer metabolite taxol, resulting in smaller and more isolated populations. To understand the phylogeography and genetic consequences of habitat fragmentation of this endangered species, using 11 polymorphic microsatellites, we genotyped 288 individuals from 14 populations from a range-wide sampling in China. Our results suggest that two different population groups that were once isolated have persisted in situ during glacial periods in both areas, and have not merged since. Habitat fragmentation has led to significant genetic bottlenecks, high inbreeding and population divergence in this species. The two different population groups of T. yunnanensis could be attributed to restricted gene flow caused through isolation by geographical barriers and by habitat heterogeneity during uplift of the QTP, or the existence of two separate glacial refugia during the Pleistocene. In situ and ex situ conservation of the two Evolutionarily Significant Units (ESUs), artificial gene flow between populations and a comprehensive understanding of the pollination system in this endangered species are suggested from this study.

Genetic variation of 5 SNPs of MC1R gene in Chinese indigenous sheep breeds.

The purpose of this study was to assess genetic diversity, genetic differentiation.relationship and population structure among 10 Chinese sheep populations using 5 single nucleotide polymorphisms (SNPs). in MC1R gene. The genetic diversity indices suggested that the intra-population variation levels of Chinese Merino and Large-tailed Han,breeds were lowest than Kazakh Fat-Rumped. Chinese sheep breeds have maintained a high intra-population variation levels (95.23%). The genetic differentiation patterns and genetic relationships among Chinese sheep breeds displayed a high consistency with the traditional classification. The cluster trees were constructed by UPMGA method. The results showed that Chinese indigenous sheep populations have distinct genetic differentiation. The inter-population variation levels in Chinese sheep populations indicated three geographically independent domestication events have occurred. The Bayesian cluster analyses also showed a reliable clustering pattern, which revealed three major clusters in.Chinese indigenous sheep populations (Mongolian group, Kazakh group and Tibetan group), except for Duolang and Minxian Black-fur. There were probably caused by different breeding history, geography isolation and different levels of inbreeding. The findings supported the related records in literature, ten sheep populations originated on different time stage from the primogenitor population and communicated genetically with each other in the process of natural and artificial selection, and in different ecological environment. It is concluded that Chinese indigenous sheep have higher genetic variation and diversity, genetic differentiation exist between Chinese sheep populations. The majority breeds are consistent with the geographical distribution and breed characteristic.