Long noncoding RNA MEG3 silencing protects against hypoxia-induced pheochromocytoma-12 cell injury through inhibition of TIMP2 promoter methylation.

Hypoxia is a common pathological process caused by insufficient oxygen. Long noncoding RNAs (lncRNAs) have been proven to participate in this pathology. Hypoxia is reported to significantly reduce the secretion of tissue inhibitor of metalloproteinase 2 (TIMP2) and TIMP2 induces pheochromocytoma-12 (PC12) cell cycle arrest. Thus, our study aimed to explore the mechanism by which lncRNA maternally expressed gene 3 (MEG3) was implicated in hypoxia-induced PC12 cell injury through TIMP2 promoter methylation. To elucidate the potential biological significance of MEG3 and the regulatory mechanism between MEG3 and TIMP2, a hypoxia-induced PC12 cell injury model was generated. The hypoxia-exposed cells were subjected to a series of overexpression plasmids and short hairpin RNAs, followed by the measurement of levels of MEG3, TIMP2, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), Bcl-2-associated X protein, B-cell lymphoma-2, and caspase-3, as well as the changes in MMP, cell proliferation, apoptosis, and cell cycle progression. On the basis of the findings, MEG3 was upregulated in hypoxia-injured PC12 cells. MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression. Moreover, PC12 cells following MEG3 silencing and TIMP2 overexpression exhibited significantly decreased levels of LDH, MDA, and ROS along with cell apoptosis, yet increased SOD and MMP levels, as well as cell cycle entry to the S phase and cell proliferation. In conclusion, MEG3 silencing suppresses hypoxia-induced PC12 cell injury by inhibiting TIMP2 promoter methylation. This study may provide novel therapeutic targets for hypoxia-induced injury.

Effectiveness of Neuromuscular Electrical Stimulation on Lower Limbs of Patients With Hemiplegia After Chronic Stroke: A Systematic Review.

OBJECTIVE: To investigate the effectiveness of neuromuscular electrical stimulation (NMES) with or without other interventions in improving lower limb activity after chronic stroke. DATA SOURCES: Electronic databases, including PubMed, EMBase, Cochrane Library, PEDro (Physiotherapy Evidence Database), and PsycINFO, were searched from the inception to January 2017. STUDY SELECTION: We selected the randomized controlled trials (RCTs) involving chronic stroke survivors with lower limb dysfunction and comparing NMES or combined with other interventions with a control group of no electrical stimulation treatment. DATA EXTRACTION: The primary outcome was defined as lower limb motor function, and the secondary outcomes included gait speed, Berg Balance Scale, timed Up and Go, 6-minute walk test, Modified Ashworth Scale, and range of motion. DATA SYNTHESIS: Twenty-one RCTs involving 1481 participants were identified from 5759 retrieved articles. Pooled analysis showed that NMES had a moderate but statistically significant benefit on lower limb motor function (standard mean difference 0.42, 95% confidence interval 0.26-0.58), especially when NMES was combined with other interventions or treatment time within either 6 or 12 weeks. NMES also had significant benefits on gait speed, balance, spasticity, and range of motion but had no significant difference in walking endurance after NMES. CONCLUSIONS: NMES combined with or without other interventions has beneficial effects in lower limb motor function in chronic stroke survivors. These data suggest that NMES should be a promising therapy to apply in chronic stroke rehabilitation to improve the capability of lower extremity in performing activities.

Nicotinic Acetylcholine Receptor Alpha7 Subunit Mediates Vagus Nerve Stimulation-Induced Neuroprotection in Acute Permanent Cerebral Ischemia by a7nAchR/JAK2 Pathway.

BACKGROUND The role of nicotinic acetylcholine receptor alpha7 subunit (a7nAchR) in the treatment of acute cerebral ischemia by VNS has not been thoroughly clarified to date. Therefore, this study aimed to investigate the specific role of a7nAchR and explore whether this process is involved in the mechanisms of VNS-induced neuroprotection in rats undergoing permanent middle cerebral artery occlusion (PMCAO) surgery. MATERIAL AND METHODS Rats received a7nAChR antagonist (A) or antagonist placebo injection for control (AC), followed by PMCAO and VNS treatment, whereas the a7nAChR agonist (P) was utilized singly without VNS treatment but only with PMCAO pretreatment. The rats were randomly divided into 6 groups: sham PMCAO, PMCAO, PMCAO+VNS, PMCAO+VNS+A, PMCAO+VNS+AC, and PMCAO+P. Neurological function and cerebral infarct volume were measured to evaluate the level of brain injury at 24 h after PMCAO or PMCAO-sham. Moreover, the related proteins levels of a7nAChR, p-JAK2, and p-STAT3 in the ischemic penumbra were assessed by Western blot analysis. RESULTS Rats pretreated with VNS had significantly improved neurological function and reduced cerebral infarct volume after PMCAO injury (p<0.05). In addition, VNS enhanced the levels of a7nAchR, p-JAK2, and p-STAT3 in the ischemic penumbra (p<0.05). However, inhibition of a7nAchR not only attenuated the beneficial neuroprotective effects induced by VNS, but also decreased levels of p-JAK2 and p-STAT3. Strikingly, pharmacological activation of a7nAchR can partially substitute for VNS-induced beneficial neurological protection. CONCLUSIONS These results suggest that a7nAchR is a pivotal mediator of VNS-induced neuroprotective effects on PMCAO injury, which may be related to suppressed inflammation via activation of the a7nAchR/JAK2 anti-inflammatory pathway.

Association of TNFSF4 (rs3850641) gene polymorphisms and coronary heart disease: an evidence-based meta-analysis.

OBJECTIVE: To clarify the effects of TNFSF4 (rs3850641) polymorphisms on coronary heart disease (CHD) risk. METHOD: Published literature from Pubmed, Embase, ISI Wed of Knowledge, Cochrane Library, and Chinese databases were retrieved. All studies evaluating the association between TNFSF4 (rs3850641) polymorphisms and CHD risk were included. Summary odds ratios (ORs) and 95% confidence intervals (CI) were calculated employing random-effects models irrespective of between-study heterogeneity. RESULTS: A total of 9 eligible studies was included in this meta-analysis. Overall analysis showed that the rs3850641 G allele was not associated with CHD, compared with the A allele, with OR of 1.10 (95% CI, 0.96-1.27; p = 0.174). Genotypic analysis showed that there was no significant association between the GG, GA, GG + GA, and CHD, compared with participants with AA, with ORs of 1.23 (95% CI, 0.75-2.03; p = 0.409), 1.04 (95% CI, 0.84-1.29; p = 0.705), and 1.07 (95% CI, 0.85-1.34; p = 0.589), respectively. On the other hand, in the subgroup analysis by ethnicity, source of controls, genotyping methods, or matching criteria, there was still no statistically significant association between TNFSF4 (rs3850641) polymorphisms and CHD risk. CONCLUSIONS: This meta-analysis reveals that TNFSF4 (rs3850641) polymorphisms is not associated with CHD risk.

Long-term efficacy and safety of statin treatment beyond six years: a meta-analysis of randomized controlled trials with extended follow-up.

Large-scale randomized controlled trials (RCTs) have well demonstrated the beneficial effects of cholesterol-lowering treatment with statins in patients at high risk of vascular disease. However, large statin RCTs were usually restricted to the typical 5-6 years. Moreover, non-cardiovascular events, especially the risk of cancer, probably failed to emerge within a restricted period of 6 years. The aim of this study was to evaluate the long-term efficacy and safety of statin treatment by performing a meta-analysis of statin RCTs with extended follow-up beyond 6 years. Six RCTs with post-trial follow-up were eligible for inclusion, involving 47,296 patients with total follow-up ranging from 6.7 to 14.7 years. During the post-trial period, all the surviving participants were advised to take a statin and the cholesterol level were almost identical between the original statin group and the original placebo group. Over the entire 6.7-14.7 years of follow-up, a significant reduction in the rates of all-cause mortality (relative risk 0.90, 95% confidence interval 0.85-0.96; P=0.0009), cardiovascular mortality (0.87, 0.81-0.93; P<0.0001) and major coronary events (0.79, 0.72-0.86; P<0.00001) was observed in favour of the original statin group. During 2-year post-trial period, further reduction in all-cause mortality (0.83, 0.74-0.93; P=0.001), cardiovascular mortality (0.81, 0.69-0.95; P=0.01) and major coronary events (0.77, 0.63-0.95; P=0.01) was observed among initially statin-treated patients. Over the entire follow-up period, statin treatment did not increase the incidence of cancers (0.99, 0.95-1.04; P=0.79), deaths from cancers (1.00, 0.93-1.07; P=0.98) and non-cardiovascular mortality (0.95, 0.90-1.00; P=0.07). In conclusion, statin treatment beyond 6 years is effective and safe in patients at high risk of vascular events. Moreover, earlier treatment with statin may not only preserve the initial benefit but also have further survival benefit for additional 2 years. Further studies are called for to explore the underlying mechanisms.

Alpine climate alters the relationships between leaf and root morphological traits but not chemical traits.

Leaves and fine roots are among the most important and dynamic components of terrestrial ecosystems. To what extent plants synchronize their resource capture strategies above- and belowground remains uncertain. Existing results of trait relationships between leaf and root showed great inconsistency, which may be partly due to the differences in abiotic environmental conditions such as climate and soil. Moreover, there is currently little evidence on whether and how the stringent environments of high-altitude alpine ecosystems alter the coordination between above- and belowground. Here we measured six sets of analogous traits for both leaves and fine roots of 139 species collected from Tibetan alpine grassland and Mongolian temperate grassland. N, P and N:P ratio of leaves and fine roots were positively correlated, independent of biogeographic regions, phylogenetic affiliation or climate. In contrast, leaves and fine roots seem to regulate morphological traits more independently. The specific leaf area (SLA)-specific root length (SRL) correlation shifted from negative at sites under low temperature to positive at warmer sites. The cold climate of alpine regions may impose different constraints on shoots and roots, selecting simultaneously for high SLA leaves for rapid C assimilation during the short growing season, but low SRL roots with high physical robustness to withstand soil freezing. In addition, there might be more community heterogeneity in cold soils, resulting in multidirectional strategies of root in resource acquisition. Thus our results demonstrated that alpine climate alters the relationships between leaf and root morphological but not chemical traits.

CYR61 is Involved in Neonatal Hypoxic-ischemic Brain Damage Via Modulating Astrocyte-mediated Neuroinflammation.

The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in astrocytes has been found in the hypoxic-ischemic brain damage (HIBD) model. Cysteine rich angiogenic inducer 61 (CYR61) is secreted by reactive astrocytes. However, the effects of CYR61 on HIBD and its related mechanisms remain unclear. This study sought to explore the role of CYR61 in the activation of astrocytes and the NLRP3 inflammasome in neonatal HIBD. HIBD models were established in 7-day Sprague-Dawley rat pups. Neurobehavioral evaluation and 2,3,5-triphenyl-tetrazolium chloride staining were performed. In addition, rat primary astrocytes were used to establish the cell model of HIBD in vitro by oxygen-glucose deprivation/reperfusion (OGD/R). Then, CYR61-overexpression and sh-CYR61 viruses mediated by lentivirus were transduced into ODG/R-treated primary astrocytes. The expressions of related genes were evaluated using real-time quantitative PCR, western blot, immunofluorescence staining, and Enzyme-linked immunosorbent assay. The results showed that hypoxia-ischemia induced short-term neurological deficits, neuronal damage, and cerebral infarction in neonatal rats. In vivo, the expressions of CYR61, NLRP3, and glial fibrillary acidic protein (GFAP) were up-regulated in the HIBD model. In vitro, CYR61 exhibited high expression. CYR61 overexpression increased the expressions of GFAP and C3, whereas decreased S100A10 expression. CYR61 overexpression increased the expression of NLRP3, ASC, caspase-1 p20 and IL-1ß. CYR61 overexpression activated NF-κB by promoting the phosphorylation of IκBα and p65. Thus, CYR61 is involved in neonatal HIBD progress, which may be related to the activation of astrocytes, the NLRP3 inflammasome, and the NF-κB signaling pathway.

Entrepreneurial role models and college students' entrepreneurial calling: A moderated mediation model.

Introduction: College entrepreneurship education should not only cultivate a group of college students who have strong willingness to start a business immediately after graduation, but also pay attention to future entrepreneurship success of college students. Correspondingly, in addition to attaching importance to improving college students' entrepreneurial intention, college entrepreneurship education should pay attention to improving college students' entrepreneurial calling. At present, there is insufficient research on the association between entrepreneurial role models and entrepreneurial calling. We aim to study the mechanism and boundary condition of the association between entrepreneurial role models and entrepreneurial calling. Methods: A longitudinal survey was distributed among 519 students from 16 colleges and universities in China. In the survey, the college students answered questions on entrepreneurial role models, entrepreneurial calling, entrepreneurial perceived behavioral control and entrepreneurial hands-on practice. Hierarchical regression was conducted, testing the association between entrepreneurial role models and entrepreneurial calling of college students, mediated by entrepreneurial perceived behavioral control and moderated by entrepreneurial hands-on practice. Results: Therefore, based on the social learning theory, the theory of planned behavior and the entrepreneurial event model, and by hierarchical regression of the data, this study confirmed that entrepreneurial role models were positively associated with college students' entrepreneurial calling by partially mediating with entrepreneurial perceived behavioral control. Moreover, Entrepreneurial hands-on practice positively moderated not only the relationship between entrepreneurial perceived behavioral control and entrepreneurial calling, but also the mediating association of entrepreneurial perceived behavioral control between entrepreneurial role models and entrepreneurial calling. Discussion: This study not only enriches the theoretical research on entrepreneurial calling and entrepreneurial role models, but also provides valuable educational enlightenment for colleges and universities to improve the students' entrepreneurial calling.

Effect of Reactivity of Hydrated Portland Cement on Hydrothermal Synthesis of Xonotlite.

Significant interest in waste-cement recycling has been stimulated because of the high contents of calcium and silicon in waste cement. The reactivity of calcium and silicon in the raw material is one of the important factors for the hydrothermal synthesis of xonotlite. Therefore, the effect of the reactivity of calcium and silicon in the waste cement on the hydrothermal synthesis of xonotlite was studied in this paper. Portland cement that was hydrated for 6 months, with the aim of simulating the waste cement, was used for the first time as the calcium and silicon source in the hydrothermal synthesis of xonotlite. As calcination would raise the reactivity of the hydrated cement, the effect of calcination of the Portland hydrated cement on the hydrothermal synthesis of xonotlite was investigated. The hydrated cement was calcined at 900 °C, and the hydrothermal synthesis was carried out at 220 °C for different times. The phases of the hydrothermal products were analyzed by XRD and TG-DSC, and it was noted that the calcination of hydrated cement affected the formation rate of xonotlite. The content of xonotlite increased from 18% (synthesized with hydrated cement without calcination) to 74% (synthesized from hydrated cement with calcination at 900 °C) during a reaction time of 24 h. Furthermore, the micromorphologies of xonotlite using calcined and hydrated cement were compared and discussed from the perspective of the reactivity of the starting materials.

Simplified Genomic Data Revealing the Decline of Aleuritopteris grevilleoides Population Accompanied by the Uplift of Dry-Hot Valley in Yunnan, China.

Understanding the evolutionary history of endangered species is crucial for identifying the main reasons for species endangerment in the past and predicting the changing trends and evolutionary directions of their future distribution. In order to study the impact of environmental changes caused by deep valley incision after the uplift of the Qinghai-Tibet Plateau on endangered species, we collected 23 samples belonging to four populations of Aleuritopteris grevilleoides, an endangered fern endemic to the dry-hot valleys (DHV) of Yunnan. Single-nucleotide variation sites (SNPs) were obtained by the genotyping-by-sequencing (GBS) method, and approximately 8085 SNP loci were identified. Through the reconstruction and analysis of genetic diversity, population structure, population dynamics, evolution time, and ancestral geographical distribution, combined with geological historical events such as the formation of dry-hot valleys, this study explores the formation history, current situation, reasons for endangerment and scientifically sound measures for the protection of A. grevilleoides. In our study, A. grevilleoides had low genetic diversity (Obs_Het = 0.16, Exp_Het = 0.32, Pi = 0.33) and a high inbreeding coefficient (Fis = 0.45). The differentiation events were 0.18 Mya, 0.16 Mya, and 0.11 Mya in the A. grevilleoides and may have been related to the formation of terraces within the dry-hot valleys. The history of population dynamics results shows that the diversion of the river resulted in a small amount of gene flow between the two clades, accompanied by a rapid increase in the population at 0.8 Mya. After that, the effective population sizes of A. grevilleoides began to contract continuously due to topographic changes resulting from the continuous expansion of dry-hot valleys. In conclusion, we found that the environmental changes caused by geological events might be the main reason for the changing population size of A. grevilleoides.

Cilostazol-based triple antiplatelet therapy compared to dual antiplatelet therapy in patients with coronary stent implantation: a meta-analysis of 5,821 patients.

BACKGROUND: Uncertainties still remain in terms of what kinds of patients benefit most from cilostazol-based triple antiplatelet therapy (TAT) after coronary stenting. METHODS: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to investigate the effect of TAT versus dual antiplatelet therapy (DAT) in terms of major adverse cardiovascular events (MACEs) in patients undergoing coronary stenting. RESULTS: Fourteen RCTs with 5,821 patients were included in this study. TAT was associated with a significant reduction in the risk of MACEs compared to DAT [9.2 vs. 13.4%; odds ratio 0.59 (0.46, 0.76)] with consistent benefits among patients with diabetes, long lesions and small vessels. There were no significant between-group differences in the risk of cardiac death, myocardial infarction, stent thrombosis and bleeding events; however, the risk of target lesion revascularization was significantly lower in the TAT group. TAT resulted in borderline significant reduction in the risk of cardiovascular thrombotic events in unselected patients and significant decrease in patients with acute coronary syndrome [odds ratio 0.51 (0.27, 0.94)]. CONCLUSION: Under the treatment of standard DAT, the addition of cilostazol is an effective and relatively safe strategy in preventing MACEs after coronary stenting, especially for patients at high risk of restenosis or clinical events.

Comparison of adjuvant chemoradiotherapy versus radiotherapy in early-stage cervical cancer patients with intermediate-risk factors: A systematic review and meta-analysis.

The presence of intermediate risk factors reduces the predictability of radical hysterectomy, demanding the use of adjuvant therapy for treatment of Early stage cervical cancer (ESCC) patients. Adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) has been widely used with varied efficacy and safety issues. Therefore, the aim of this systematic review and meta-analysis was to update the available evidence and assess the effect of post-surgical adjuvant RT versus adjuvant CRT on survival rate and complications/toxicities in management of ESCC patients with intermediate risk factors. PubMed, EMBASE and Web of Science (WOS) and CENTRAL were searched using a combination of relevant keywords. All studies comparing outcomes of adjuvant RT versus CRT in ESCC patients with intermediate-risk factors in terms of recurrence free survival (RFS), overall survival (OS) and toxicities/complications were included. Both qualitative and quantitative analysis was carried out. The risk of bias assessment was done using Newcastle-Ottawa scale (NOS) for retrospective cohort studies and Cochrane risk of bias assessment tool was used for randomized clinical trials. Eleven retrospective cohort studies and two randomized clinical trials were included in this review. Adjuvant CRT was found to have better RFS with ESCC patients with multiple intermediate risk factors with OR 3.11 95% CI [1.04, 4.99], p < 0.0001; i2 = 6%. However, similar benefit was observed between both regimens in presence of a single intermediate risk factor OR 1.80 95% CI [0.96, 3.36], p = 0.07; i2 = 0%. Grade 3 or 4 haematological toxicity among patients receiving post-surgical adjuvant RT versus adjuvant CRT showed increased association of toxicity with adjuvant CRT with OR 7.73 95%CI [3.40, 17.59], p < 0.0001; i2 = 62%. Adjuvant CRT shows favourable RFS and OS in ESCC patients with multiple intermediate risk factors. CRT also showed greater incidence of grade 3 or 4 haematological and non-haematiological toxicity, however, the same could be well tolerated when used within the recommended dosage.

Genome size evolution of the extant lycophytes and ferns.

Ferns and lycophytes have remarkably large genomes. However, little is known about how their genome size evolved in fern lineages. To explore the origins and evolution of chromosome numbers and genome size in ferns, we used flow cytometry to measure the genomes of 240 species (255 samples) of extant ferns and lycophytes comprising 27 families and 72 genera, of which 228 species (242 samples) represent new reports. We analyzed correlations among genome size, spore size, chromosomal features, phylogeny, and habitat type preference within a phylogenetic framework. We also applied ANOVA and multinomial logistic regression analysis to preference of habitat type and genome size. Using the phylogeny, we conducted ancestral character reconstruction for habitat types and tested whether genome size changes simultaneously with shifts in habitat preference. We found that 2C values had weak phylogenetic signal, whereas the base number of chromosomes (x) had a strong phylogenetic signal. Furthermore, our analyses revealed a positive correlation between genome size and chromosome traits, indicating that the base number of chromosomes (x), chromosome size, and polyploidization may be primary contributors to genome expansion in ferns and lycophytes. Genome sizes in different habitat types varied significantly and were significantly correlated with habitat types; specifically, multinomial logistic regression indicated that species with larger 2C values were more likely to be epiphytes. Terrestrial habitat is inferred to be ancestral for both extant ferns and lycophytes, whereas transitions to other habitat types occurred as the major clades emerged. Shifts in habitat types appear be followed by periods of genomic stability. Based on these results, we inferred that habitat type changes and multiple whole-genome duplications have contributed to the formation of large genomes of ferns and their allies during their evolutionary history.

Effects of 17ß-estradiol pre-treated adult neural stem cells on neuronal differentiation and neurological recovery in rats with cerebral ischemia.

PRIMARY OBJECTIVE: To evaluate the effects of estradiol-pre-treated neural stem cells (NSCs) derived from rat hippocampi post-ischemic neurological recovery and neuronal survival, migration and differentiation in rats with cerebral ischemia. RESEARCH DESIGN: A controlled laboratory study in animal model. METHODS AND PROCEDURE: NSCs were cultured with (CE) or without (CN) 17ß-estradiol (E2) and transplanted into the lateral ventricles of rats with middle cerebral artery occlusion (MCAO). A MCAO model alone group and treatment control group served as controls. MAIN OUTCOME AND RESULTS: Transplantation recipients (CN and CE groups) had ameliorated neurological deficits, less severe morphological changes and reduced total infarct volume, while there were no significant differences in these outcomes or in nestin and glial fibrillary acidic protein expression between the CN and CE groups at all time points. On day 1 post-transplantation, the CE group exhibited significantly higher neuron-specific enolase expression compared to all other groups, but there were no significant differences between the CE group and CN groups on days 4 and 7 post-transplantation. CONCLUSIONS: The results indicated no measurable improvements of E2 pre-treatment NSCs in neuronal survival, migration or neurological recovery. The findings provide pre-clinical support for the use of NSC transplantation in ischemic injury.

Development and Validation of a Nomogram for Preoperative Prediction of Localization of Neonatal Gastrointestinal Perforation.

Background: Information regarding the localization of gastrointestinal perforation is crucial for the following surgical procedure. This study was to determine the key indicators and develop a prediction model for the localization in neonates with gastrointestinal perforation. Methods: A nomogram to predict the location of neonatal gastrointestinal perforation was developed using a cohort of patients who underwent surgery between July 2009 and May 2021. Baseline variables were analyzed using logistics regression and nomogram developed using significant predictors. The predictive performance of the nomogram was assessed by the concordance index (C-index), calibration curve, and area under the receiver operating characteristic (ROC) curve (AUC). The nomogram was further validated in an integrated external cohort. Results: We investigated the data of 201 patients, of which 65 (32.3%) were confirmed with upper gastrointestinal perforation by surgery. Multivariate logistic regression analysis identified the following as independent predictors: preterm [OR: 5.014 (1.492-18.922)], time of onset [OR: 0.705 (0.582-0.829)], preoperative hemoglobin [OR:1.017 (1.001-1.033)], bloody stool: No [OR: 4.860 (1.270-23.588)], shock [OR: 5.790 (1.683-22.455)] and sepsis: No [OR 3.044 (1.124-8.581)]. Furthermore, the nomogram was effective in predicting the perforation site, with an AUC of 0.876 [95% confidence interval (CI): 0.830-0.923]. Internal validation showed that the average AUC was 0.861. Additionally, the model achieved satisfactory discrimination (AUC, 0.900; 95% CI, 0.826-0.974) and calibration (Hosmer-Lemeshow test, P = 0.4802) in external validation. Conclusions: The nomogram based on the six factors revealed good discrimination and calibration, suggesting good clinical utility. The nomogram could help surgeons predict the location of gastrointestinal perforation before surgery to make a surgical plan.

Effect of Dihydropyridine Calcium Channel Blocker on Mortality of Hypertension Patients With Moderate-Severe Pulmonary Acute Respiratory Distress Syndrome: A Multicenter Retrospective Observational Cohort Study.

The aim was to evaluate the effect of dihydropyridine calcium channel blocker on the prognosis for moderate-severe pulmonary acute respiratory distress syndrome in hypertension patients. DESIGN: A retrospective, observational, multicenter cohort study. SETTING: A total of 307 patients without propensity score matching and 186 adult inpatients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome in five teaching hospitals in Jiangsu province, China, from December 2015 to December 2020 were enrolled. PATIENTS: A total of 307 patients without propensity score matching and 186 patients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome were included in the final analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic characteristics and clinical characteristics were recorded. The propensity score matching method was used to eliminate the difference between group with dihydropyridine calcium channel blocker and group without dihydropyridine calcium channel blocker. The primary outcome was in-hospital mortality. We used univariate and multivariate regression analyses for both patients with or without propensity score matching to assess the effect of these variables on mortality. In the subset of 186 patients with propensity score matching, in-hospital mortality was 53.2%. Inpatient mortality was significantly higher in patients treated with dihydropyridine calcium channel blocker than in those not treated with dihydropyridine calcium channel blocker of patients without propensity score matching (65.4% vs 40.4%; p < 0.01). Multivariate analysis for patients without propensity score matching showed that dihydropyridine calcium channel blocker (hazard ratio, 1.954; 95% CI, 1.415-2.699), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 3.809; 95% CI, 2.106-4.531), and lactate greater than or equal to 2 mmol/L (hazard ratio, 1.454; 95% CI, 1.041-2.029) were independently associated with in-hospital mortality. Based on univariate analysis for patients with propensity score matching, dihydropyridine calcium channel blocker (hazard ratio, 2.021; 95% CI, 1.333-3.064), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 4.379; 95% CI, 2.642-7.257), and lactate greater than or equal to 2 mmol/L (hazard ratio, 2.461; 95% CI, 1.534-3.951) were independently associated with in-hospital mortality. In contrast, patients not treated with dihydropyridine calcium channel blocker had a significant survival advantage over those treated with dihydropyridine calcium channel blocker in both patients without or with propensity score matching (p < 0.001; p = 0.001 by Kaplan-Meier analysis). CONCLUSIONS: Dihydropyridine calcium channel blocker, lactate dehydrogenase greater than or equal to 600 U/L, and lactate greater than or equal to 2 mmol/L at admission were independent risk factors for patients with hypertension and moderate-severe pulmonary acute respiratory distress syndrome.

Multiple roles of THY1 in gastric cancer based on data mining.

BACKGROUND: THY1 (CD90) is a heavily N-glycosylated, glycophosphatidylinositol (GPI) anchored cell surface protein, which has been implicated in several cancers. But, the specific mechanism and function of the THY1 gene remains unclear in gastric cancer (GC). METHODS: To investigate the function of THY1 in GC and illustrate the potential mechanism, TCGA and FIREBROWSE were used to detect the THY1expression. GEPIA2 and Kaplan-Meier Plotter showed significant correlation among THY1 mRNA level, TNM stage and survival probability of GC patients. RESULTS: THY1 was up-regulated apparently in GC in contrast to normal tissues and linked to TNM stage. GC patients with higher THY1 expression displayed lower overall survival (OS), first progression (FP) and post-progression survival (PPS). In vitro experiments showed that knockdown of THY1 suppressed proliferation, migration while increased autophagy level in GC cells. Immune factors may interact with THY1mRNA in GC and THY1 was found significantly linked with Tregs. CONCLUSIONS: Our findings indicate that higher THY1 level is link to poor prognosis of GC patients. THY1may as well be used as a marker molecule for evaluating the tumor microenvironment status of GC patients and a target for immunotherapy.

Combined Ankle/Knee Stretching and Pivoting Stepping Training for Children With Cerebral Palsy.

Although various treatment methods have been investigated to reduce spasticity and intoeing gait in children with cerebral palsy (CP), methods to concurrently reduce an intoeing gait and associated ankle/knee stiffness and spasticity according to a child's specific needs are lacking. This study aimed to develop a training program to improve walking function and transverse-plane (pivoting) neuromuscular control and reduce spasticity and intoeing gait deviations. Eight children with diplegic CP and intoeing gait participated in this 6-week combined robotic ankle and/or knee intelligent stretching and pivoting neuromuscular control training program (Subject-specific Stretching and Pivoting Off-axis Neuromuscular control Training, [SS-POINT]). The effects of SS-POINT were evaluated using neuromechanical, functional, and clinical outcome measures and compared to those for eight children with CP and intoeing gait who participated in pivoting neuromuscular control training (POINT) alone in a previous study. RESULTS: After the SS-POINT program, subjects with CP showed reduced knee stiffness and intoeing angle, and improvements in both joint and leg functions in terms of ankle and knee active range of motion, ankle dorsiflexor strength, proprioception, walking speed, balance, and minimum pivoting angle. Furthermore, improvements in proprioceptive acuity and minimum pivoting angle after the SS-POINT were greater than those after the POINT. CONCLUSION: The SS-POINT approach can be used as a subject-specific training program for improving leg and walking functions and reducing intoeing during gait. SIGNIFICANCE: This approach can serve as an individualized intervention at the joint and walking levels to maximize intervention effects by adjusting training targets, sequences, and intensities to meet the individual needs of children with CP.

Transcriptomic Evidence of Adaptive Evolution of the Epiphytic Fern Asplenium nidus.

Epiphytic ferns have been found to flourish after angiosperms dominated forest communities, and they play important roles in rainforest canopies. How do epiphytic ferns adapt to tropical rainforest canopy habitats? At present, we know little about the molecular mechanism underlying this adaptation. Asplenium nidus is a well-known epiphytic fern that is closely related to the terrestrial species Asplenium komarovii. Here, RNA-seq and comparative transcriptomic analyses were performed to explore the underlying basis of the adaptation of A. nidus to extreme environments. A total of 44.04 and 44.57 Mb clean reads were obtained from A. nidus and A. komarovii, respectively, and they were assembled into 89,741 and 77,912 unigenes. Functional annotation showed that 52,305 (58.28% of the total genes for A. nidus) and 45,938 (58.96% of the total genes for A. komarovii) unigenes were annotated in public databases. Genes involved in stress responses and photosynthesis were found to have undergone positive selection in A. nidus. Compared to A. komarovii, transcription factors related to stress response, leaf development, and root development were found to be considerably expanded in A. nidus, especially in the ANR1 subclade of MADS-box family genes which played roles in lateral root development. This study improves our understanding of the adaptation of A. nidus to epiphytic habitats by forming unique strategies.

Sphingomyelin synthase 2 regulates the malignant biological behaviors of ovarian cancer TOV-21G cells through Wnt/β-catenin pathway / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨鞘磷脂合成酶2（SMS2）是否通过Wnt/β-catenin信号通路调控卵巢癌（OC）TOV-21G细胞增殖、迁移、侵袭、凋亡及其机制。方法：收集武汉市第三医院2022年7月至2023年5月间确诊的21例OC患者的癌及癌旁组织标本，免疫组化法检测OC组织SMS2表达水平。体外培养TOV-21G细胞，将细胞分为对照组、shRNA慢病毒阴性对照组（sh-NC组）、SMS2 shRNA慢病毒组（sh-SMS2组）、Wnt/β-catenin通路激活剂组LiCl（LiCl组）和sh-SMS2+LiCl组。Edu染色法、Transwell法、流式细胞术分别检测各组细胞的增殖、迁移和侵袭能力及凋亡水平，WB法检测细胞中SMS2、Ki67、cyclin D1、BAX、c-caspase3、Bcl-2及Wnt/β-catenin通路蛋白（β-catenin、c-Myc、MMP-9）的表达。构建TOV-21G细胞裸鼠移植瘤模型，观察敲低SMS2对移植瘤生长和SMS2、β-catenin表达的影响。结果：与癌旁组织比较，OC组织中SMS2呈高表达（P<0.01）。转染sh-SMS2后，TOV-21G细胞中SMS2表达水平显著降低（P<0.05），细胞的增殖、迁移和侵袭能力及Bcl-2、β-catenin、c-Myc、MMP-9蛋白表达均显著降低（均P<0.05），细胞凋亡率、BAX、c-caspase3蛋白表达均显著升高（均P<0.05）；LiCl处理能逆转敲低SMS2对TOV-21G细胞增殖、迁移和侵袭及Wnt/β-catenin通路的抑制作用（均P<0.05）。体内成瘤实验显示，敲低SMS2抑制裸鼠移植瘤的生长及SMS2、β-catenin蛋白的表达（均P<0.05）。结论：敲低SMS2表达通过Wnt/β-catenin信号通路抑制OC TOV-21G细胞的增殖、迁移、侵袭并促进细胞凋亡，同时LiCl处理则能逆转敲低SMS2对TOV-21G细胞增殖、迁移和侵袭的抑制作用。