The determinants of mental health inequalities between Chinese migrants and non-migrants during the Shanghai 2022 lockdown: a Blinder-Oaxaca decomposition.

BACKGROUND: The mental health inequality between migrants and non-migrants was exacerbated by the COVID-19 pandemic. Identifying key determinants of this inequality is essential in promoting health equity. METHODS: This cross-sectional study recruited Shanghai residents by purposive sampling during the city-wide lockdown (from April 29 to June 1, 2022) using an online questionnaire. Migration statuses (non-migrants, permanent migrants, and temporary migrants) were identified by migration experience and by household registration in Shanghai. Mental health symptoms (depression, anxiety, loneliness, and problematic anger) were assessed by self-report scales. The nonlinear Blinder-Oaxaca decomposition was used to quantify mental health inequality (i.e., differences in predicted probabilities between migration groups) and the contribution of expected correlates (i.e., change in predicted probability associated with variation in the correlate divided by the group difference). RESULTS: The study included 2738 participants (771 [28.2%] non-migrants; 389 [14.2%] permanent migrants; 1578 [57.6%] temporary migrants). We found inequalities in depression (7.1%) and problematic anger (7.8%) between permanent migrants and non-migrants, and inequalities in anxiety (7.3%) and loneliness (11.3%) between temporary migrants and non-migrants. When comparing permanent migrants and non-migrants, age and social capital explained 12.7% and 17.1% of the inequality in depression, and 13.3% and 21.4% of the inequality in problematic anger. Between temporary migrants and non-migrants, age and social capital also significantly contributed to anxiety inequality (23.0% and 18.2%) and loneliness inequality (26.5% and 16.3%), while monthly household income (20.4%) and loss of monthly household income (34.0%) contributed the most to anxiety inequality. CONCLUSIONS: Significant inequalities in depression and problematic anger among permanent migrants and inequalities in anxiety and loneliness among temporary migrants were observed. Strengthening social capital and economic security can aid in public health emergency preparedness and promote mental health equity among migrant populations.

Introducing activation functions into segmented regression model to address lag effects of interventions.

The interrupted time series (ITS) design is widely used to examine the effects of large-scale public health interventions and has the highest level of evidence validity. However, there is a notable gap regarding methods that account for lag effects of interventions.To address this, we introduced activation functions (ReLU and Sigmoid) to into the classic segmented regression (CSR) of the ITS design during the lag period. This led to the proposal of proposed an optimized segmented regression (OSR), namely, OSR-ReLU and OSR-Sig. To compare the performance of the models, we simulated data under multiple scenarios, including positive or negative impacts of interventions, linear or nonlinear lag patterns, different lag lengths, and different fluctuation degrees of the outcome time series. Based on the simulated data, we examined the bias, mean relative error (MRE), mean square error (MSE), mean width of the 95% confidence interval (CI), and coverage rate of the 95% CI for the long-term impact estimates of interventions among different models.OSR-ReLU and OSR-Sig yielded approximately unbiased estimates of the long-term impacts across all scenarios, whereas CSR did not. In terms of accuracy, OSR-ReLU and OSR-Sig outperformed CSR, exhibiting lower values in MRE and MSE. With increasing lag length, the optimized models provided robust estimates of long-term impacts. Regarding precision, OSR-ReLU and OSR-Sig surpassed CSR, demonstrating narrower mean widths of 95% CI and higher coverage rates.Our optimized models are powerful tools, as they can model the lag effects of interventions and provide more accurate and precise estimates of the long-term impact of interventions. The introduction of an activation function provides new ideas for improving of the CSR model.

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization.

BACKGROUND: Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. METHODS: Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-ß and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. RESULTS: Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). CONCLUSIONS: In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.

The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice.

The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1ß, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow-derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage's response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.

The role of lipid profile in the relationship between particulate matters and hyperuricemia: A prospective population study.

CONTEXT: Recent studies in specific population subgroups (e.g., pregnant women) have suggested PM exposure increases the risk of hyperuricemia. However, no studies have examined this in the general population. Furthermore, the underlying mechanism through which PM impacts hyperuricemia risk is poorly understood. OBJECTIVE: To assess the association between long-term exposure to PM and risk of hyperuricemia and whether this association is mediated by lipid profile. METHODS: We included 5939 participants in Southwest China from the China Multi-Ethnic Cohort (baseline 2018-2019, follow-up 2020-2021). Long-term PM pollutants (PM1, PM2.5, PM10) exposure for each individual was represented by the three-year average PM levels before the baseline survey. Hyperuricemia at follow-up was defined as the serum uric acid above 7.0 mg/dL in men and 6.0 mg/dL in women. Serum lipids were measured at baseline including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). The association of PM with hyperuricemia was accessed through logistic regression. The potential mediation effects of serum lipids were evaluated through causal mediation analyses. RESULTS: A total of 837 participants were newly diagnosed with hyperuricemia. The odds ratios of hyperuricemia associated with an interquartile range (IQR) increase in PM1, PM2.5, and PM10 (IQR: 21.10, 25.78, 30.43 µg m-3) were 1.72 (95% CI: 1.23, 2.39), 2.68 (95% CI: 1.59, 4.49), and 1.81 (95% CI: 1.20, 2.72), respectively. The association between PM2.5, PM1, and PM10 on hyperuricemia was mediated by HDL-C (10%) and LDL-C (3%). CONCLUSION: Higher particulate matter exposure was associated with higher hyperuricemia incidence. The decline in HDL-C and rise in LDL-C partially mediated this association. These findings were conducive to scientific research about the underlying mechanism of PM on hyperuricemia.

High-altitude exposure decreases bone mineral density and its relationship with gut microbiota: Results from the China multi-ethnic cohort (CMEC) study.

BACKGROUND: Geographic altitude is a potent environmental factor for human microbiota and bone mineral density. However, little evidence exists in population-based studies with altitude diversity ranges across more than 3000 m. This study assessed the associations between a wide range of altitudes and bone mineral density, as well as the potential mediating role of microbiota in this relationship. METHODS: A total of 99,556 participants from the China Multi-Ethnic Cohort (CMEC) study were enrolled. The altitude of each participant was extracted from global Shuttle Radar Topography Mission (SRTM) 4 data. Bone mineral density was measured by calcaneus quantitative ultrasound index (QUI). Stool samples were collected for 16S rRNA gene sequencing (n = 1384). The metabolites of gut microbiota, seven kinds of short-chain fatty acids (SCFAs), were detected by gas chromatography-mass spectrometry (GC-MS, n = 128). After screening, 73,974 participants were selected for the "altitude-QUI" analysis and they were placed into the low-altitude (LA) and high-altitude (HA) groups. Additionally, a subgroup (n = 1384) was further selected for the "altitude-microbiota-QUI" analysis. Multivariate linear regression models and mediation analyses were conducted among participants. RESULTS: A significant negative association between high-altitude and QUI was obtained (mean difference = -0.373 standard deviation [SD], 95% confidence interval [CI]: -0.389, -0.358, n = 73,974). The same negative association was also observed in the population with microbiota data (mean difference = -0.185 SD, 95%CI: -0.360, -0.010, n = 1384), and a significant mediating effect of Catenibacteriumon on the association between altitude and QUI (proportion mediated = 25.2%, P = 0.038) was also noticed. Additionally, the acetic acid, butyric acid, and total amount of seven SCFAs of the low-altitude group were significantly higher than that of the high-altitude group (P < 0.05). CONCLUSION: High-altitude exposure may decrease bone mineral density in adults, thus increasing the risk of osteoporosis. The modulation of gut microbiota may be a potential strategy for alleviating the decrease of bone mineral density.

TTN/OBSCN 'Double-Hit' predicts favourable prognosis, 'immune-hot' subtype and potentially better immunotherapeutic efficacy in colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide. Although treatment strategies for solid tumours have been revolutionized by immunotherapy, only a small subset of CRC patients benefit. Using two-independent cohorts, we found the common frequently mutated genes TTN and OBSCN had the significant correlation with higher tumour mutation burden (TMB) and favourable overall survival. TTN and OBSCN also displayed significant commutation phenomenon. Therefore, based on the status of TTN and OBSCN, we stratified patients into 'Double-WT' phenotype, 'Single-Hit' phenotype and 'Double-Hit' phenotype. Importantly, the 'Double-Hit' phenotype had favourable prognosis, low malignant events propensity, and highest TMB, immune cells infiltration abundance, POLE mutation rate, microsatellite instability ratio, as well as immune checkpoints expression compared with the other two phenotypes. These results indicated that the 'Double-Hit' phenotype suggested 'immune-hot' tumours and potentially better immunotherapeutic efficacy. Bioinformatic algorithm assessment of immunotherapy responses also confirmed this conclusion, and the 'Double-Hit' phenotype was found to be a better predictor of immunotherapy than PD-L1, PD-1, CTLA-4, TMB and microsatellite status. This study revealed CRC patients with TTN/OBSCN 'Double-Hit' was significantly associated favourable prognosis, 'immune-hot' subtype and potentially better immunotherapeutic efficacy.

MicroRNA-520d-3p alleviates hypoxia/reoxygenation-induced damage in human cardiomyocytes by targeting ATG-12.

Hypoxia/reoxygenation (H/R) induced injury results in extensive damages to myocardial tissue in patients with coronary heart disease, which leads to heart failure. MicroRNA (miRNA) is thought to be associated with myocardial H/R injury. The purpose of this study was to investigate the in vitro role of microRNA-520d-3p in human myocardial cell (HCM) myocardial H/R injury. MTT method and Annexin V-FITC flow cytometry were employed to measure the viability and apoptosis of H/R treated HCM. RT-qPCR was employed to determine miRNA and mRNA expression. MicroRNA-520d-3p mimic and microRNA-520d-3p inhibitor were used to overexpression and inhibit the expression of microRNA-520d-3p. In addition, pcDNA3.1-ATG12 was used to upregulate ATG12 expression. The protein levels of ATG12, Bcl-2 and autophagy related-genes were determined by western blotting. Hypoxia/reoxygenation (H/R) injury could inhibit cell viability, apoptosis and inhibited microRNA-520d-3p expression in HCM. The down-regulation of microRNA-520d-3p inhibited cell viability and induced apoptosis in HCM. The overexpression of microRNA-520d-3p attenuated the effects of H/R treatment on the viability and apoptosis of HCM cells. In addition, microRNA-520d-3p inhibited the expression of autophagy-associated 12 (ATG12). More importantly, H/R treatment could promote autophagy in HCM, and microRNA-520d-3p mimic transfection could significantly reverse this effect. Our result indicated that overexpression of microRNA-520d-3p attenuated the effect of H/R treatments on cell viability, apoptosis and autophagy, through partly regulating ATG12 expression in HCM.

Association of Daytime Napping with chronic diseases among Tibetan people in China: a cross-sectional study.

BACKGROUND: Obesity, diabetes, and hypertension, as three of the most prevalent chronic diseases, remain a daunting health challenge. However, to our knowledge, no study has made a thorough examination of the association between the three chronic diseases and daytime napping, a widely accepted behavior in many countries. This is especially necessary among Tibetan populations, whose lifestyles and health outcomes may be unique, yet patterns of chronic diseases and napping are under-examined. Thus, we sought to explore the aforementioned association in the Tibetan population of China. METHODS: A total of 2902 participants aged 45-79 in 2019 were included. Multivariate logistic regressions were conducted in 2020. The sex disparity was examined through interaction and stratified analyses. RESULTS: Hypertension (40.7%) was more prevalent than obesity (20.2%) and diabetes (21.6%). Comparing to non-nappers, those who napped were more likely to have any conditions (OR = 1.30, 95% CI = 1.04-1.62 for 1-59 min/day group and OR = 1.40, 95% CI = 1.10-1.80 for ≥60 min/day group). Participants who had 1-59 min/day of napping were more likely to develop obesity (OR = 1.37, 95% CI = 1.07-1.75), and ≥ 60 min/day of napping was associated with diabetes (OR = 1.33, 95% CI = 1.01-1.74). The interactions between napping and sex were not statistically significant in the models. CONCLUSIONS: The study revealed napping was unfavorably associated with obesity, diabetes, and any conditions in Tibetan people living on the Tibetan Plateau. Future interventions regarding the three chronic diseases may pay more attention to napping. TRIAL REGISTRATION: Not applicable.

Comparative Study of Oral Bacteria and Fungi Microbiota in Tibetan and Chinese Han Living at Different Altitude.

Knowledge about the impact of altitude and ethnicity on human oral microbiota is currently limited. To obtain the baseline of normal salivary microbiota, we analyzed the bacteria and fungi composition in Tibetan (HY group) and Han population (CD group) living at different altitudes by using next-generation sequencing (NGS) technology combined with PICRUSt and FUNGuild analyses. There were significant differences in oral microbiota composition between the two groups at phylum and genus levels. At the phylum level, the HY group had higher relative abundances of Firmicutes and Ascomycota, whereas the Bacteroidetes and Basidiomycota in the CD group were richer. These changes at the phylum level reflected different dominant genus compositions. Compared with the Han population, Candida, Fusarium, Zopfiella, Streptococcus, Veillonella and Rothia in Tibetan were higher. Surprisingly, the Zopfiella was found almost exclusively in the Tibetan. The PICRUSt and FUNGuild analysis also indicated that the function of the bacterial and fungal communities was altered between the two groups. In conclusion, our results suggest that there are significant differences in oral microbial structure and metabolic characteristics and trophic modes among Tibetan and Han population living at different altitudes. We first established the oral microbiota framework and represented a critical step for determining the diversity of oral microbiota in the Tibetan and Han population.

NEAT1 is a potential prognostic biomarker for patients with nasopharyngeal carcinoma.

Nuclear paraspeckle assembly transcript 1 (NEAT1) has been found to be dysregulated and associated with clinical progression in various human cancers. The clinical and prognostic value of NEAT1 in nasopharyngeal carcinoma (NPC) was still controversial. The aim of our study was to provide more sufficient evidence that NEAT1 expression is correlated with overall survival in patients with NPC. NEAT1 expression was detected in NPC tissue samples, and the relationship between NEAT1 expression and clinical parameters, including prognosis, was analyzed. The meta-analysis was performed to further assess the prognostic significance of NEAT1 expression in patients with NPC. In our study, we found that the levels of NEAT1 expression were increased in NPC clinical tissue specimens, and associated with advanced M classification and clinical stages. Moreover, the Kaplan-Meier analysis suggested that the levels of NEAT1 expression were negatively associated with the overall survival of patients with NPC. Furthermore, univariate and multivariate Cox regression analyses showed that NEAT1 high-expression was an independent unfavorable prognostic factor in patients with NPC. Finally, we conducted a meta-analysis including 297 patients with NPC from the three studies, and found the pooled HR (95% confidence interval [CI]) was 1.64 (95% CI: 0.68-3.93) for the random effects model and 2.04 (95% CI: 1.42-2.95) for the fixed effect model. In conclusion, NEAT1 is a potential prognostic biomarker for NPC, but more studies are needed to further verify the prognostic value of NEAT1 in patients with NPC.

Toll-like receptor 4 protects against irradiation-induced hematopoietic injury by promoting granulopoiesis and alleviating marrow adipogenesis.

Irradiation induces severe damage in the hematopoietic system, which leads to bone marrow hyperplasia, pancytopenia, and aggravated tissue formation in bone marrow. Studies have shown that Toll-like receptor 4 (TLR4) has a protective effect against irradiation, but the underlying mechanism remains unclear. In this study, we used a TLR4 knockout (TLR4-/-) mouse irradiation model and found that the white blood cell and platelet counts in the peripheral blood of TLR4-/- mice recovered slowly after irradiation, with bone marrow hyperplasia and increased mortality. Additionally, we found that the proportion of CD11b+Gr1+ granulocytes in the peripheral blood and bone marrow of TLR4-/- mice was lower than that of wild-type mice after irradiation. Further, we found that the expression of NADPH Oxidases (NOXs) in the bone marrow was down-regulated after irradiation of TLR4-/- mice, and administration of the NOXs inhibitor VAS2870 reduced the proportion of CD11b+Gr1+ cells in the bone marrow and peripheral blood of wild-type mice after irradiation. Irradiation induced severe marrow adipocytes accumulation in TLR4-/- mice, TLR4 ligand lipopolysaccharide promoted proliferation and inhibited adipogenic differentiation of mesenchymal stromal cells. In summary, our data suggest that TLR4 promotes myeloid hyperplasia by up-regulating the expression of NOXs after irradiation, prohibits marrow adipogensis and increases the tolerance of mice to irradiation.

Retraction Note to: Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC­1 cell apoptosis via activating the mROS­HtrA2/Omi pathways.

[This retracts the article DOI: 10.1186/s12935-018-0665-1.].

Liver-specific deletion of TSHR inhibits hepatic lipid accumulation in mice.

The effect of thyroid-stimulating hormone receptor (TSHR) on hepatic lipid accumulation in vivo is not fully understood. Further, while TSHR in the thyroid has been studied extensively, whether and how the absence of TSHR in the liver affects systemic energy metabolism has not yet been reported. To examine these effects, we generated hepatic TSHR conditional knockout (LT-KO) mice using Cre/LoxP recombination technology. The liver-specific TSHR-knockout (LT-KO) mice exhibited not only lower hepatic triglyceride and cholesterol contents due to modified synthesis and catabolism of lipids in the liver, but also decreased serum lipids, especially serum LDL-C levels. Abnormalities of TSHR in the thyroid affect whole-body energy balance; however, measurements taken in metabolic chambers showed that the hepatic TSHR conditional deletion had no impact on systemic energy metabolism. Unlike its critical role in maintaining the normal growth and function of the thyroid gland, our results demonstrated that hepatic TSHR is involved in liver lipid metabolism and has little effect on energy metabolism.

Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways.

BACKGROUND: Mitochondrial fragmentation drastically regulates the viability of pancreatic cancer through a poorly understood mechanism. The present study used erlotinib to activate mitochondrial fragmentation and then investigated the downstream events that occurred in response to mitochondrial fragmentation. METHODS: Cell viability and apoptosis were determined via MTT assay, TUNEL staining and ELISA. Mitochondrial fragmentation was measured via an immunofluorescence assay and qPCR. siRNA transfection and pathway blockers were used to perform the loss-of-function assays. RESULTS: The results of our study demonstrated that erlotinib treatment mediated cell apoptosis in the PANC-1 pancreatic cancer cell line via evoking mitochondrial fragmentation. Mechanistically, erlotinib application increased mitochondrial fission and reduced mitochondrial fusion, triggering mitochondrial fragmentation. Subsequently, mitochondrial fragmentation caused the overproduction of mitochondrial ROS (mROS). Interestingly, excessive mROS induced cardiolipin oxidation and mPTP opening, finally facilitating HtrA2/Omi liberation from the mitochondria into the cytoplasm, where HtrA2/Omi activated caspase-9-dependent cell apoptosis. Notably, neutralization of mROS or knockdown of HtrA2/Omi attenuated erlotinib-mediated mitochondrial fragmentation and favored cancer cell survival. CONCLUSIONS: Together, our results identified the mROS-HtrA2/Omi axis as a novel signaling pathway that is activated by mitochondrial fragmentation and that promotes PANC-1 pancreatic cancer cell mitochondrial apoptosis in the presence of erlotinib.

Effects of percutaneous endoscopic gastrostomy on survival of patients in a persistent vegetative state after stroke.

AIMS AND OBJECTIVES: To assess the effect of percutaneous endoscopic gastrostomy on short- and long-term survival of patients in a persistent vegetative state after stroke and determine the relevant prognostic factors. BACKGROUND: Stroke may lead to a persistent vegetative state, and the effect of percutaneous endoscopic gastrostomy on survival of stroke patients in a persistent vegetative state remains unclear. DESIGN: Prospective study. METHODS: A total of 97 stroke patients in a persistent vegetative state hospitalised from January 2009 to December 2011 at the Second Hospital, University of South China, were assessed in this study. Percutaneous endoscopic gastrostomy was performed in 55 patients, and mean follow-up time was 18 months. Survival rate and risk factors were analysed. RESULTS: Median survival in the 55 percutaneous endoscopic gastrostomy-treated patients was 17·6 months, higher compared with 8·2 months obtained for the remaining 42 patients without percutaneous endoscopic gastrostomy treatment. Univariate analyses revealed that age, hospitalisation time, percutaneous endoscopic gastrostomy treatment status, family financial situation, family care, pulmonary infection and nutrition were significantly associated with survival. Multivariate analysis indicated that older age, no gastrostomy, poor family care, pulmonary infection and poor nutritional status were independent risk factors affecting survival. Indeed, percutaneous endoscopic gastrostomy significantly improved the nutritional status and decreased pulmonary infection rate in patients with persistent vegetative state after stroke. Interestingly, median survival time was 20·3 months in patients with no or one independent risk factors of poor prognosis (n = 38), longer compared with 8·7 months found for patients with two or more independent risk factors (n = 59). CONCLUSION: Percutaneous endoscopic gastrostomy significantly improves long-term survival of stroke patients in a persistent vegetative state and is associated with improved nutritional status and decreased pulmonary infection. RELEVANCE TO CLINICAL PRACTICE: Percutaneous endoscopic gastrostomy is a promising option for the management of stroke patients in a persistent vegetative state.

Let-7a inhibits migration, invasion and epithelial-mesenchymal transition by targeting HMGA2 in nasopharyngeal carcinoma.

BACKGROUND: Let-7a has been shown to play important roles in nasopharyngeal carcinoma (NPC) cell proliferation and apoptosis, but little is known about the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis. We aimed to investigate the function and mechanism of let-7a in nasopharyngeal carcinoma metastasis and clarified the regulation of high mobility group A2 (HMGA2) by let-7a. METHODS: The expression levels of let-7a and HMGA2 were examined in NPC clinical specimens using quantitative reverse transcription-PCR (RT-qPCR). HMGA2 was confirmed as a target of let-7a through luciferase reporter assays, RT-qPCR, and Western blotting. Furthermore, the roles of let-7a and HMGA2 in regulating NPC cells biological properties including proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were analyzed with let-7a mimics and si-HMGA2 transfected cells. RESULTS: Our study demonstrated that let-7a was downregulated and inversely associated with the clinical stage, T classification and N classification, and HMGA2 was upregulated and directly associated with the clinical stage and N classification in patients with NPC. Moreover, there was an inverse correlation between let-7a expression and HMGA2 expression in NPC patient. In addition, HMGA2 was negatively regulated at the posttranscriptional level by let-7a via a binding site of HMGA2-3'UTR. In addition, synthetic let-7a mimics suppressed NPC cells migration, invasion and EMT process and knockdown of HMGA2 was consistent with the effects of let-7a in NPC cells. CONCLUSION: Let-7a directly downregulates HMGA2 protein expression, which suppress NPC cell migration, invasion and EMT process. Let-7a could serve as a potential diagnostic marker and therapeutic target for NPC.

High-mobility group A2 overexpression is an unfavorable prognostic biomarker for nasopharyngeal carcinoma patients.

Our previous study showed that knockdown of high-mobility group A2 (HMGA2) could suppress nasopharyngeal carcinoma (NPC) cell migration, invasion, and epithelial-mesenchymal transition (EMT) process, and HMGA2 is a direct functional target of let-7 to regulate NPC cell migration, invasion, and EMT process. However, little is known about the clinical and prognostic significance of HMGA2 protein in NPC patients. The purpose of this study is to identify the clinical and prognostic roles of HMGA2 in NPC patients. We initially analyzed the microarray data and verified mRNA and protein levels of HMGA2 in NPC tissues. Immunohistochemical staining for HMGA2 protein was performed in 116 NPC patients. The associations between HMGA2 protein expression and clinicopathologic features and its prognostic significance were analyzed. In our results, we found mRNA and protein expressions of HMGA2 were upregulated in NPC tissues and cell lines. In 116 NPC tissue samples, we observed that HMGA2 protein overexpression was associated with clinical stage, lymph node metastasis, and distant metastasis. Moreover, NPC patients with high levels of HMGA2 protein expression had shorter overall survival in comparison to patients with low levels of HMGA2 protein. In multivariate analysis, HMGA2 protein overexpression was an unfavorable prognostic factor for NPC patients. In conclusion, HMGA2 is an important biomarker to predicting NPC patient's survival time.

Correlation of serum- and glucocorticoid-regulated kinase 1 expression with ischemia-reperfusion injury after heart transplantation.

IRI of a transplanted heart may result in serious early and late disadvantageous effects such as increased allograft immunogenicity, primary graft dysfunction, and initiation of fibroproliferative cascades that compromise the survival of the recipient. Sgk-1 has recently been linked to cell growth and survival. It has been reported that through a renal transplantation model, Dexa increases Sgk-1 expression and therefore protects from renal IRI. In our current study, we aim to assess the expression of Sgk-1 and its protective effects on cardiomyocyte IRI after heart transplantation. Heart allograft model was performed from Wistar into Lewis, and isograft model was from Lewis into Lewis. Grafts were then harvested at one, six, 12, or 24 h post-transplantation for Sgk-1 expression analyses. In some groups, part donors were treated with Dexa 2 h prior at doses of 0.05, 0.5 and 2 mg/BWkg, respectively. Sgk-1 expression was markedly increased in grafted heart 6-12 h post-transplantation in both the allogenic and isogenic models. Immunostaining experiments confirmed that Sgk-1 was expressed in cardiomyocytes rather than infiltrated immune cells. Furthermore, Dexa treatment significantly increased Sgk-1 expression and the donor cardiomyocyte injury was greatly minimized by Dexa treatment. These results suggest that induction of Sgk-1 might explain some of the beneficial impact of corticosteroids in IRI and hence might have therapeutic implications.