The zinc finger protein Miz1 suppresses liver tumorigenesis by restricting hepatocyte-driven macrophage activation and inflammation.

Chronic inflammation plays a central role in hepatocellular carcinoma (HCC), but the contribution of hepatocytes to tumor-associated inflammation is not clear. Here, we report that the zinc finger transcription factor Miz1 restricted hepatocyte-driven inflammation to suppress HCC, independently of its transcriptional activity. Miz1 was downregulated in HCC mouse models and a substantial fraction of HCC patients. Hepatocyte-specific Miz1 deletion in mice generated a distinct sub-group of hepatocytes that produced pro-inflammatory cytokines and chemokines, which skewed the polarization of the tumor-infiltrating macrophages toward pro-inflammatory phenotypes to promote HCC. Mechanistically, Miz1 sequestrated the oncoprotein metadherin (MTDH), preventing MTDH from promoting transcription factor nuclear factor κB (NF-κB) activation. A distinct sub-group of pro-inflammatory cytokine-producing hepatocytes was also seen in a subset of HCC patients. In addition, Miz1 expression inversely correated with disease recurrence and poor prognosis in HCC patients. Our findings identify Miz1 as a tumor suppressor that prevents hepatocytes from driving inflammation in HCC.

Cervical Epidural Electrical Stimulation Increases Respiratory Activity through Somatostatin-Expressing Neurons in the Dorsal Cervical Spinal Cord in Rats.

We tested the hypothesis that dorsal cervical epidural electrical stimulation (CEES) increases respiratory activity in male and female anesthetized rats. Respiratory frequency and minute ventilation were significantly increased when CEES was applied dorsally to the C2-C6 region of the cervical spinal cord. By injecting pseudorabies virus into the diaphragm and using c-Fos activity to identify neurons activated during CEES, we found neurons in the dorsal horn of the cervical spinal cord in which c-Fos and pseudorabies were co-localized, and these neurons expressed somatostatin (SST). Using dual viral infection to express the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD), hM4D(Gi), selectively in SST-positive cells, we inhibited SST-expressing neurons by administering Clozapine N-oxide (CNO). During CNO-mediated inhibition of SST-expressing cervical spinal neurons, the respiratory excitation elicited by CEES was diminished. Thus, dorsal cervical epidural stimulation activated SST-expressing neurons in the cervical spinal cord, likely interneurons, that communicated with the respiratory pattern generating network to effect changes in ventilation.SIGNIFICANCE STATEMENT A network of pontomedullary neurons within the brainstem generates respiratory behaviors that are susceptible to modulation by a variety of inputs; spinal sensory and motor circuits modulate and adapt this output to meet the demands placed on the respiratory system. We explored dorsal cervical epidural electrical stimulation (CEES) excitation of spinal circuits to increase ventilation in rats. We identified dorsal somatostatin (SST)-expressing neurons in the cervical spinal cord that were activated (c-Fos-positive) by CEES. CEES no longer stimulated ventilation during inhibition of SST-expressing spinal neuronal activity, thereby demonstrating that spinal SST neurons participate in the activation of respiratory circuits affected by CEES. This work establishes a mechanistic foundation to repurpose a clinically accessible neuromodulatory therapy to activate respiratory circuits and stimulate ventilation.

Impact of COVID-19-Induced Academic Stress on Insomnia and Suicidal Ideation among Taiwanese Health Trainees and Junior Doctors.

BACKGROUND Clinical training for allied health trainees (AHTs) and postgraduate-year (PGY) doctors needed to go online during the outbreak of coronavirus disease 2019 (COVID-19), which may have caused academic stress and consequent outcomes among this cohort. MATERIAL AND METHODS To evaluate academic-related stress, clinical confidence, psychological distress, and insomnia, an online survey-based study was conducted among Taiwanese AHTs and PGY doctors between July and December, 2022, during the COVID-19 pandemic. The survey included the 21-item Depression, Anxiety, and Stress Scale (DASS-21), the Insomnia Severity Index (ISI), and self-designed questions. It was distributed using convenience sampling and snowball sampling and was completed by 522 participants. RESULTS Structural equational modelling showed that academic stress was negatively associated with clinical confidence (standardized coefficient [ß]=-0.382, p<0.001). Clinical confidence was negatively associated with psychological distress (ß=-0.397, p<0.001), which was associated with insomnia (ß=0.648, p<0.001). Additionally, clinical confidence and psychological distress were the significant mediators. Results indicated that higher academic stress was associated with higher level of insomnia via the mediation of clinical confidence and psychological distress. CONCLUSIONS Academic stress related to changes in clinical training may have led to insomnia among AHTs and PGY doctors during the pandemic. Factors to reduce academic stress should be investigated to promote good mental health while providing sufficient clinical training, especially during events that can cause increased stress (eg, epidemics, pandemics).

Immunogenic Cell Death-related Signature Evaluates the Tumor Microenvironment and Predicts the Prognosis in Diffuse Large B-Cell Lymphoma.

Current literatures suggest a growing body of evidence highlighting the pivotal role of Immunogenic Cell Death (ICD) in multiple tumor types. Nevertheless, the potential and mechanisms of ICD in diffuse large B-cell lymphoma (DLBCL) remain inadequately studied. To address this gap, our current study aims to examine the impact of ICD on DLBCL and identify a corresponding gene signature in DLBC. Using the expression profiles of ICD-associated genes, the gene expression omnibus (GEO) samples were segregated into ICD-high and ICD-low subtypes utilizing non-negative matrix factorization clustering. Next, univariate and LASSO Cox regression analyses were employed to establish the ICD-related gene signature. Subsequently, the CIBERSORT tool, ssGSEA, and ESTIMATE algorithm were utilized to examine the association between the signature and tumor immune microenvironment of DLBC. Finally, the oncoPredict algorithm was implemented to evaluate the drug sensitivity prediction of DLBCL patients. These findings suggest that the immune microenvironment of the ICD-high group with a poor prognosis was significantly suppressed. An 8-gene ICD-related signature was identified and validated to prognosticate and evaluate the tumor immune microenvironment in DLBCL. Similarly, the high-risk group exhibited a worse prognosis compared to the low-risk group, and the immune function was considerably suppressed. Moreover, the results of oncoPredict algorithm indicated that patients in the high-risk group exhibited higher sensitivity to Cisplatin, Cytarabine, Epirubicin, Oxaliplatin, and Vincristine with low IC50. In conclusion, the present study provides novel insights into the role of ICD in DLBCL by identifying a new biomarker for the disease and may have implications for the development of immune-targeted therapies for the tumor.

ACAT1-mediated METTL3 acetylation inhibits cell migration and invasion in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive disease with poor prognosis. Acetylation modifications affect a great number of biological processes of malignant tumors. The current study aims at revealing the role of acetylation-related mechanism in TNBC progression. Methyltransferase like-3 (METTL3) was found to be downregulated in TNBC cells via quantitative polymerase chain reaction (qPCR) and western blot analyses. Co-Immunoprecipitation (Co-IP) and GST pulldown assays revealed the interaction between acetyl-CoA acetyltransferase 1 (ACAT1) and METTL3. Through further immunoprecipitation (IP) assay, we determined that ACAT1 stabilizes METTL3 protein via inhibiting the degradation of ubiquitin-proteasome. Functionally, ACAT1 inhibits TNBC cell migration and invasion. Moreover, nuclear receptor subfamily 2 group F member 6 (NR2F6) regulates ACAT1 expression at transcriptional level. Finally, we demonstrated that NR2F6/ACAT/METTL3 axis suppresses the migration and invasion of TNBC cells via METTL3. In conclusion, NR2F6 transcriptionally activates ACAT1 and promotes the suppressive effects of ACAT1-mediated METTL3 acetylation on TNBC cell migration and invasion.

Epidural electrical stimulation of the cervical spinal cord opposes opioid-induced respiratory depression.

Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90 s at 5 or 30 Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30 Hz EES at C4 and 5 Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5 Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30 Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30 Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.

Evaluation of two weight stigma scales in Malaysian university students: weight self-stigma questionnaire and perceived weight stigma scale.

BACKGROUND: This study aimed to examine the psychometric properties of the Weight Self-Stigma Questionnaire (WSSQ) and Perceived Weight Stigma Scale (PWS) among Malaysian university students. METHODS: University students who were studying in a Malaysia university with a mean age of 24.0 years (n = 380; females 71.6%) were recruited through convenience sampling between 19 August and 30 September 2021. They completed a Google Form consisting of information on sociodemographic background, weight stigma, psychological distress and self-reported body weight and height. Psychometric testing was conducted using the classical test theory (including confirmatory factor analysis) and Rasch models to confirm the two-factor structure of WSSQ and the unidimensional structure of the PWS using the various fit indices. Concurrent validity of the total scores of WSSQ and PWS with psychological distress and body mass index (BMI) was also investigated. Internal consistency using Cronbach's alpha was conducted. RESULTS: The confirmatory factor analyses and Rasch analyses verified the two-factor structure for the WSSQ and the single-factor structure for the PWS. Both the WSSQ and PWS showed good internal consistency and good concurrent validity as demonstrated by their significant correlations with psychological distress and BMI. CONCLUSION: The WSSQ and PWS have strong validity and reliability, and they can both be used to assess weight stigma among Malaysian university students. LEVEL OF EVIDENCE: V: Descriptive study.

Health literacy and cancer screening behaviors among community-dwelling female adults in Taiwan.

This study was designed to explore the association among health literacy and cancer screening behaviors in Taiwanese females. A total of 353 community-dwelling females were recruited in this cross-sectional study from February to October 2015. Demographic, socioeconomic and personal behavior variables including physical activity, community activity, smoking, alcohol consumption, and betel nut chewing were recorded. Health literacy was evaluated using the Mandarin version of the European Health Literacy Survey Questionnaire. Data on screening behaviors for cervical, breast and colorectal cancers were confirmed by the Taiwanese National eHealth Database. Most respondents with inadequate or problematic general health literacy had no or irregular screening behaviors for cervical, breast and colorectal cancers. In multivariable regression analysis, women with inadequate health literacy were at a greater risk (Odds ratio = 5.71; 95% CI: 1.40-23.26) of having no previous Pap smear screening or >3 years screening interval regardless of education level. However, this association was not detected for breast or colorectal cancer. Women with inadequate health literacy were more likely to have irregular cervical cancer screening, however no associations among health literacy and breast or colorectal cancer were detected. The impact of health literacy on cancer screening behavior warrants further attention and research.

Long-term Outcomes of Primary Endoscopic Resection vs Surgery for T1 Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: There is controversy over the best therapeutic approach for T1 colorectal cancer. We performed a systematic review and meta-analysis of long-term outcomes of endoscopic resection (ER) vs those of primary or additional surgery. METHODS: We performed a systematic review of the PubMed, Embase, and Cochrane databases through October 2019 for studies that reported outcomes (overall survival, disease-specific survival, recurrence-free survival at 5 years, recurrence, and metastasis) of ER vs surgery in patients with colorectal neoplasms. Hazard ratios (HR) were calculated based on time to events. RESULTS: In total, 17 published studies with 19,979 patients were included. The median follow-up time among the studies was 36 months. The meta-analysis found no significant differences between primary ER and primary surgery in overall survival (79.6% vs 82.1%, HR, 1.10; 95% CI, 0.84-1.45), recurrence-free survival (96.0% vs 96.7%, HR, 1.28; 95% CI, 0.87-1.88), or disease-specific survival (94.8% vs 96.5%; HR, 1.09; 95% CI, 0.67-1.78). Additional surgery and primary surgery did not produce significant differences in recurrence-free survival (HR, 1.27; 95% CI, 0.85-1.89). A significantly lower proportion of patients who underwent primary ER had procedure-related adverse events (2.3%) than patients who underwent primary surgery (10.9%) (P < .001). Lymphovascular invasion and rectal cancer, but not depth of submucosal invasion, were independently associated with recurrence for all T1 colorectal cancers. CONCLUSIONS: In a systematic review and meta-analysis, we found that ER should be considered as the first-line treatment for endoscopically resectable T1 colorectal cancers. In cases of noncurative resection, additional surgery can have comparable outcomes to primary surgery.

Factors associated with low health literacy among community-dwelling women in Taiwan.

The present study investigated factors associated with health literacy in community-dwelling Taiwanese women, particularly focusing on those associated with prevalent unhealthy behaviors. This cross-sectional study recruited 353 community-dwelling women aged 39-89 years from February to October 2015 in urban, suburban, and rural areas. Variables investigated included physical activity, community activity, tobacco usage, alcohol consumption, and betel-nut chewing. Degree of health literacy was evaluated using the Chinese-language version of the European Health Literacy Survey Questionnaire. Most respondents had inadequate (17.6%), or problematic (49.3%), general health literacy. Multiple logistic regression analyses showed that low educational attainment was closely associated with inadequate or problematic general health literacy. Women who did not engage in regular physical activity or direct community activity were more likely to have inadequate and problematic general health literacy, respectively. Selected unhealthy behaviors (tobacco usage, alcohol consumption, betel-nut chewing) were not associated with health literacy. Low health literacy was prevalent among participants. Lower educational attainment and a lack of physical or community activity were associated with low health literacy. Health literacy should be considered during the process of delivering health information, and health education programs must enhance health literacy tailored to address individuals' lifestyles.

The benefit of adding oral simethicone in bowel preparation regimen for the detection of colon adenoma: A systematic review and meta-analysis.

BACKGROUND AND AIM: Simethicone is an anti-foaming agent commonly used during colonoscopy. Although several randomized trials have shown that oral simethicone in the bowel preparation regimen may improve bowel cleanness, whether it improves adenoma detection rate (ADR) or polyp detection rate remains undetermined. The aim of this study was to determine if oral simethicone in bowel preparation regimen before colonoscopy improves the ADR. METHODS: A comprehensive literature review was conducted using PubMed, SDOL, Cochrane Library, and ProQuest databases through December 2017. Randomized controlled trials that compared bowel preparation regimens with simethicone versus those without it were included. Effect estimates from each study were extracted and underwent meta-analysis using appropriate models. The primary outcomes were ADR and polyp detection rate, and secondary outcomes included bowel preparation, bubble score, and withdrawal time. RESULTS: Twelve published randomized controlled studies with 6003 participants were included for meta-analysis. There was no difference in the overall ADR (pooled risk ratio = 1.06, 95% confidence interval = 0.91-1.24) and right-side ADR (risk ratio = 1.50, 95% confidence interval = 0.82-2.75) between the groups with or without simethicone. However, the addition of simethicone improved adenoma detected per patient (2.20 ± 1.36 vs 1.63 ± 0.89) according to one of the included studies. Meta-regression revealed that the baseline ADR < 25% of the included studies was associated with significant benefit of oral simethicone; the number needed to treat was 15. CONCLUSIONS: The adjunction of oral simethicone significantly improved bowel preparation quality and might benefit adenoma detection in specific settings with low baseline ADR.

Prognostic Value of Phosphotyrosine Phosphatases in Hepatocellular Carcinoma.

BACKGROUND/AIMS: During the occurrence and progression of hepatocellular carcinoma (HCC), phosphotyrosine phosphatases (PTPs) are usually described as tumor suppressors or proto-oncogenes, and to some degree are correlated with the prognosis of HCC. METHODS: A total of 321 patients from the Cancer Genome Atlas (TCGA) database and 180 patients from our validated cohort with hepatocellular carcinoma were recruited in this study. Kaplan-Meier, univariate and multivariate Cox proportional hazards model were used to evaluate the risk factors for survival. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were applied to detect the expression levels of PTP genes. RESULTS: After screening the data of TCGA, we identified five PTPs as HCC overall survival related PTP genes, among which only three (PTPN12, PTPRN, PTPN18) exhibited differential expression levels in our 180 paired HCC and adjacent tissues (P< 0.001). Further analysis revealed that expression of PTPN18 was positively, but PTPRN was negatively associated with prognosis of HCC both in TCGA cohort and our own cohort. As to PTPN12, results turned out to be opposite according to HBV status. In detail, higher expression of PTPN12 was associated with better outcome in HBV group but worse prognosis in Non-HBV group. CONCLUSION: Our results suggested that PTPN12, PTPRN and PTPN18 were independent prognostic factors in HCC.

Is traumatic brain injury a risk factor for neurodegeneration? A meta-analysis of population-based studies.

BACKGROUND: To determine the association of prior traumatic brain injury (TBI) with subsequent diagnosis of neurodegeneration disease. METHODS: All studies from 1980 to 2016 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, Embase, study references, and review articles. The data and study design were assessed by 2 investigators independently. A meta-analysis was performed by RevMan 5.3. RESULTS: There were 18 studies comprising 3,263,207 patients. Meta-analysis revealed a significant association of prior TBI with subsequent dementia. The pooled odds ratio (OR) for TBI on development of dementia, FTD and TDP-43 associated disease were 1.93 (95% CI 1.47-2.55, p < 0.001), 4.44 (95% CI 3.86-5.10, p < 0.001), and 2.97 (95% CI 1.35-6.53, p < 0.001). However, analyses of individual diagnoses found no evidence that the risk of Alzheimer's disease, and Parkinson's disease in individuals with previous TBI compared to those without TBI. CONCLUSIONS: History of TBI is not associated with the development of subsequent neurodegeneration disease. Care must be taken in extrapolating from these results because no suitable criteria define post TBI neurodegenerative processes. Therefore, further research in this area is needed to confirm these questions and uncover the link between TBI and neurodegeneration disease.

Alpha1-ACT Functions as a Tumour Suppressor in Hepatocellular Carcinoma by Inhibiting the PI3K/AKT/mTOR Signalling Pathway via Activation of PTEN.

BACKGROUND & AIMS: To investigate the expression and prognostic value of α1-ACT (Alpha1-antichymotrypsin) in patients with HCC (hepatocellular carcinoma) and identify the mechanism by which α1-ACT inhibits proliferation and promotes apoptosis of HCC. METHODS: We first measured α1-ACT expression levels and determined their relationship with the clinicopathological characteristics and prognosis of patients with HCC.We then established stable HCC cell lines with both α1-ACT overexpression and knockdown and performed a functional analysis in vitro.We first examined the relationship between α1-ACT and the PTEN/PI3K/AKT/mTOR pathway using Western blotting. Then, we determined whether α1-ACT can directly bind to PTEN using co-immunoprecipitation. Finally, we measured α1-ACT expression to evaluate its correlation with the PI3K/AKT/mTOR pathway-related apoptosis proteins in a xenograft tumour mouse model using immunohistochemistry. RESULTS: The α1-ACT expression level was significantly lower in the HCC tissues than in the paratumour tissues and was negatively positively correlated with the level of Ki67, AFP, the AJCC stage, tumour size and tumour invasion. The overexpression of α1-ACT can inhibit cell proliferation and increase cell apoptosis by activating PI3K/AKT/mTOR-mediated apoptosis via binding to PTEN and activating it in vitro. Additionally, the overexpression of α1-ACT can also increase the proportion of cells in the G0/G1 stage by increasing cyclin p21 expression and inhibiting the migration and invasion abilities of HCC cells by regulating MMP2 and MMP9. The xenotransplantation studies with nude mice also showed that overexpression of α1-ACT inhibited tumourigenesis and knockdown of α1-ACT had the opposite effect. CONCLUSIONS: Our study demonstrates that α1-ACT suppresses liver cancer development and metastasis via targeting the PTEN/PI3K/AKT/mTOR signalling pathway, which may be a potential target for therapeutic intervention in HCC.

Down-Regulation of LncRNA DGCR5 Correlates with Poor Prognosis in Hepatocellular Carcinoma.

BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) have been reported to play pivotal roles in multiple tumors and can act as tumor biomarkers. In this study, we explored the association of the expression of an lncRNA, DGCR5 with clinicopathological features and prognosis in HCC. METHODS: Expression levels of DGCR5 were detected by quantitative real-time PCR (qRT-PCR) and the clinical data was obtained, including basic information, data of clinicopathology and cancer specific survival rate. Receiver operating characteristic (ROC) curve, Kaplan-Meier methods and multivariable Cox regression models were used to analyze predictive efficiency, long-term survival outcomes and risk factors. RESULTS: DGCR5 was found down-regulated in HCC tissues (P<0.001) and serum (P = 0.0035) and low expression of DGCR5 was correlated with a poor cancer specific survival (CSS) (P = 0.0019), as the overall 5-year CSS rates were 10.3% (low expression group) and 36.6% (high expression group), respectively. A stratified analysis demonstrated that low DGCR5 expression was an independent negative prognostic factor for HCC. In addition, the area under the ROC curve was 0.782 with a sensitivity of 0.633 and a specificity of 0.833. CONCLUSIONS: Our results suggest that DGCR5 may be a participator in HCC and can serve as potential biomarker for the diagnosis and prognosis in HCC.

Vegetarian Diets and Weight Reduction: a Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Vegetarian diets may promote weight loss, but evidence remains inconclusive. METHODS: PubMed, EMBASE and UpToDate databases were searched through September 22, 2014, and investigators extracted data regarding study characteristics and assessed study quality among selected randomized clinical trials. Population size, demographic (i.e., gender and age) and anthropometric (i.e., body mass index) characteristics, types of interventions, follow-up periods, and trial quality (Jadad score) were recorded. The net changes in body weight of subjects were analyzed and pooled after assessing heterogeneity with a random effects model. Subgroup analysis was performed based on type of vegetarian diet, type of energy restriction, study population, and follow-up period. RESULTS: Twelve randomized controlled trials were included, involving a total of 1151 subjects who received the intervention over a median duration of 18 weeks. Overall, individuals assigned to the vegetarian diet groups lost significantly more weight than those assigned to the non-vegetarian diet groups (weighted mean difference, -2.02 kg; 95 % confidence interval [CI]: -2.80 to -1.23). Subgroup analysis detected significant weight reduction in subjects consuming a vegan diet (-2.52 kg; 95 % CI: -3.02 to -1.98) and, to a lesser extent, in those given lacto-ovo-vegetarian diets (-1.48 kg; 95 % CI: -3.43 to 0.47). Studies on subjects consuming vegetarian diets with energy restriction (ER) revealed a significantly greater weight reduction (-2.21 kg; 95 % CI: -3.31 to -1.12) than those without ER (-1.66 kg; 95 % CI: -2.85 to -0.48). The weight loss for subjects with follow-up of <1 year was greater (-2.05 kg; 95 % CI: -2.85 to -1.25) than those with follow-up of ≥1 year (-1.13 kg; 95 % CI: -2.04 to -0.21). CONCLUSIONS: Vegetarian diets appeared to have significant benefits on weight reduction compared to non-vegetarian diets. Further long-term trials are needed to investigate the effects of vegetarian diets on body weight control.

SIP30 is required for neuropathic pain-evoked aversion in rats.

SIP30 (SNAP25 interacting protein of 30) is a SNAP25 interaction protein of 30 kDa that functions in neurotransmitter release. Using a chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord and brain and identified sip30, which was upregulated after CCI. Here, we show that CCI induced a bilateral increase of SIP30 in the rostral anterior cingulate cortex (rACC), a key brain region that has been implicated in pain affect. We put rats in a chamber with one half painted white (light area) and the other half painted black (dark area), and measured neuropathic pain-evoked place escape/avoidance paradigm (PEAP) to quantify the level of negative emotion evoked by painful stimuli using a Von Frey hair. Inhibition of CCI-mediated induction of SIP30 by intra-rACC injection of shRNA targeting the rat sip30 gene reduced PEAP. Interestingly, knockdown of SIP30 did not affect CCI-induced evoked pain such as heat hyperalgesia and mechanical allodynia. Neither did it affect general learning and memory. CCI-induced upregulation of SIP30 was correlated with activation of ERK, PKA, and CREB in the rACC. Intra-rACC administration of PKA or ERK inhibitors suppressed CCI-induced SIP30 upregulation and blocked the induction of PEAP. Additionally, knockdown of SIP30 suppressed the frequency of mEPSCs and increased paired-pulse ratios in rACC slices and decreased extracellular glutamate concentrations. Together, our results highlight SIP30 as a target of PKA and ERK in the rACC to mediate neuropathic pain-evoked negative emotion via modulation of glutamate release and excitatory synaptic transmission.

Potential role of miR-100 in cancer diagnosis, prognosis, and therapy.

MicroRNAs (miRNAs) are small non-coding RNAs that function by base pairing with messenger RNAs, thereby regulating protein expression. Functional studies indicate that miRNAs are involved in the regulation of almost every biological pathway. Moreover, changes in miRNA expression are associated with several human pathologies, including cancer. Dysregulation and aberrant expression of microRNA-100 (miR-100) have been reported to be involved in tumorigenesis and tumor progression of several cancer types, suggesting that miR-100 might serve as a diagnostic and/or prognostic marker for human malignancy. In this review, we summarize the potential application of miR-100 in cancer treatment and as a new molecular marker for cancer prognosis and diagnosis. We will provide a brief introduction to miR-100 and discuss its role as a non-invasive biomarker and a potential therapeutic target in human cancers.

The effect of intergenerational support from children on loneliness among older adults-the moderating effect of internet usage and intergenerational distance.

Objective: Loneliness is a key social and public health issue, mainly affecting the mental health of older adults. The article aimed to explore the influence of intergenerational support from children on loneliness among older adults. Meanwhile, the article also analyzed the moderating effects of internet usage and intergenerational distance in this process. Methods: Based on the data received from 2018 China Longitudinal Aging Social Survey (CLASS), the ordinary least square (OLS) regression model was used to analyze the influence of intergenerational support from children on loneliness among older adults. Furthermore, the Bootstrap method was used to test the moderating effect of internet usage and intergenerational distance on the relationship between intergenerational support from children on loneliness among older adults. Results: Baseline regression showed that economic support (ß = -0.059, p < 0.001), caregiving support (ß = -0.070, p < 0.001), and emotional support (ß = -0.108, p < 0.001) from children can positively influence loneliness among older adults. Meanwhile, the results of the moderated effects analysis showed that internet usage and intergenerational distance moderates the relationship between caregiving support, emotional support from children and loneliness among older adults. Conclusion: The article demonstrates that family support, particularly intergenerational support from children plays a pivotal role in alleviating loneliness among older adults, so the government should further regulate the behavior of children's alimony support, improve the digital infrastructure, these measures help to reduce loneliness among older adults and expand the depth and breadth of family care of older adults.