Structural characterization and anti-inflammatory activities of a purified polysaccharide from fruits remnants of Alpinia zerumbet (Pers.) Burtt. et Smith.

We reported here an interesting source of Alpinia zerumbet Polysaccharides (named AZPs) from the residues after extracting essential oil by steam distillation from Alpinia zerumbet fructus. After a series of purifications, a homogeneous polysaccharide (AZP-2) of molecular weight 1.25 × 105 Da was obtained. Structure, anti-inflammatory activity, and anti-inflammatory mechanism were investigated. AZP-2 was mainly composed of galactose, arabinose, xylopyranose, glucose, and galacturonic acid. The main linkage structure of AZP-2 was determined after integrating the nuclear magnetic resonance (NMR) and methylation analysis, and the structure was comparatively complex. The results indicated that AZP-2 significantly decreased the production of NO and ROS in the inflammatory model established by lipopolysaccharide (LPS) stimulated RAW264.7, particularly at the concentration of 200 µg/mL. Furthermore, AZP-2 significantly modulated the secretion of both pro-inflammatory and anti-inflammatory cytokines. Notably, the mechanism of AZP-2 exhibiting inhibitory effects was related to regulating the NF-κB signaling pathway. Overall, AZP-2 could be used as a potential anti-inflammatory agent for further in-depth studies.

Chemical Composition and Potential Antimicrobial and Anti-Inflammatory Activities of Essential Oil from Fruits of Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm.

Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm. was extensively used in traditional medicine for its several properties, but continuous investigation is needed to discover the properties of its essential oils (EOs). This work evaluated the properties of an EO obtained by steam distillation (named ESD) as well as extracts obtained by petroleum ether (named EP) both from Alpinia zerumbet fruits. Gas chromatography-mass spectrometry (GC-MS) was chosen to identify the composition, and eleven compounds were identified as the main components of the EO and EP of Alpinia zerumbet fruits. The antimicrobial properties were investigated by minimum inhibitory concentration (MIC) and the inhibition area. The results identified the differences in antimicrobial activities attributed to different extraction methods. Enzyme-linked immunosorbent assay (ELISA) and Western Blot (WB) assay were conducted to assess the anti-inflammatory effects of ESD. In conclusion, our study suggested that EO from Alpinia zerumbet fruits might be a prospective candidate for antimicrobial and anti-inflammatory therapy.

Molecular typing and mutational characterization of rectal neuroendocrine neoplasms.

BACKGROUND: Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. METHODS: The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets. RESULTS: C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFß signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000). CONCLUSIONS: This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.

Transarterial Chemoembolization Combined With PD-1 Inhibitors Plus Lenvatinib Showed Improved Efficacy for Treatment of Unresectable Hepatocellular Carcinoma Compared With PD-1 Inhibitors Plus Lenvatinib.

Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

Neural Correlates of Facial Emotion Recognition in Non-help-seeking University Students With Ultra-High Risk for Psychosis.

Background: Since the introduction of the neurodevelopmental perspective of schizophrenia research on individuals at ultra-high risk for psychosis (UHR) has gained increasing interest, aiming at early detection and intervention. Results from fMRI studies investigating behavioral and brain functional changes in UHR during facial emotion recognition, an essential component of social cognition, showed heterogenous results, probably due clinical diversity across these investigations. This fMRI study investigated emotion recognition in a sub-group of the UHR spectrum, namely non-help-seeking, drug-naïve UHR with high cognitive functioning to reveal the neurofunctional underpinnings of their social functioning in comparison to healthy controls. Methods: Two large cohorts of students from an elite University (n 1 = 4,040, n 2 = 4,364) were screened firstly with the Prodromal Questionnaires and by surpassing predefined cut-offs then interviewed with the semi-structured Interview for Psychosis-Risk Syndromes to verify their UHR status. Twenty-one identified non-help-seeking UHR and 23 non-UHR control subjects were scanned with functional magnetic resonance imaging while classifying emotions (i.e., neutral, happy, disgust and fear) in a facial emotion recognition task. Results: Behaviorally, no group differences were found concerning accuracy, reaction times, sensitivity or specificity, except that non-help-seeking UHR showed higher specificity when recognizing neutral facial expressions. In comparison to healthy non-UHR controls, non-help-seeking UHR showed generally higher activation in the superior temporal and left Heschl's gyrus as well as in the somatosensory, insular and midcingulate cortex than the control subjects during the entire recognition task regardless of the emotion categories. In an exploratory analysis, in the non-help-seeking UHR group, functional activity in the left superior temporal gyrus was significantly correlated with deficits in the ability to experience emotions at uncorrected statistical thresholds. Conclusions: Compared to healthy controls, non-help-seeking UHR show no behavioral deficits during facial emotion recognition, but functional hyperactivities in brain regions associated with this cognitive process. Our study may inspire future early intervention and provide loci for treatment using neural stimulation.

Prognosis of hepatocellular carcinoma and its association with immune cells using systemic inflammatory response index.

Aim: To explore the prognostic value of the systemic inflammatory response index (SIRI) and peripheral blood T-cell subsets in patients with hepatocellular carcinoma (HCC) and the relationship between them. Materials & methods: We treated 352 patients with HCC with sorafenib and/or immune checkpoint inhibitors (ICIs) and analyzed SIRI and peripheral blood T cells. Results: SIRI was an independent prognostic factor for patients with HCC receiving systemic therapy. Patients with high SIRI and low baseline peripheral blood T-cell counts showed a poor response to ICIs. SIRI was significantly and negatively correlated with CD3+, CD4+ and CD8+ T-cell counts. Conclusion: SIRI markers can be employed to noninvasively assess the presence of cancer-promoting inflammation in the tumor microenvironment and predict the efficacy of targeted therapy and immunotherapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The change of immune microenvironment plays an important role in the occurrence and development of HCC. Recently, targeted therapy and immunotherapy have brought new hope to patients with advanced HCC. However, owing to the complexity of the immune microenvironment, not all patients can benefit from it. This study explores a simple, non-invasive method based on blood cell count to assess the immune microenvironment of HCC and predict the efficacy of treatment.

Sarcopenia and Systemic Inflammation Response Index Predict Response to Systemic Therapy for Hepatocellular Carcinoma and Are Associated With Immune Cells.

Background: Systemic therapies, including immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have challenged the use of conventional therapies for hepatocellular carcinoma (HCC). It is crucial to determine which patients could benefit most from combination therapy. This study aims to examine the associations of sarcopenia and systemic inflammation response index (SIRI) with the treatment responses and efficacies in patients with HCC treated with ICIs and tyrosine kinase inhibitors TKIs, as well as investigate the correlation between sarcopenia and inflammatory or immune states. Methods: We reviewed 160 patients with HCC treated with TKIs and ICIs. The patients' psoas muscle size was measured on axial computed tomography scans and normalized for the patients' height squared. This value was referred to as the psoas muscle index (PMI). Sarcopenia was determined from PMI and their relationships with patients' clinicopathological characteristics, inflammation indexes, peripheral blood T-cell subsets and survival were evaluated. Results: Sarcopenia and systemic inflammation response index (SIRI) were independent predictors for overall survival and progression-free survival. Patients with high PMI and low SIRI demonstrated significantly better median overall survival and progression-free survival (36.0 months and 9.6 months, respectively) than those with either low PMI or high SIRI (20.8 months and 6.0 months, respectively) and those with both high SIRI and low PMI (18.6 months and 3.0 months, respectively). Portal vein tumor thrombus (P=0.003), eastern cooperative oncology group performance status score of 1 (P=0.048), high alkaline phosphatase (P=0.037), high neutrophil-to-lymphocyte ratio (NLR) (P=0.012), low lymphocyte-to-monocyte ratio (LMR) (P=0.031), high platelet-to-lymphocyte ratio (PLR) (P=0.022) and high SIRI (P=0.012) were closely associated with an increased incidence of sarcopenia. PMI was negatively correlated with SIRI (r = -0.175, P=0.003), NLR (r = -0.169, P=0.036), and PLR (r = -0.328, P=0.000) and was significantly positively correlated with LMR (r = 0.232, P=0.004). The CD3+ and CD4+ T-cell counts of the high PMI group were significantly higher than those of the low PMI group. Conclusion: Sarcopenia and high SIRI were associated with reduced survival in patients with HCC treated with ICIs and TKIs. Sarcopenia could affect inflammatory states and the immune microenvironment.

The mental health of transgender and gender non-conforming people in China: a systematic review.

Transgender and gender non-conforming (TGNC) individuals are at a high risk of adverse mental health outcomes due to minority stress-the stress faced by individuals categorised as stigmatised social minority groups. This systematic review sought to summarise the key mental health findings of the research on TGNC individuals in mainland China. We also aimed to consolidate research on the topic, identify specific mental health disparities, and offer new perspectives for future research to inform both policy and clinical practice. An extensive search of the literature, published in English and Chinese, was done between Jan 1, 1990, and Aug 1, 2021, using PubMed, PsycINFO, Scopus, Wanfang (in Chinese), and CNKI (in Chinese). Overall, two qualitative and 28 quantitative articles were identified. The quantitative findings showed a high prevalence of mental health problems, such as depression, anxiety, substance use disorders, and stress-related issues, and greater disparities in psychological wellbeing. High prevalence is also reported in suicidality and self-harm behaviours in this group. Across the two qualitative studies, attributable factors included gender-related discrimination, barriers to accessing health services, low social support, decreased knowledge and awareness of HIV prevention, and demographic characteristics-such as marital status, educational level, and gender identity. This Review also found little evidence of gender-affirming care and mental health interventions in mainland China. Following from these results, the next step is to integrate multi-level, social-psychological interventions with education to reduce cultural stereotypes and transphobia in mainland China. Political and social implications are also discussed to inform a standard set of guidelines for transgender-inclusive health-care services, including advocating for funding to create these special care programmes and services.

Low Diastolic Blood Pressure Predicts Good Clinical Outcome in Patients With Cerebral Venous Thrombosis.

Background: Cerebral venous thrombosis (CVT) refers to a stroke subtype characterized by the disturbance of cerebral venous outflow caused by venous thrombosis. Previous studies have reported a range of factors that predict the prognosis of CVT. This study is aimed to find out whether systolic blood pressure (SBP) and diastolic blood pressure (DBP) are suitable as potential indicators of the severity and clinical outcome in CVT patients. Methods: The CVT patients admitted to Xuanwu Hospital from January 2014 to December 2019 were enrolled. The severity of CVT was assessed by the National Institute of Health Stroke Scale (NIHSS) and intracranial pressure (ICP) at the time of admission. The modified Rankin score (mRS) was assessed at 6 months of follow-up. Results: One hundred fifty-six CVT patients were enrolled with a mean age of 35.8 ± 12.8 years. A percentage of 55.8% of the CVT patients recruited were female, and 17.3% were either pregnant or in perinatal period. Headache was the most common symptom. SBP and DBP were not correlated with NIHSS at admission. Furthermore, SBP and DBP had no impact on the disturbance of consciousness, epilepsy, intracranial hemorrhage, and mental disorders. However, SBP and DBP were positively correlated with ICP at admission. SBP > 129.5 mmHg and/or DBP > 77.5 mmHg suggested the presence of intracranial hypertension (IH). Based on current results, SBP was not correlated with mRS at 6 months of follow-up. However, DBP was found to be positively correlated with mRS at 6 months of follow-up. DBP in CVT patients with good prognosis was significantly lower than in those with poor prognosis. DBP > 79.5 mmHg was identified as a cutoff value to predict a poor clinical outcome. A higher mRS and a higher rate of poor clinical outcome were found in CVT patients with SBP > 146 mmHg or DBP > 79.5 mmHg compared to those with SBP ≤ 146 mmHg or DBP ≤ 79.5 mmHg. Conclusion: SBP > 129.5 mmHg and DBP > 77.5 mmHg suggested the presence of IH in CVT patients. DBP > 79.5 mmHg predicted a poor clinical outcome.

Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus.

Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic ß-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic ß-cells and subsequent insulin secretion in T2DM.

Metabolomic Profiles of Shift Workers and Day Workers: A Cross-Sectional Study.

OBJECTIVE: The purpose of this study was to characterize the metabolomic profiles of shift workers and day workers and to discover the effect of shift work on workers' metabolic health. METHODS: A total of 824 participants aged 25 to 55 years were recruited, and 485 (275 shift workers and 210 day workers) completed the study. The mean age of the shift workers was 37.32 (5.53) years old, and that of day workers was 36.50 (7.83) years old. Serum and salivary samples were collected for the detection of key biochemical indicators (melatonin, cholesterol, and low-density lipoprotein cholesterol) and for metabolome profile analyses. RESULTS: Compared with female day workers, female shift workers had a higher BMI, waist circumference, and hip circumference. Correspondingly, we identified 76 significant metabolites (false discovery rate < 0.05) in shift workers, including L-tryptophan, acylcarnitines, and several fatty acids. Three pathways that presented significant differences were biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and ubiquinone and other terpenoid-quinone biosynthesis. CONCLUSIONS: Compared with day workers, shift workers were more prone to weight gain and central obesity and were at a higher risk for impaired lipid metabolism with disrupted circadian rhythms.

A Novel Autoantibody Induced by Bacterial Biofilm Conserved Components Aggravates Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple autoantibody production and often affects the kidneys, known as lupus nephritis. However, the mechanism underlying lupus nephritis development is unclear. Biofilms that protect bacteria from stress are ubiquitous in almost every environment. Here, we identified that a conserved peptide (HU1) derived from DNABII proteins, one of major bacterial biofilm components, was specifically recognized by sera from about 47% patients with SLE. Moreover, the serum anti-HU1 levels showed a significant positive correlation with lupus nephritis occurrence. Presence of antibodies against HU1 in pristane-induced mice aggravated lupus nephritis, although these antibodies also attenuated bacterial biofilm formation. We further identified that antibodies against HU1 cross-recognized protein disulfide isomerase (P4HB) located on the renal cell surface and inhibited the activities of this enzyme. Our findings reveal a novel mechanism underlying the development of lupus nephritis triggered by bacterial biofilms.

siRNA-mediated Eppin testicular silencing causes changes in sperm motility and calcium currents in mice.

Epididymal protease inhibitor (EPPIN) is differentially expressed in the reproductive tissues (such as testicles, outlet tubes, epididymis, vas deferens, and seminal vesicles). Its critical role in sperm function and male reproduction has shed light on EPPIN as a candidate target for male contraceptive vaccines. In this study, we endeavored to further reveal the mechanism through which EPPIN exerts its function. We created a mouse model of reduced Eppin expression by microinjecting small interfering RNA targeting Eppin expression into seminiferous tubules of mice. This mouse model was then used to explore the effects of low Eppin expression on sperm function, which was assessed by Computer Assisted Semen Analysis and patch clamp recording of T-type Ca2+ current in spermatogenic cells. We found that the sperm motility significantly declined when Eppin was downregulated. Further investigation demonstrated that Eppin downregulation significantly affected T-type Ca2+ currents and messenger RNA expression of three subtypes of T-type Ca2+ channels in spermatogenic cells. These findings indicate that low Eppin gene expression induces decreased T-type Ca2+ currents and mRNA expression, which in turn results in the reduced sperm motility.

Corrigendum: A Novel Autoantibody Induced by Bacterial Biofilm Conserved Components Aggravates Lupus Nephritis.

[This corrects the article DOI: 10.3389/fimmu.2021.656090.].

Cortical Complexity in People at Ultra-High-Risk for Psychosis Moderated by Childhood Trauma.

Subjects with ultra-high risk (UHR) states for psychosis show brain structural volume changes similar to first-episode psychosis and also elevated incidence of environmental risk factors like childhood trauma. It is unclear, however, whether early neurodevelopmental trajectories are altered in UHR. We screened a total of 12,779 first-year Chinese students to enroll 36 UHR subjects (based on clinical interviews) and 59 non-UHR healthy controls for a case-control study of markers of early neurodevelopment. Subjects underwent 3T MRI scanning and clinical characterization, including the childhood trauma questionnaire (CTQ). We then used the CAT12 toolbox to analyse structural brain scans for cortical surface complexity, a spherical harmonics-based marker of early neurodevelopmental changes. While we did not find statistically significant differences between the groups, a trend level finding for reduced cortical complexity (CC) in UHR vs. non-UHR subjects emerged in the left superior temporal cortex (and adjacent insular and transverse temporal cortices), and this trend level association was significantly moderated by childhood trauma (CTQ score). Our findings indicate that UHR subjects tend to show abnormal cortical surface morphometry, in line with recent research; more importantly, however, this association seems to be considerably modulated by early environmental impacts. Hence, our results provide an indication of environmental or gene × environment interactions on early neurodevelopment leading up to elevated psychosis risk.

The effects of job satisfaction and psychological resilience on job performance among residents of the standardized residency training: a nationwide study in China.

High resident job performance is essential for effective medical professionalism. To date, few studies have investigated the potential predictors of job performance among residents in standardized residency training (SRT) program in China. Therefore, a nationwide survey among Chinese residents in SRT program was conducted to evaluate the impact of job satisfaction and psychological resilience on job performance. A total of 1146 residents from 9 hospitals were recruited in this study. Demographic and work-related information, job satisfaction, psychological resilience and job performance were collected through questionnaires. Hierarchical regression analyses indicated that, "work pressure", "doctor-patient conflict", "intrinsic job satisfaction" and "psychological resilience" were significant predictors of job performance for residents in SRT programs and explained 61.3% of variance, while the three dimensions of psychological resilience (tenacity, strength and optimism) accounted for 27.2% of variance. The area under curve (AUC) of the receiver operating characteristic (ROC) curve showed that resilience had the highest predictive accuracy than another three subscales. This study indicated that intrinsic job satisfaction and psychological resilience had a significant influence on job performance. Strategies and measures to improve residents' intrinsic job satisfaction and psychological resilience may be efficacious ways to enhance their job performance.

[Automatic Robotic Puncture System for Accurate Liver Cancer Ablation Based on Optical Surgical Navigation].

This paper designed an automatic robotic puncture system for accurate liver cancer ablation based on optical surgical navigation. The near-infrared optical surgical navigation system we constructed for liver ablation was applied to carry out surgical planning and simulation, the near-infrared cameras dynamically tracked the current position of puncture needle relative to the location of the patient's anatomy, then guided the surgery robot to position precisely in three-dimensional space and performed the surgery.

Similar Aquaporin9 and MAPK Expression Profiles in the Liver of Types 1 and 2 Diabetes Mellitus.

Aquaporin-9 (AQP9) is an aquaglyceroporin that biophysically conducts water, glycerol, and other small solutes. AQP9 is expressed in hepatocytes on the sinusoidal surfaces of hepatocyte plates in the liver, where it is considered responsible for the glycerol uptake in gluconeogenesis. However, limited information is available on the expression and regulating mechanism of AQP9 in different hyperglycemia models. Thus, this study examined the expression patterns of AQP9 and mitogen-activated protein kinase (MAPK) in Types 1 and 2 diabetes mellitus (DM) to clarify the roles and regulating mechanism of AQP9 in gluconeogenesis. Compared with the control group, the AQP9 expression significantly increased in both Types 1 and 2 DM, and the increased expression was associated with the activation of phosphorylated JNK (p-JNK) and the inhibition of phosphorylated p38 (p-p38). By contrast, phosphorylated ERK remained stable in the liver with Type 1 or 2 DM. These effects could be reversed by insulin treatment. That is, insulin downregulated AQP9 by inhibiting p-JNK and activating p-p38. The upregulation of AQP9 could be involved in gluconeogenesis and co-regulated by the JNK and p38 MAPK pathway in both Types 1 and 2 DM.

General Self-Efficacy Mediates the Effect of Family Socioeconomic Status on Critical Thinking in Chinese Medical Students.

Background: Critical thinking (CT) is an essential competence for medical students. Family socioeconomic status (family SES) and general self-efficacy (GSE) play crucial roles in the development of CT. However, the association among family SES, GSE, and CT in Chinese medical students has yet to be fully investigated. Objectives: To investigate the role of family SES and GSE in the development of CT in Chinese medical students. Methods: 1,338 medical students were recruited using multistage stratified cluster sampling from three institutions in China. The Chinese critical thinking disposition inventory (CTDI-CV), General Self-Efficacy Scale (GSES), and a self-made inventory assessing family SES were administered to collect data. The relationship between CT and family SES as well as GSE was evaluated by structural equation modeling. Results: Students of higher family SES obtained higher CTDI-CV and GSES scores. A positive correlation was found between family SES and CT (r = 0.101-0.141, p < 0.05 or p < 0.01), as well as between family SES and GSE (r = 0.111-0.129, p < 0.01). Moreover, GSE was moderately correlated with CT (r = 0.418, p < 0.01). The model of partial mediate effect of GSE showed the best fit index with X 2 = 29.698, df = 9 and X2/df = 3.300, NFI = 0.990, IFI = 0.993, TLI = 0.984, CFI = 0.993, RMSEA = 0.041. Conclusion: Family SES has a positive albeit limited influence on GSE and CT in Chinese medical students. GSE mediates the effect of family SES on CT and plays a larger role. Enhancing medical student' GSE maybe an efficacious way to improve medical students' CT.

Down-Regulation of AQP4 Expression via p38 MAPK Signaling in Temozolomide-Induced Glioma Cells Growth Inhibition and Invasion Impairment.

Glioma is the most common and lethal central nervous system tumors. Temozolomide (TMZ) is an effective drug for malignant glioma, however, the intracellular and molecular mechanisms behind this anti-cancer effect have yet to be fully understood. The aim of the present study was to determine whether TMZ inhibits proliferation, invasion of glioma cells in vitro and whether these effects can be mediated through modulation of aquaporin 4 (AQP4) and phosphorylation of the MAPK pathway. The viability of U87 and U251 human glioma cells was evaluated using MTT assay. The cell cycle distribution was detected with flow cytometry. Migration ability and invasion ability were tested by scratch assays and transwell assays, respectively. The levels of AQP4 and MAPK were measured using immunoblot analyses. Our results showed that TMZ inhibited proliferation, migration and invasion, and induced G2/M arrest in U87 and U251 glioma cell lines. These changes were associated with a decrease in the levels of AQP4 expression as well as activation phosphorylated level of p38. Treatment with a p38 chemical activator (anisomycin) resulted in similar effects as TMZ treatment on glioma cells. And p38 chemical inhibitor (SB203580) could block these effects in glioma treated with TMZ, suggesting a direct up-regulation of the p38 signaling pathway. Therefore, we identified that TMZ might have therapeutic potential for controlling proliferation, invasion of malignant glioma by inhibiting AQP4 expression through activation of p38 signal transduction pathway. J. Cell. Biochem. 118: 4905-4913, 2017. © 2017 Wiley Periodicals, Inc.