Overexpression of TMEM150A in glioblastoma multiforme patients correlated with dismal prognoses and compromised immune statuses.

Transmembrane proteins have exhibited a significant correlation with glioblastoma multiforme (GBM). The current study elucidates the roles of transmembrane protein 150A (TMEM150A) in GBM. Data on patients with GBM were collected from The Cancer Genome Atlas and Xena databases. The objective was to identify the expression levels of TMEM150A in patients with GBM, and evaluate its diagnostic and prognostic values, accomplished using the receiver operating characteristic and survival analyses. On a cellular level, Cell Counting Kit-8, Wound healing, and Transwell experiments were performed to gauge the impact of TMEM150A on cell growth and migration. The study further investigated the correlation between TMEM150A expression and immune status, along with ribonucleic acid (RNA) modifications in GBM. The findings demonstrated TMEM150A overexpression in the cancerous tissues of patients with GBM, with an area under the curve value of 0.95. TMEM150A overexpression was significantly correlated with poor prognostic indicators. TMEM150A overexpression and isocitrate dehydrogenase (IDH) mutation status were predictive of poor survival time among patients with GBM. In vitro experiments indicated that suppressing TMEM150A expression could inhibit GBM cell proliferation, migration, and invasion. Moreover, TMEM150A overexpression was associated with stromal, immune, and estimate scores, immune cells (such as the T helper (Th) 17 cells, Th2 cells, and regulatory T cells), cell markers, and RNA modifications. Therefore, TMEM150A overexpression might serve as a promising biomarker for predicting poor prognosis in patients with GBM. Inhibiting TMEM150A expression holds the potential for improving the survival time of patients with GBM.

Triptolide injection reduces Alzheimer's disease-like pathology in mice.

Triptolide is an epoxidized diterpene lactone isolated from Tripterygium wilfordii. Studies have shown that triptolide exerts organ-protective effects. However, it remains unknown whether triptolide improves Alzheimer's disease (AD)-like presentations. Thirty healthy 8-week-old male C57BL/6J mice were randomly divided into control (n = 10), model (n = 10), and triptolide (n = 10) groups. Amyloid-ß (Aß)42 was injected bilaterally into the ventricles of mice in the model group. Triptolide was injected intraperitoneally daily after injecting Aß42 (a total of 30 days) in the triptolide group. Learning and memory were tested using the Morris water maze test. The deposition of Aß42 in the hippocampus was detected using immunohistochemical staining. In the hippocampus, three synaptic-associated proteins-gephyrin, collybistin, and GABRA1 -were detected by western blotting. Furthermore, we used ELISA to detect proinflammatory cytokines, including TNF-α and IL-1ß, in the blood and hippocampus. Moreover, superoxide dismutase (SOD), malondialdehyde (MDA), and GSH levels were measured using the corresponding kits. We found that triptolide improved spatial learning and memory in AD-like mice. Additionally, triptolide maintained the expression of gephyrin, collybistin, and GABRA1 and reduced Aß in these mice. Additionally, triptolide reduced the expression of inflammatory cytokines and decreased oxidative damage in AD-like mice. Our study suggests that triptolide attenuates AD-like changes in the mouse brain.

The predictors of necrotizing enterocolitis in newborns with low birth weight: A retrospective analysis.

ABSTRACT: There are needs to investigate the influencing factors of necrotizing enterocolitis (NEC) in low birth weight (LBW) newborns, to provide insights into the clinical management of NEC.This study was a retrospective cohort study. Infants admitted to our hospital from January 1, 2019 to June 30, 2021 were selected. The clinical characteristics of NEC and no-NEC infants were evaluated. Logistic regression analyses were conducted to assess the risk factors of NEC in LBW infants.A total of 192 LBW infants were included, the incidence of NEC in LBW infants was 35.42%. There were significant differences in the congenital heart disease, sepsis, breastfeeding, blood transfusion and probiotics feeding between NEC and no-NEC group (all P < .05), and there were no significant differences in birth weight, gestational age, mother's pregnancy-induced hypertension, premature rupture of fetal membrane, amniotic fluid pollution, fetal asphyxia, neonatal respiratory distress syndrome and mechanical ventilation between NEC and no-NEC group (all P > .05). Congenital heart disease (OR: 2.128, 95% CI: 1.103-3.511), sepsis (OR: 1.630, 95% CI: 1.022-2.549), and blood transfusion (OR: 1.451, 95% CI: 1.014-2.085) were the independent risk factors for NEC in LBW infants, and breastfeeding (OR: 0.494, 95% CI: 0.023-0.928), probiotics feeding (OR: 0.816, 95% CI: 0.782-0.982) were the protective factors for the NEC in LBW infants. The prognosis of NEC infants undergone surgery treatment was better than that of infants undergone conservative treatments (P = .043).The incidence of NEC in LBW is high, which is affected by many factors, and comprehensive interventions targeted on the risk and protective factors should be made to improve the prognosis of LBW infants.

Career choice and influential factors among medical students majoring in psychiatry in China.

BACKGROUND: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. METHOD: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career. RESULTS: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career. CONCLUSION: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

The Long-Noncoding RNA lnc-NONH Enhances the Early Transcription of Prototype Foamy Virus Via Upregulating Expression of miR-34c-5p and Tas Protein.

BACKGROUND: Prototype foamy virus (PFV) is a complex and unique retrovirus with the longest genome among the retroviruses and is used as a vector for gene therapies. The viral Tas protein transactivates the viral long terminal repeat promoter and is required for viral replication. We have utilized RNA sequencing to identify and characterize the long-noncoding RNA NONHSAG000101 (lnc-NONH), which markedly increases in PFV-infected cells. However, little is known about the function of lnc-NONH. OBJECTIVES: We aim to explore the role of lnc-NONH during PFV infection. METHODS: To assess the lnc-NONH role during PFV infection, the siRNAs were used to silence the lnc-NONH expression. The microRNA (miRNA) mimic and inhibitor were employed to explore the function of lnc-NONH-related miRNA miR-34c-5p. Quantitative real-time polymerase chain reaction assay and Western blotting were applied to measure the mRNA and protein levels of PFV transactivator Tas. Luciferase assay was used to determine the transcriptional activity of the PFV unique internal promoter (IP). RESULTS: lnc-NONH promotes the expression of PFV Tas and miR-34c-5p. The interaction between lnc-NONH and miR-34c-5p enhances the transcriptional activity of the PFV IP. CONCLUSIONS: In the current study, we report a novel mechanism for the lnc-NONH-mediated upregulation of Tas expression. Our findings contribute to the understanding of regulatory network of Tas expression and PFV replication.

Guillain-Barré syndrome in southern China: retrospective analysis of hospitalised patients from 14 provinces in the area south of the Huaihe River.

OBJECTIVES: The clinical and epidemiological profiles of Guillain-Barré syndrome (GBS) in southern China have yet to be fully recognised. We aimed to investigate the subtypes of GBS in southern China, compare the clinical features of demyelinating form with that of axonal form and test whether preceding infections and age have influence on the clinical phenotype, disease course and severity of GBS. METHODS: Medical records of patients with a diagnosis of GBS admitted to 31 tertiary hospitals, located in 14 provinces in southern China, from 1 January 2013 to 30 September 2016, were collected and retrospectively reviewed. RESULTS: Finally. 1056 patients, including 887 classic GBS and 169 variants, were enrolled. The 661 classic patients with available electromyographic data were grouped as having acute inflammatory demyelinating polyneuropathy (AIDP, 49.0%), acute motor axonal neuropathy (AMAN, 18.8%), inexcitable (0.9%) and equivocal (31.3%). In contrast to AIDP, patients with AMAN were characterised by earlier nadir (P=0.000), higher Hughes score at nadir (P=0.003) and at discharge (P=0.000). Preceding upper respiratory infections were identified in 369 (34.9%) patients, who were more inclined to develop AIDP (P=0.000) and Miller-Fisher syndrome (P=0.027), whereas gastrointestinal infection were found in 89 (8.4%) patients, who were more prone to develop AMAN (P=0.000), with more severe illness (P=0.001) and longer hospital stay (P=0.009). Children (≤15 years) and the elderly (≥56 years) were more severe at nadir, the elderly had the longest hospital stay (P=0.023). CONCLUSION: AIDP is the predominant form in southern China, which is different from data of northern China. The different subtypes, preceding infection and age of onset can partially determine the disease progression, severity and short-term recovery speed of GBS. CLINICAL TRIAL REGISTRATION: ChiCTR-RRC-17014152.

Cocaine Withdrawal Reduces Gamma-Aminobutyric Acid-Ergic Transmission and Gephyrin Expression at Medial Prefrontal Cortex in Cocaine-Conditioned Place-Preference Rats, Which Shows Increased Cocaine Seeking.

AIMS: Chronic cocaine abuse decreases the inhibitory synaptic transmission via unknown mechanisms, while pharmacologically augmenting gamma-aminobutyric acid-ergic (GABAergic) transmission attenuates cocaine craving. Here, we propose that prolonged cocaine withdrawal downregulates GABAergic transmission and its important regulator gephyrin in medial prefrontal cortex (mPFC), in cocaine-conditioned place-preference (CPP) rats. METHODS: CPP test, patch clamp, and Western blot analysis are engaged to test this proposal. RESULTS: Two-week cocaine withdrawal further increased CPP score, as compared to the 24-hour withdrawn group. The amplitude of GABAergic inhibitory postsynaptic currents (IPSCs) was decreased in 2-week-withdrawn mPFC neurons from cocaine-CPP rats, compared to that of saline-CPP rats. Two-week withdrawal did not alter the amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) in mPFC in cocaine-CPP rats. Two-week withdrawal increased the ratio of EPSCs/IPSCs (E/I) in the same mPFC neuron in cocaine-CPP rats. In addition, Western blots showed 2-week cocaine-withdrawn down-regulated gephyrin at postsynaptic density (PSD) sites of mPFC. CONCLUSION: We found decreased GABAergic IPSCs and downregulated gephyrin in PSD at mPFC in 2-week cocaine-withdrawn rats that showed increased CPP, suggesting that an increased E/I ratio and neuron excitability in mPFC may associate with a cocaine-seeking tendency. Strategies aimed at GABAergic synapses in mPFC may therapeutically benefit to cocaine addiction treatment.

[Effect of pioglitazone on the expression of TLR4 in renal tissue of diabetic rats].

OBJECTIVE: To investigate the effect of pioglitazone on the expression of Toll-like receptor 4 (TLR4) in renal tissue of diabetic rats. METHODS: The male Sprague Dawlry rats (n=57) were randomly divided into the control group (n=9) and experimental group (n=48). The experimental rats were injected introperatoneally with 50 mg/kg streptozotocin (STZ) and the controls were given sodium citrate buffer instead. Then the experimental rats were randomized into five groups: pioglitazone 5 mg/(kg.d), pioglitazone 10 mg/(kg.d), pioglitazone 5 mg/(kg.d) plus TLR4-specific antagonist Eritoran 5 mg/(kg.d), pioglitazone 10 mg/(kg.d) plus TLR4-specific antagonist Eritoran 5 mg/(kg.d), non-intervented group, with 5 rats in each group. The pioglitazone was administrated intragastrically, and normal saline was given to the contro group in the same way. Five weeks after pioglitazone administration, Eritoran was injected intraperitoneally for consecutive one week. At the end of the eighth week, 24-hour microalbuminuria and the serum concentrations of C-reactive protein (CRP) were determined by radioimmunoassay. Expressions of TLR4 and peroxisome proliferator-activated receptor γ (PPARγ) in kidney were determined by Western blotting and immunohistochemistry. RESULTS: Compared with the control group, the 24-hour urine protein, plasma concentration of CRP, the expression of TLR4 in kidney increased significantly in the experimental groups (P<0.05). Furthermore, these indicators in all intervention groups obviously decreased compared with the non-intervention group (P<0.05). In addition, the expression of TLR4 in high-dose pioglitazone significantly decreased compared with low-dose pioglitazone (P<0.05). The study also found that high-dose pioglitazone and TLR4 antagonist Eritoran could reduce the expression of TLR4 in the diabetic rats, but the difference from the group of low-dose pioglitazone plus Eritoran was not significant statistically (P>0.05). CONCLUSION: Pioglitazone may exert the anti-inflammatory action by decreasing the expression of TLR4 in renal tissue and regulating the balance between proinflammatory and anti-inflammatory.

Comparison of neurodegeneration and cognitive impairment in neonatal mice exposed to propofol or isoflurane.

BACKGROUND: While previous studies have demonstrated neuronal apoptosis and associated cognitive impairment after isoflurane or propofol exposure in neonatal rodents, the effects of these two anesthetics have not been directly compared. Here, we compare and contrast the effectiveness of isoflurane and propofol to cause neurodegeneration in the developing brain and associated cognitive dysfunction. METHODS: Seven-day-old mice were used. Mice in the isoflurane treatment group received 6 h of 1.5% isoflurane, while mice in propofol treatment group received one peritoneal injection (150 mg/kg), which produced persistent anesthesia with loss of righting for at least 6 h. Mice in control groups received carrying gas or a peritoneal injection of vehicle (intralipid). At 6 h after anesthetic treatment, a subset of each group was sacrificed and examined for evidence of neurodegeneration, using plasma levels of S100ß, and apoptosis using caspase-3 immunohistochemistry in the cerebral cortex and hippocampus and Western blot assays of the cortex. In addition, biomarkers for inflammation (interleukin-1, interleukin-6, and tumor necrosis factor alpha) were examined with Western blot analyses of the cortex. In another subset of mice, learning and memory were assessed 32 days after the anesthetic exposures using the Morris water maze. RESULTS: Isoflurane significantly increased plasma S100ß levels compared to controls and propofol. Both isoflurane and propofol significantly increased caspase-3 levels in the cortex and hippocampus, though isoflurane was significantly more potent than propofol. However, there were no significant differences in the inflammatory biomarkers in the cortex or in subsequent learning and memory between the experimental groups. CONCLUSION: Both isoflurane and propofol caused significant apoptosis in the mouse developing brain, with isoflurane being more potent. Isoflurane significantly increased levels of the plasma neurodegenerative biomarker, S100ß. However, these neurodegenerative effects of isoflurane and propofol in the developing brain were not associated with effects on inflammation or with cognitive dysfunction in later life.

[Study on Tie2 mRNA level in peripheral blood associated with the severity of sepsis].

OBJECTIVE: To investigate the possibility that the level of Tie2 mRNA in peripheral blood could reflect the severity of sepsis. METHODS: Trauma patients in intensive care unit (ICU) were recruited, and they were divided into sepsis group (n=13) and non-sepsis group (n=19). The severity of disease was evaluated with acute physiology and chronic health evaluation II (APACHEII) score on the day of ICU admission. Blood of patients was sampled on day 1, 3, 7 after ICU admission to determination of the white blood cell (WBC) count, contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr), mRNA levels of Tie2 in blood measured by quantitative real-time polymerase chain reaction (PCR), and the contents of plasma von Willebrand factor (vWF) with enzyme linked immunosorbent assay (ELISA). RESULTS: No significant difference in contents of ALT, AST and plasma vWF was found between sepsis group and non-sepsis group [ALT (U/L): 53.30 (199.58) vs. 80.65 (202.62), AST (U/L): 316.53 (49.90) vs. 66.10 (285.03), vWF: (272.47+/-114.61)% vs. (246.66+/-128.77)%, all P>0.05]. The number of WBC [x10(9)/L, 18.26 (21.82) vs. 10.11 (4.72)], the contents of BUN [mmol/L, 20.70 (11.20) vs. 7.70 (5.45)] and Cr [micromol/L: 252.00 (364.55) vs. 68.00(23.20)], and the circulating mRNA levels of Tie2 (1.86+/-0.67 vs. 0.91+/-0.42) in sepsis group were higher than those in the non-sepsis group (all P<0.01). The Tie2 mRNA level in peripheral blood of each patient was positively correlated with APACHEII score (r=0.532, P<0.01). The linear regression equation was Y=12.66+4.922 X (R2=0.283). Besides, there was a significant correlation between the amount of Tie2 mRNA and plasma levels of vWF (r=0.334, P<0.05). The linear regression equation was Y=180.932+57.93 X (R2=0.112). CONCLUSION: The level of Tie2 mRNA in peripheral blood could reflect the damage of endothelial cell and severity of sepsis.

Protective effect of erythropoietin against ketamine-induced apoptosis in cultured rat cortical neurons: involvement of PI3K/Akt and GSK-3 beta pathway.

Erythropoietin (EPO) prevents neuronal cell death through the activation of cell survival signals and the inhibition of apoptotic signals in models of neurodegenerative diseases. Here we investigated the neuroprotective effect of EPO in ketamine-induced neurotoxicity in primary cortical neurons. EPO in combination with ketamine greatly increased the cell viability and reduced the number of TUNEL-positive cells. To elucidate a possible mechanism by which EPO exerts its neuroprotective effect, we investigated the phosphoinositide3-kinase pathway using LY294002. The neuroprotection of EPO was prevented by LY294002. Immunoblotting revealed that EPO induced the phosphorylation/activation of Akt and phosphorylation/inactivation of glycogen synthase kinase-3beta (GSK-3beta). Moreover, the caspase-3-like activity was increased by addition of ketamine, and decreased by administration of ketamine with EPO. Decreased caspase-3-like activity by administration of ketamine with EPO was restored by LY294002. Our results suggest that PI3K/Akt and GSK-3beta pathway are involved in the neuroprotective effect of EPO.

Protective effect of erythropoietin against 1-methyl-4-phenylpyridinium-induced neurodegenaration in PC12 cells.

OBJECTIVE: The neuroprotective effect of erythropoietin (EPO) against 1-methyl-4-phenylpyridinium (MPP(+))-induced oxidative stress in cultured PC12 cells, as well as the underlying mechanism, were investigated. METHODS: PC12 cells impaired by MPP(+) were used as the cell model of Parkinson's disease. Methyl thiazolyl tetrazolium (MTT) was used to assay the viability of the PC12 cells exposed to gradient concentrations of EPO, and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay was used to analyze the apoptosis ratio of PC12 cells. The expression of Bcl-2 and Bax in PC12 cells were examined by Western blot, and the reactive oxygen species (ROS), the mitochondrial transmembrane potential and the activity of caspase-3 in each group were detected by spectrofluorometer. RESULTS: Treatment of PC12 cells with MPP(+) caused the loss of cell viability, which may be associated with the elevation in apoptotic rate, the formation of ROS and the disruption of mitochondrial transmembrane potential. It was also shown that MPP(+) significantly induced the upregulation of Bax/Bcl-2 ratio and the activation of caspase-3. In contrast, EPO significantly reversed these responses and had the maximum protective effect at 1 U/mL. CONCLUSION: The inhibitive effect of EPO on the MPP(+)-induced cytotoxicity may be ascribed to its anti-oxidative property and anti-apoptotic activity, and EPO may provide a useful therapeutic strategy for treatment of neurodegenerative diseases such as Parkinson's disease.