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Yu-Pei Wang,1,* Hui-Xia Wei,2,* Yuan-Yuan Hu,3 Yu-Ming Niu3,4 1Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, People’s Republic of China; 2Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, People’s Republic of China; 3Department of Stomatology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, People’s Republic of China; 4Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Ming Niu, Department of Stomatology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, People’s Republic of China, Tel: +86 13581370999, Email niuyuming@yeah.netObjective: This study was conducted to investigate the bidirectional causal relationship between obstructive sleep apnea (OSA) and temporomandibular disorders (TMD).Methods: Using an online pooled dataset of genome-wide association studies (GWAS), a two-sample bi-directional Mendelian randomization (MR) method was implemented. Inverse variance weighting was used as the primary analyses approach, and other methods of MR Egger, weighted median method, MR-Egger, Simple mode, and Weighted mode analysis were conducted as supplements to evaluate the causal relationship between OSA and TMD with odds ratios (OR) and 95% confidence interval (CI). Furthermore, the Cochran Q, MR-Egger, and MR-PRESSO approaches were used to perform the heterogeneity test and multiple validity.Results: The general results of the forward MR analysis indicated that OSA had a significant causal influence on TMD (OR=1.241, 95% CI: 1.009– 1.526, P=0.041), but no significant correlation was observed in the reverse MR analysis (IVW: OR=0.975, 95% CI=0.918– 1.036, P=0.411).Conclusion: In summary, our research demonstrated a hereditary causative relationship between OSA and TMD, indicating that appropriate intervention is required for both prevention and treatment of TMD.Keywords: Mendelian randomization analysis, obstructive sleep apnea, temporomandibular disorders

Yue-Long Xu,1 Yuan-Yuan Hu,2 Ji-Wei Li,1 Lan Zhou,3 Li Li,1 Yu-Ming Niu21Department of Neurology, Linyi Central Hospital, Linyi 276400, Shandong Province, People’s Republic of China; 2Department of Stomatology and Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, People’s Republic of China; 3Department of Neurology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, People’s Republic of ChinaIntroduction: Recently, molecular epidemiological studies have suggested that aldehyde dehydrogenase 2 (ALDH2) rs671 G>A polymorphism may be a risk factor for ischemic stroke (IS). However, the results reported have not been consistent.Methods: We conducted the meta-analysis to explore the precise association between ALDH2 rs671 G>A polymorphism and IS risk. Five online databases were searched and the relative studies were reviewed from inception to October 1, 2018. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated in each genetic model of the general and subgroup. Furthermore, the heterogeneity, accumulative analyses, sensitivity analyses and publication bias were calculated simultaneously.Results: Overall, nine case-control studies involving 6,129 subjects were included in this meta-analysis. All studies were focused on the Chinese population and some significant associations were found between ALDH2 rs671 G>A polymorphism and IS risk (A vs G: OR=1.29, 95% CI=1.01–1.65, P=0.04, I2=78.2%; AA vs GG: OR=1.86, 95% CI=1.27–2.21, PA polymorphism may play an important role in the occurrence of IS by reducing the activity of ALDH2 and interfering with the metabolic processes involving acetaldehyde.Keywords: aldehyde dehydrogenase 2, rs671, ischemic stroke, polymorphism, meta-analysis

Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced ( P< 0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella ( P< 0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice ( P< 0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley‐VCH GmbH.)

Objective: To investigate the effects of RNA m6A demethylase ALKBH5 gene deficiency on cerebellar morphology and function in the aged mice, and to explore the role of ALKBH5 in cerebellar degeneration. Methods: Western blot was performed to detect the protein level of ALKBH5 in the cerebellum of wild-type mice of various ages. The expression of NeuN, Calbindin-D28K, MAP2, GFAP and other proteins in the cerebella of middle-aged (12-month-old) and aged (18-month-old) wild-type mice and ALKBH5 -/- mice was examined using immunohistochemistry. The balance beam test and gait analysis were performed to test the balance ability and motor coordination of the mice. Results: With aging of the mice, the expression of ALKBH5 in the cerebellum increased gradually in an age-dependent manner. In the aged mice, but not middle-aged mice, the body weight, whole brain weight and cerebellum weight of ALKBH5 -/- mice decreased by 15%, 10% and 21%, respectively ( P <0.05). The expression of ALKBH5 in the Purkinje cells was much higher than that in other types of neural cells. Correspondingly, ALKBH5 - deficiency caused 40% reduction in the number of Purkinje cells, as well as the length and density of neuronal dendrites in the aged mice ( P <0.01). In addition, the time for the aged ALKBH5 -/- mice to pass the balance beam was 70% longer than that of the wild type mice of the same age, with unstable gaits ( P <0.01). Conclusions: Gene deficiency of RNA m6A demethylase ALKBH5 causes cerebellar atrophy, Purkinje neuron loss and damage in the aged mice. These changes eventually affect mice's motor coordination and balance ability. These results suggest that imbalanced RNA m6A methylation may lead to neurodegenerative lesions in the cerebellum of mice.

Background: Previous studies have suggested that the DRD2/ANKK1 rs1800497 C > T polymorphism plays a critical role in the risk of post-traumatic stress disorder (PTSD). However, published data are inconsistent or even contradictory. Therefore, we conducted a meta-analysis to explore the underlying correlation between the rs1800497 C > T polymorphism and PTSD risk., Materials and Methods: A total of five online databases were searched, and all related studies were reviewed up to 1 October 2022. Critical information was extracted, and quality assessment was conducted for all included studies. Multivariate meta-analyses were performed for the genetic model choice, and the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of the genetic models. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power., Result: Overall, 12 observational studies involving 5,515 subjects were included and analyzed in this meta-analysis. Multivariate analysis indicated that a co-dominant genetic model was most likely the best choice. Pooled results revealed an elevated PTSD risk in mutated homozygote TT carriers in the general population (TT vs. CC: OR = 1.73, 95% CI = 1.14-2.62, P = 0.01, I 2 = 58.9%) and other specific subgroups. Moreover, similar results were observed in other genetic models using univariate analysis., Conclusion: Current evidence suggests that the DRD2/ANKK1 rs1800497 C > T polymorphism may contribute to PTSD susceptibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Niu, Zhang, Tang, Cao, Jiang and Hu.)

Bisphenol A (BPA) is one of the most widely produced compounds in the world and was listed as a substance of very high concern by the European Chemicals Agency in 2016. Because of its toxicity, many countries and regions, including China, have banned BPA addition in feeding-bottles. And the European Union (EU) has banned BPA use in other food contact materials and thermal paper. Restrictions on BPA have contributed to the widespread use of alternatives. As the toxicity of BPA alternatives continues to be revealed, the alternatives of BPA alternatives are being developing. As the most extensive alternative for BPA, bisphenol S (BPS) was proven to have estrogen-disrupting effects and developmental toxicity of the neuroendocrine system. Therefore, BPS alternatives are used in thermal paper. In this study, alternatives to both BPA and BPS are collectively referred to as bisphenols (BPs). As a pooling matrix of many indoor chemicals, dust is an important pathway for human exposure to BPs. BPA and its alternatives are routinely detected in dust. As BPS alternatives have been detected in recycled paper and sludge, it is also very important to detected in dust. However, common analytical methods for BPs have low sensitivity and contain few BPS alternatives. Therefore, a high-throughput, high-accuracy, and high-sensitivity method must be established for the determination of BPs in dust; this will lay the foundation for subsequent studies on the environmental behavior and exposure risk of BPs. In this study, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of 26 variations of BPs in dust. UPLC-MS/MS parameters of the variations were optimized to compare the separation effect and response intensity in different columns and mobile phases. The influence of the extraction solvent and solid phase extraction (SPE) on the extraction efficiency and purification effect of target compounds were optimized by using the isotopic internal standard method, and the 26 variations of BPs in dust was quantitatively analyzed. Finally, the dust samples were extracted by using 3 mL of acetonitrile and 3 mL of a 50% methanol aqueous solution in an ultrasound bath. The combined extract was further purified by using an Oasis HLB cartridge (60 mg/3 mL). The cartridge was then washed with a 40% methanol aqueous solution (0.5 mL) and eluted with methanol (2 mL). The target compounds were separated on a CORTECS ® UPLC ® C 18 column (100 mm×2.1 mm, 1.6 μm), with methanol and 1 mmol/L ammonium fluoride solution as mobile phases and a flow rate of 0.3 mL/min. Electrospray ionization (ESI) was applied in the positive, negative, and multiple reaction monitoring (MRM) modes for the mass scan. Under optimized conditions, the linear ranges of the 26 targets behaved well linearly in their respective ranges with correlation coefficients ( r 2 )>0.999. The limits of detection (LODs) and limits of quantification (LOQs) were assessed using signal-to-noise ( S/N ) ratios of 3 and 10, respectively. The LODs and LOQs of the method were 0.01-0.75 μg/kg and 0.02-2.50 μg/kg, respectively. The accuracy of the method was evaluated by conducting a recovery test at three spiked levels: LOQ, two times the LOQ, and 10 times the LOQ, with the average recoveries ranging from 83.7% to 114.9%. The precision of the method was evaluated by using the relative standard deviation (RSD). The intra-day RSDs and inter-day RSDs were 0.86%-9.79% ( n =6) and 5.16%-19.5% ( n =6), respectively. The established method was used to determine 11 dust samples. Fifteen BPs were detected at a detection rate of 9.1%-100.0%. The detection rate for BPA, BPS, bisphenol F (BPF), 4-hydroxy-4'-isopropoxydiphenylsulfone (BPSIP), and diphenyl sulfone (DPS) was 100.0%. BPSIP, 4-allyloxy-4'-hydroxydiphenyl sulfone (BPS-MAE), and bis-(3-allyl-4-hydroxyphenyl) sulfone (TGSA) were first detected in Chinese dust, whereas 4-benzyloxy-4'-hydroxydiphenyl sulfone (BPS-MPE), 4-hydroxybenzoic acid benzyl (PHBB), and DPS were first detected in dust samples worldwide. This method is simple, rapid, and sensitive, and is suitable for the qualitative screening and quantitative analysis of the 26 BPs in dust samples.

Objectives: Myocarditis, a health-threatening heart disease, is attracting increasing attention. This systematic study was conducted to study the prevalence of disease through the trends of incidence, mortality, disability-adjusted life years (DALYs) over the last 30 years, which would be helpful for the policymakers to better the choices for reasonable decisions., Methods: The global, regional, and national burdens of myocarditis from 1990-2019 were analyzed by using the 2019 Global Burden of Disease (GBD) database. This study on myocarditis produced new findings according to age, sex, and Social-Demographic Index (SDI) by investigating DALYs, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and corresponding estimated annual percentage change (EAPC)., Results: The number of myocarditis incidence increased by 62.19%, from 780,410 cases in 1990 to 1,265,770 cases in 2019. The ASIR decreased by 4.42% (95%CI, from -0.26% to -0.21%) over the past 30 years. The number of deaths from myocarditis increased by 65.40% from 19,618 in 1990 to 324,490 in 2019, but the ASDR was relatively stable over the investigated period. ASDR increased in low-middle SDI regions (EAPC=0.48; 95%CI, 0.24 to 0.72) and decreased in low SDI regions (EAPC=-0.97; 95%CI, from -1.05 to -0.89). The age-standardized DALY rate decreased by 1.19% (95%CI, from -1.33% to -1.04%) per year., Conclusions: Globally, the ASIR and DALY for myocarditis decreased and the ASDR was stable over the past 30 years. The risk of incidences and death cases increased with age. Measures should be taken to control the risk of myocarditis in high-burden regions. Medical supplies should be improved in the high-middle SDI regions and middle SDI regions to reduce the deaths from myocarditis in these regions., (© 2023. The Author(s).)

The detection of paralytic shellfish toxins in human biological matrices is important for the diagnosis and treatment of food poisoning caused by them. An ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the determination of 14 paralytic shellfish toxins in plasma and urine. The effect of solid phase extraction (SPE) cartridges was also investigated and the pretreatment and chromatographic conditions were optimized. Under these optimal conditions, 0.2 mL water, 0.4 mL methanol, and 0.6 mL acetonitrile were successively added to plasma and urine samples for extraction. The supernatants from plasma extraction were subjected to an UHPLC-MS/MS analysis, whereas the supernatants from urine extraction were further purified using polyamide (PA) SPE cartridges and then analyzed by UHPLC-MS/MS. Chromatographic separation was conducted on a Poroshell 120 HILIC-Z column (100 mm×2.1 mm, 2.7 μm) with a flow rate of 0.5 mL/min. The mobile phase was 0.1% (v/v) formic acid aqueous solution containing 5 mmoL/L ammonium formate and acetonitrile containing 0.1% (v/v) formic acid. The analytes were detected in the multiple reaction monitoring (MRM) mode after being ionized by an electrospray ion (ESI) in positive and negative modes. Quantitation of the target compounds was performed using the external standard method. Under the optimal conditions, the method showed good linearity in the range of 0.24-84.06 μg/L, with correlation coefficients greater than 0.995. The limits of quantification (LOQs) for the plasma and urine samples were 1.68-12.04 ng/mL and 4.80-34.4 ng/mL, respectively. The average recoveries for all the compounds were 70.4%-123.4% at spiked levels of 1, 2, and 10 times the LOQs, the intra-day precisions were 2.3%-19.1% and the inter-day precisions were 5.0%-16.0%. The established method was used to determine the target compounds in the plasma and urine from mice intraperitoneally injected with 14 shellfish toxins. All 14 toxins were detected in the 20 urine and 20 plasma samples, with contents of 19.40-55.60 μg/L and 8.75-13.86 μg/L, respectively. The method is simple, sensitive, and only requires a small amount of sample. Therefore, it is highly suitable for the rapid detection of paralytic shellfish toxins in plasma and urine.

The aim of this study is to explore the effect of tumor necrosis factor-α (TNF-α) inhibition in rats with neonatal hypoxic-ischemic encephalopathy (HIE) and ascertain the relevant signaling pathways. The Zea-Longa score was used to evaluate the neurological function of the rats. ImageJ was used for quantification of the brain edema volume. Triphenyl tetrazolium chloride (TTC) staining of brain tissue was performed 24 h after hypoxic-ischemic (HI) to detect right brain infarction. The expression of TNF-α was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Immunofluorescence staining was used to identify the localization of TNF-α; Then, the effective shRNA fragment of TNF-α was used to validate the role of TNF-α in HIE rats, and the change of neurotrofin-3 (NT-3) and tyrosine kinase receptor-C (TRKC) was examined after TNF-α-shRNA lentivirus transfection to determine downstream signaling associated with TNF-α. Protein interaction analysis was carried out to predict the links among TNF-α, NT-3, and TRKC. Cerebral edema volume and infarction increased in the right brain after the HI operation. The Zea-Longa score significantly increased within 24 h after the HI operation. The relative expression of TNF-α was upregulated after the HI operation. TNF-α was highly expressed in the right hippocampus post HI through immunofluorescence staining. Bioinformatics analysis found a direct or an indirect link among TNF-α, NT-3, and TRKC. Moreover, the interference of TNF-α increased the expression of NT-3 and TRKC. TNF-α interference might alleviate brain injury in HIE by upregulating NT-3 and TRKC., Competing Interests: There authors declare no conflict of interest., (© 2023 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

Background and Objective: Chronic obstructive pulmonary disease (COPD) is the most prevalent chronic respiratory disease. This study investigated the global, regional and country burden of COPD based on gender, age and socio-demographic indices (SDIs) in the last 30-year period from 1990 to 2019., Methods: The COPD data, including incidence, mortality and disability-adjusted life years (DALYs), were obtained from the 2019 Global Burden of Disease Study. If age-standardized incidence rate (ASIR) or death rate (ASDR) remains almost constant or decreases, the number of cases will still increase as the global population increases substantially. Estimated annual percentage change (EAPC) was calculated to assess incidence, mortality and DALY trends., Results: The incidence of COPD increased by 85.89% from 8,722,966 cases in 1990 to 16,214,828 cases in 2019, and the ASIR decreased from 216.48/100,000 persons in 1990 (95%UI, 204.56-227.33) to 200.49 per 100,000 persons (95%UI, 188.63-212.57) in 2019. The ASIR increased (EAPC = 0.05, 95%CI, 0.01-0.10) in the low SDI region, was stable in the high SDI region, and fell in the other three SDI regions. Men had a higher ASIR than women over the past 30 years, and there were differences in the incidence rates for different age groups. Male mortality and DALYs were higher than female mortality. ASDR decreased by 2.13% (95%CI, -2.23% to -2.02%) per year and the annual age-standardized DALY rate decreased by 1.97% (95%CI, -2.05% to -1.89%)., Conclusions: The ASIR, ASDR and age-standardized DALY rate of COPD declined overall in the last 30 years, and were highest in the low-middle SDI region., (© 2022 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Ethylene glycol is the main component of antifreeze, due to its special sweetness, it is easy to cause misuse. In this paper, the clinical data of 4 cases of acute ethylene glycol poisoning admitted to Beijing Chao-Yang Hospital from August 2016 to August 2021 were retrospectively analyzed to explore the clinical characteristics of acute ethylene glycol poisoning cases. Early and accurate assessment of the disease and early hemodialysis treatment is the key to cure acute ethylene glycol poisoning.

The aim was to investigate the independent prognostic factors and construct a prognostic risk prediction model to facilitate the formulation of oral squamous cell carcinoma (OSCC) clinical treatment plan. We constructed a prognostic model using univariate COX, Lasso, and multivariate COX regression analysis and conducted statistical analysis. In this study, 195 randomly obtained sample sets were defined as training set, while 390 samples constituted validation set for testing. A prognostic model was constructed using regression analysis based on nine survival-associated metabolic genes, among which PIP5K1B, NAGK, and HADHB significantly down-regulated, while MINPP1, PYGL, AGPAT4, ENTPD1, CA12, and CA9 significantly up-regulated. Statistical analysis used to evaluate the prognostic model showed a significant different between the high and low risk groups and a poor prognosis in the high risk group ( P < 0.05) based on the training set. To further clarify, validation sets showed a significant difference between the high-risk group with a worse prognosis and the low-risk group ( P < 0.05). Independent prognostic analysis based on the training set and validation set indicated that the risk score was superior as an independent prognostic factor compared to other clinical characteristics. We conducted Gene Set Enrichment Analysis (GSEA) among high-risk and low-risk patients to identify metabolism-related biological pathways. Finally, nomogram incorporating some clinical characteristics and risk score was constructed to predict 1-, 2-, and 3-year survival rates (C-index = 0.7). The proposed nine metabolic gene prognostic model may contribute to a more accurate and individualized prediction for the prognosis of newly diagnosed OSCC patients, and provide advice for clinical treatment and follow-up observations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Yao, Chen, Zhao, Zhang and Niu.)

Background: Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk., Methods: A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power., Results: Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I 2  = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I 2  = 81.9%)., Conclusions: In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians., (© 2020 by the Research Society on Alcoholism.)

A close association between peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) and the development of diabetic retinopathy (DR) has been previously suggested. Herein, a meta-analysis was conducted to explore the association between PPAR-γ2 polymorphisms and DR risk by performing a systematic search and quantitative analysis. Overall, fourteen articles involving 10,527 subjects were included. The pooled results did not reveal an association between PPAR-γ2 rs1801282 C/G and DR susceptibility in the overall population (e.g., the dominant model: CG+GG vs. CC, OR=0.85, 95% CI=0.69-1.06, P=0.15, I 2 =62.9%). Furthermore, heterogeneity tests, cumulative analyses, sensitivity analyses, and publication bias analyses were conducted and showed that the results were robust. Similarly, race-based subgroup analyses and other subgroup analyses did not reveal an association between the rs1801282 C/G and DR susceptibility. In addition, no significant association was observed between PPAR-γ2 rs3856806 C/T polymorphism and DR risk (e.g., the dominant model: CT+TT vs. CC, OR=1.12, 95%CI=0.91-1.37, P=0.28, I 2 =27.0%). Overall, based on the current sample size and the level of evidence presented in the study, the results suggest that PPAR-γ2 gene polymorphisms are not associated with DR risk.

Isodon amethystoides (Benth.) Hara (IA) tea is a commonly used dietetic Chinese herb and employed for the treatments of tumor and lung abscess. To assess chemical composition and antioxidant capacity of IA leaves extract, a UPLC-LTQ-Orbitrap-MS method and antioxidant tests were used, respectively. 17 compounds were identified including Vinyl caffeate (1), 3,4-dimethoxyphenyl-β-D-glucopyranoside (2), Rutin (3), Quercetin (4), Loliolide (5), Caffeic acid (6), Rubesanolide D (7), Isorhamnetin (8), Lambertic acid (9), 6, 7-Dehydroroyleanone (10), Dihydrorabdokunmin C (11), Nervosin (12), Quercitrin (13), Vitexin (14), β-sitosterol (15), Wangzaozin A (16), Amethystonoic acid (17). Among these, 1-14 compounds were novel and have not been reported ever before in IA while component 10 was a novel finding within this genus. Flavonoid components showed better free radical scavenging ability and profound correlation was observed between diterpenoid compounds content and flavonoids activity. Our results provide experimental basis for extraction and separation of chemical constituents of IA which are antioxidant in nature., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is a malignant tumor associated with a high recurrence rate after hepatectomy. Recently, preoperative inflammatory and liver function reserve indices were found to predict increased risk of recurrence and decreased survival in HCC patients. This study aims to evaluate the ability of the γ-glutamyl transpeptidase-to-albumin ratio (GAR) and aspartate aminotransferase-to-lymphocyte ratio (ALRI), individually and in combination, to predict the prognosis of HCC patients after hepatectomy.We retrospectively reviewed 206 HCC patients who underwent radical resection at the General Hospital of Ningxia Medical University from January 2011 to November 2016. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for GAR and ALRI. The Pearson Chi-Squared test was used to analyze the correlations between GAR, ALRI and clinicopathological characteristics. Univariate and multivariate analyses were used to determine the predictive value of these factors for disease-free survival (DFS) and overall survival (OS). Survival rates were drawn according to the Kaplan-Meier method and differences between subgroups were compared by the log-rank statistics.GAR and ALRI were significantly correlated with gender, history of smoking, prothrombin time, tumor diameter, T stage and early intrahepatic recurrence by the Pearson Chi-Squared test (all P < .05). Univariate analysis indicated that T stage, GAR and ALRI were significantly correlated with DFS and OS in HCC patients after hepatectomy. Multivariate analysis illustrated that GAR and ALRI were independently related to DFS and OS in HCC patients. Preoperative GAR > 0.946 or ALRI > 18.734 predicted poor prognosis in HCC patients after hepatectomy. Additionally, the predictive scope of GAR combined with ALRI was more sensitive than that of either individual measurement alone.Our data indicate that there is a close association between the clinicopathological characteristics in HCC patients and increased GAR or ALRI. Higher levels of GAR and ALRI could sensitively and specifically predict a poor prognosis in HCC patients after hepatectomy. Furthermore, combined usage of GAR and ALRI could improve the accuracy of this prediction.

MiR-26 has been suggested to play a tumor-suppressive role in cancer development, which could be influenced by the mutate pri-miR-26ª-1. Molecular epidemiological studies have demonstrated some inconsistent associations between pri-miR-26ª-1 rs7372209 C>T polymorphism and cancer risk. We therefore performed this meta-analysis with multivariate statistic method to comprehensively evaluate the associations between rs7372209 C>T polymorphism and cancer risk. Eleven publications involving 6,709 patients and 6,514 controls were identified. Multivariate analysis indicated that the over-dominant genetic model was most likely. Pooled results indicated no significant association in the overall population (CC+TT vs. CT: OR=1.08, 95%CI=0.96-1.22, P =0.20, I 2 =54.4%), as well as the subgroup analysis according to ethnicity, control source, tumor locations, and HWE status of controls. In addition, heterogeneity, accumulative, sensitivity analysis, publication bias and trial sequential analysis (TSA) were conducted to test the statistical power. Overall, our results indicated that the pri-miR-26a-1 rs7372209 C>T polymorphism may not be a potential risk for cancer development.

Epidemiological studies have demonstrated that interleukin-10 (IL-10) polymorphisms may be associated with the development of Behcet's disease (BD). However, the published results were inconsistent. Therefore, this meta-analysis was conducted to derive a more precise relationship between IL-10 polymorphisms and BD susceptibility. Online databases (PubMed, Embase, Science Citation Index (SCI), CNKI, and WanFang) were searched to identify eligible studies. Odds ratio (OR) and a 95% confidence interval (CI) were applied to assess the relationship strength between IL-10 -1082A>G (rs1800896), -819T>C (rs1800871), and -592A>C (rs1800872) polymorphisms and BD susceptibility. Publication bias, sensitivity, and cumulative analyses were conducted to measure the robustness of our findings. Finally, fifteen articles (36 independent case-control studies) involving 5,971 patients and 8,913 controls were included. Overall, significant associations between -819T>C polymorphisms and BD risk were observed in the total population (C vs. T: OR = 0.72, 95%CI = 0.67-0.77, P < 0.01, I 2 = 36.6%; TC vs. TT: OR = 0.73, 95%CI = 0.66-0.80, P < 0.01, I 2 = 23.0%; CC vs. TT: OR = 0.52, 95%CI = 0.39-0.70, P < 0.01, I 2 = 53.7%; TC+CC vs. TT: OR = 0.67, 95%CI = 0.61-0.71, P < 0.01, I 2 = 22.1%; and CC vs. TT+TC: OR = 0.66, 95%CI = 0.53-0.82, P < 0.01, I 2 = 57.8%). Moreover, the IL-10 -592 A>C polymorphism and the ACC haplotype exhibited a significant, protective effect against BD susceptibility. In summary, our meta-analysis suggested that IL-10 gene polymorphisms may play a salient role for BD development., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Xue-Feng Li et al.)

Background: Currently, many clinical trials have shown that inulin-type fructans (ITF) supplementation is associated with glycemic control; nevertheless, the results are inconclusive. The aim of this meta-analysis of randomized controlled trials was to assess the effects of ITF supplementation on glycemic control., Methods: PubMed, EMBASE and the Cochrane Library were searched for eligible articles up to March 6, 2019. A random-effects model was used to analyze the pooled results, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was applied to assess the quality of evidence. The dose-response model was used to recommend the daily dose and duration for ITF supplementation., Results: Thirty-three trials involving 1346 participants were included. Overall, ITF supplementation could significantly reduce concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR). In the prediabetes and type 2 diabetes (T2DM) population, a more significant reduction in FBG [weighted mean difference (WMD): - 0.60 mmol/l; 95% CI - 0.71, - 0.48 mmol/l; high rate], HbA1c (WMD: - 0.58%; 95% CI - 0.83, - 0.32%; high rate), FINS (WMD: - 1.75 µU/ml; 95% CI - 2.87, - 0.63 µU/ml; low rate), and HOMA-IR (WMD: - 0.69; 95% CI - 1.10, - 0.28; low rate) were observed, and ITF supplementation with a daily dose of 10 g for a duration of 6 weeks and longer was recommended. Moreover, subgroup analyses suggested that the effects of glycemic control were significantly influenced by the sex of the subjects and the type and the method of intake of ITF., Conclusions: Our analyses confirmed that these four main glycemic indicators were significantly reduced by ITF supplementation, particularly in the prediabetes and T2DM population. Evidence supports that reasonable administration of ITF supplementation may have potential clinical value as an adjuvant therapy for prediabetes and T2DM management. Trial registration The trial was registered at PROSPERO as CRD42018115875 on November 23, 2018.

To comprehensively shed light on whether viewing football games is associated with a higher risk of cardiovascular disease (CVD). Electronic databases were searched through 17 May 2018. All studies focusing on the association between viewing football matches and the fatal or non-fatal CVD were identified. Viewing football matches was associated with a higher risk of fatal overall CVD (RR: 1.06, 95%CI: 1.01-1.12) in both men (RR: 1.13, 95%CI: 1.004-1.28) and women (RR: 1.08, 95%CI: 1.01-1.15). Subgroup analysis showed that failure of the team has a higher risk of fatal overall CVD (RR: 1.29, 95%CI: 1.15-1.45). However, lower risk of fatal overall CVD from spectators was observed when team obtained a victory (RR: 0.80, 95%CI: 0.66-0.96). For non-fatal CVD, viewing football matches was associated with a higher risk of non-fatal overall CVD (RR: 1.24, 95%CI: 1.09-1.41) in both men (RR: 1.73, 95%CI: 1.12-2.69) and women (RR: 1.25, 95%CI: 1.08-1.45). Subgroup analysis showed that viewing football matches was associated with a higher risk of non-fatal myocardial infarction (RR: 1.20, 95%CI: 1.04-1.38) in both men and women (RR: 1.51, 95%CI: 0.99-2.28; RR: 1.21, 95%CI: 1.08-1.36, respectively). No significant increase was found in fatal or non-fatal stroke. Viewing football matches was associated with a higher risk of the fatal and non-fatal CVD, especially in male spectators. The victory of team could have a lower risk of fatal CVD. Therefore, precautionary measures should be required for the reduction of healthcare burden in football matches.

Osteoarthritis (OA) is a prevalent joint disorder worldwide. Recent studies suggested that macrophages play an important role in the progression of OA. However, the detailed pathology related to macrophages is still ambiguous, especially where related to mechanotransduction. In this study, polycaprolactone (PCL) and Eucommia Ulmoides Gum (EUG) composite scaffolds were first fabricated by electrospinning. The stiffness of as-fabricated scaffolds was altered by adjusting the PCL-to-EUG ratio. The mechanical properties, structural characteristics and chemical composition of the scaffolds were investigated using various materials characterization techniques. The results show that stiffness of the scaffolds was in the same range as that of cartilage tissues with OA. Confocal microscopy and reverse transcription-polymerase chain reaction (RT-PCR) were performed to investigate the macrophages cultured on the scaffolds. Significant morphological changes of cells were observed on PCL/EUG scaffolds with different stiffness. The expression of inflammatory and fibrosis-related cytokines increases as scaffold stiffness decreases, similar to the trend observed in OA progression., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To investigate the expression and potential role of heterogeneous nuclear ribonucleo-protein A2B1 (HNRNPA2B1) in mouse cerebellar development and the significance of HNRNPA2B1 in human medulloblastoma. Methods: The data of HNRNPA2B1 RNA expression in mouse and human cerebella were obtained from databases. Western blot and immunohistochemical staining were performed to detect the protein level of HNRNPA2B1 in mouse cerebella at different ages. The expression level of HNRNPA2B1 in control human cerebellum and medulloblastoma was detected by immunohistochemical staining. m6A-IP-qPCR method was applied to confirm whether HNRNPA2B1 RNA in Daoy cells was modified with m6A.Western blot was used to detect the effect of MG132 treatment on the HNRNPA2B1 protein level in Daoy cells. Results: The level of HNRNPA2B1 protein in postnatal mouse cerebella was higher than that in adult mouse cerebella, with weak HNRNPA2B1 staining in external granular cells while strong staining in mature Purkinje cells and molecular layer. Compared with control normal human cerebella, the RNA expression level of HNRNPA2B1 increased in medulloblastoma, while immunohistochemical staining showed that the mean intensity of HNRNPA2B1 decreased in medulloblastoma. HNRNPA2B1 RNA in medulloblastoma and Daoy cells was modified by m6A. The HNRNPA2B1 protein level in Daoy cells increased upon MG132 treatment. Conclusions: HNRNPA2B1 is dynamically expressed during mouse cerebellar development. Compared with normal human cerebella, HNRNPA2B1 is significantly up-regulated at transcriptional level but obviously down-regulated at translational level in medulloblastoma. These results indicate that HNRNPA2B1 may be involved in cerebellar development process and medulloblastoma tumorigenesis. The m6A methylation in HNRNPA2B1 transcript and protein ubiquitin-proteasome pathway may account for the down-regulation of HNRNPA2B1 at protein level.

Bipolar disorder (BD) is a complex mental disorder with high mortality and disability rates worldwide; however, research on its pathogenesis and diagnostic methods remains limited. This study aimed to elucidate potential candidate hub genes and key pathways related to BD in a pre-frontal cortex sample. Raw gene expression profile files of GSE53987, including 36 samples, were obtained from the gene expression omnibus (GEO) database. After data pre-processing, 10,094 genes were selected for weighted gene co-expression network analysis (WGCNA). After dividing highly related genes into 19 modules, we found that the pink, midnight blue, and brown modules were highly correlated with BD. Functional annotation and pathway enrichment analysis for modules, which indicated some key pathways, were conducted based on the Enrichr database. One of the most remarkable significant pathways is the Hippo signaling pathway and its positive transcriptional regulation. Finally, 30 hub genes were identified in three modules. Hub genes with a high degree of connectivity in the PPI network are significantly enriched in positive regulation of transcription. In addition, the hub genes were validated based on another dataset (GSE12649). Taken together, the identification of these 30 hub genes and enrichment pathways might have important clinical implications for BD treatment and diagnosis.

Objective: Published studies have demonstrated a closer association between vitamin D receptor (VDR) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We therefore performed this meta-analysis to explore the precise associations between VDR gene polymorphisms and PCOS risk. Methods: Five online electronic databases (PubMed, Embase, SCI index, CNKI and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between VDR Fok I C/T (rs10735810), BsmI A/G (rs1544410), ApaI A/C (rs7975232), and TaqI T/C (rs731236) polymorphisms and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis and publication bias were conducted to check the statistical power. Results: Overall, 10 publications (31 independent case-control studies) involving 1,531 patients and 1,174 controls were identified. We found that the C mutation of ApaI A/C was a risk factor for PCOS (C vs. A: OR = 1.20, 95%CI = 1.06-1.35, P < 0.01, I 2 = 29.7%; CC vs. AA: OR = 1.49, 95%CI = 1.17-1.91, P < 0.01, I 2 = 0%; CC vs. AA+AC: OR = 1.36, 95%CI = 1.09-1.69, P = 0.01, I 2 = 12.8%). Moreover, the BsmI A/G polymorphism also showed a dangerous risk for PCOS in Asian population (G vs. A: OR = 1.62, 95%CI = 1.24-2.11, P < 0.01, I 2 = 0%; AG vs. AA: OR = 2.08, 95%CI = 1.26-3.20, P < 0.01, I 2 = 0%; GG vs. AA: OR = 2.21, 95%CI = 1.29-3.77, P < 0.01, I 2 = 0%; AG+GG vs. AA: OR = 2.12, 95%CI = 1.42-3.16, P < 0.01, I 2 = 0%). In addition, no significant association of Fok I C/T, and TaqI T/C polymorphisms was observed. Conclusions: In summary, our meta-analysis suggested that VDR gene polymorphisms contribute to PCOS development, especially in Asian populations.

Objective: To investigate the biological functions of protein phosphatase 2AC(PP2AC) in the brain, and to detect its spatio-temporal expression and its involvement in neurological disorders in the brains of mice and Alzheimer's patients. Methods: Western blot was used to evaluate the expression level of PP2AC in different organs. Immunohistochemical staining was performed to detect the in situ expression levels of PP2AC in the brains of mice and patients, and the pathological changes were confirmed in the brains of patients with Alzheimer's disease. Results: Among all the tested organs in adult mouse, the expression of PP2AC protein was the highest in the brain. From embryonic day 18.5 to postnatal 2-year-old mice, PP2AC exhibited spatio-temporal specific expression in the brains. Furthermore, an age-dependent increased expression in the cerebral cortex at both protein and RNA levels was observed. Compared to control group, PP2AC protein expression was lower in the frontal cortex of Alzheimer's patients. Conclusions: The spatio-temporal specific expression profiles of PP2AC in mouse brain implicate its biological significance. Its diminished expression in the frontal cortex of Alzheimer's disease patients implies that PP2AC plays a potential role in the pathogenesis of Alzheimer's disease.

Background: Cytochrome P450 family 17 subfamily A member 1 (CYP17A1) gene encodes a key enzyme in the synthesis and metabolism of steroid hormones and has been associated with various factors, such as hypertension, insulin resistance, and polycystic ovary syndrome. However, whether the gene was associated with type 2 diabetes mellitus (T2DM) has not been reported yet. Therefore, we sought to investigate whether CYP17A1 was associated with T2DM and related traits among Han Chinese., Methods: Three tagging single nucleotide polymorphisms (rs1004467, rs17115149, and rs12413409), in the CYP17A1 gene region were selected and genotyped in a case-control study that included 440 diabetes and 1,320 control subjects. Effects of genetic loci were studied using univariate unconditional logistic regression and multivariate logistic regression analysis adjusted for age, sex, family history, body mass index, smoking, and drinking. Bioinformatics analysis was also conducted using the GEO DataSets and PROMO database to gain hints of possible mechanism., Results: Rs17115149 and rs12413409 polymorphisms were significantly associated with the risk of T2DM, even after adjusting for age, sex, family history, body mass index, smoking, and drinking. In stratified analyses, rs1004467 and rs12413409 showed significant association with T2DM in the older age group (≥65 years) and, in the case of rs12413409, the risk of T2DM was significant in men but not in women. Rs17115149 had significant association with T2DM in the hypertension subgroup, and rs12413409 in the non-hypertension subgroup. Moreover, rs12413409 showed significant association with plasma glucose levels in the recessive model ( P  = 0.020) among subjects not taking hypoglycemic measures. Bioinformatics analysis revealed significantly higher CYP17A1 gene expression in T2DM patients compared to healthy controls. Finally, the mutant T allele of the rs17115149 polymorphism allowed binding to the RBP-Jkappa transcription factor., Conclusion: This is the first report to identify that variants rs1004467, rs17115149, and rs12413409 of CYP17A1, are related to plasma glucose levels and T2DM among Han Chinese. Our results suggest that CYP17A1 might constitute a risk gene for progression to T2DM.

Previous epidemiologic studies have revealed a possible association between microRNA-608 rs4919510 G>C polymorphism and digestive system cancers (DSCs) risk, but the results were not consistent. We therefore performed an updated meta-analysis to explore the association between microRNA-608 rs4919510 G>C polymorphism and DSCs risk. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the relationship between the microRNA-608 rs4919510 G>C polymorphism and DSCs risk. Heterogeneity, cumulative analyses, sensitivity analyses, and publication bias were also conducted to examine the statistical power. Eight published articles with nine independent case-control studies involving 10,836 individuals were included in this meta-analysis. Overall, no significant association was found between microRNA-608 rs4919510 G>C polymorphism and DSCs risk in general populations. But some significant protective effects were observed in the subgroup of Caucasian population group in three genetic models (C vs. G: OR = 0.82, 95% CI, 0.68-0.99, P = 0.03, I 2 = 0%; CC vs. GG: OR = 0.59, 95% CI = 0.36-0.97, P = 0.04, I 2 = 0%; GC+CC vs. GG: OR = 0.61, 95% CI = 0.37-0.99, P = 0.05, I 2 = 0%). In summary, current evidence indicates that the microRNA-608 rs4919510 G>C polymorphism maybe an important factor of DSCs susceptibility, especially in Caucasian population.

Amatoxin poisoning induces delayed-onset acute liver failure, which are responsible for more than 90% of deaths in mushroom poisoning. It has been postulated from animal and human studies that biliary drainage interrupting enterohepatic amatoxin circulation may affect amatoxin poisoning. Dogs were randomly divided into four groups of six animals each. In 20 mg/kg and 60 mg/kg with biliary drainage groups, after accepting bile drainage operation, beagles were fed Amanita exitialis powder (20 or 60 mg/kg) in starch capsules. In control and bile drainage groups, the beagle dogs were fed with empty capsules. They were assessed for toxicity signs, biochemical and pathological changes, and peptide toxins in plasma, urine and bile. The data were directly compared with those from our published studies on Amanita exitialis -exposed beagles without biliary drainage. Amatoxins were rapidly absorbed and eliminated from plasma after Amanita exitialis ingestion. Amatoxins in 0⁻1-day urine accounted for more than 90% of the total urine excretion, and amatoxins in bile accounted for less than 20% of the total urine and bile excretion. The dogs with biliary drainage showed less severe toxicity signs and biochemical and pathological changes and much lower internal exposure than dogs without biliary drainage. Biliary drainage caused a more than 70% reduction in intestinal amatoxin absorption and could reduce amatoxin absorption from the gastrointestinal tract.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.pbiomolbio.2018.05.008. The duplicate article has therefore been withdrawn., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke., Data Sources: PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies., Methods: Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software., Results: A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I 2  = 71%, P = 0.0005)., Conclusion: Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

In this study, the toxicology of A. exitialis, a lethal mushroom found in China, and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which they were assessed for signs of toxicity, as well as biochemical and pathological changes. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to assay the peptide toxins. The total peptide toxins in A. exitialis was 3482.6 ± 124.94 mg/kg. The beagles showed signs of toxicity, such as vomiting and diarrhea, at 12-48 h following ingestion of A. exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in plasma, as well as prothrombin time and activated partial thromboplastin time peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three dogs that were administered 60 mg/kg A. exitialis died at 24-72 h after ingesting the capsules. Additionally, liver histopathological examinations showed hemorrhagic necrosis of hepatocytes. α-Amanitin, β-amanitin, and phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis was ingested. A long latency period (12-24 h post A. exitialis ingestion) was observed in the dogs before the onset of gastrointestinal symptoms. There was acute liver damage thereafter. Gastric lavage and enhanced plasma clearance methods such as hemodialysis, hemoperfusion, or plasma exchange may be ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion. Enhanced excretion of amatoxins in urine could be effective within 2 days after ingestion of A. exitialis because amatoxins in 0-2 d urine accounted for more than 90% of the total urine excretion., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To systematically review the clinical efficacy of coblation tonsillectomy and conventional tonsillectomy in China. Method: Randomized controlled trials (RCT) of coblation tonsillectomy and conventional tonsillectomy were searched and retrieved through online databases (PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Library, CBM, CNKI, VIP, WanFang, SUMsearch and Google search engine) and related literatures were reviewed up to 30 April, 2017. Two investigators independently screened literatures,extracted data and evaluated the risk of bias assessment tools for RCT using the Version 5.1.0 of Cochrane Handbook for Systematic Reviews of Interventions. Then, Meta analysis was performed using RevMan 5.3 software provided by the Cochrane Collaboration. Result: A total of 32 RCTs involving 3 197 tonsillectomy patients were included. The results of meta-analysis showed that: the operation time (MD=-17.03, 95% CI -19.78 to -14.28, P ＜0.00 001), intraoperative blood loss (MD=-27.00, 95% CI -30.44 to -23.56, P ＜0.00 001), postoperative pain in 24 hours (MD=-2.00, 95% CI -2.65 to -1.35, P ＜0.00 001), time needed to regain the normal diet (MD=-2.01, 95% CI -2.60 to -1.42, P ＜0.00001), formation time of white membrane (MD=-2.44, 95% CI -3.96 to -0.93, P =0.002) of patients in the coblation tonsillectomy group were all significantly lower than the conventional tonsillectomy group; while the exfoliation time of white membrane (MD=2.02, 95% CI 0.65 to 3.39, P =0.004) in the coblation tonsillectomy group was significantly longer than the conventional tonsillectomy group. Conclusion: Current evidence shows that, compared with the conventional tonsillectomy group, the coblation tonsillectomy group can significantly shorten the operation time, decrease intraoperative blood loss, alleviate postoperative pain degree during 24 hours, regain the normal diet early and form white membrane early, but delaye the exfoliation time of white membrane. Due to the limited kinds of literature and quality of the included studies, the above conclusions still need to be verified by carrying out more large scale samples and high quality randomized controlled trials (RCTs) studies.

Background: Molecular epidemiological studies have demonstrated a closer association between Fas/FasL polymorphisms and head and neck cancer (HNC) risk, and the results of these published studies were inconsistent. We therefore performed this meta-analysis to explore the associations between Fas/FasL polymorphisms and HNC risk., Methods: Four online databases (PubMed, Embase, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (95% CIs) were calculated to assess the association between Fas -670A>G, Fas -1377G>A, and FasL -844C>T polymorphisms and HNC risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power., Results: Overall, 9 related publications (20 independent case-control studies) involving 3179 patients and 4217 controls were identified. Significant association of protective effects was observed between FasL -844C>T polymorphism and HNC risk in codominant and dominant model models (CT vs CC: OR = 0.89, 95% CI = 0.79-1.00, P = .05, I = 38.3%, CT+TT vs CC: OR = 0.88, 95% CI = 0.79-0.98, P = .02, I = 35.8%). Furthermore, the similar protective effects were observed the subgroup analysis of in Asian population and population-based controls group., Conclusion: Our meta-analysis indicated that FasL -844C>T polymorphism plays a protective role against HNC development, but the Fas -670A>G and Fas -1377G>A polymorphisms maybe not associated with HNC risk.

Previous studies have suggested that interleukin-10 (IL-10) polymorphisms may be associated with an increased risk of developing cervical cancer. However, the published results on this subject matter are controversial. The aim of this study was to conduct a meta-analysis of published reports to more precisely investigate the relationship between IL-10 polymorphisms and cervical cancer risk. Five online databases (PubMed, Embase, Web of SCI, CNKI and Wanfang) were searched, and seventeen articles with sufficient quantitative information were included in our meta-analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between IL-10 polymorphisms and cervical cancer risk. Publication bias, sensitivity and cumulative analyses were also performed to support our findings. Overall, there was a significant association between the IL-10 -1082A > G polymorphism and cervical cancer risk observed in the total population (G vs. A: OR = 1.60, 95% CI = 1.12-2.29, P = 0.01, I 2 = 92.3%; AG vs. AA: OR = 1.34, 95% CI = 1.04-1.74, P = 0.03, I 2 = 65.9%; AG + GG vs. AA: OR = 1.58, 95% CI = 1.11-2.25, P = 0.01, I 2 = 84.4%), and the same results were obtained in the subgroup analysis. Moreover, the IL-10 -819 T > C polymorphism exhibited a significant, protective effect against cervical cancer. In summary, our meta-analysis suggests that IL-10 polymorphisms may play a variety of roles in regard to cervical cancer risk, especially in Asians., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Purpose: To assess the effectiveness and safety of botulinum toxin A (BTX-A) at different dosages for overactive bladder (OAB)., Materials and Methods: The MEDLINE, EMBASE, and Cochrane Controlled Trials Register databases were searched through November 3, 2016 to identify relevant randomized controlled trials (RCTs)., Results: Eleven studies were identified in this meta-analysis. Compared with placebo, the urinary incontinence (UI) episodes per week as the primary outcomes, urodynamic parameters including maximum cystometric capacity (MCC), and maximum detrusor pressure (MDP) for neurogenic detrusor overactivity (NDO) at 6 weeks, and for idiopathic detrusor overactivity (IDO) at 36 weeks were evaluated. These and other outcomes for effectiveness of BTX-A at different dosages in two observation periods indicate that a dose greater than 50 U is significantly more effective for certain symptoms of OAB compared with placebo. However, there were no significant differences between some dosages. Compared with placebo, the outcomes of total adverse events for NDO and for IDO show that doses of 300 U and 200 U for NDO are associated with more complications., Conclusions: In consideration that the treatments of BTX-A were with minimal, local, and manageable adverse effects, this meta-analysis demonstrates that BTX-A 200 U is recommended for management of NDO for short-term treatment for there was no significant difference from the larger dose of 300U. The short-term efficacies of BTX-A for IDO remain to be investigated., Competing Interests: CONFLICTS OF INTEREST The author(s) of this work have nothing to disclose.

Previous epidemiological research suggests polymorphisms in long non-coding RNA (lncRNA) H19 are associated with an increased risk of cancer, but the results are inconsistent. We therefore conducted a meta-analysis to more accurately determine the association between lncRNA H19 polymorphisms and cancer risk. The PubMed, Embase, and Science Citation Index online databases were searched and 11 relevant studies involving a total of 33,209 participants were identified. Odds ratios (ORs) and corresponding 95% confidence interval (CIs) from these studies were used to detect associations between H19 polymorphisms and cancer risk using five genetic models. The pooled result suggested that the rs2839698 G>A polymorphism was associated with digestive cancer risk in all five models. Moreover, a protective effect against cancer development was observed for the T allele variant of the rs2107425 C>T polymorphism, especially in Caucasian patient populations. No significant associations were found between lncRNA H19 rs217727 G>A polymorphism and cancer risk. In summary, the rs2839698 G>A and rs2107425 C>T polymorphisms in lncRNA H19 may therefore play opposing roles during cancer development, and their effects may vary depending on cancer type and patient ethnicity.

Objective: To investigate the role of Mic60 in cardiac aging. Methods: Wild-type and Mic60(+ /-) male mice at age of 4-6 months (young group, n =6) and 18-20 months (aged group, n =9) were used. H&E and Masson staining of frozen and paraffin sections were subjected to morphologic evaluation of the cardiac tissue samples. SA-β-Gal staining was utilized to detect the activity of senescence-associated β-galactosidase. Western blot was performed to detect the expression of Mic60 and p21 in cardiac tissues. Results: Expression of Mic60 in mouse cardiac tissue increased in an age-dependent manner. Haploid insufficiency of Mic60 resulted in an increased left ventricular wall thickness [(1.32±0.09) mm vs .(1.12±0.09) mm, P <0.05], cardiomyocyte hypertrophy[(474.9±27.6) μm(2) vs .(358.8±48.7) μm(2), P <0.05] and interstitial fibrosis [ (38.24±7.58) ×10(3)μm(2) vs .(25.81±4.12)×10(3)μm(2,) P <0.05], increased activity of SA-β-Gal (2.26±0.24 vs .0.25±0.05, P <0.01) and higher expression of p21 ( P <0.01) in aged mouse cardiac tissue, but not in young mice. Conclusion: Haploid insufficiency of Mic60 leads to cardiac hypertrophy, interstitial fibrosis, increased activity of SA-β-Gal and higher expression of p21 in aged cardiac tissue in mice, suggesting that Mic60 may prevent cardiac aging.

Purpose: The purpose of this study was to evaluate conventional acupuncture therapy in the management of clinical outcomes for temporomandibular disorders (TMD) in adults., Methods: The electronic databases PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trails.gov were searched for reports published until March 31, 2016., Results: Nine eligible studies from 8 publications involving 231 patients were included in the meta-analysis. A comparison of the main outcome of visual analog scale (VAS) values of pain between the acupuncture group and control group showed a significant decrease (MD = -0.98, 95% CI [-1.62, -0.34], I=54%, P = 0.003) in the VAS following acupuncture treatment. However, subgroup analysis according to the type of sham control group indicated that there were significant differences in the results when sham acupuncture was used as the control group (MD = -1.54, 95% CI [-2.63, -0.45], I=58%, P = 0.006) as well as when sham laser treatment was used as the control group (MD = -1.29, 95% CI [-2.32, -0.27], I = 0%, P = 0.01). However, there was no significant difference when the splint treatment group was used as the control group (MD = -0.09, 95% CI [-0.69, 0.50], I = 0%, P = 0.76). Subgroup analyses of VAS for pain by the classification of diseases indicated that the myogenous TMD subgroup demonstrated a significant difference (MD = -1.49, 95% CI [-2.45, -0.53], I = 47%, P = 0.002), and TMD showed no statistically significant difference (MD = -0.42, 95% CI [-1.14, 0.30], I = 46%, P = 0.25). Subgroup analysis according to whether the subgroup penetrated the skin showed that nonpenetrating sham acupuncture as the control group showed a significant difference (MD = -1.56, 95% CI [-2.70, -0.41], I = 58%, P = 0.008) compared with the conventional acupuncture as the treatment modality, while penetrating sham acupuncture as the control group showed no significant difference (MD = -1.29, 95% CI [-3.40, 0.82], I = not applicable, P = 0.23). No publication bias was observed considering the symmetry of the funnel plots., Conclusions: Our results indicate that conventional acupuncture therapy is effective in reducing the degree of pain in patients with TMD, especially those with myofascial pain symptoms.

Association between let-7-KRAS rs712 polymorphism and cancer risk was inconsistent. We therefore conducted this meta-analysis to clarify the association between let-7-KRAS rs712 polymorphism and cancer risk with STATA 14.0 software. A systemic literature search in online databases (PubMed, Embase, CNKI and Wanfang database) was preformed to obtain relevant articles. A total of 13 case-control studies involving 3,453 patients and 4,470 controls were identified up to May 16, 2015. The pooled results indicated that significantly increased risk were observed in Chinese population in T vs. G (OR = 1.21, 95% CI = 1.03-1.42) and TT vs. GG + GT genetic models (OR = 1.69, 95% CI = 1.17-2.42). Sensitivity analysis was conducted and the result without heterogeneity showed significant associations in all five genetic models. Subgroup analyses of cancer type indicated a similar result in digestive cancer (for T vs. G: OR = 1.41, 95% CI = 1.26-1.57; GT vs. GG: OR = 1.24, 95% CI = 1.07-1.43; TT vs. GG: OR = 2.53, 95% CI = 1.86-3.44; GT + TT vs. GG: OR = 1.36, 95% CI = 1.19-1.56; TT vs. GG + GT: OR = 2.35, 95% CI = 1.73-3.19). In summary, these evidences demonstrate that let-7-KRAS rs712 G > T polymorphism might be associated with digestive system cancer risk in the Chinese population.