Hyperekplexia is a rare hereditary neurological disorder; only 5 glycine receptor alpha 1 subunit gene (GLRA1) mutations have been reported in 5 Chinese patients. We report a Chinese infant with hyperekplexia and a novel mutation at c.292G > A.

Genome-wide association studies have identified more than 150 susceptibility loci for coronary artery disease (CAD); however, there is still a large proportion of missing heritability remaining to be investigated. This study sought to identify population-based genetic variation associated with acute coronary syndromes (ACS) in individuals of Chinese Han descent. We proposed a novel strategy integrating a well-developed risk prediction model into control selection in order to lower the potential misclassification bias and increase the statistical power. An exome-wide association analysis was performed for 1,669 ACS patients and 1,935 healthy controls. Promising variants were further replicated using the existing in silico dataset. Additionally, we performed gene- and pathway-based analyses to investigate the aggregate effect of multiple variants within the same genes or pathways. Although none of the association signals were consistent across studies after Bonferroni correction, one promising variant, rs10409124 at STRN4, showed potential impact on ACS in both European and East Asian populations. Gene-based analysis explored four genes (ANXA7, ZNF655, ZNF347, and ZNF750) that showed evidence for association with ACS after multiple test correction, and identification of ZNF655 was successfully replicated by another dataset. Pathway-based analysis revealed that 32 potential pathways might be involved in the pathogenesis of ACS. Our study identified several candidate genes and pathways associated with ACS. Future studies are needed to further validate these findings and explore these genes and pathways as potential therapeutic targets in ACS.

Brachial-ankle pulse wave velocity (baPWV) was proven to be a prognostic indicator of cardiovascular events. However, the modifying effect of blood pressure (BP) on the longitudinal association between baPWV and new-onset hypertension is not well established. This study included 1849 non-hypertensive Chinese subjects from Shougang cohort study during December 2011 to July 2014. BaPWV was obtained using an Omron Colin BP-203RPE III device. Multivariate logistic regression models were used to evaluate associations of baPWV and outcomes. During a mean follow-up time of 2.36 years, 248 (13.41%) developed hypertension. BaPWV independently and gradably predicted the risk of incident hypertension and the SBP level at revisit (odds ratio or β (95% confidence interval) for participants with baPWV in quartile 4 vs. quartile 1: 2.72 (1.54, 4.78) for incident hypertension and 5.92 (4.26, 7.58) for SBP, P for trend: <0.001) after adjusting demonstrated risk factors. Besides, the effects of baseline baPWV on either incident hypertension or SBP at revisit were interactively modified by the level of baseline SBP; the effect size increased as the SBP level decreased. baPWV independently predicted the risk of hypertension and BP progression, modified by the level of SBP at baseline in this Chinese community-based population. The combination of baPWV and SBP can help differentiate the potential high-risk candidates who will develop hypertension quickly and benefit from early diagnosis and treatment.

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.

Increasing evidence uncover the essential role of long noncoding RNA (lncRNAs) in bone metabolism and the association of lncRNA with genetic risk of osteoporosis. However, whether lncRNA nuclear paraspeckle assembly transcript 1 (Neat1) is involved remains largely unknown. In the present study, we found that Neat1 is induced by osteoclastic differentiation stimuli. Knockdown of Neat1 attenuates osteoclast formation whereas overexpression of Neat1 accelerates osteoclast formation. In vivo evidence showed that enhanced Neat1 expression stimulates osteoclastogenesis and reduces bone mass in mice. Mechanically, Neat1 competitively binds with microRNA 7 (miR-7) and blocks its function for regulating protein tyrosine kinase 2 (PTK2). Intergenic SNP rs12789028 acts as allele-specific long-range enhancer for NEAT1 via chromatin interactions. We establish for the first time that Neat1 plays an essential role in osteoclast differentiation, and provide genetic mechanism underlying the association of NEAT1 locus with osteoporosis risk. These results enrich the current knowledge of NEAT1 function, and uncover the potential of NEAT1 as a therapeutic target for osteoporosis. © 2020 American Society for Bone and Mineral Research.

Objective: Bevacizumab is a recombinant humanized monoclonal antibody that blocks vascular endothelial growth factor (VEGF) with clear clinical benefits. However, overall survival of some cancer types remains low owing to resistance to bevacizumab therapy. While resistance is commonly ascribed to tumor cell invasion induced by hypoxia-inducible factor (HIF), less attention has been paid to the potential involvement of endothelial cells (ECs) in vasculature activated by anti-angiogenic drugs. Methods: Human umbilical vein ECs (HUVECs), bEnd.3 cells, and mouse retinal microvascular ECs (MRMECs) were treated with bevacizumab under conditions of hypoxia and effects on biological behaviors, such as migration and tube formation, examined. Regulatory effects on TGFβ1 and CD105 (endoglin) were established via determination of protein and mRNA levels. We further investigated whether the effects of bevacizumab could be reversed using the receptor tyrosine kinase inhibitor anlotinib. Results: Bevacizumab upregulated TGFβ1 as well as CD105, a component of the TGFβ receptor complex and an angiogenesis promoter. Elevated CD105 induced activation of Smad1/5, the inflammatory pathway and endothelial-mesenchymal transition. The migration ability of HUVECs was enhanced by bevacizumab under hypoxia. Upregulation of CD105 was abrogated by anlotinib, which targets multiple receptor tyrosine kinases including VEGFR2/3, FGFR1-4, PDGFRα/β, C-Kit, and RET. Conclusions: Bevacizumab promotes migration and tube formation of HUVECs via activation of the TGFβ1 pathway and upregulation of CD105 expression. Anlotinib reverses the effects of bevacizumab by inhibiting the above signals.

Enterocytozoon bieneusi is an intestinal pathogen that infects a wide range of species, including humans. Cattle constitute an important host for E. bieneusi; however, there is a scarcity of information on the prevalence and genotyping of E. bieneusi in cattle in the Hainan Province of China. In this study, PCR analysis of 314 fecal samples from cattle in six cities of Hainan was performed for genotype identification. The average prevalence of E. bieneusi in these animals was 9.9% (31/314), and ranged from 0.0% (0/12) to 20.5% (8/39). Five known genotypes - EbpC (n = 14), BEB4 (n = 12), J (n = 2), I (n = 1), and CHG5 (n = 1) - and a novel genotype: HNC-I (n = 1) - were identified. Genotypes EbpC and HNC-I were placed in zoonotic Group 1, and the remaining four genotypes (BEB4, J, I, and CHG5) were placed in Group 2. Since 93.5% of the genotypes found in the cattle (29/31) (EbpC, BEB4, J, and I) have previously been found in humans, these genotypes are probably involved in the transmission of microsporidiosis to humans.

The tree peony (Paeonia suffruticosa Andr.) cultivar 'Er Qiao' is appreciated for its unstable variegated flower coloration, with cyanic and acyanic flowers appearing on different branches of the same plant and occasionally in a single flower or petal. However, the variegation mechanism is still unclear.

Alcohol‑associated hepatocellular carcinoma (HCC) is a subtype of HCC with poor prognosis. The present study aimed to identify key biomarkers for alcohol‑associated HCC. The gene data profiles and corresponding clinical traits of patients with alcohol‑associated HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Firstly, good genes and good samples were identified, which were subsequently used to conduct weighted gene co‑expression network analysis (WGCNA). Hub genes in the significant modules were selected following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and from constructing a protein‑protein interaction (PPI) network. Real hub genes among hub genes were determined following progression, survival analysis and gene set enrichment analysis (GSEA), as well as reverse transcription‑quantitative PCR and immunohistochemical staining of non‑alcohol‑ and alcohol‑associated HCC samples. In total, 64 good samples of alcohol‑associated HCC with height score <160 were selected, from which 15,195 good genes were identified and used to conduct WGCNA; 8 gene co‑expressed modules were identified using WGCNA, while 3 modules (including pink, magenta and turquoise) were significantly associated with Child‑Pugh score, T‑stage and body weight. Following GO and KEGG analysis and construction of the PPI network, a total of 30 hub genes were identified in the aforementioned 3 gene co‑expressed modules, while 16 hub genes (including AURKB, BUB1, BUB1B, CCNB1, CCNB2, CDC20, CDCA8, CDK1, PLK1, RPS5, RPS7, RPS8, RPS14, RPS27, RPSA and TOP2A) were associated with the development of alcohol‑associated HCC, and had a significant prognosis value. Among these genes, only RPS8 was highly expressed in alcohol‑associated HCC, but not in non‑alcohol‑associated HCC, while RPS5 was not significantly associated in either alcohol‑ or non‑alcohol‑associated HCC. GSEA demonstrated that 10 pathways, including RNA polymerase and ribosome pathways were enriched in alcohol‑associated HCC samples where RPS8 was highly expressed. Taken together, the results of the present study demonstrate that RPS8 may be a novel biomarker for the diagnosis of patients with alcohol‑associated HCC.

Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease. Despite the significant progress made in identifying susceptibility genes for SLE, the genetic architecture of the disease is far from being understood. In this study, we set to replicate a number of suggestive association signals found in genome-wide association studies (GWASs) in additional independent cohorts. Replication studies were performed on Han Chinese cohorts from Hong Kong and Anhui, involving a total of 2,269 cases and 5,073 controls. We identified a missense variant in IRF3 (rs7251) reaching genome-wide significance through a joint analysis of GWAS and replication data (OR = 0.876, P = 4.40E-08). A significant correlation was observed between rs7251 and lupus nephritis (LN) by subphenotype stratification (OR = 0.785, P = 0.0128). IRF3 is a key molecule in type I interferon production upon nucleic acid antigen stimulations and may inhibit regulatory T cell differentiation. Further elucidation of the mechanism of this association could help us better understand the pathogenesis of SLE.

Neuropathic pain is caused by damage to the nervous system. Increasing studies have confirmed that jagged 1 (JAG1) plays a significant role in nervous system diseases. However, the regulatory mechanisms of JAG1 in neuropathic pain remain vague. In this study, a chronic constriction injury (CCI) rat model was performed. JAG1 was found to be upregulated in CCI rats. The recombinant lentiviruses containing sh-JAG1 were injected to the CCI rats for knockdown of JAG1 in rats. JAG1 knockdown improved the mechanical allodynia and thermal hyperalgesia in CCI rats, and decreased the concentrations and mRNA expression of inflammatory cytokines (IL-6, TNF-α and IL-1β) in spinal cord dorsal horn of CCI rats, suggesting that JAG1 knockdown attenuated neuropathic pain. In addition, we explored for the upstream mechanism of JAG1. Through RNA pull down assay and luciferase reporter assay, we confirmed that miR-124-3p and miR-141-3p bound with JAG1. Long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG16) was verified to be the upstream molecule of miR-124-3p and miR-141-3p to negatively regulate miR-124-3p and miR-141-3p. SNHG16 positively regulated JAG1 expression through competitively binding with miR-124-3p and miR-141-3p. Moreover, SNHG16 was found to be upregulated in CCI rats. SNHG16 knockdown improved the mechanical allodynia and thermal hyperalgesia as well as reduced the concentrations and mRNA expression of inflammatory cytokines in CCI rats. Finally, SNHG16 was confirmed to aggravate neuropathic pain in CCI rats via upregulating JAG1. In conclusion, this study verified that SNHG16 aggravated neuropathic pain in CCI rats via binding with miR-124-3p and miR-141-3p to upregulate JAG1, which may provide new insights into the development of gene therapy for neuropathic pain.

To investigate the correlation between patients' medication adherence and their psychological contract with hospital pharmacists under the background of the pharmacist-patient relationship, providing a reference for improving the pharmacist-patient relationship and the patients' medication adherence based on the patients' psychological contract with the hospital pharmacists.

To characterize the clinical, resistance, and virulence features of carbapenem-resistant Klebsiella pneumonaie (CRKP) and hypervirulent Klebsiella pneumoniae (hvKP) and also provide an effective selection of drug in CRKP and hvKP treatment.

Obesity predisposes to cancer and a virtual universality of nonalcoholic fatty liver disease (NAFLD). However, the impact of hepatic steatosis on liver metastasis is enigmatic. We find that while control mice were relatively resistant to hepatic metastasis, those which were lipodystrophic or obese, with NAFLD, had a dramatic increase in breast cancer and melanoma liver metastases. NAFLD promotes liver metastasis by reciprocal activation initiated by tumor-induced triglyceride lipolysis in juxtaposed hepatocytes. The lipolytic products are transferred to cancer cells via fatty acid transporter protein 1, where they are metabolized by mitochondrial oxidation to promote tumor growth. The histology of human liver metastasis indicated the same occurs in humans. Furthermore, comparison of isolates of normal and fatty liver established that steatotic lipids had enhanced tumor-stimulating capacity. Normalization of glucose metabolism by metformin did not reduce steatosis-induced metastasis, establishing the process is not mediated by the metabolic syndrome. Alternatively, eradication of NAFLD in lipodystrophic mice by adipose tissue transplantation reduced breast cancer metastasis to that of control mice, indicating the steatosis-induced predisposition is reversible.

Background: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) has emerged as a novel biomarker for coronary atherosclerosis. However, the association between Lp-PLA2 and plaque vulnerability in atherosclerosis of cervicocerebral arteries remains poorly defined, especially for intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the association between Lp-PLA2 and plaque vulnerability in transient ischemic attack (TIA) patients with unilateral middle cerebral artery stenoses (MCAs). Methods: In this study, a total of 207 patients were enrolled from April 2017 to April 2020. Clinical data were collected, and MCA plaques were examined with high-resolution magnetic resonance imaging (HRMRI). Baseline characteristics of patients were collected during hospitalization. Statistical comparisons were performed using Pearson's chi-squared test, Mann-Whitney U test, and the Breslow-Day/Tarone's test for the determination of heterogeneity in different age strata. Multivariate binary logistic analysis was used to investigate the potential independent predictors that were highly correlated to plaque vulnerability. Results: The results showed that a high Lp-PLA2 level (>221 ng/ml) was associated with plaque vulnerability in TIA patients with unilateral MCAs. High Lp-PLA2 was independently associated with plaque vulnerability in patients ≤ 60 years old [multivariate adjusted odds ratio (OR) = 9.854; 95% CI, 2.458-39.501] but not in patients >60 years old (multivariate adjusted OR = 1.901; 95% CI, 0.640-5.650). Predictors of plaque vulnerability in different age strata were also different. Conclusion: Lp-PLA2 levels may be correlated to plaque vulnerability in TIA patients with unilateral MCAs and might be a diagnostic biomarker for plaque vulnerability in this kind of patients, especially for ones aged ≤ 60 years old.

Phthalate acid esters (PAEs) are one of the essential plastic additives which may lead to plenty of harmful effects, including reproductive toxicity, teratogenicity, and carcinogenicity. Increasing attention has been paid to the migration of plasticizer. In this article, the disposable plastic lunch boxes were taken as the research object. The result showed that dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP) have been mainly found, whose content was 1.5 mg/kg and 2.4 mg/kg, respectively. The LOD was 2 ng/g, and LOQ was 6.7 ng/g. We further investigated the migration of PAEs into the simulated liquid at different temperature conditions. Then, the linear fitting performing by first-order kinetic migration model revealed that the lower the polarity of the simulated liquid, the larger the rate constant K 1 and initial release rate V 0. The higher the temperature, the bigger the K 1 and V 0.

Obesity is a significant risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia with increased mortality and morbidity. High-fat diet (HFD)-induced obesity is associated with the activation of endoplasmic reticulum stress (ERS). However, the role of ERS in HFD-induced AF remains elusive. Human atrium samples were examined for the ERS activation test. C57BL/6J mice were divided into four groups, including the control group, the HFD group, the 4-phenylbutyric acid (4-PBA) group, and the HFD + 4-PBA group. At the age of 4 weeks, the HFD group and the HFD + 4-PBA group were given HFD to construct the obesity model, while the other two groups were given a normal diet (ND). Transesophageal programmed electrical stimulation was conducted to evaluate the AF inducibility and duration. Atrial fibrosis and ERS activation were also investigated.We found that CHOP and GRP-78 protein were significantly higher in overweight patients than the controls (both P < 0.05). AF inducibility and duration of the HFD group were significantly higher than the other groups (both P < 0.05), while there was no difference between those groups (P > 0.05). The mice of the HFD group had significantly higher collagen volume fraction (CVF%) than the other groups (P < 0.05). ERS marker protein of GRP78, p-PERK, ATF6 and CHOP protein expression level was increased in the HFD group, which were significantly mitigated in the HFD + 4-PBA group. In summary, HFD-induced ERS activation facilitates atrial fibrosis and AF. The inhibition of ERS might alleviate atrial fibrosis and reduce the incidence of AF-associated obesity.

Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamate hypothesis describes one possible pathogenesis of SZ. The solute carrier family 1 gene (SLC1A1) is one of several genes thought to play a critical role in regulating the glutamatergic system and is strongly implicated in the pathophysiology of SZ. In this study, we identify polymorphisms of the SLC1A1 gene that may confer susceptibility to SZ in the Han Chinese population.

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies with poor prognosis. There are many selectable treatments with good prognosis in Barcelona Clinic Liver Cancer- (BCLC-) 0, A, and B HCC patients, but the most crucial factor affecting survival is the high recurrence rate after treatments. Therefore, it is of great significance to predict the recurrence of BCLC-0, BCLC-A, and BCLC-B HCC patients.

Biomarkers based on immune context may guide prognosis prediction. T-cell inactivation, exclusion, or dysfunction could cause unfavorable tumor microenvironments, which affect immunotherapy and prognosis. However, none of the immuno-biomarkers reported to date can differentiate colorectal-cancer (CRC) patients. Thus, we aimed to classify CRC patients according to the levels of T-cell activation, exclusion, and dysfunction in the tumor microenvironment.