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Background and Aims: Research on the association between activity levels and sedentary behaviour with frailty in patients affected by hepatitis B cirrhosis is sparse. This study aimed to explore the association of frailty with activity levels and sedentary behaviours in patients with hepatitis B cirrhosis. Design: This cross‐sectional study followed the STROBE checklist. Methods: This study was conducted in Guangzhou, China, between August 2021 and October 2022. The frailty condition of patients with hepatitis B cirrhosis was assessed using the liver frailty index (LFI). Their physical activity levels and sedentary time were assessed using the International Questionnaire of Physical Activity. Pearson correlation and binary logistic regression were used to analyse the data. Results: Among the 503 patients with hepatitis B cirrhosis in the final analysis, 107 (21.3%) were identified as frail. Frailty was negatively correlated with walking time (r = −0.174, p < 0.001), moderate‐intensity activity time (r = −0.185, p < 0.001), high‐intensity activity time (r = −0.243, p < 0.001) and total activity time (r = −0.256, p < 0.001). Patients with insufficient activity (<150 min/week) and sedentary behaviour (≥420 min/day) were found to have 2.829 times higher risk of frailty than those with sufficient activity (≥150 min/week) and no sedentary behaviour (<420 min/day) (95% CI: 1.380, 5.799). Conclusion: Patients with hepatitis B cirrhosis who exhibited frailty demonstrated limited physical activity and engaged in sedentary behaviours. No patient or public contribution: Patients with hepatitis B cirrhosis contributed their data to the study. [ABSTRACT FROM AUTHOR]

Objectives: To assess the diagnostic performance of the modified LR‐M method of CEUS LI‐RADS version 2017 with nodules of different sizes. Methods: This retrospective study included consecutive patients with high risk for HCC who underwent CEUS between 2019 and 2021, demonstrating an LR‐M observed using CEUS LI‐RADS version 2017. Four modified LR‐M methods were used to evaluate nodules of different sizes. The diagnostic performances of the four modified LR‐M methods were assessed in LR‐M nodules of different sizes by the area under the receiver operating characteristic curve (AUC). Results: The 261 patients with LR‐M observations included 166 HCCs and 95 non‐HCCs. A total of 133 nodules were <30 mm and defined as group A, 78 nodules were 30–50 mm in size and defined as group B, and 50 nodules were >50 mm and defined as group C. The AUCs between criterion I, II, III, and IV were not significantly different in all LR‐M nodules. The AUCs of the ROC curves between criterion I, II, III, and IV were not significantly different in group A. However, the AUC of criterion IV was significantly higher than that of criterion I and III in group B, and the AUCs of criterion I and criterion III were both not significant in group B; the AUC of criterion IV was not significant in group C. Conclusions: The modified LR‐M method could moderate the detection effectiveness in differentiating HCC from other lesions. According to tumor size, the selection of appropriate modified LR‐M diagnostic criteria could effectively improve the diagnostic performance of LR‐M. [ABSTRACT FROM AUTHOR]

Scientifically defining the scope of mountain distribution and understanding the spatial patterns of mountainous areas in China is critical for formulating development policies tailored to the diverse needs of different regions and promoting rural revitalization in mountainous areas. This study aims to scientifically define the scope of mountain distribution and understand the spatial pattern characteristics of mountainous areas in China to aid in the formulation of differentiated development policies and support the rural revitalization strategies of mountainous areas. Using measurements of the areas of mountains and hills in Mainland China, and drawing on European scholars' definitions of mountain cities, a classification system of mountainous areas was constructed based on the proportion differences between hills and mountains within counties. The results showed that hills and mountains were widely distributed across 81.52% and 85.35% of the 2847 total counties in China, respectively. Moreover, 14 provinces accounted for over 90% of the mountainous area, and 5 provinces accounted for 100%. These findings indicate that China's provinces have obvious mountainous characteristics, which need to be considered in policy‐making for regional development. [ABSTRACT FROM AUTHOR]

Background: KRT80 is a human epithelial intermediate filament type II gene; its expression product is a component of intracellular intermediate filaments (IFs) and is involved in the assembly of the cytoskeleton. There is evidence that IFs form a dense network mainly in the perinuclear area, but they can also reach the cortex. They are essential for mechanical cushioning of cells, organelle positioning, cell apoptosis, migration, adhesion, and interactions with other cytoskeletal components. Humans possess 54 functional keratin genes, and KRT80 is one of the more unique genes. It is widely expressed in almost all epithelial cells, although it is structurally more similar to type II hair keratins than to type II epithelial keratins. Aim: In this review, we summarize the basic facts about the keratin family and KRT80, the essential role of KRT80 in neoplasms, and its potential as a therapeutic target. We hope that this review will inspire researchers to at least partially focus on this area. Result: In many neoplastic diseases, the high expression status of KRT80 and its role in regulating the biological functions of cancer cells have been well established. KRT80 can effectively enhance the proliferation, invasiveness and migration of cancer cells. However, the effects of KRT80 on prognosis and clinically relevant indices in patients with various cancers have not been extensively studied, and even opposite conclusions have been reached in different studies of the same cancer. Based on this, we should add more clinically relevant studies to clarify the prospect of clinical application of KRT80. Many researchers have made great progress in studying the mechanism of action of KRT80. However, their studies should be extended to more cancers to find common regulators and signaling pathways of KRT80 in different cancers. KRT80 may have far‐reaching effects on the human body, and this marker may play a crucial role in the function of cancer cells and the prognosis of cancer patients, so it has a promising future in the field of neoplasms. Conclusion: In neoplastic diseases, KRT80 is overexpressed in many cancers and plays an essential role in promoting proliferation, migration, invasiveness and poor prognosis. The mechanisms of KRT80 functions in cancer have been partially elucidated, suggesting that KRT80 is a potentially useful cancer therapeutic target. However, more systematic, in‐depth and comprehensive studies are still needed in this field. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma (DLBCL) is a common and aggressive form of B cell lymphoma. Approximately 40% of DLBCL patients are incurable despite modern therapeutic approaches. To explore the molecular mechanisms driving the growth and progression of DLBCL, we analyzed genes with differential expression in DLBCL using the Gene Expression Profiling Interactive Analysis database. Enkurin domain‐containing protein 1 (ENKD1), a centrosomal protein‐encoding gene, was found to be highly expressed in DLBCL samples compared with normal samples. The phylogenetic analysis revealed that ENKD1 is evolutionarily conserved. Depletion of ENKD1 in cultured DLBCL cells induced apoptosis, suppressed cell proliferation, and blocked cell cycle progression in the G2/M phase. Moreover, ENKD1 expression positively correlates with the expression levels of a number of cellular homeostatic regulators, including Sperm‐associated antigen 5, a gene encoding an important mitotic regulator. These findings thus demonstrate a critical function for ENKD1 in regulating the cellular homeostasis and suggest a potential value of targeting ENKD1 for the treatment of DLBCL. [ABSTRACT FROM AUTHOR]

Background: HCFC1 encodes transcriptional co‐regulator HCF‐1, which undergoes an unusual proteolytic maturation at a centrally located proteolysis domain. HCFC1 variants were associated with X‐linked cobalamin metabolism disorders and mental retardation‐3. This study aimed to explore the role of HCFC1 variants in common epilepsy and the mechanism underlying phenotype heterogeneity. Methods: Whole‐exome sequencing was performed in a cohort of 313 patients with idiopathic partial (focal) epilepsy. Functional studies determined the effects of the variants on the proteolytic maturation of HCF‐1, cell proliferation and MMACHC expression. The role of HCFC1 variants in partial epilepsy was validated in another cohort from multiple centers. Results: We identified seven hemizygous HCFC1 variants in 11 cases and confirmed the finding in the validation cohort with additional 13 cases and six more hemizygous variants. All patients showed partial epilepsies with favorable outcome. None of them had cobalamin disorders. Functional studies demonstrated that the variants in the proteolysis domain impaired the maturation by disrupting the cleavage process with loss of inhibition of cell growth but did not affect MMACHC expression that was associated with cobalamin disorder. The degree of functional impairment was correlated with the severity of phenotype. Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated with mainly intellectual disability. Conclusion: HCFC1 is potentially a candidate gene for common partial epilepsy with distinct underlying mechanism of proteolysis dysfunction. The HCF‐1 domains played distinct functional roles and were associated with different clinical phenotypes, suggesting a sub‐molecular effect. The distinct difference between cobalamin disorders and idiopathic partial epilepsy in phenotype and pathogenic mechanism, implied a clinical significance in early diagnosis and management. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine whether HIV infection was independently associated with frailty status and its individual components. Methods: This cross‐sectional investigation included people living with HIV (PLWH) and HIV‐negative individuals from the baseline survey of the Comparative HIV and Aging Research in Taizhou (CHART) cohort, China. Frailty phenotype was based on five components: weight loss, low physical activity, exhaustion, weak grip strength and slow gait speed. Frailty was defined as the presence of at least three components, and prefrailty was defined as one or two components. Logistic regression models were used to analyse the factors associated with frailty and its components. Results: In all, 2475 people living with HIV (age 45.5 ± 14.9 years; 76.2% male) and 4948 HIV‐negative individuals (age 45.5 ± 14.8 years; 76.3% male) were included. Among PLWH, median CD4 count was 395 cells/μL and 78% were currently on antiretroviral therapy (ART). Frailty and prefrailty were significantly more prevalent in PLWH (3.2% vs 1.9% and 32.9% vs 27.9%) overall and at ages 18–39 (1.4% vs 0.2% and 22.7% vs 19.0%), 40–59 (2.5% vs 0.9% and 30.9% vs 27.9%) and 60–90 years (8.4% vs 7.4% and 57.1% vs 45.8%). HIV infection was associated with frailty and prefrailty [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.06–2.08; and aOR = 1.18, 95% CI: 1.05–1.33, respectively] after adjusting for confounding variables, but were strengthened with further adjustment for multimorbidity (aOR = 1.62, 95% CI: 1.14–2.28; and aOR = 1.22, 95% CI: 1.09–1.37), and were no longer significant with further adjustment for depressive symptoms and sleep disorders (aOR = 1.02, 95% CI: 0.71–1.46; and aOR = 1.06, 95% CI: 0.94–1.20). Among individual components, HIV infection was positively associated with weak grip strength and slow gait speed, but negatively associated with low physical activity and exhaustion in all the adjusted models described. Conclusions: Frailty and prefrailty occur more often and earlier in PLWH. However, grip strength and gait speed are affected to a greater extent, highlighting their potential as screening and intervention targets to prevent or slow frailty among PLWH. [ABSTRACT FROM AUTHOR]

Tibetan sheep is a unique breed living in Qinghai‐Tibet Plateau. Since MSTN/Smad signaling pathway plays a critical role in the regulation of muscle development, we aimed to study the mutton quality, mRNA expression of main transduction genes in the MSTN/Smad signaling pathway, and the effects of those genes on the mutton quality of Tibetan sheep in this study. Six‐month‐old Qinghai‐Tibetan sheep were selected, slaughtered, and their Longissimus lumborum, semitendinosus muscle, arm triceps, and quadriceps femoris muscle were collected. The mutton quality was evaluated, and gene expression and their association with the mutton quality were analyzed using RT‐qPCR. The results showed that the indexes of mutton quality were not significantly different between ewes and rams (p >.05) except for Warner–Bratzler shear force (WBSF) (p <.05). A total of 21 different fatty acids were detected in the muscles of Tibetan sheep, including nine types of SFA, four types of MUFA, and eight types of PUFA. The main transduction genes of the MSTN/Smad signaling pathway were found to be widely expressed in muscle tissues, but no significant differences were observed (p >.05). The correlation analysis of the main genes and mutton quality showed that MSTN was significantly correlated with redness and cooking time; Smad2, Smad3, Smad4, and TGFβRI had significant positive correlations with marbling in arm triceps; Smad3 and TGFβRII had strong negative correlations with pH24 h in Longissimus lumborum; Smad2 was negatively correlated with drip loss in Longissimus lumborum. In short, the expression level of MSTN in muscles was positively correlated with Smad2, Smad3, and Smad4 genes and negatively correlated with TGFβRII genes. Thus, the results of this study provide a theoretical basis for the regulation mechanism of the MSTN/Smad pathway on mutton quality. [ABSTRACT FROM AUTHOR]

Backgrounds: Transforming growth factor‐β (TGF‐β) type I receptor (TGFβRI) and type II receptor (TGFβRII) are the members of the TGFβ superfamily, which are potent regulators of cell proliferation and differentiation in many organ systems, and they play key roles in multiple aspects of follicle development. Objectives: We aimed to explore the characterization, expression analysis of TGFβRI and TGFβRII genes, and the association with litter size in Tibetan sheep. Methods: In this study, we cloned the complete coding sequences of TGFβRI and TGFβRII genes in Tibetan sheep and analyzed their genomic structures. Results: The results showed that percentages of sequences homology of the two proteins in Tibetan sheep were the most similar to Ovis aries (100%), followed by Bos mutus (99%). The RT‐qPCR showed that two genes were expressed widely in the different tissues of Tibetan sheep. The TGFβRI expression was the highest in the lung (p < 0.05), followed by the spleen and ovary (p < 0.05). The TGFβRII expression was significantly higher in uterus than that in lung and ovary (p < 0.05). In addition, the χ2 test indicated that all ewes in the population were in Hardy–Weinberg equilibrium, and the population was in medium or low polymorphic information content status. We also found four Single Nucleotide Polymorphism (SNPs), g.9414A > G, g.28881A > G, g.28809T > C, g.10429G > A in sheep TGFβRI gene and g.63940C > T, g.63976C > T, g.64538C > T, g.64504T > A in TGFβRII gene. Three genotypes, except for g.64504T > A, and three haplotypes were identified in each gene. linkage disequilibrium analysis indicated that there was strong linkage disequilibrium in each gene. The association analysis showed that the four SNPs of TGFβRI were associated with litter size (p < 0.05), and g.63940C > T of TGFβRII was confirmed to be associated with litter size (p < 0.05). Conclusions: Based on these preliminary results, we can assume that TGFβ receptors (TGFβRI and TGFβRII) may play an important role in sheep reproduction. [ABSTRACT FROM AUTHOR]

Aims: Etiology of the majority patients with idiopathic partial epilepsy (IPE) remains elusive. We thus screened the potential disease‐associated variants in the patients with IPE. Methods: Trios‐based whole exome sequencing was performed in a cohort of 320 patients with IPE. Frequency and molecular effects of variants were predicted. Results: Three novel BRWD3 variants were identified in five unrelated cases with IPE, which were four male cases and one female case. The variants included two recurrent missense variants (c.836C>T/p.Thr279Ile and c.4234A>C/p.Ile1412Leu) and one intronic variant close to splice site (c.2475 + 6A>G). The two missense variants were located in WD40 repeat domain and bromodomain, respectively. They were predicted to be damaging by silico tools and change hydrogen bonds with surrounding amino acids. The frequency of mutant alleles in this cohort was significantly higher than that in the controls of East Asian and all population of gnomAD. All these variants were inherited from the asymptomatic mothers. Four male cases presented frequent seizures at onset, while the female case only had two fever‐triggered seizures. They showed good responses to valproate and lamotrigine, then finally became seizure free. All the cases had no intellectual disability. Further analysis demonstrated that all previously reported destructive variants of BRWD3 caused intellectual disability, while missense variants located in WD40 repeat domains and bromodomains of BRWD3 were associated with epilepsy. Conclusion: BRWD3 gene is potentially associated with X‐linked partial epilepsy without intellectual disability. The genotypes and locations of BRWD3 variants may explain for their phenotypic variation. [ABSTRACT FROM AUTHOR]

Mahuang Xuanfei Zhike (MXZ) syrup, a Chinese patent medicine, has been widely used in the clinical treatment of cough. However, there is no reported method for the quantitative analysis of the effective components of MXZ syrup in biological samples. In this study, the effective components of MXZ syrup were screened by network pharmacology and molecular docking technology. A sensitive and rapid ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established to test the active components of MXZ syrup in rat plasma and tissue homogenates, including ephedrine, amygdalin, chlorogenic acid, harpagoside, forsythin and forsythoside A. Chromatographic separation was performed on a Waters Acquity UPLC HSS T3 column (2.1 × 50 mm, 1.8 μm) and the mass analysis was conducted using a Waters Xevo TQ mass spectrometer using multiple reaction positive and negative ion simultaneous monitoring mode. The results showed that the linearity ranged from 0.3 to 409.4 ng/ml. The extraction recoveries were all <8.33%, and the matrix effects were all <8.45, which met the requirements. The pharmacokinetic and tissue distribution results indicated that the main active components of MXZ syrup were absorbed quickly and eliminated slowly in vivo, and there may be a reabsorption process. [ABSTRACT FROM AUTHOR]

Background and Aim: Over 10% of hepatocellular carcinoma (HCC) cases recur each year, even after surgical resection. Currently, there is a lack of knowledge about the causes of recurrence and the effective prevention. Prediction of HCC recurrence requires diagnostic markers endowed with high sensitivity and specificity. This study aims to identify new key proteins for HCC recurrence and to build machine learning algorithms for predicting HCC recurrence. Methods: The proteomics data for analysis in this study were obtained from the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database. We analyzed different proteins based on cases with or without recurrence of HCC. Survival analysis, Cox regression analysis, and area under the ROC curves (AUROC > 0.7) were used to screen for more significant differential proteins. Predictive models for HCC recurrence were developed using four machine learning algorithms. Results: A total of 690 differentially expressed proteins between 50 relapsed and 77 non‐relapsed hepatitis B‐related HCC patients were identified. Seven of these proteins had an AUROC > 0.7 for 5‐year survival in HCC, including BAHCC1, ESF1, RAP1GAP, RUFY1, SCAMP3, STK3, and TMEM230. Among the machine learning algorithms, the random forest algorithm showed the highest AUROC values (AUROC: 0.991, 95% CI 0.962–0.999) for identifying HCC recurrence, followed by the support vector machine (AUROC: 0.893, 95% Cl 0.824–0.956), the logistic regression (AUROC: 0.774, 95% Cl 0.672–0.868), and the multi‐layer perceptron algorithm (AUROC: 0.571, 95% Cl 0.459–0.682). Conclusions: Our study identifies seven novel proteins for predicting HCC recurrence and the random forest algorithm as the most suitable predictive model for HCC recurrence. [ABSTRACT FROM AUTHOR]

Hypertensive disorders during pregnancy (HDP) are associated with cardiovascular disease among mothers and offspring. This meta‐analysis was conducted to further explore the associations between maternal HDP and offspring blood pressure (BP). The authors performed a search strategy in PubMed, Embase, Web of Science, and Cochrane library from database inception to January 2022. Twenty‐four studies regarding HDP were included, with pregnancy‐associated hypertension (PAH), preeclampsia (PE), gestational hypertension (GH), and chronic hypertension included in 12, 16, 6, and 3 studies, respectively. Offspring who were exposed to HDP and PAH in utero had higher systolic BP (2.46 mm Hg, 95% CI: 1.88–3.03 mm Hg; 2.70 mm Hg 95% CI: 1.89–3.51 mm Hg) and diastolic BP (1.38 mm Hg 95% CI: 0.94–1.83 mm Hg; 1.39 mm Hg 95% CI: 0.71–2.06 mm Hg) than those birthed to normotensive mothers. The offspring exposure to PE, GH, and chronic hypertension had higher systolic BP by 1.90 mm Hg (95% CI: 1.39–2.40 mm Hg), 2.47 mm Hg (95% CI: 1.59–3.35 mm Hg), and 7.85 mm Hg (95% CI: 4.10–11.61 mm Hg), respectively, and higher diastolic BP by 0.99 mm Hg (95% CI: 0.50–1.49 mm Hg), 1.04 mm Hg (95% CI: 0.60–1.47 mm Hg), and 2.92 mm Hg (95% CI: 0.98–4.86 mm Hg), respectively. An Egger test and funnel plot confirmed no significant publication bias. In conclusion, offspring exposure to all subtypes of HDP in utero led to higher BP than no exposure. It is necessary to investigate the potential mechanisms to clarify the roles of genetic and environmental factors in these associations, which could provide insight on preventing hypertension and related cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Patients have a low survival rate and a high recurrence rate, and AML is a highly heterogeneous disease without an effective and specific targeted therapy. Aims: Therefore, it is urgent to explore new AML markers to enable early diagnosis and find drug targets for individualized treatment. Results: Herein, we demonstrate that O‐linked‐N‐acetylglucosamine transferase (OGT) is significantly upregulated in AML tissues compared with normal tissues. The high level of OGT expression is significantly related to poor overall survival (OS) in AML. Inhibition of OGT can inhibit AML cell proliferation and promote AML cell apoptosis. Conclusion: These results suggest that OGT plays an important role in the pathogenesis of AML, and may become a potential biomarker and molecular drug target for precision therapy for AML. [ABSTRACT FROM AUTHOR]

Background: The prevalence of liver complications is increasing among people living with HIV, and microbial translocation (MT) might play a vital role. We conducted a prospective cohort study to evaluate the association between plasma biomarkers of MT and liver fibrosis (LF) among people living with HIV in southwest China. Method: A total of 665 people living with HIV were enrolled at baseline and had at least one follow‐up visit during the 3‐year study period. We calculated the Liver Fibrosis Index (FIB‐4) to evaluate LF and measured plasma soluble CD14 (sCD14) and lipopolysaccharide‐binding protein (LBP) as surrogate biomarkers for MT. We used ordinal logistic regression to investigate correlates of LF at baseline and used a linear mixed model to examine the association between dynamic changes in MT biomarkers and LF. Results: Of the participants, 61 (9.17%) had advanced LF (FIB‐4 >3.25), and 193 (29.02%) had moderate LF (1.45 ≤ FIB‐4 ≤ 3.25). Patients with advanced LF had higher plasma levels of sCD14 and LBP than those with moderate or no LF, both at baseline and at follow‐up. The following factors were significantly associated with advanced LF: the highest quartile of LBP (adjusted odds ratio [aOR] = 1.69; 95% confidence interval [CI] 1.02~2.81), current intravenous drug use (aOR = 1.82; 95% CI 1.06~3.12), baseline CD4 <200 cells/μl (aOR = 3.25; 95% CI 2.13~4.95), hepatitis C virus coinfection (aOR = 2.52; 95% CI 1.41~4.51) and age >50 years (aOR = 32.66; 95% CI 15.89~66.36). LF progression (increasing FIB‐4) was significantly associated with increasing sCD14 level (β = 1.11; 95% CI 0.97~1.26; p < 0.001) with covariate adjustment. Conclusion: The significant relationship between MT and LF may reveal pathogenic mechanisms and potential intervention targets of liver complications among people living with HIV in China. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) is the most common cause of cancer mortality worldwide. NSCLC has an aggressive phenotype and poor prognosis, and is quite heterogeneous without effective and specific targeted therapies. Therefore, exploring new tumor markers and drug targets for NSCLC is crucial towards individualized treatment. Here, we demonstrate that enkurin domain containing 1 (ENKD1), a protein with unknown structure and function, is significantly downregulated in NSCLC tumor tissues compared with their non‐tumor counterparts. We also show that ENKD1 expression is decreased in NSCLC cells compared to normal human lung epithelial cells. EdU incorporation, wound healing, and transwell invasion assays reveal that ENKD1 regulates the proliferation, migration, and invasion of NSCLC cells. Collectively, these results suggest that ENKD1 plays an important role in NSCLC progression and that ENKD1 is a tumor marker and a potential molecular drug target for the treatment of NSCLC patients. [ABSTRACT FROM AUTHOR]

Aims: To identify novel pathogenic gene of febrile seizures (FS)/epilepsy with antecedent FS (EFS+). Methods: The trio‐based whole‐exome sequencing was performed in a cohort of 462 cases with FS/EFS+. Silico programs, sequence alignment, and protein modeling were used to predict the damaging of variants. Statistical testing was performed to analyze gene‐based burden of variants. Results: Five heterozygous missense variants in CELSR3 were detected in five cases (families) with eight individuals (five females, three males) affected. Two variants were de novo, and three were identified in families with more than one individual affected. All the variants were predicted to be damaging in silico tools. Protein modeling showed that the variants resulted in disappearance of multiple hydrogen bonds and one disulfide bond, which potentially caused functional impairments of protein. The frequency of CELSR3 variants identified in this study was significantly higher than that in controls. All affected individuals were diagnosed with FS/EFS+, including six patients with FS and two patients with EFS+. All cases presented favorable outcomes without neurodevelopmental disorders. Conclusions: CELSR3 variants are potentially associated with FS/EFS+. [ABSTRACT FROM AUTHOR]

Ubiquitin‐specific protease 21 (USP21) has been implicated in several types of cancer. It promotes or suppresses tumor growth in a cell‐context dependent manner. Cholangiocarcinoma is a malignant tumor with a high mortality rate. However, the role of USP21 in cholangiocarcinoma remains unknown. Here, we identify that the level of USP21 is upregulated in cholangiocarcinoma using bioinformatics analysis and confirm this elevation in RBE cell lines. Cell counting and 5‐ethynyl‐2′‐deoxyuridine incorporation assays reveal that USP21 promotes the proliferation of cholangiocarcinoma. Wound healing and transwell assays demonstrate that USP21 accelerates RBE cell migration. In addition, rescue assays reveal that reintroduction of USP21 wildtype other than the deubiquitinase‐deficient C221A mutant restores USP21 depletion‐induced attenuation in cell proliferation and migration, indicative of the requirement of the deubiquitinase activity. Collectively, these data indicate that USP21 is critically involved in cholangiocarcinoma tumorigenesis and may be an effective target for the treatment of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Aims: CHD4 gene, encoding chromodomain helicase DNA‐binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy. Methods: Trios‐based whole‐exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical‐genetic aspects were used to determine the association between CHD4 variants and epilepsy. Results: Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co‐segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub‐regional point of view, the missense mutations located in the central regions from SNF2‐like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy‐related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical‐genetic aspects suggested an association between CHD4 variants and epilepsy. Conclusions: CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub‐regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations. [ABSTRACT FROM AUTHOR]

Oxidative stress of retinal ganglion cells (RGCs) has been established as a main contributor to retinal degeneration in the pathogenesis of glaucoma. Polo‐like kinase 2 (PLK2) has recently been reported to be a potent antioxidant protein that enhances cell survival in response to oxidative stress. To date, the involvement of PLK2 in RGC‐associated oxidative stress is undermined. In the present work, we evaluated whether PLK2 regulates oxidative stress evoked by hydrogen peroxide (H2O2) in RGCs. PLK2 expression was induced by H2O2 stimulation in RGCs. Upregulation of PLK2 had a profoundly cytoprotective effect on H2O2‐stimulated RGCs by attenuating cellular apoptosis and reactive oxygen species (ROS) level. Further data revealed that upregulation of PLK2 strikingly enhanced the activation of Nrf2 signaling. Moreover, PLK2 overexpression promoted glycogen synthase kinase (GSK)‐3β phosphorylation, whereas PLK2 knockdown reduced the levels of GSK‐3β phosphorylation. Notably, GSK‐3β inhibition using a chemical inhibitor markedly abrogated the suppressive effects of PLK2 knockdown on Nrf2 activation. Repression of Nrf2 blocked the PLK2 overexpression‐induced protective effects in H2O2‐stimulated RGCs. Overall, this study elucidates that upregulation of PLK2 protects RGCs against H2O2‐induced oxidative stress injury by upregulating Nrf2 activation via modulation of GSK‐3β phosphorylation. These findings underline the pivotal role of PLK2 in mediating oxidative stress‐evoked retinal degeneration in the pathogenesis of glaucoma. [ABSTRACT FROM AUTHOR]

Background: The presence of significant liver fibrosis is a key determinant of long‐term prognosis in non‐alcoholic fatty liver disease (NAFLD). We aimed to develop a novel machine learning algorithm (MLA) to predict fibrosis severity in NAFLD and compared it with the most widely used non‐invasive fibrosis biomarkers. Methods: We used a cohort of 553 adults with biopsy‐proven NAFLD, who were randomly divided into a training cohort (n = 278) for the development of both logistic regression model (LRM) and MLA, and a validation cohort (n = 275). Significant fibrosis was defined as fibrosis stage F ≥ 2. MLA and LRM were derived from variables that were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm. Results: In the training cohort, the variables selected by LASSO algorithm were body mass index, pro‐collagen type III, collagen type IV, aspartate aminotransferase and albumin‐to‐globulin ratio. The diagnostic accuracy of MLA showed the highest values of area under the receiver operator characteristic curve (AUROC: 0.902, 95% CI 0.869‐0.904) for identifying fibrosis F ≥ 2. The LRM AUROC was 0.764, 95% CI 0.710‐0.816 and significantly better than the AST‐to‐Platelet ratio (AUROC 0.684, 95% CI 0.605‐0.762), FIB‐4 score (AUROC 0.594, 95% CI 0.503‐0.685) and NAFLD Fibrosis Score (AUROC 0.557, 95% CI 0.470‐0.644). In the validation cohort, MLA also showed the highest AUROC (0.893, 95% CI 0.864‐0.901). The diagnostic accuracy of MLA outperformed that of LRM in all subgroups considered. Conclusions: Our newly developed MLA algorithm has excellent diagnostic performance for predicting fibrosis F ≥ 2 in patients with biopsy‐confirmed NAFLD. [ABSTRACT FROM AUTHOR]

To explore the structure‐activity relationships (SAR) of vancomycin and find more effective new chemical entities than known glycopeptides for the treatment of antibacterial infection, 11 novel vancomycin analogues 7 carrying N‐acyl‐substituted lipophilic substitutions on the vancosamine moiety and polar moieties on the seventh‐amino acid phenyl ring were designed and synthesized. These analogues 7 a–k have been evaluated in vitro for their antibacterial activities against S. epidermidis, S. aureus, E. faecalis and E. faecium (sensitive and resistant strains). Compounds 7 c, 7 f, and 7 i showed more potent antibacterial activity against S. aureus than vancomycin. In addition, compounds 7 f and 7 j showed promising antibacterial activity against sensitive S. epidermidis. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that general control nonderepressible 2 (GCN2) is a critical regulator of oxidative stress and cell apoptosis in response to various stimuli. However, the role of GCN2 in diabetic retinopathy remains unclear. The aim of the present study was to investigate the effects of GCN2 on oxidative stress and apoptosis in ARPE‐19 cells exposed to high glucose. The results showed that GCN2 was highly expressed in high glucose‐induced ARPE‐19 cells. Moreover, knockdown of GCN2 greatly improved ARPE‐19 cell viability in response to high glucose. In addition, GCN2 knockdown significantly suppressed the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) activity in high glucose‐stimulated ARPE‐19 cells. Furthermore, GCN2 knockdown reduced cell apoptosis and enhanced the activation of nuclear factor E2‐related factor 2/heme oxygenase‐1 (Nrf2/HO‐1) pathway in high glucose‐stimulated ARPE‐19 cells. However, knockdown of Nrf2 reversed the effects of GCN2 on oxidative stress and cell apoptosis. Taken together, our findings suggest that knockdown of GCN2 inhibits high glucose‐induced oxidative stress and apoptosis in ARPE‐19 cells through activation of the Nrf2/HO‐1 pathway. [ABSTRACT FROM AUTHOR]

Mammalian erythrocytes are highly specialized cells that have adapted to lose their nuclei and cellular components during maturation to ensure oxygen delivery. Nuclear extrusion, the most critical event during erythropoiesis, represents an extreme case of asymmetric partitioning that requires a dramatic reorganization of the cytoskeleton. However, the precise role of the microtubule cytoskeleton in the enucleation process remains controversial. In this study, we show that microtubule reorganization is critical for microtubule clearance and nuclear extrusion during erythropoiesis. Using a rodent anemia model, we found that microtubules were present in erythroblasts and reticulocytes but were undetectable in erythrocytes. Further analysis demonstrated that microtubules became disordered in reticulocytes and revealed that microtubule stabilization was critical for tubulin degradation. Disruption of microtubule dynamics using the microtubule‐stabilizing agent paclitaxel or the microtubule‐destabilizing agent nocodazole did not affect the efficiency of erythroblast enucleation. However, paclitaxel treatment resulted in the retention of tubulin in mature erythrocytes, and nocodazole treatment led to a defect in pyrenocyte morphology. Taken together, our data reveals a critical role for microtubules in erythrocyte development. Our findings also implicate the disruption of microtubule dynamics in the pathogenesis of anemia‐associated diseases, providing new insight into the pathogenesis of the microtubule‐targeted agent‐associated anemia frequently observed during cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Background & Aims: The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined. Methods: We conducted a population‐based case‐control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero‐markers were assayed using blood samples. Semi‐Bayes (SB) adjustments were applied to provide posterior estimates. Results: Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25‐5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33‐11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16‐13.82) for HBsAg‐ and HBcAb‐positive; 7.57 (95% CI: 4.87‐11.77) for HBsAg‐, HBeAg‐ and HBcAb‐positive; and 3.62 (95% CI: 2.47‐5.31) for HBsAg‐, HBeAb‐ and HBcAb‐positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03‐1.32). The SB‐adjusted OR of HBV‐positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69‐72.12) compared with those HBV‐negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41‐5.75). Conclusions: Super‐additive and super‐multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer. [ABSTRACT FROM AUTHOR]

Summary: Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of rice bacterial blight disease, which causes a reduction in rice production. The interaction between Xoo and rice is a model for the study of the gene‐for‐gene hypothesis, in which a resistance (R) gene encoding a product interacts with an effector molecule encoded by a corresponding bacterial avirulence (avr) gene. Rice XA21 functions as a plant innate immune receptor (R protein) and recognizes the avirulence protein (RaxX) of Xoo to induce the immune response and cope with pathogen attack. The sulphuration of RaxX by the tyrosine sulphotransferase RaxST is essential to its activity. The expression of raxST is regulated by the RaxH/RaxR and phoP/phoQ two‐component systems. However, the regulation of raxX expression remains unclear. Here, we showed that a gene (raxM) encodes a small protein, which functions as a regulator of raxX expression. raxX and raxM are located upstream of raxST. Transcriptional analysis indicates that raxX and raxM are separately transcribed and the promoter of raxX is located at the raxM coding region. The RaxM protein regulates its own and raxX expression, and is required for the XA21‐mediated immunity response. Therefore, we identified a regulator of raxX expression and of the Xoo–rice interaction. Our findings suggest that RaxX is not only regulated at the post‐translational level, but also at the transcriptional level. [ABSTRACT FROM AUTHOR]

Four regimes of rainfall that preceded strong regional rainfall events (RREs) over the plain area of Beijing City (BJP) were studied using hourly station‐based rainfall observations during the warm season (May–October) of the past 8 years. The RREs were outlined by the maximum rainfall at all stations over the BJP each hour. The strong RREs were classified into four groups based on the rainfall that occurred in the 3 hr before the start of the events, which originated from areas northwest, southeast, northeast and southwest of the BJP. The four groups of RREs exhibited different characteristics. The number of RREs from the northwestern mountains was the highest, that is, approximately twice (four times) that from the northeastern mountains and the southwestern plain (southeastern coastal areas). The amounts, intensities and durations of the RREs from the southwestern plain were two to fourfold higher than those from the three other directions. The mean rainfall centres of the RREs from the northeast and southeast were located outside the BJP. Correspondingly, the spatial coverages and homogeneities of the RREs in the BJP from the northeast and southeast were poorer than those from the two other directions. All four groups of RREs ended to the southeast of the BJP and occurred mainly from the late afternoon to the early morning. Detailed rainfall classification based on the origination and feature analyses of all rainfall processes will enrich our knowledge of the rainfall evolutions of the BJP. In addition, combined with a study of the circulation of the rainfall processes, comprehensive understanding of fine‐scale rainfall features will provide further information for rainfall forecasting. In the future, our analyses will be applied to the corresponding atmospheric circulations of those RREs with different origins to identify the key factors that lead to different rainfall distributions. Using the hourly station‐based rainfall observations during the warm seasons (May–October) of the past 8 years, four regimes of the rainfall preceding strong regional rainfall events (RREs) over the plain area of Beijing City (BJP) were studied. The strong RREs were classified into four groups based on the regimes of the rainfall occurring in the 3 hr before the start of the events, which originated from the northwest, southeast, northeast and southwest of the BJP and all ended to the southeast of the BJP. The number of RREs from the northwest was the largest, and the intensities and durations of the RREs from the southwest were twice to four times those from the other three directions. [ABSTRACT FROM AUTHOR]

Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population‐based case–control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti‐HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi‐Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33–1.96) among male and 0.82 (95% CI: 0.53–1.26) among female. Age at first cigarette, duration of smoking and pack‐years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg‐negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03–1.52) for HBsAg‐negative ever smokers, 7.66 (95% CI: 6.05–9.71) for HBsAg‐positive never smokers, and 15.68 (95% CI: 12.06–20.39) for HBsAg‐positive ever smokers. These different odds ratios indicated super‐additive (RERI: 7.77, 95% CI: 3.81–11.73) and super‐multiplicative interactions (ROR: 1.64, 95% CI: 1.17–2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer. [ABSTRACT FROM AUTHOR]

Objective The data on patients with short-term remission of Cushing's disease ( CD) might provide information that is not available from previous long-term remission studies. We aimed to investigate structural changes in the brain in these patients and to examine whether these changes were associated with clinical characteristics. Design A cross-sectional study was performed. Methods Thirty-four patients with CD (14 with CD in short-term remission and 20 with active CD) and 34 controls matched for age, sex and education underwent clinical evaluation and magnetic resonance imaging brain scans. Biometric measurements, disease duration and remission duration data were collected. Grey matter volumes in the whole brain were examined using voxel-based morphometry ( VBM). Results No differences were observed in the grey matter volumes of the medial frontal gyrus ( MFG) and cerebellum between the patients with remitted CD and healthy controls, whereas patients with active CD had smaller grey matter volumes in these two regions compared with controls and patients with remitted CD. Furthermore, significant correlations were found between remission time and grey matter values in these regions in short-term remission patients with CD. Additionally, greater grey matter volumes in the bilateral caudate of short-term remission patients with CD were observed. Conclusions Trends for structural restoration were found in CD patients with short-term remission. This finding was associated with the number of days elapsed since curative surgery and the current age of the patients. This study enhances our understanding of potential reversibility after the resolution of hypercortisolism in CD patients. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), which primarily affects human immunodeficiency virus (HIV)-infected adults with advanced immunodeficiency. Xinjiang province in China is an endemic area for Kaposi's sarcoma (KS), however, currently, only limited data for KSHV infection among HIV-infected individuals living in this endemic area is available. A cross-sectional study of 86 HIV positive participants was conducted in Xinjiang, China from 2014 through 2015. Plasma samples were collected and screened for KSHV and HIV infection. HIV pol gene and KSHV ORF-K1 gene were amplified and sequenced, genotypes were determined by phylogenetic analysis. Over all, prevalence was 48.9% (42/86; 95%CI 38.4-59.3%) for KSHV. Only CRF07_BC subtype has been identified among all these HIV positive individuals, while the subtype A and C of KSHV were detected in the participants. Meanwhile, we found that those with high CD4 counts (>500) showed a lower anti-KSHV titer, compared with other groups. Our study indicated a high prevalence of KSHV among HIV positive individuals in Xinjiang, China. Thus, management of HIV/AIDS patients should include KSHV screen and should consider the risk of KSHV-associated malignancies. [ABSTRACT FROM AUTHOR]

Men who have sex with men (MSM) are an important risk group for human immunodeficiency virus (HIV) and at high-risk of herpesvirus infection. However, limited information on epidemiologic patterns of HHV8 and HSV2 among MSM is available in mainland China. A cross-sectional study of 486 participants was performed in Shanghai, China from January 2013 to December 2014 to explore epidemiologic features of HHV8 and HSV2 among MSM. Serum samples were collected and tested for HHV8 by immunofluoresence assay and HSV2 antibodies by ELISA. Logistic regression analysis was conducted to determine the risk factors of HHV8 and HSV2 infections, respectively. The overall seroprevalence was 23.0% for HHV8 infection and 22.4% for HSV2 infection. HHV8 seropositivity was significantly associated with being a money boy (odds ratio (OR) = 1.64; 95%CI: 1.04-2.58), having a steady sex partner (OR = 0.52; 95%CI: 0.31-0.87), having ever had anal sex with men (OR = 2.05; 95%CI: 1.09-3.86), and being HSV2 positive (OR = 2.14; 95%CI: 1.22-3.76). HSV2 seropositivity was significantly associate with being positive for HIV (OR = 2.12; 95%CI: 1.01-4.42), syphilis (OR = 1.98; 95%CI: 1.12-3.52), HHV8 (OR = 2.17; 95%CI: 1.24-3.83), and was marginally associated with being a money boy (OR = 1. 61; 95%CI: 0.97-2.86), and having ever had unprotected casual sex (OR = 1. 72; 95%CI: 0.99-2.99). HHV8 and HSV2 infections are common in Chinese MSM. It is important to implement programs for preventing herpes virus infection among MSM, particularly high-risk groups such as money buys. And protected sexual intercourse should be propagated. J. Med. Virol. 89:887-894, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Context and objective Cushing's disease ( CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs- fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. Subjects and methods Active CD patients ( n = 18), remitted CD patients ( n = 14) and healthy control subjects ( n = 22) were included in this study. Amplitude of low-frequency fluctuation ( ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Results Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex ( PCC)/precuneus (PCu), occipital lobe ( OC)/cerebellum, thalamus, right postcentral gyrus (Po CG) and left prefrontal cortex ( PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/ PCu, a small cluster in the OC and the right IPL. Conclusions This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies. [ABSTRACT FROM AUTHOR]

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers. [ABSTRACT FROM AUTHOR]

Mutations in TIE2/TEK gene have been identified as the major cause for cutaneomucosal venous malformations (VMCM) that were previously reported to occur in Caucasian families. We report here for the first time a Chinese VMCM family of 19 affected individuals in five generations with multiple vascular lesions on their oral mucosa and extremities. Histological analyses showed that the lesions comprised of irregular vascular spaces with a continuous layer of endothelial cells and variable smooth muscle cells. Although these VMCM characters were consistent with those in Caucasian families, difference was observed in hyperplastic SMC layer and vascular walls. Haplotype analyses and DNA sequencing indicated that both the mutation-associated haplotype and a R849W (c.2545C>T) change of the TIE2 gene cosegregated perfectly with the VMCM phenotype. This result suggested that, like those in Caucasian families, the R849W mutation in TIE2 could be one of the major causes for VMCM in Asian families. [ABSTRACT FROM AUTHOR]

The image is based on the Original article, “Altered Spontaneous Brain Activity in Cushing's disease: A Resting‐State Functional MRI Study,” by QING‐FANG SUN et al., 10.1111/cen.13277. [ABSTRACT FROM AUTHOR]

Introduction Compared with western countries, China started to provide free medicine for AIDS patients years later, which leads to the late emergence of problems on health service demands of AIDS long-surviving patients with non-AIDS-related diseases. Government hasn't laid enough stress on it. Materials and Methods The interviews and questionnaire surveys are conducted and analyzed to get information. The interviewees include 81 AIDS long-surviving patients in three villages and several hospitals in Shangcai, Zhumadian, and 18 AIDS-related decision makers and health service providers. Results There are 79 long-surviving patients out of 81. 58 patients have non-AIDS-related diseases. 21 patients get hypertension and 28 get HCV. 100% patients have been to the clinics with their real-name IC cards for minor illness. 43 patients have been transferred to assigned hospitals at the county level. Seven have the experience utilizing health services in the municipal or provincial assigned hospitals. The problem is on accessibility. 40 patients hope to get more convenient and cheap health services. Among them, 37 say the kinds and the amount of medicine in village clinics are not adequate. Seven give up because of the expensive treatment expense. For 21 patients with hypertension, 3 buy medicine at the county-level hospitals. The other 18 choose to buy at private pharmacy. For 28 patients with HCV, 3 are not aware they actually got HCV. Free hepatic protector medicine is provided at village clinics. Up to 11 patients have not taken any treatment for HCV. Conclusions Patients with hypertension go to the private pharmacy for medicine instead of higher level hospital because of lack of medicine in clinics, far distance from hospitals, cumbersome procedures in hospitals, limited dosage of prescriptions and too little discount. The situation for patients with HCV is even worse. It is predicted 70% of AIDS long-surviving patients have HCV. The treatment is expensive and out of pocket. And free liver-protection medicine does not work sometimes. Some patients working outside their home town do not want to reveal their health situation to get free medicine. The elderly with multiple co-morbidities need more caring. Government should expand the scale of free medicine. Hospitals need to improve medicine plans and assist on medicine purchase. For patients, attitude decides everything. [ABSTRACT FROM AUTHOR]