IL-22-producing CD3 + CD8- T cells increase in immune clearance stage of chronic HBV infection and correlate with the response of Peg-interferon treatment.

Interleukin (IL)-22 regulates host defense. This study investigated the predominant IL-22-producing cell subsets under HBV associated immune stages. We found circulating IL-22-producing CD3 + CD8- T cells were significantly increased in immune active (IA) stage than those in immunotolerant stage, inactive carrier and healthy controls (HCs). The plasma IL-22 level was higher in IA and HBeAg-negative CHB compared to HCs. Importantly, CD3 + CD8- T cells were identified as the predominant source of plasma IL-22 production. Up-regulated IL-22-producing CD3 + CD8- T cells obviously correlated with the grade of intrahepatic inflammation. The proportions of IL-22-producing CD3 + CD8- T cells were significantly down-regulated after 48 weeks of Peg-interferon treatment, and the differences were of great significance in patients with normalize ALT levels at 48 weeks, rather than those with elevated ALT levels. In conclusion, IL-22 might play a proinflammatory function in. chronic HBV infected patients with active inflammation and Peg-interferon treatment could attenuate the degree of liver inflammation through down-regulating IL-22-producing CD3 + CD8- T cells.

Volatility Parametrization of Low-Volatile Components of Ambient Organic Aerosols Based on Molecular Formulas.

Evaluating the volatility of organic compounds based solely on their molecular formulas would avoid tough demands in deriving molecular structures. Here, we deployed an iodide-adduct Long Time-of-Flight Chemical Ionization Mass Spectrometry (LToF-CIMS) combined with a Filter Inlet for Gases and AEROsols (FIGAERO) to investigate molecular formulas and thermograms of organic compounds on ambient particulate samples collected in the summer of 2021 in a suburban site of Shanghai and to estimate saturation vapor pressures of low- and semivolatile components of ambient organic aerosols. Then, a hierarchical cluster analysis and a subsequent classification of obtained clusters by similarity calculation were applied to the measured data set of molecular formulas and saturation vapor pressures of organic aerosols with at least a 2/3 appearance frequency, together with a similar data set collected at a rural site in the Beijing-Tianjin-Hebei region during the winter of 2018 (Ren et al., 2018), to classify all compounds into multiple groups. For each group of compounds, parametrizations between volatility and elemental composition were derived, and then relationships between each group of parameters and the mean O:C were established to achieve a volatility-molecular formula parametrization with the O:C as a key input. Statistical comparison of estimated volatilities of low-volatile organic compounds shows a much better performance of our parametrization than previous molecular formula-based ones.

Ox-LDL aggravates contrast-induced injury of renal tubular epithelial cells.

Hypercholesterolemia can aggravate contrast-induced acute kidney injury, and the exacerbation of renal tubular epithelial cell (RTEC) injury is a major cause. However, the exact mechanisms remain obscure. Mitophagy, a type of autophagy, selectively eliminates damaged mitochondria and reduces mitochondrial oxidative stress, which is strongly implicated in cell homeostasis and acute kidney injury. Oxidized low-density lipoprotein (Ox-LDL) is accumulated in hypercholesterolemia and has a cytotoxic effect. This study aimed to determine whether and how ox-LDL exacerbates contrast-induced injury in RTECs and to further explore whether PINK1/Parkin-dependent mitophagy is involved in this process. Iohexol and ox-LDL were used alone or in combination to treat HK-2 cells. Rapamycin pretreatment was utilized to enhance mitophagy. Cell viability, apoptosis, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS) were detected by cell counting kit-8, TUNEL staining, JC-1 kit and MitoSOX fluorescence, respectively. The expression of mitophagy-related proteins (including PINK1, Parkin, and so on) and cleaved caspase-3 was confirmed by western blot. Colocalization of MitoTracker-labeled mitochondria and LysoTracker-labeled lysosomes was observed by fluorescence microscopy to evaluate mitophagy. The results of our study showed that ox-LDL aggravated MMP decline, mtROS release and apoptosis in iohexol-treated HK-2 cells, accompanied by a further increased autophagy level. Enhancement of PINK1/Parkin-dependent mitophagy by rapamycin alleviated apoptosis and mitochondrial injury in HK-2 cells in response to iohexol under ox-LDL condition. Therefore, our findings indicate that ox-LDL aggravates contrast-induced injury of RTECs by increasing mitochondrial damage and mitochondrial oxidative stress, which may be associated with the relative insufficiency of PINK1/Parkin-dependent mitophagy.

PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment.

Podocytes play a critical role in maintaining normal glomerular filtration, and podocyte loss from the glomerular basement membrane (GBM) initiates and worsens chronic kidney disease (CKD). However, the exact mechanism underlying podocyte loss remains unclear. Fructose-2,6-biphosphatase 3 (PFKFB3) is a bifunctional enzyme that plays crucial roles in glycolysis, cell proliferation, cell survival, and cell adhesion. This study aimed to determine the role of PFKFB3 in angiotensin II (Ang II) kidney damage. We found that mice infused with Ang II developed glomerular podocyte detachment and impaired renal function accompanied by decreased PFKFB3 expression in vivo and in vitro. Inhibition of PFKFB3 with the PFKFB3 inhibitor 3PO further aggravated podocyte loss induced by Ang II. In contrast, activating PFKFB3 with the PFKFB3 agonist meclizine alleviated the podocyte loss induced by Ang II. Mechanistically, PFKFB3 knockdown likely aggravate Ang II-induced podocyte loss by suppressing talin1 phosphorylation and integrin beta1 subunit (ITGB1) activity. Conversely, PFKFB3 overexpression protected against Ang II-induced podocyte loss. These findings suggest that Ang II leads to a decrease in podocyte adhesion by suppressing PFKFB3 expression, and indicates a potential therapeutic target for podocyte injury in CKD.

Allyl phenyl selenides as H2O2 acceptors to develop ROS-responsive theranostic prodrugs.

Reactive oxygen species (ROS)-responsive prodrugs have received significant attention due to their capacity to target tumors to relieve the side effects caused by chemotherapy. Herein, a series of novel H2O2-activated theranostic prodrugs (CPTSe1-CPTSe7) were developed containing allyl phenyl selenide moieties as H2O2 acceptors. Compared with conventional boronate ester-based prodrug CPT-B, CPTSe1 was more stable in human plasma and showed a more complete release of camptothecin (CPT) in H2O2 inducing experiment. The selectively activated fluorescence signals of CPTSe1 in tumor cells make it useful for real-time monitoring of CPT release and H2O2 detection. Furthermore, excellent selectivity of CPTSe1 was achieved for tumor cells over normal cells. Our results provide a new platform for the development of H2O2-responsive theranostic prodrugs.

Risky or protective? Online social support's impact on NSSI amongst Chinese youth experiencing stressful life events.

BACKGROUND: This study was designed to investigate potential gender differences in the interrelations between different types of stressful life events and non-suicidal self injury (NSSI) among Chinese youth, as well as to test the direct and moderating impacts of online social support on Chinese students' NSSI engagement under the pressure of different types of stressful life events. METHODS: Based on the data of 2200 students from middle - highschools and universities in Northwestern China, gender difference (male/female binary) in stressful life events, online social support, NSSI and their correlations were analyzed in the study. RESULTS: Among different types of stressful life events, male students were reported to experience a significantly higher impact of punishment and interpersonal relationship than females. Female students only experienced significantly higher learning pressure than males; Gender difference was not indentified in NSSI among youth; Stressful life events related to punishment could significantly predict NSSI engagement among males. Stressful life events related to learning pressures, interpersonal relationships, and adaption were significantly correlated to NSSI engagement among females; Online social support didn't had a significant direct effect on youth's NSSI, although it did significantly moderate the relationship between specific types of stressful life events (i.e., loss, interpersonal relationships, adaption among males and all types among females) and their NSSI. CONCLUSION: The present study has provided evidence of specified types of stressful life events being risk factors in affecting youth's NSSI: For male students, the higher impacts of stressful life events related to punishment they experienced, the more likely they were about to engage in NSSI. For female students, stressful life events related to learning pressure, interpersonal relationships and adaption were all proved as significant predictors and risky factors of female youth's NSSI; Online social support did not impact on individual's NSSI engagement directly, but moderated it significantly as a protective factor.

Roles of SIRT6 in kidney disease: a novel therapeutic target.

SIRT6 is an NAD+ dependent deacetylase that belongs to the mammalian sirtuin family. SIRT6 is mainly located in the nucleus and regulates chromatin remodeling, genome stability, and gene transcription. SIRT6 extensively participates in various physiological activities such as DNA repair, energy metabolism, oxidative stress, inflammation, and fibrosis. In recent years, the role of epigenetics such as acetylation modification in renal disease has gradually received widespread attention. SIRT6 reduces oxidative stress, inflammation, and renal fibrosis, which is of great importance in maintaining cellular homeostasis and delaying the chronic progression of kidney disease. Here, we review the structure and biological function of SIRT6 and summarize the regulatory mechanisms of SIRT6 in kidney disease. Moreover, the role of SIRT6 as a potential therapeutic target for the progression of kidney disease will be discussed. SIRT6 plays an important role in kidney disease. SIRT6 regulates mitochondrial dynamics and mitochondrial biogenesis, induces G2/M cycle arrest, and plays an antioxidant role in nephrotoxicity, IR, obstructive nephropathy, and sepsis-induced AKI. SIRT6 prevents and delays progressive CKD induced by hyperglycemia, kidney senescence, hypertension, and lipid accumulation by regulating mitochondrial biogenesis, and has antioxidant, anti-inflammatory, and antifibrosis effects. Additionally, hypoxia, inflammation, and fibrosis are the main mechanisms of the AKI-to-CKD transition. SIRT6 plays a critical role in the AKI-to-CKD transition and kidney repair through anti-inflammatory, antifibrotic, and mitochondrial quality control mechanisms. AKI Acute kidney injury, CKD Chronic kidney disease.

Dynamics of Race Structures of Pyricularia oryzae Populations Across 18 Seasons in Guangdong Province, China.

Rice blast, caused by Pyricularia oryzae, is one of the most damaging fungal diseases affecting rice. Understanding how the pathogen's race structure varies over time supports the efforts of rice breeders to develop improved cultivars. Here, the race structure of P. oryzae in Guangdong province, China, where rice is cropped twice per year, was assessed over 18 seasons from 1999 through 2008. The analysis was based on the reactions of a panel of seven differential Chinese cultivars to inoculation with a set of 1,248 isolates of P. oryzae in the province. The "total race frequency" parameter ranged from 14.7 to 39.7%, and the "race diversity index" ranged from 0.63 to 0.93. Twelve (ZA63, ZA31, ZA29, ZA21, ZA13, ZA9, ZB30, ZB17, ZB8, ZB2, ZC14, and ZC8) and two (ZD8 and ZD3) races were recognized as specific to indica and japonica rice types, respectively. Of the 59 distinct races identified, only two indica type races (ZC13 and ZC15) were identified as population-common, and nine indica type races (ZB1, ZB5, ZB6, ZB7, ZB13, ZB15, ZC5, ZC13, and ZC15) and one japonica type race (ZG1) were deemed to be population-dominant; the "total top two race isolate frequency" parameter ranged from 29.8 to 74.5%. On the host side, dynamics of resistance structures of the differential set were divided into three patterns: Both Tetep and Kanto 51 expressed the highest and most stable resistance, both Sifeng 43 and Lijiangxintuanheigu conveyed much lower and unstable resistance, and Zhenlong 13, Dongnong 363, and Heijiang 18 performed intermediate and seasonally dynamic resistance. Three interesting points distinguishing race structures of P. oryzae populations in southern and northeastern China were also discussed.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Rare mutations in the autophagy-regulating gene AMBRA1 contribute to human neural tube defects.

Neural tube defects (NTDs) are severe congenital malformations caused by failed neural tube closure. Recently, autophagy is revealed to play a vital role in neuroepithelium development and neurulation. Autophagy and beclin 1 regulator 1 (Ambra1) is a crucial regulator of autophagy initiation, and its deficiency in mice leads to exencephaly and/or spina bifida. However, the genetic contribution of AMBRA1 to the etiology of human NTDs remains unknown. In this study, we identified five rare missense mutations of AMBRA1 in 352 NTDs cases, which were absent in 224 matched controls. Western blotting and fluorescence puncta counting for MAP1LC3A/LC3 in HEK293T cells suggested that four of the mutations (AMBRA1 p.Thr80Met, p.Leu274Phe, p.Ser743Phe, and p.Met884Val) affected autophagy initiation to various extents. Furthermore, these four mutations also displayed loss-of-function effects compared with wild-type AMBRA1 when we injected messenger RNA (mRNA) to overexpress or rescue ambra1a-morpholino oligos (MO) knockdown in zebrafish. It is intriguing that trehalose, a natural disaccharide, could rescue ambra1a-MO knockdown in a dose-dependent manner independently or together with AMBRA1 mRNA. Taken together, our findings suggest that rare mutations of the autophagy regulator gene AMBRA1 may contribute to the etiology of human neural tube defects, and trehalose is a promising treatment for a subset of NTDs caused by autophagy impairment.

The impact of internet use frequency on non-suicidal self injurious behavior and suicidal ideation among Chinese adolescents: an empirical study based on gender perspective.

BACKGROUND: We attempted to find if there were gender differences in Non-suicidal self injurious (NSSI) behaviors and Suicidal ideation among Chinese adolescents, then analyze the impact of Internet use frequency on these variables among adolescents of different genders. METHODS: Based on the data from 6 high-schools and 4 universities in 4 cities in China, the gender difference in NSSI behaviors and Suicidal ideation and their related factors were analyzed in the study. RESULTS: Gender differences were found during different purposes of Internet use; There was no significant gender difference in NSSI behaviors among Chinese adolescents, yet females reported significantly higher intensity of suicidal ideation compared to males; Internet use frequency could explain the prevalence of NSSI behaviors and Suicidal ideation by gender, to some categories. CONCLUSIONS: There were gender differences in Internet use frequency among adolescents; Gender difference of NSSI engagement among Chinese adolescents was not statistically significant; Females had higher suicidal ideation than males; the overuse of social softwares was found to be a risk factor to both NSSI engagements and suicidal ideations for both genders; males would engage less NSSI behaviors when they spent more time on knowledge sharing softwares while might have more suicidal ideation when they spent too much time on gaming.

The effect of soy isoflavone combined with calcium on bone mineral density in perimenopausal Chinese women: a 6-month randomised double-blind placebo-controlled study.

This study was a prospective, randomised, double-blind, placebo-controlled clinical trial and aimed to compare the effect of placebo, soy isoflavone, calcium and soy isoflavone combined with calcium on bone mineral density (BMD). One hundred and sixty perimenopausal women with osteoporosis or osteopenia were enrolled and randomised into four groups: control, soy isoflavone, calcium and soy isoflavone combined with calcium groups. After intervention, compared with control, isoflavone and calcium groups, mean changes from their corresponding baseline values of BMD, calcium/phosphorus, vitamin D and glutathione peroxidase (GSH-pX) activity were significantly increased, however, those of phosphorus, osteocalcin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly decreased in isoflavone combined with calcium group. The results showed that soy isoflavone, calcium and isoflavone combined with calcium therapy were effective and safe on attenuating BMD loss in perimenopausal women and isoflavone combined with calcium therapy was better than soy isoflavone and calcium alone.

Nobiletin Delays Aging and Enhances Stress Resistance of Caenorhabditis elegans.

Nobiletin (NOB), one of polymethoxyflavone existing in citrus fruits, has been reported to exhibit a multitude of biological properties, including anti-inflammation, anti-oxidation, anti-atherosclerosis, neuroprotection, and anti-tumor activity. However, little is known about the anti-aging effect of NOB. The objective of this study was to determine the effects of NOB on lifespan, stress resistance, and its associated gene expression. Using Caenorhabditis elegans, an in vivo nematode model, we found that NOB remarkably extended the lifespan; slowed aging-related functional declines; and increased the resistance against various stressors, including heat shock and ultraviolet radiation. Also, NOB reduced the effects of paraquat stressor on nematodes and scavenged reactive oxygen species (ROS). Furthermore, gene expression revealed that NOB upregulated the expression of sod-3, hsp-16.2, gst-4, skn-1, sek-1, and sir-2.1, which was suggested that anti-aging activity of NOB was mediated most likely by activation of the target genes of the transcription factors including dauer formation (DAF)-16, heat-shock transcription factor (HSF)-1, and skinhead (SKN)-1. In summary, NOB has potential application in extension of lifespan, and its associated healthspan and stress resistances.

Novel mutations of AXIN2 identified in a Chinese Congenital Heart Disease Cohort.

Congenital heart defects (CHDs), the most common congenital human birth anomalies, involves complex genetic factors. Wnt/ß-catenin pathway is critical for cardiogenesis and proved to be associated with numerous congenital heart abnormities. AXIN2 has a unique role in Wnt/ß-catenin pathway, as it is not only an important inhibitor but also a direct target of Wnt/ß-catenin pathway. However, whether AXIN2 is associated with human CHDs has not been reported. In our present study, we found a differential expression of Axin2 mRNA during the development of mouse heart, indicating its importance in mouse cardiac development. Then using targeted next-generation sequencing, we found two novel case-specific rare mutations [c.28 C > T (p.L10F), c.395 A > G (p.K132R)] in the sequencing region of AXIN2. In vitro functional analysis suggested that L10F might be a loss-of-function mutation and K132R is a gain-of-function mutation. Both mutations disrupted Wnt/ß-catenin pathway and failed to rescue CHD phenotype caused by Axin2 knockdown in zebrafish model. Collectively, our study indicates that rare mutations in AXIN2 might contribute to the risk of human CHDs and a balanced canonical Wnt pathway is critical for cardiac development process. To our knowledge, it is the first study of AXIN2 mutations associated with human CHDs, providing new insights into CHD etiology.

A functional indel polymorphism rs34396413 in TFAP2A intron-5 significantly increases female encephalocele risk in Han Chinese population.

PURPOSE: Transcription factor AP-2 alpha (TFAP2A) is an important transcriptional factor involved in various aspects of embryo development including neural tube closure. Tfap2a deficiency led to the failure of cranial neural-tube closure in mice and other model organisms. However, it remains largely unknown about the relationship between TFAP2A variants and human cranial neural tube defects (NTDs). The aim of this study was to find the association between TFAP2A intronic SNP rs3439413 and NTDs and to explore its function. METHODS: We found an indel polymorphism rs3439413 in TFAP2A intron-5 from our previous target sequencing project. In this study, we validate its association with human NTDs in Shanxi group containing 266 NTD cases and 295 matched controls. Then, we investigated its function on transcriptional activity by dual-luciferase assays and EMSA. RESULTS: The minor allele of rs34396413 significantly increased the risk of NTD in a Han Chinese population of Shanxi Province (P = 0.0082, OR = 1.45, 95%CI = 1.10-1.90), especially the risk of encephalocele for female (P = 0.0064, OR = 2.46, 95%CI = 1.22-4.94). Functional analysis revealed the minor allele of rs34396413 decreases transcriptional activity and attenuates transcription factor binding affinity. CONCLUSION: We have demonstrated that the minor allele of rs34396413 was a risk factor of NTD in the Shanxi group, providing new insight into the study of NTD etiology.

MIB1 mutations reduce Notch signaling activation and contribute to congenital heart disease.

Congenital heart disease (CHD) is one of the most common birth defects in humans, but its genetic etiology remains largely unknown despite decades of research. The Notch signaling pathway plays critical roles in embryonic cardiogenesis. Mind bomb 1 (Mib1) is a vital protein that activates the Notch signaling pathway through promoting ubiquitination, endocytosis and subsequent activation of Notch ligands. Previous studies show that Mib1 knockout in mice completely abolishes Notch signaling, leading to cardiac deformity. However, the function of MIB1 and its potential disease-causing mutations are poorly studied in human CHD. In this research, we identified four novel non-synonymous heterozygous rare mutations of MIB1 from 417 Han Chinese CHD patients. The following biochemical analyses revealed that mutations p.T312K fs*55 and p.W271G significantly deplete MIB1's function, resulting in a lower level of JAGGED1 (JAG1) ubiquitination and Notch signaling induction. Our results suggest that pathologic variants in MIB1 may contribute to CHD occurrence, shedding new light on the genetic mechanism of CHD in the context of the Notch signaling pathway.

Synthesis and biological evaluation of irreversible EGFR tyrosine kinase inhibitors containing pyrido[3,4-d]pyrimidine scaffold.

In the present study, a new class of compounds containing pyrido[3,4-d]pyrimidine scaffold with an acrylamide moiety was designed as irreversible EGFR-TKIs to overcome acquired EGFR-T790M resistance. The most promising compound 25h inhibited HCC827 and H1975 cells growth with the IC50 values of 0.025 µM and 0.49 µM, respectively. Meanwhile, 25h displayed potent inhibitory activity against the EGFRL858R (IC50 = 1.7 nM) and EGFRL858R/T790M (IC50 = 23.3 nM). 25h could suppress EGFR phosphorylation in HCC827 and H1975 cell lines and significantly induce the apoptosis of HCC827 cells. Additionally, compound 25h could remarkably inhibit cancer growth in established HCC827 xenograft mouse model at 50 mg/kg in vivo. These results indicated that the 2,4-disubstituted 6-(5-substituted pyridin-2-amino)pyrido[3,4-d]pyrimidine derivatives can serve as effective EGFR inhibitors and potent anticancer agents.

Calpain inhibitor I attenuates atherosclerosis and inflammation in atherosclerotic rats through eNOS/NO/NF-κB pathway.

We previously reported that calpain, the Ca2+-sensitive cysteine protease, gets involved in atherogenesis. This study aimed to investigate the effects of calpain inhibitor I (CAI, 5 mg/kg per day) with or without NG-nitro-l-arginine-methyl ester (l-NAME) (100 mg/kg per day), the inhibitor of nitric oxide synthase (NOS), on atherosclerosis and inflammation in a rat model induced by high-cholesterol diet (HCD). The results demonstrated HCD increased protein expression of calpain-1 but not calpain-2 in aortic tissue. In addition, CAI reduced the thickness of atherosclerotic intima compared with HCD group, which was weakened by the l-NAME combination. CAI with or without l-NAME decreased the activity of calpain in the aorta. Also, CAI decreased the expressions of vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aorta at the levels of both mRNA and protein. Furthermore, CAI increased the activity and the protein expression of endothelial NOS (eNOS) accompanied by increased content of NO and downregulated the protein expression of nuclear factor κB (NF-κB) of the nucleus in the aorta. However, the abovementioned effects were at least partly cancelled by l-NAME except for the protein expression of eNOS. The results suggested that CAI attenuated atherosclerosis and inflammation through eNOS/NO/NF-κB pathway.

[Effects of medium-chain fatty acids on high-density-lipoprotein in rats fed with high fat diet].

OBJECTIVE: To explore the effects of medium-chain fatty acid( MCFA) on high-density-lipoprotein( HDL) in serum, liver and small intestine in Sprague Dawley rats fed with high fat diet. METHODS: Thirty obese rats were divided into 3 groups randomly, and were fed high fat diet mixed with 2% octanoic acid, 2% decanoic acid, 2% oleic acid respectively for 8 weeks. The levels of blood HDL, apolipoprotein A1( ApoA1), apolipoprotein A2( ApoA2), triglyceride( TG), total cholesterol( TC), high-densitylipoprotein cholesterol( HDL-c), low-density lipoprotein cholesterol( HDL-c) in serum were measured at the fourth and eighth week. The levels of HDL, ApoA1, and ApoA2 in liver and small intestine were measured by ELISA. Real-time PCR was used to detect the mRNA expression of ApoA1 and ApoA2 in liver and small intestine from rats at the eighth week. RESULTS: At the eighth week, significant decreases in levels of serum TG and TC were observed in octanoic acid and decanoic acid groups as compared with oleic acid group( P < 0. 05). Greater increases in levels of serum HDL and HDL-c/LDL-c were observed in octanoic acid group than in oleic acid group( P < 0. 05). Greater increases in protein expression of HDL and ApoA1 and in mRNA expression of ApoA1 in small intestine were observed in octanoic acid group than in oleic acid group( P < 0. 05). CONCLUSION: MCFA can elevate the levels of HDL, HDL-c/LDL-c in serum, and increase the expressions of HDL and ApoA1 in small intestine.

A reversed gender pattern? A meta-analysis of gender differences in the prevalence of non-suicidal self-injurious behaviour among Chinese adolescents.

BACKGROUND: A reversed gender pattern has been observed in the suicide rate in China compared to elsewhere. Like suicidal behaviour, non-suicidal self-injurious (NSSI) behaviour is a health-risk behaviour. We examined whether a reversed gender pattern existed in the prevalence of NSSI. METHODS: Online literature databases were searched for English and Chinese articles on NSSI behaviours among the Chinese. A meta-analysis with a random-effects model and a subgroup analysis were used to estimate the odds ratios of gender differences in NSSI prevalence among Chinese adolescents including college students, middle school students, and clinical samples, as well as rural, urban, and Hong Kong middle school students. RESULTS: There was a male bias in NSSI prevalence among college students (OR = 1.56, 95% CI = [1.30, 1.87], p < 0.001), and a female bias among middle school students (OR = 0.83, 95% CI = [0.73, 0.94], p < 0.01), but there was no gender difference among clinical samples (OR = 0.88, 95% CI = [0.41, 1.89], p > 0.1). The NSSI prevalence among middle school students had a female bias in the rural (OR = 0.58, 95% CI = [0.47, 0.72], p < 0.001) and Hong Kong areas (OR = 0.91, 95% CI = [0.86, 0.96], p < 0.001), with the gender difference in NSSI prevalence in the Hong Kong areas being greater than in rural areas. No gender difference in NSSI prevalence was found in urban areas (OR = 1.01, 95% CI = [0.84, 1.22], p > 0.1) among middle school students. CONCLUSIONS: Our analysis indicated the existence of specific gender and age patterns in NSSI prevalence among Chinese adolescents. The sample type, age, and the areas that have different gender norms and culture could partly explain this pattern.

Genetic analysis of rare coding mutations of CELSR1-3 in congenital heart and neural tube defects in Chinese people.

The planar cell polarity (PCP) pathway is critical for proper embryonic development of the neural tube and heart. Mutations in these genes have previously been implicated in the pathogenesis of neural tube defects (NTDs), but not in congenital heart defects (CHDs) in humans. We systematically identified the mutation patterns of CELSR1-3, one family of the core PCP genes, in human cohorts composed of 352 individuals with NTDs, 412 with CHDs and matched controls. A total of 72 disease-specific, rare, novel, coding mutations were identified, of which 37 were identified in patients with CHDs and 36 in patients with NTDs. Most of these mutations differed between the two cohorts, because only one novel missense mutation in CELSR1 (c.2609G>A p.P870L) was identified in both NTD and CHD patients. Both in vivo and in vitro assays revealed that CELSR1 P870L is a gain-of-function mutation. It up-regulates not only the PCP pathway, but also canonical WNT signalling in cells, and also induces both NTDs and CHDs in zebrafish embryos. As almost equal numbers of mutations were identified in each cohort, our results provided the first evidence that mutations in CELSR genes are as likely to be associated with CHDs as with NTDs, although the specific mutations differ between the two cohorts. Such differences in mutation panels suggested that CELSRs [cadherin, EGF (epidermal growth factor), LAG (laminin A G-type repeat), seven-pass receptors)] might be regulated differently during the development of these two organ systems.