Glia maturation factor beta deficiency protects against diabetic osteoporosis by suppressing osteoclast hyperactivity

Shi Si,Gu Huijie,Xu Jinyuan,Sun Wan,Liu Caiyin,Zhu Tong,Wang Juan,Gao Furong,Zhang Jieping,Ou Qingjian,Jin Caixia,Xu Jingying,Chen Hao,Li Jiao,Xu Guotong,Tian Haibin,Lu Lixia 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Excessive osteoclast activation, which depends on dramatic changes in actin dynamics, causes osteoporosis (OP). The molecular mechanism of osteoclast activation in OP related to type 1 diabetes (T1D) remains unclear. Glia maturation factor beta (GMFB) is considered a growth and differentiation factor for both glia and neurons. Here, we demonstrated that Gmfb deficiency effectively ameliorated the phenotype of T1D-OP in rats by inhibiting osteoclast hyperactivity. In vitro assays showed that GMFB participated in osteoclast activation rather than proliferation. Gmfb deficiency did not affect osteoclast sealing zone (SZ) formation but effectively decreased the SZ area by decreasing actin depolymerization. When GMFB was overexpressed in Gmfb-deficient osteoclasts, the size of the SZ area was enlarged in a dose-dependent manner. Moreover, decreased actin depolymerization led to a decrease in nuclear G-actin, which activated MKL1/SRF-dependent gene transcription. We found that pro-osteoclastogenic factors (Mmp9 and Mmp14) were downregulated, while anti-osteoclastogenic factors (Cftr and Fhl2) were upregulated in Gmfb KO osteoclasts. A GMFB inhibitor, DS-30, targeting the binding site of GMFB and Arp2/3, was obtained. Biocore analysis revealed a high affinity between DS-30 and GMFB in a dose-dependent manner. As expected, DS-30 strongly suppressed osteoclast hyperactivity in vivo and in vitro. In conclusion, our work identified a new therapeutic strategy for T1D-OP treatment. The discovery of GMFB inhibitors will contribute to translational research on T1D-OP.

Use of Clozapine for the Treatment of Schizophrenia: Findings of the 2006 Research on the China Psychotropic Prescription Studies

Tian-Mei Si,Yun-shu Zhang,Liang Shu,Ke-Qing Li,Xie-He Liu,Qi-Yi Mei,Gao-Hua Wang,Pei-Shen Bai,Li-Ping Ji,Xian-Sheng Cheng,Cui Ma,Jian-Guo Shi,Hong-Yan Zhang,Hong Ma,Xin Yu 대한정신약물학회 2012 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.10 No.2

Objective: Clozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. Methods: Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10provinces with differing levels of economic development. Results: Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36±128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. Conclusion: Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.

Factors that Influence the Presciption of Antipsychotics for Patients with Schizophrenia in China

Tian-Mei Si,Liang Shu,Ke-Qing Li,Xie-He Liu,Qi-Yi Mei,Gao-Hua Wang,Pei-Shen Bai,Li-Ping Ji,Xian-Sheng Chen,Cui Ma,Jian-Guo Shi,Hong-Yan Zhang,Hong Ma,Xin Yu 대한정신약물학회 2011 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.9 No.3

Objective: To investigate the patterns of antipsychotic use in China and to analyze the factors that influence antipsychotic prescriptions. Methods: A standardized survey was conducted from May 20 to 24 2002 in five different regions of China with varying economic levels. The patterns of antipsychotic medication use were analyzed in a sample of 4,779 patients with schizophrenia. The survey gathered information on demographic characteristics, clinical profiles, and antipsychotic medications prescribed. Multiple logistic regression was used to analyze factors related to patterns of antipsychotic medication use. Results: A plurality of patients with schizophrenia was treated with clozapine (39%); this was followed by risperidone, sulpride,chlorpromazine, perphenazine, and haloperidol. More than 56.3% of patients were treated with only one atypical antipsychotic. The mean daily dose of chlorpromazine was 365±253 mg (mean±standard deviation), and 6.5% of patients were treated with depot injections of typical antipsychotic medications. A total of 73.7% (n=3,523) of patients with schizophrenia received monotherapy,24.8% (n=1,183) received two antipsychotics, 1.1% (n=52) received three antipsychotics, and one received four different antipsychotics. Patients often simultaneously received other classes of medications including anticholinergic agents, benzodiazepines,β-blockers, antidepressants, and mood stabilizers. Economic status and clinical symptoms were the main factors that contributed to the patterns of antipsychotic prescription. Conclusion: The present study suggests that atypical antipsychotic medications, especially clozapine, are the primary psychiatric treatments of choice in the management of schizophrenia in China. Moreover, the economic status and clinical profile of the patient are the major factors affecting the prescription of antipsychotic medication.

Mutations of TYR and MITF Genes are Associated with Plumage Colour Phenotypes in Geese

Wang, Ye,Li, Si-Ming,Huang, Jing,Chen, Shi-Yi,Liu, Yi-Ping Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.6

The polymorphism of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) genes have been proposed to play a vital role in coat colour genesis in mammals, but their role remains ambiguous in geese at best. Here, we cloned and sequenced 1,397 bp coding region of MITF gene and a 588 bp fragment of TYR exon 1 for polymorphism analysis among 157 domestic geese showing three types of plumage colour. We detected a total of three SNPs (c.280T>C, c.345G>A, and c.369G>A) in TYR and six haplotypes (H1-H6). Among them, haplotypes H1, H2, H3, and H5 were significantly associated with white plumage trait of Zhedong White Geese. However, only diplotype H1H1 and H3H5 were significantly associated with white plumage trait of Zhedong White Geese (p<0.01). We only detected one SNP (c.1109C>T) for MITF gene and found that genotype CT and TT were significantly associated with white plumage trait of Zhedong White Geese. Briefly, our study suggested an association between polymorphisms of TYR and MITF genes and the plumage colour trait in domestic geese.

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Zhao, Cheng-Xiao,Liu, Ming,Xu, Yong,Yang, Kuo,Wei, Dong,Shi, Xiao-Hong,Yang, Fan,Zhang, Yao-Guang,Wang, Xin,Liang, Si-Ying,Zhao, Fan,Zhang, Yu-Rong,Wang, Na-Na,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Yuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. Results: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, $P=7.3{\times}10^{-5}$), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, $Padj=1.1{\times}10^{-4}$). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ${\geq}65$ years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype ($P=4.6{\times}10^{-5}-3.0{\times}10^{-2}$). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, $P=1.0{\times}10^{-5}$) across Asian, Caucasian and African American populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.

Dynamics of waste-to-energy incineration R&D collaboration networks: a social network analysis based on patent data

Ding Ma,Yongsheng Yu,Si-shi Liu,Ya-rui Zhang 한국자원공학회 2017 Geosystem engineering Vol.20 No.2

The municipal solid waste in China is increasing at an unprecedented pace due to the upgrading urbanization and improving living standard. The waste-to-energy (WTE) incineration technology offers a viable and potentially profitable technical solution to this booming phenomenon. The highly complex and systematic nature of WTE technologies have led to the emergence of WTE innovation network in the past decade. This study applies complex network theory as well as social network analysis to investigate the social network structure evolution of WTE technologies in terms of global network properties, major actors’ centrality and collaboration relationships. Based on the data-set covering joint filing patents pertaining to waste heat over the period 2006–2015, this study finds that the overall WTE innovation network exhibits the properties of scale-free network with minority organizations linking to abundant organizations. A large fraction of major actors represent the first-movers in the WTE research and still control the technological trajectories. The collaboration relationships have moved toward higher level of multidisciplinary and larger technological distance. Overall, the evolution of WTE innovation network features a young state of industry with high regime dependence. Finally, some suggestions are proposed to shed light on benign development of WTE innovation network.

Development of a multiplex qRT-PCR assay for detection of African swine fever virus, classical swine fever virus and porcine reproductive and respiratory syndrome virus

Yating Chen,Kaichuang Shi,Huixin Liu,Yanwen Yin,Jing Zhao,Feng Long,Wenjun Lu,Hongbin Si 대한수의학회 2021 Journal of Veterinary Science Vol.22 No.6

Background: African swine fever virus (ASFV), classical swine fever virus (CSFV), and porcine reproductive and respiratory syndrome virus (PRRSV) are still prevalent in many regions of China. Co-infections make it difficult to distinguish their clinical symptoms and pathological changes. Therefore, a rapid and specific method is needed for the differential detection of these pathogens. Objectives: The aim of this study was to develop a multiplex real-time quantitative reverse transcription polymerase chain reaction (multiplex qRT-PCR) for the simultaneous differential detection of ASFV, CSFV, and PRRSV. Methods: Three pairs of primers and TaqMan probes targeting the ASFV p72 gene, CSFV 5′ untranslated region, and PRRSV ORF7 gene were designed. After optimizing the reaction conditions, including the annealing temperature, primer concentration, and probe concentration, multiplex qRT-PCR for simultaneous and differential detection of ASFV, CSFV, and PRRSV was developed. Subsequently, 1,143 clinical samples were detected to verify the practicality of the assay. Results: The multiplex qRT-PCR assay could specifically and simultaneously detect the ASFV, CSFV, and PRRSV with a detection limit of 1.78 × 100 copies for the ASFV, CSFV, and PRRSV, but could not amplify the other major porcine viruses, such as pseudorabies virus, porcine circovirus type 1 (PCV1), PCV2, PCV3, foot-and-mouth disease virus, porcine parvovirus, atypical porcine pestivirus, and Senecavirus A. The assay had good repeatability with coefficients of variation of intra- and inter-assay of less than 1.2%. Finally, the assay was used to detect 1,143 clinical samples to evaluate its practicality in the field. The positive rates of ASFV, CSFV, and PRRSV were 25.63%, 9.36%, and 17.50%, respectively. The co-infection rates of ASFV+CSFV, ASFV+PRRSV, CSFV+PRRSV, and ASFV+CSFV+PRRSV were 2.45%, 2.36%, 1.57%, and 0.17%, respectively. Conclusions: The multiplex qRT-PCR developed in this study could provide a rapid, sensitive, specific diagnostic tool for the simultaneous and differential detection of ASFV, CSFV, and PRRSV.

PKM2 Regulates Hepatocellular Carcinoma Cell Epithelial-mesenchymal Transition and Migration upon EGFR Activation

Fan, Fang-Tian,Shen, Cun-Si,Tao, Li,Tian, Chao,Liu, Zhao-Guo,Zhu, Zhi-Jie,Liu, Yu-Ping,Pei, Chang-Song,Wu, Hong-Yan,Zhang, Lei,Wang, Ai-Yun,Zheng, Shi-Zhong,Huang, Shi-Le,Lu, Yin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Pyruvate kinase isozyme type M2 (PKM2) was first found in hepatocellular carcinoma (HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by the ERK pathway, regulated ${\beta}$-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

Zhang, Yu-Rong,Xu, Yong,Yang, Kuo,Liu, Ming,Wei, Dong,Zhang, Yao-Guang,Shi, Xiao-Hong,Wang, Jian-Ye,Yang, Fan,Wang, Xin,Liang, Si-Ying,Zhao, Cheng-Xiao,Wang, Fei,Chen, Xin,Sun, Liang,Zhu, Xiao-Quan,Zh Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

Diagnostic value of alcoholic liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) index combined with γ-glutamyl transferase in differentiating ALD and NAFLD

( Junling Wang ),( Ping Li ),( Zhilong Jiang ),( Qiuhui Yang ),( Yuqiang Mi ),( Yonggang Liu ),( Ruifang Shi ),( Yonghe Zhou ),( Jinsheng Wang ),( Wei Lu ),( Si Li ),( Dan Liu ) 대한내과학회 2016 The Korean Journal of Internal Medicine Vol.31 No.3

Background/Aims: This study aimed to verify the reliability of the alcoholic liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) index (ANI) for distinguishing ALD in patients with hepatic steatosis from NAFLD, and to investigate whether ANI combined with γ-glutamyl transferase (GGT) would enhance the accuracy of diagnosis in China. Methods: A hundred thirty-nine cases of fatty liver disease (FLD) were divided into two groups of ALD and NAFLD. The ANI was calculated with an online calculator. All indicators and ANI values were analyzed using statistical methods. Results: ANI was significantly higher in patients with ALD than in those with NAFLD (7.11 ± 5.77 vs. .3.09 ± 3.89, p < 0.001). With a cut-off value of .0.22, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of diagnosed ALD cases was 87.1%, 92.5%, and 0.934 (95% confidence interval [CI], 0.879 to 0.969), respectively. The corresponding values for aspartate aminotransferase (AST)/alanine transaminase (ALT), mean corpuscular volume (MCV), and GGT were 75.29%, 72.94%, and 0.826 (95% CI, 0.752 to 0.885); 94.34%, 83.02%, and 0.814 (95% CI, 0.739 to 0.875) and 80.23%, 79.25%, and 0.815 (95% CI, 0.740 to 0.876), respectively. ANI AUROC was significantly higher than the AST/ ALT, MCV, or GGT AUROCs (all p < 0.001), moreover, ANI showed better diagnostic performance. The combination of ANI and GGT showed a better AUROC than ANI alone (0.976 vs. 0.934, p = 0.016). The difference in AUROCs between AST/ALT, MCV, and GGT was not statistically significant (all p > 0.05). Conclusions: ANI can help distinguish ALD from NAFLD with high accuracy; when ANI was combined with GGT, its effectiveness improved further.