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Objective To perform a meta-analysis that investigates the prevalence and seroprevalence of celiac disease (CD) in Chinese general population and high-risk populations, and to summarize data from a serological survey of high-risk populations in Guangdong, China. Methods We collected data from the serological survey of high-risk populations in Guangdong, China (n = 1390) by testing serum tissue transglutaminase immunoglobulin A (tTG-IgA), deamidated gliadin peptides immunoglobulin A (DGP-IgA) and deamidated gliadin peptides immunoglobulin G (DGP-IgG), and also searched Medline, PubMed, Embase, Cochrane and 3 Chinese databases up to December 20, 2020 to estimate the pooled prevalence and seroprevalence of CD in China. Results In the serological survey, 0.94% (13/1390) individuals were positive for CD antibodies. In a meta-analysis of 18 studies, the seroprevalence of CD in Chinese general population was 0.27% (95% CI, 0.02-0.71). The seroprevalence of CD in Chinese high-risk populations was 8.34% (95% CI, 4.90-12.54), significantly higher than that in general population (OR 7.27, 95% CI, 4.06-13.04). The prevalence of biopsied-proven CD in high-risk Chinese populations was 4.44% (95% CI, 1.53-8.58). The seroprevalence of CD was varying with geographic origin, higher in Northern China than that in Southern China. Conclusions The basis for diagnosis of CD in Chinese patients should be through early case-finding by serological screening in high-risk groups; generous serological testing in patients with vague symptoms, especially in Northern Chinese.

Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributed to cardiac fibrosis. In this study, we aimed to investigate whether IMD mitigates cardiac fibrosis by inhibiting NLRP3. Cardiac fibrosis was induced by angiotensin II (Ang II) infusion for 2 weeks in rats. Western blot, real-time PCR, histological staining, immunofluorescence assay, RNA sequencing, echocardiography and hemodynamics were used to detect the role and the mechanism of IMD in cardiac fibrosis. Ang II infusion resulted in rat cardiac fibrosis, shown as over-deposition of myocardial interstitial collagen and cardiac dysfunction. Importantly, NLRP3 activation and endoplasmic reticulum stress (ERS) was found in Ang II treated rat myocardium. Ang II infusion decreased the expression of IMD and increased the expression of the receptor system of IMD in the fibrotic rat myocardium. IMD treatment attenuated the cardiac fibrosis and improved cardiac function. In addition, IMD inhibited the upregulation of NLRP3 markers and ERS markers induced by Ang II. In vitro, IMD knockdown by small interfering RNA significantly promoted the Ang II-induced cardiac fibroblast and NLRP3 activation. Moreover, silencing of inositol requiring enzyme 1 α (IRE1α) blocked the effects of IMD inhibiting fibroblast and NLRP3 activation. Pre-incubation with PKA pathway inhibitor H89 blocked the effects of IMD on the anti-ERS, anti-NLRP3 and anti-fibrotic response. In conclusion, IMD alleviates cardiac fibrosis by inhibiting NLRP3 inflammasome activation via suppressing IRE1α and cAMP/PKA pathway.

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.

Deficiency in α-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD) 1–53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD 1–53 inhibits vascular calcification by upregulating α-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D 3 was used for study. The aortas of rats with CKD showed reduced IMD content but an increase of its receptor, calcitonin receptor-like receptor, and its receptor modifier, receptor activity-modifying protein 3. IMD 1–53 treatment reduced vascular calcification. The expression of α-Klotho was greatly decreased in the aortas of rats with CKD but increased in the aortas of IMD 1–53 -treated rats with CKD. In vitro , IMD 1–53 increased α-Klotho protein level in calcified vascular smooth muscle cells. α-Klotho knockdown blocked the inhibitory effect of IMD 1–53 on vascular smooth muscle cell calcification and their transformation into osteoblast-like cells. The effect of IMD 1–53 to upregulate α-Klotho and inhibit vascular smooth muscle cell calcification was abolished by knockdown of its receptor or its modifier protein, or treatment with the protein kinase A inhibitor H89. Thus, IMD 1–53 may attenuate vascular calcification by upregulating α-Klotho via the calcitonin receptor/modifying protein complex and protein kinase A signaling.

Cell-targeted therapies (smart drugs), which selectively control cancer cell progression with limited toxicity to normal cells, have been developed to effectively treat some cancers. However, many cancers such as metastatic prostate cancer (PC) have yet to be treated with current smart drug technology. Here, we describe the thorough preclinical characterization of an RNA aptamer (A9g) that functions as a smart drug for PC by inhibiting the enzymatic activity of prostate-specific membrane antigen (PSMA). Treatment of PC cells with A9g results in reduced cell migration/invasion in culture and metastatic disease in vivo. Importantly, A9g is safe in vivo and is not immunogenic in human cells. Pharmacokinetic and biodistribution studies in mice confirm target specificity and absence of non-specific on/off-target effects. In conclusion, these studies provide new and important insights into the role of PSMA in driving carcinogenesis and demonstrate critical endpoints for the translation of a novel RNA smart drug for advanced stage PC.

Leucine-rich repeats and WD repeat domain containing protein 1 (LRWD1) is a testis-specific protein that mainly expressed in the sperm neck where centrosome is located. By using microarray analysis, LRWD1 is identified as a putative gene that involved in spermatogenesis. However, its role in human male germ cell development has not been extensively studied. When checking in the semen of patients with asthenozoospermia, teratozoospermia, and asthenoteratozoospermia, the level of LRWD1 in the sperm neck was significantly reduced with a defective neck or tail. When checking the sub-cellular localization of LRWD1 in the cells, we found that LRWD1 resided in the centrosome and its centrosomal residency was independent of microtubule transportation in NT2/D1, the human testicular embryonic carcinoma, cell line. Depletion of LRWD1 did not induce centrosome re-duplication but inhibited microtubule nucleation. In addition, the G1 arrest were observed in LRWD1 deficient NT2/D1 cells. Upon LRWD1 depletion, the levels of cyclin E, A, and phosphorylated CDK2, were reduced. Overexpression of LRWD1 promoted cell proliferation in NT2/D1, HeLa, and 239T cell lines. In addition, we also observed that autophagy was activated in LRWD1 deficient cells and inhibition of autophagy by chloroquine or bafilomycin A1 promoted cell death when LRWD1 was depleted. Thus, we found a novel function of LRWD1 in controlling microtubule nucleation and cell cycle progression in the human testicular embryonic carcinoma cells. J. Cell. Biochem. 119: 314-326, 2018. © 2017 Wiley Periodicals, Inc.

In this study, we examined differences in serum laminin expression in patients with intractable epilepsy. Our results suggest that elevated laminin may contribute to the pathogenesis of intractable epilepsy. ELISA and western blots were used to measure laminin in the serum of 30 intractable epilepsy patients, 46 nonintractable epilepsy patients, and 20 normal subjects. By ELISA, serum laminin levels were greater in intractable epilepsy patients (177.396 +/- 30.602) and nonintractable epilepsy patients (121.915 +/- 35.215) than in normal control subjects (67.474 +/- 7.197); laminin was significantly greater in the intractable epilepsy group than in the nonintractable epilepsy group. In western blots, the optical density ratio of laminin to ss-actin was 0.871 +/- 0.032 for the intractable epilepsy group, 0.686 +/- 0.017 for the nonintractable epilepsy group, and 0.385 +/- 0.024 for the normal control group. The optical density ratios of the intractable and nonintractable epilepsy groups were higher than those for the normal control group, and the intractable epilepsy group was even greater than the nonintractable epilepsy group. Thus, laminin is significantly increased in epilepsy patients, and this increase is more profound in intractable epilepsy patients.

Objective: To evaluate the efficacy of the bronchial arterial infusion (BAI) plus radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC). Methods: 79 patients.with locally advanced NSCLC were divided randomly into two groups. In the RT group, the radiation was given by 8Mv X-ray or 18Mv X-ray .with 2Gy/fraction, 5 fraction per week with a total dose of 60Gy-65Gy/6-7 weeks. In the BAI+RT group, the radiation was given as RT group. Bronchial arterial infusion was performed before RT. The regimen consisted of DDP 100 mg/m 2 , MMC 10 rag, and 5-Fu 1000 mg. Each patient received two or three cycles. Results: The overall response rates were 80.5% in BAI+RT group and 50% in RT group. The 1-, 3-, 5-year survival rates in the BAI+RT group were significantly improved when compared to the RT group, being 87.8% vs 36.8%, 39.0% vs 7.9%, and 17.1% vs 2.6% respectively. The median time of radiation treatment to recurrence of primary lesion was 11 months in the BAI+RT group and 5 months in the RT group (P

Objective: To evatuate the results of high dose fraction radiotherapy for mucosal malignant melanoma of the head and neck (HNMM). Methods: From 1984–1994, 35 patients with HNMM were enrolled in this study. Among them, 27 cases localized to the nasal cavity or para-nasal sinus, 8 to the oral cavity. All patients received high dose fraction radiotherapy (6–8 Gy/fraction) with the total dose ranged from 40 to 60 Gy. Results: The minimum follow-up was 2 years (ranged 2–7 years). The overall 3- and 5-year survival rate was 45.7% and 24%, respectively. Conclusion: High dose fraction radiotherapy is effective for local control of HNMM.

Asthenozoospermia is a major cause of male infertility. However, the molecular mechanisms underlying sperm-motility defects remain largely unknown in the majority of cases. In our previous study, we applied a proteomic approach to identify unknown proteins that were downregulated in spermatozoa with low motility compared to spermatozoa with good motility. Several sperm motility- related proteins have been identified. In this study, 3-hydroxyisobutyrate dehydrogenase (HIBADH), one of the proteins identified using the proteomic tools, is further characterized.Reverse-transcription polymerase chain reactions (RT-PCR), western blotting, and immunofluorescence assays (IFA) were preformed to investigate the expression pattern. The enzymatic activity of HIBADH was evaluated in sperm with good (50 %), moderate (50 %) and lower motility (20 %).Using RT-PCR, we found that transcripts of HIBADH are enriched in the cerebellum, heart, skeletal muscle, uterus, placenta, and testes of male humans. In western blotting, it is expressed in the placenta, testes, and spermatozoa. During spermiogenesis, HIBADH is located at the mid-piece (a specialized development from the mitochondria) of elongating, elongated, and mature sperm. The enzymatic activity of HIBADH in sperm with moderate and lower motility were significantly reduced compared with good motility (P0.0001 and P0.05, respectively).Our study indicated that HIBADH is involved in the mitochondrial function of spermatozoa, and maintains sperm motility. It may serve as a sperm-motility marker.

We evaluated the relationship among the leptin receptor (LEPR) gene Gln223Arg polymorphism, body mass index (BMI), waist and hip circumference ratio (WHR), dietary structure, lifestyle, and other biomarkers with breast cancer and determined whether they could be effective for the prevention and treatment of breast cancer. The Gln223Arg polymorphisms in the LEPR gene were investigated in blood deoxyribonucleic acid (DNA) available for 240 breast cancer cases and 500 controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Leptin, insulin were determined by enzyme-linked immunosorbent assays. We found that the serum levels of leptin, insulin, triglyceride (TG), free cholesterol (FCH), apolipoprotain (APO) A1, and BMI were significantly higher in breast cancer cases than the controls, while physical activity was clearly less in breast cancer cases (P < 0.02 approximately P < 0.001, respectively). Moreover, there were significant association between the Gln223Arg genotype and breast cancer risk; homozygotes for AA and heterozygotes for AG,AG + GG genotypes had been proved to increase the risk of breast cancer, and their corresponding odds ratio were 7.14 (95% confidence interval [CI] = 1.92-25.64), 1.33(95% CI = 1.03-2.70), and 2.04 (95% CI = 1.09-3.82). Interestingly, logistic regression analysis showed that LEPR gene Gln223Arg polymorphism and elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB increased the risk of developing breast cancer, respectively. And, it also suggested that LEPR gene Gln223Arg polymorphisms, elevated leptin, insulin, TG, FCH, APOA1, WHR, and reduced APOB should play a major role in the development of breast cancer.

Epidemiological studies have found obesity to be a risk factor for women's breast cancer. The present study was to investigate whether there is a relationship between serum levels of leptin, insulin, and lipids and breast cancer incidence, in order to find experimental evidence that would be helpful in the diagnosis and prevention of breast cancer. Blood samples were collected from 130 patients with mammary disease and 103 healthy control subjects. Serum leptin, insulin, and lipids were determined by radioimmunoassay (RIA), enzyme-linked immunosorbent assays (ELISA), and Biochemistry Auto-analyzer, respectively. The data analysis was performed by use of the SPSS10.0 computer software. We found that the serum levels of leptin, insulin, and triglyceride (TG) were clearly higher in patients with breast cancer than in patients with benign breast disease and healthy controls, while serum HDL-C levels were lower in breast cancer patients (p0.03). Moreover, serum leptin levels were significantly correlated with BMI (body mass index) among three groups, whereas serum insulin levels were unrelated to BMI among three groups. Furthermore, the serum levels of leptin and insulin were not associated with menopausal status in patients with mammary disease (p0.05); however, the serum levels of F-Chol, T-Chol, TG, LDL-C, and APOB were significant higher in postmenopausal cases than those in premenopausal cases (p0.025). Interestingly, logistic regression analysis showed that subjects with elevated serum levels of leptin, insulin, TG, APOA1, and reduced level of serum HDL-C displayed increased risk of developing breast cancer than those with the normal levels, respectively. In conclusion, the present study suggested that aberrant serum levels of leptin, insulin, and lipids might play an important role in carcinogenesis of breast cancer. The elevated serum levels of leptin, insulin, TG, APOA1, and reduced level of serum HDL-C may be correlated with increased risk of breast cancer, suggesting that one way of preventing breast cancer would be carried out by controlling the intake of food.

Proliferating cell nuclear antigen (PCNA) is used widely to assess cell proliferation status. It is proved that PCNA is related to the tumor pathological grade, clinical staging, node metastases and prognosis. To study how the prognosis is affected by the extent of parapharyngeal space involved in nasopharyngeal carcinoma (NPC) at molecular level, we discussed the relation between PCNA and the parapharyngeal space involved of nasopharyngeal carcinoma.