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ObjectiveTo explore the protective effect of Xielitang on ulcerative colitis （UC） mice induced by dextran sodium sulfate （DSS） and its possible mechanism. MethodSixty C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group and and low-， medium-， and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group， other groups were given 1.5% DSS for 3 cycles of drinking （days 1-7， days 22-28 and days 43-49） and distilled water for the rest of the time （days 8-21， days 29-42 and days 50-63）. After the first cycle， corresponding drugs were given for 42 days. The changes of general condition， body weight and disease activity index （DAI） score of mice were daily recorded during the experiment. At the end of the treatment， serum and colon tissue samples were collected， colon length was measured， intestinal weight index and colonic mucosal injury （CMDI） score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin （HE） staining. The levels of interleukin-6 （IL-6）， interleukin-10 （IL-10） and tumour necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The gene and protein expressions of Toll like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB） and hypoxia inducible factor-1α （HIF-1α） in colon tissue was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the body weight， colon length and IL-10 content in the model group were significantly decreased （P<0.01）， DAI score， intestinal weight index， CMDI score， IL-6 and TNF-α contents， and mRNA and protein expression levels of TLR4， NF-κB and HIF-1α in the model group were significantly increased （P<0.01）. Moreover， the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group， body weight， colon length and IL-10 content in each dose group of Xielitang were significantly increased （P<0.05， P<0.01）， DAI score， intestinal weight index and CMDI score， IL-6 and TNF-α contents， mRNA and protein expression levels of TLR4， NF-κB and HIF-1α were notably decreased （P<0.05， P<0.01）. The pathological injury of colon was obviously alleviated. ConclusionXielitang can significantly improve the inflammatory response of UC mice induced by DSS， and its mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α signaling pathway.
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Polymer self-healing is mainly based on the molecular structure and interaction of polymers, and some need external stimulation, such as light, heat, pH, etc. In recent years, many studies have found that the self-healing properties of polymers can prolong the life of materials, while maintaining the mechanical properties of polymers after healing. According to the different action modes of polymer materials, it can be divided into autonomous self-healing and non-autonomous self-healing. Among them, autonomous self-healing mainly works through reversible covalent bonds (Schiff base bond, Diels-Alder reaction, hydrazide bond), reversible non-covalent bonds (hydrogen bond, metal-ligand coordination bond, electrostatic interaction, π-π stacking interaction, hydrophobic interaction) and a combination of the two interactions. Drug carriers with unique self-healing properties play an important role in the encapsulation and stable release of biomacromolecules. In this review, the self-healing mechanism of polymers and their applications in the field of biomedicine were briefly summarized and discussed.
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Objective:To investigate the association between plaque vulnerability characteristics and infarction sub-types in patients with acute unilateral anterior circulation cerebral infarction due to intracranial atherosclerotic disease.Methods:A total of 58 eligible patients who underwent intracranial high-resolution magnetic resonance imaging (HRMRI) were finally enrolled in the retrospective study from December 2018 to December 2020. In the current study, all patients were classified into the group with artery-to-artery (A-to-A) embolic infarction ( n=32) and the group without ( n=26), according to infarction sub-types on diffusion-weighted imaging. Baseline information, the presence/absence of hyperintense plaque, irregular plaque surface, remodeling pattern and quadrant distribution by HRMRI were collected and evaluated. Multivariate Logistic regression analysis was performed to determine the relationship between plaque vulnerability and infarction sub-types. Furthermore, the analysis of interaction between hyperintense plaque and positive remodeling in response to A-to-A embolism was visualized by Sankey diagram. Results:The presence of hyperintense plaque ( OR=3.90, 95% CI 1.21-12.59, P=0.023) and arterial remodeling patterns (positive remodeling vs intermediate state, OR=4.32, 95% CI 0.86-21.49, P for trend=0.027) were the strong independent predictors for A-to-A embolism. Importantly, a significantly positive synergy between the remodeling pattern and hyperintense plaque in response to infarction sub-types was found by Sankey diagram ( Wald=10.044, P for interaction=0.007). Similarly, in receiver operating characteristic curve analysis, the discrimination of hyperintense plaque combined with positive remodeling for A-to-A embolism was significantly superior to that of either biomarker alone (area under the curve=0.710, 95% CI 0.576-0.845, P=0.006). Conclusion:A synergistic effect between positive remodeling and hyperintense plaque can promote plaque vulnerability, suggesting a potential target sub-population may benefit from stroke prevention with intensive antithrombotic therapy, although this must be confirmed in future.
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Objective:To investigate the mental health status and its influencing factors in people under COVID-19 quarantine.Methods:A total of 130 people under quarantine in a centralized isolation site in Beijing from October 21 2021 to November 12 2021 were included in the study. The demographic data were collected, and the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used for evaluation of mental health status.Results:One hundred and eleven people completed the survey; there were 10 people with anxiety (9.0%) and 34 people with depression (30.6%) among the study subjects. Multivariate logistic regression analysis showed that the number of physical diseases ≥2 was the independent risk factor for anxiety ( OR=119.76,95% CI: 5.31-2 702.08, P=0.003) and depression ( OR=41.41,95% CI:6.06- 282.75, P<0.001). Conclusions:The incidence of psychological problems among people under COVID-19 quarantine is relatively high, particularly for people with multiple physical diseases, it is necessary to carry out early intervention for vulnerable people in centralized isolation sites.
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Objective:To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE 3) levels and XLI. Methods:A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE 3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results:Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE 3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant ( Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions:The decrease levels of uE 3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE 3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.
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Tendon and enthesis injuries are common sports injuries that seriously impair patients′ daily activities and quality of life. Surgical reconstruction is the main treatment for tendon and enthesis injuries. However, the surgical effect is often unsatisfactory due to the structure of repaired tendon and enthesis remaining different from those of the native ones, and re-rupture is prone to occur. Exosomes are lipid bilayer vesicles containing varieties of active substances, which play a crucial role in the communication of different cells. As a new cell-free therapy, stem cell-derived exosomes have been widely studied in the fields of drug delivery, tissue engineering and degenerative diseases, but their role in tendon and enthesis repair is rarely concerned. Therefore, the authors review tendon and enthesis injuries from aspects of histological features, repair process, and repair effect and mechanism of action of stem cells-derived exosomes, aiming to provide new insights into the basic research and clinical treatment of tendon and enthesis injuries.
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A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine the plasma concentration of progesterone in Beagle dogs, and apply it to the study of the pharmacokinetics of progesterone sustained-release formulation in Beagle dogs. The plasma samples were processed by protein precipitation method and megestrol acetate was used as an internal standard (IS). The quantitation analysis was performed using multiple-reaction monitoring (MRM) mode at the specific ion transitions of m/z 315.2→97.0 for progesterone and m/z 385.2→267.1 for megestrol acetate (IS) under the positive ion condition. Male Beagle dogs were injected intramuscularly with progesterone sustained-release microspheres and the plasma samples were collected at different time points after administration. The relevant pharmacokinetic parameters were calculated by WinNonlin 8.1 software. A good linearity over the range of 0.1-500.0 ng·mL-1 was yielded by this method. The intra- and inter-day precision (RSD) were all less than 13.25% and the accuracy (RE) was within 8.92%. Stability test showed that progesterone in dog plasma was stable at room temperature for 12 h, up to 60 days at -20 ℃ and after three cycles of freeze-thaw. The recovery of it ranged from 71.43%-77.97%. After intramuscular injection of progesterone sustained-release microspheres in Beagle dogs, tmax was 19.00 ± 25.36 h, Cmax was 137.72 ± 11.59 ng·mL-1, t1/2 was 83.83 ± 26.43 h. The drug was released continuously in vivo and in a continuous absorption process for many times with good sustained-release effect. The method developed in this study is sensitive, rapid and stable. It is suitable for the determination of progesterone plasma concentration in Beagle dogs, and can be applied to the preclinical pharmacokinetic study of progesterone-related formulations. The animal experiment scheme of this study was approved by the Animal Ethics Committee of the Academy of Military Medical Sciences.
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OBJECTIVE@#To investigate the expression of aldehyde dehydrogenase 3B1 (ALDH3B1) in gastric cancer and explore its correlation with the pathological parameters and long-term prognosis of the patients.@*METHODS@#We analyzed the clinical data of 101 patients who underwent radical gastrectomy for gastric cancer in our hospital between January, 2013 and November, 2016, and examined the expression of ALDH3B1 in paraffin-embedded samples of gastric cancer tissues and adjacent tissues from these cases by immunohistochemical staining. We evaluated the correlation between ALDH3B1 expressions and histopathological parameters and assessed the predictive value of ALDH3B1 expression for long-term survival of the patients. We also examined the effect of lentivirus-mediated interference and overexpression of ALDH3B1 on the malignant behaviors of MGC-803 gastric cancer cells.@*RESULTS@#The expressions of ALDH3B1 and Ki67 were significantly higher in gastric cancer tissues than in adjacent tissues (P < 0.05). In gastric cancer patients, ALDH3B1 expression was positively correlated with peripheral blood CEA and CA19-9 levels (P < 0.01). The proportion of patients with CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T stage of 3- 4, and N stage of 2-3 was significantly greater in high ALDH3B1 expression group than in low expression group. Kaplan-Meier survival analysis showed that the 5-year survival rate was significantly lower in gastric cancer patients with high ALDH3B1 expressions (P < 0.01). Univariate and Cox multiple regression analyses identified a high expression of ALDH3B1 (P < 0.05, HR= 0.231, 95% CI: 0.064-0.826), CEA≥5 μg/L (P < 0.01, HR=4.478, 95% CI: 1.530-13.110), CA19-9≥37 kU/L (P < 0.01, HR=3.877, 95% CI: 1.625-9.247), T stage of 3-4 (P < 0.01, HR=4.953, 95% CI: 1.768-13.880), and N stage of 2-3 (P < 0.05, HR=2.152, 95% CI: 1.152-4.022) as independent risk factors affecting 5-year survival after radical gastrectomy. The relative ALDH3B1 expression level, at the cut-off point of 4.66, showed a sensitivity of 76.47% and a specificity of 76% for predicting 5-year postoperative death (P < 0.01). In the cell experiment, overexpression of ALDH3B1 obviously promoted the proliferation, migration and invasion of MGC-803 cells.@*CONCLUSION@#As an independent risk factor affecting 5-year survival after radical gastrectomy, ALDH3B1 is highly expressed in gastric cancer and correlated with pathological parameters of the tumor, and a high ALDH3B1 expression may promote proliferation, invasion and metastasis of gastric cancer cells.
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Humans , Aldehyde Oxidoreductases , CA-19-9 Antigen , Carcinoembryonic Antigen , Gastrectomy , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/pathologyABSTRACT
OBJECTIVE@#To analyze the expression of immunoglobulin mucin molecule 3 (TIM-3) in epithelial ovarian cancer (EOC) and the effects of TIM-3 knockdown and overexpression on proliferation and migration of ovarian cancer cells.@*METHODS@#We analyzed TIM-3 expression in EOC and normal ovarian tissues using GEPIA database. We also detected TIM-3 expression levels in 82 surgical specimens of EOC and 18 specimens of normal ovarian tissues using immunohistochemistry, and analyzed the correlation of TIM-3 expression with clinicopathological parameters and survival outcomes of the patients. The expression of TIM-3 and Wnt1 mRNA in the tissues were detected using qRT-PCR. We constructed SKOV3 cell models of TIM-3 knockdown and overexpression and examined the changes in proliferation, apoptosis, migration and invasion of the cells using MTT assay, Annexin V-FITC/PI staining, scratch test and Transwell assay. The activity of Wnt/β-catenin pathway in the transfected was detected using dual luciferase reporter assay, and the mRNA levels of TCF-7, TCCFL-2 and CD44 were detected using qPCR. The protein expressions of MMP-9, CD44, Wnt1, β-catenin and E-cad in the transfected cells were detected with Western blotting.@*RESULTS@#The positive expression rate of TIM-3 was significantly higher in EOC tissues than in normal ovarian tissues (P < 0.05). The expression of TIM-3 was significantly correlated with FIGO stage, histological differentiation and lymph node metastasis, and was positively correlated with Wnt1 level (P < 0.05). In SKOV3 cells, TIM-3 knockdown significantly lowered the activity of Wnt/ β-catenin pathway, inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. TIM-3 knockdown significantly down-regulated the mRNA levels of TCF-7, TCFL-2 and CD44 and the protein levels of MMP-9, CD44, Wnt1 and β-catenin, and significantly up-regulated the expression level of E-cad (P < 0.05). Overexpression of TIM-3 caused opposite effects in SKOV3 cells.@*CONCLUSION@#TIM-3 is highly expressed in EOC tissue to promote malignant behaviors of the tumor cells possibly by activating the Wnt/β-catenin signal pathway.
Subject(s)
Female , Humans , Carcinoma, Ovarian Epithelial/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Hepatitis A Virus Cellular Receptor 2/metabolism , Ovarian Neoplasms/metabolismABSTRACT
Long-term repeated regular blood donation may result in the loss and deficiency of iron. Epidemiological studies have indicated that blood donation frequency, demographical characteristics, and genetic factors are associated with iron deficiency. Our review summarizes the progress in research of etiology of iron deficiency in blood donors and intervention measures to provide evidence for the health management of non-remunerated blood donors in China.
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Humans , Blood Donors , Ferritins , Iron , Iron Deficiencies , Risk FactorsABSTRACT
Objective:To analyze the pathogenic gene and prenatal diagnosis of a family with intellectual disability.Methods:Out of this family consisting of 17 members in three generations, four males had intellectual disability. The proband's elder sister (Ⅱ-7) visited Henan Provincial People's Hospital in Oct 2019 for genetic counseling at 8 weeks of gestation. After informed consent was obtained, peripheral blood samples of the family members were collected. The whole exome sequencing was performed on the genome DNA of the proband (Ⅱ-9, male) and his parents to screen the candidate variants for phenotype co-segregated analysis by Sanger sequencing. The expression vectors were constructed by homologous recombination and the splicing experiments were performed in vitro. Reverse transcription polymerase chain reaction, Sanger sequencing, and TA clone sequencing were used to analyze the effect of candidate variants on splicing. After the pathogenic variant was determined the proband's elder sister underwent prenatal diagnosis (Ⅲ-7) using goldeneyeTM20A genotyping system and Sanger sequencing. Results:A hemizygous synonymous variant of c.1302G>A (p. S434S) in DLG3 gene was found in the proband by whole exome sequencing, which was carried by his mother (Ⅰ-1) and co-segregated with the phenotype in other family patients. In vitro splicing experiment showed that c.1302G>A variant led to abnormal splicing of 88.24% transcripts, which further resulted in the reading frame shift and protein function impairment. The mutation was not detected in the fetus (Ⅲ-7), who was born alive later and showed no abnormal mental or behavioral development at the age of one and a half year and is still being followed up. Conclusions:The synonymous mutation c.1302G>A in DLG3 gene was the etiopathogenesis of X-linked intellectual disability in this family.
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Objective:To analyze adverse drug reactions (ADR) and reasons for drug discontinuation during acitretin therapy in patients with psoriasis vulgaris.Methods:A total of 292 patients with psoriasis vulgaris treated with acitretin were collected from the First Affiliated Hospital of Guangxi Medical University from 2014 to 2019. According to the inclusion and exclusion criteria, 193 patients who received periodic follow-up were included in this study, clinical data were collected from these patients and retrospectively analyzed. ADRs occurring during the acitretin treatment and reasons for drug discontinuation were analyzed.Results:Totally, 519 cases of ADRs occurred in 171 of the 193 patients, with the incidence rate being 88.6%. Of these cases, 174 (33.5%) involved the epithelial tissues, 126 (24.3%) the endocrine system, 1 (0.2%) the reproductive system, 29 (5.6%) the motor system, 77 (14.8%) the circulatory system, 3 (0.6%) the nervous system, 71 (13.7%) the digestive system, and 38 (7.3%) involved the urinary system. Relatively common ADRs included dryness of skin and mucous membranes, as well as musculoskeletal pain, and common biochemical changes included dyslipidemia, elevated platelets, and abnormal aminotransferase levels. Most ADRs (81.6%) were reported within 1 month after the start of acitretin therapy. Rare ADRs included alopecia, tinnitus, paronychia, myasthenia, sensory abnormalities, headache, menstrual disorders and hyperbilirubinemia, which were mainly (70.6%) reported within 1 to 6 months after the start of therapy. Of the 519 cases of ADRs, 324 could be alleviated or subsided without drug intervention, 195 were alleviated or subsided after drug withdrawal and/or drug intervention, and there were no cases of serious illness or death. Among the 193 patients, 186 had discontinued acitretin therapy, of whom 116 (62.4%) discontinued due to improvement in disease condition, 35 (18.8%) discontinued due to ADR-induced poor medication compliance, 27 (14.5%) discontinued under the guidance of clinicians due to ADRs, and 8 (4.3%) discontinued due to poor disease control.Conclusion:The incidence of adverse reactions to acitretin is high in the treatment of psoriasis vulgaris, but most of them have a good prognosis.
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Adult-onset Still′s disease (AOSD) is a rare systemic autoinflammatory disorder. In China, standardized diagnosis and treatment for AOSD is insufficient. Based on the evidence from China and other countries, Chinese Rheumatology Association developed standardization of diagnosis and treatment of AOSD in China. The purpose is to standardize the methods for diagnosis of AOSD, treatment strategies, and reduce misdiagnosis, missed diagnosis and irreversible damage.
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Objective:To evaluate the efficacy and safety of the combination of conventional western medicine therapy and oral traditional Chinese medicine (TCM) compound in the prevention and treatment of radiotherapy-inducedoral mucositis (RTOM) of nasopharyngeal carcinoma patients treated with concurrent radiotherapy and chemotherapy.Methods:A randomized, single-center, and open-label controlled experiment was conducted. Software Stata was used to generate random numbers, and 100 subjects were randomly assigned to two groups ata 1∶1 ratio, namely the integrated Chinese and western medicine group(the integrated group) and the conventional western medicine group. This study focused on the incidence of level-ⅢRTOM, followed by these verity degree of RTOM, therisk of malnutrition, and safety.Results:The incidences of level-III RTOM in the integrated group and the conventional western medicine group were 18% and 46%, respectively, with a statistically significant difference ( χ2=9.007, P=0.003). Compared to the integrated group, the conventional western medicine group showed a significantly increase dseverity degree of RTOM ( OR=3.269, 95% CI: 1.627-6.567, P<0.001) and higher risk of malnutrition ( OR=3.021, 95% CI: 1.786-5.109, P<0.001). Moreover, compared to the integrated group, the conventional western medicine group showed decrease dincidence of thirst (48.97% and 72.00% respectively; χ2=5.493, P=0.019) and decreased incidence of neutrophilcount reduction(12.24% and 30.00%, respectively, χ2=4.668, P=0.031). The incidence of mild/moderate adverse events related to TCM compound was 4.08%(2/49), and no serious adverse events related to TCM compound were observed. Conclusions:Compared to the conventional western medicine regimen, the integrated Chinese and western medicine regimen IS more effective in the prevention and treatment of RTOM. Meanwhile, its clinical application is safe and reliable.
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Purpose@#To determine the risk factors predicting upper urinary tract (UUT) damage using a grading system for upper urinary tract dilation (UUTD) and a descriptive system for all urinary tract dysfunction (AUTD) in patients with myelodysplasia. @*Methods@#Six hundred thirty-seven patients with myelodysplasia were evaluated at our center from January 2008 to November 2019. Clinical data, ultrasonography, magnetic resonance urography, and video-urodynamics (VUDS) parameters were collected. Univariate and multivariate analyses were used to determine the risk factors predicting UUT damage. @*Results@#Three hundred eighty-three males and 254 females were included. The average course of lower urinary tract symptoms (LUTS) was 14.08±7.07 years (range, 3–31 years). The urodynamic diagnoses of all patients were as follows: detrusor overactivity, 26.8%; detrusor underactivity, 6.44%; and acontractile detrusor, 66.72%. UUT damage was determined in 66.56% of the patients. Of the patients, 28.73 % had vesicoureteral reflux (VUR) during filling (bilateral, n=50; unilateral, n=133) on fluoroscopy during VUDS testing. Two hundred thirty-four patients had UUTD (bilateral, n=203; unilateral, n=31). The occurrence of hydronephrosis based on ultrasonography was closely related to ipsilateral VUR (P<0.05). Absent of bladder sensation, long-term course of LUTS, decreased maximum cystometric capacity (MCC) and bladder compliance (BC), and increased postvoid residual urine (PVR) were shown to be independent risk factors in logistic regression analysis. @*Conclusions@#This retrospective study using UUTD and AUTD systems indicated that patients with myelodysplasia have a high incidence of UUT damage. Absence of bladder sensation, long-term course of LUTS, decreased MCC and BC, and increased PVR were independent risk factors predicting UUT damage.
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Progesterone is currently the first-line drug for the treatment and prevention of threatened abortion and habitual abortion. With the gradual liberalization of China's childbirth policy, the number of elderly parturients has increased significantly. As a result, the market demand for progesterone and the individual requirements have been continuously improved. Clinical studies have found that the indications of progesterone are not limited to gynecological diseases, but can also be used for the treatment of renal colic, traumatic brain injury and other diseases. Existing progesterone preparations include oral capsules, intramuscular injections, vaginal gels, etc., but they can no longer meet the current market situation and the increase of indications. Improving existing preparations, developing new preparations, and opening up new routes of administration have become one of the directions of progesterone drug research. This article will review the research progress of new dosage forms in existing administration, new routes of administration and related preparation methods of progesterone.
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A large number of putative risk genes for autism spectrum disorder (ASD) have been reported. The functions of most of these susceptibility genes in developing brains remain unknown, and causal relationships between their variation and autism traits have not been established. The aim of this study was to predict putative risk genes at the whole-genome level based on the analysis of gene co-expression with a group of high-confidence ASD risk genes (hcASDs). The results showed that three gene features - gene size, mRNA abundance, and guanine-cytosine content - affect the genome-wide co-expression profiles of hcASDs. To circumvent the interference of these features in gene co-expression analysis, we developed a method to determine whether a gene is significantly co-expressed with hcASDs by statistically comparing the co-expression profile of this gene with hcASDs to that of this gene with permuted gene sets of feature-matched genes. This method is referred to as "matched-gene co-expression analysis" (MGCA). With MGCA, we demonstrated the convergence in developmental expression profiles of hcASDs and improved the efficacy of risk gene prediction. The results of analysis of two recently-reported ASD candidate genes, CDH11 and CDH9, suggested the involvement of CDH11, but not CDH9, in ASD. Consistent with this prediction, behavioral studies showed that Cdh11-null mice, but not Cdh9-null mice, have multiple autism-like behavioral alterations. This study highlights the power of MGCA in revealing ASD-associated genes and the potential role of CDH11 in ASD.
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Animals , Mice , Autism Spectrum Disorder/genetics , Brain , Cadherins/genetics , Gene Expression , Mice, KnockoutABSTRACT
Objective To identify factors that affect the occurrence of tuberculosis (TB) in the elderly over 60 years old in Urumqi, and to provide a basis for the prevention and treatment of tuberculosis in the elderly. Methods A 1:2 matched case-control study was conducted using a self-designed questionnaire from April 2016 to April 2017 in Urumqi, China. A conditional logistic regression analysis was carried out to identify the influencing factors for the occurrence of TB in the elderly. Results A total of 575 valid questionnaires were collected in the present study, and the age range was 60-89 years old. There were 302 males, accounting for 52.5% of the total. Multivariate logistic regression model analysis showed that an increase of one person per 100 square meters in a home elevated the risk of the development of TB by 67% (odds ratio (OR) 1.67; 95% confidence interval (CI) 1.36-2.06; P<0.001). Family income level was also important, and the risk of TB development was 4.72 times higher in families with less than 5,000 CNY a month than those with monthly incomes over 10 000 CNY (OR 4.72; 95%CI 2.29-9.75; P<0.001). The risk was significantly higher among people going out more than 3 to 7 days a week compared to those going out 0 to 2 days a week (OR 4.53; 95%CI 2.72-7.53; P<0.001). Compared with people who were not in contact with TB patients, the risk increased among those who had TB contacts (OR 3.72; 95%CI 1.45-9.70; P=0.006). In addition, the risk of TB onset in hypertension patients was significantly decreased (OR 0.57; 95%CI 0.35-0.91; P=0.018). Conclusion In the present study five factors are found to be associated with the occurrence of TB among the elderly in Urumqi, China. The future TB control program should pay special attention to the elderly population with the above risk factors.
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OBJECTIVE@#To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci.@*METHODS@#A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke.@*RESULTS@#A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033).@*CONCLUSION@#Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.
Subject(s)
Aged , Humans , Middle Aged , Genome-Wide Association Study , Ischemic Stroke , Sleep/genetics , Stroke/genetics , Surveys and QuestionnairesABSTRACT
OBJECTIVE@#To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios.@*METHODS@#The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07).@*RESULTS@#After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10-4).@*CONCLUSION@#This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.