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Objective To investigated the spatial and temporal expression of Atoh1 mRNA and protein level during the cerebellar development. Methods The frozen cerebellum sections of mice at different developmental stages were used to analyze the temporal and spatial expression patterns of Atoh1 mRNA by RNA scope technique, n= 3 for each group. Meanwhile, two reporter mice with different genetic modification method were utilized to analyze the spatial and temporal expression of Atoh1 at the protein level by immunofluorescence staining, n= 3 for each group. Results Atoh1 mRNA was highly expressed in the embryonic cerebellar rhombic lip (RL) and the external granule layer (EGL). At the protein level, staining result of Atoh1-3
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BACKGROUND@#Functional constipation (FC) is one of the most prevalent functional gastrointestinal disorders. Dissatisfaction with medications prescribed to treat FC may lead patients to seek alternative treatments. Numerous systematic reviews (SRs) examining the use of acupuncture to treat FC have reported inconsistent results, and the quality of these studies has not been fully evaluated.@*OBJECTIVE@#In this overview, we evaluated and summarized clinical evidence on the effectiveness and safety of acupuncture for treating FC and evaluated the quality and bias of the SRs we reviewed.@*SEARCH STRATEGY@#The search strategy was structured by medical subject headings and search terms such as "acupuncture therapy" and "functional constipation." Electronic searches were conducted in eight databases from their inception to September 2020.@*INCLUSION CRITERIA@#SRs that investigated the effectiveness and safety of acupuncture for managing FC were included.@*DATA EXTRACTION AND ANALYSIS@#Two authors independently extracted information and appraised the methodology, reporting accuracy, quality of evidence, and risk of bias using the following critical appraisal tools: (1) A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); (2) Risk of Bias in Systematic Reviews (ROBIS); (3) Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A); and (4) the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). A κ index was used to score the level of agreement between the 2 reviewers.@*RESULTS@#Thirteen SRs that examined the clinical utility of acupuncture for treating FC were identified. Using the AMSTAR 2 tool, we rated 92.3% (12/13) of the SRs as "critically low" confidence and one study as "low" confidence. Using the ROBIS criteria, 38.5% (5/13) of the SRs were considered to have "low risk" of bias. Based on PRISMA-A, 76.9% (10/13) of the SRs had over 70% compliance with reporting standards. The inter-rater agreement was good for AMSTAR 2, ROBIS, and PRISMA-A. Using the GRADE tool, we classified 22.5% (9/40) of the measured outcomes as "moderate" quality, 57.5% (23/40) as "low" quality, and 20.0% (8/40) as "very low" quality. The inter-rater agreement was moderate when using GRADE. Descriptive analyses indicated that acupuncture was more efficacious than sham acupuncture for improving weekly complete spontaneous bowel movements (CSBMs) and for raising the Bristol Stool Form Scale (BSFS) score. Acupuncture appeared to be superior to anti-constipation drugs for improving weekly spontaneous bowel movements, the total effective rate, and the Patient Assessment of Constipation Quality of Life score. Although ten SRs mentioned the occurrence of adverse events, serious adverse events were not associated with acupuncture treatment.@*CONCLUSION@#Acupuncture may be more efficacious than sham acupuncture for improving CSBMs and BSFS scores and may be superior to anti-constipation drugs for improving bowel movement frequency, as well as quality of life. Limitations to current studies and inconsistent evidence suggest a need for more rigorous and methodologically sound SRs to draw definitive conclusions.@*SYSTEMATIC REVIEW REGISTRATION@#PROSPERO CRD42020189173.
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Humans , Acupuncture Therapy , Constipation/therapy , Quality of Life , Systematic Reviews as TopicABSTRACT
The toxicity data of chemicals and drugs increases rapidly, while the animal experimental-based tests method could not meet the current demand of health risk assessment. The high-throughput screening techniques based on in vitro alternative models, integrating with computational methods and information technology to establish toxicity tests strategy promises to address this problem. High-content screening (HCS) technology uses automated microscopy and quantitative image platforms to perform multi-parameter and high-throughput phenotypic analysis via a visualization and quantification manner, and to quickly and effectively assess toxicity and prioritization of chemicals, which promotes the development of in vitro toxicity tests and computational toxicology. HCS technology has been included as an important tool for Toxicity Testing in the 21st Century (Tox21) and chemical risk prioritization. Its applications have been widely utilized in the research field of toxicity tests and chemical toxicity mechanisms. In this review, we describe the development of HCS technology, technical points, toxicological applications, and the future directions and challenges of HCS, so as to provide references for the toxicity testing technology and risk assessment methodology.
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Animals , High-Throughput Screening Assays , Research Design , Risk Assessment , Toxicity TestsABSTRACT
Objective:To explore the syndrome distribution of cough cases in ancient Chinese medical books. Method:A total of 9 323 cough cases in the database of lung diseases in ancient Chinese medical books were extracted. Lantern 5.0 was used to construct the latent structure model for the 100 manifest variables based on the first 50 symptoms and 50 Chinese herbal medicines, and different latent nodes were interpreted. The syndrome differentiation patterns of syndromes with symptoms and Chinese herbal medicine (formula) were quantitatively revealed by the comprehensive clustering weights of latent structure. The correlation of diseases with syndromes was fitted through the binary Logistic regression analysis. Result:There were 204 syndromes involved in 9 323 cough cases with 18 syndromes showing a frequency higher than 100. As demonstrated by the model established on the first 50 symptoms and 50 Chinese herbal medicines, 35 latent variables, 98 latent classes, and 10 comprehensive clustering models were obtained, where <italic>Z</italic>5<italic> </italic>was the highest in the threshold value (6.7), <italic>Z</italic>6 in the information coverage of productive cough (52%), and <italic>Z</italic>7 in the score (19). The binary Logistic regression model fitted the correlation between different disease types and five syndromes, where the dominance ratio of external wind to the syndrome of wind-heat invading lung reaching up to 88.919, those of syndrome of phlegm-heat accumulating in lung to diseased heat and sputum 51.594 and 15.861, and those of the syndrome of phlegm-dampness obstructing lung to dampness, phlegm, and fluid retention 31.415, 34.370, and 4.936, respectively. Conclusion:The newly discovered cough syndromes included lung heat and yin deficiency, external cold and internal fluid retention, weakness of spleen and stomach, and phlegm and blood stasis in lung. In most cases, multiple syndromes were observed clinically, such as syndrome of deficiency of both Qi and Yin in lung combined with yin deficiency in lung and kidney. Since differentiation of traditional Chinese medicine (TCM) syndrome is subjective, the weight can indicate the difference in the contributions of different symptoms to the syndrome, which is of guiding significance for syndrome inference. The latent structure model combined with Logistic regression analysis can solve the problem of quantification in TCM syndrome differentiation and can be used to explore the syndrome distribution of diseases.
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BACKGROUND@#The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.@*METHODS@#All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.@*RESULTS@#At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.@*CONCLUSIONS@#Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.@*TRIAL REGISTRATION@#ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132.
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Objective:To explore cough cases recorded in ancient traditional Chinese medicine (TCM) books based on the Rules of Latent Structure Differentiation. Method:The 9 323 cough cases in the database of ancient TCM books and pulmonary diseases were extracted. At first, Lantern 5.0 software was used to construct the top 120 TCM hidden structure model with the frequency>100. Then, the obtained hidden variables were comprehensively clustered and interpreted. Result:The 46 hidden variables and 114 hidden classes were obtained through the modeling of 120 traditional Chinese medicines. According to the bayesian information measure (BIC) score, the model score was -161 242.92. The model diagram was formed with Y0, Y5, Y7, Y13, Y35 and Y38 as the cores, and Y36, Y38, Y24, Y19 and Y17 involved 4 hidden classes. Ten comprehensive clustering models were summarized according to the hidden structure flow chart, among which the highest score of Z5 external cold and internal decoction syndrome was 8.4, indicating that the result of syndrome differentiation rules of Z5 had a high degree of support, and the highest mutual information degree and information coverage of Pinellia sinensis were 0.31 and 63%. Z2 had a low score for the syndrome of deficiency of lung qi and Yin, which was -2, and Schisandra had the lowest score of -15, indicating that the syndrome differentiation rules of Z2 was less supportive. Forsythia and Notopterygium both had the highest score of Z6 wind-heat attack lung syndrome and Z10 phlegm and blood-stasis pulmonary syndrome, which was 19.1, indicating that these two TCMs had a great contribution to it. According to the test, the common syndromes of cough were cold and dryness attacking the lung, kidney-Yin deficiency, kidney-Yin deficiency of the lung, cold and internal decoction, wind heat invading the lung, liver fire invading the lung, lung heat burning, phlegm-dampness blocking the lung, phlegm-stasis blocking the lung. The newly discovered cough syndromes were external cold and internal rheum syndrome and phlegm-stasis blocking the lung syndrome. Conclusion:Based on the syndrome differentiation rules of hidden structure, the improved classification of cough syndromes provides ideas for the demonstration of tacit knowledge of TCM and methodological reference for the improvement of syndromes of other diseases, and is conducive to the development of valuable new prescriptions.
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@#【Objective】To investigate the effect of cinnamaldehyde on the apoptosis of RL95- 2 cell in endometrial carcinoma. 【Methods】 Endometrial carcinoma RL95- 2 cells were treated with cinnamaldehyde,and the proliferation activity and IC50 of endometrial carcinoma RL95-2 cells were detected by MTT colorimetry assay. Apoptotic morphology was observed after Hoechst 33258 staining. The percentage of apoptosis in RL95-2 cells was measured by flow cytometry. Western blot analysis was used to test the effect of cinnamaldehyde on the expression of Cleaved caspase- 3,caspase-3, NF-κB·p65,IL-6 and IGF-R in RL95-2 cells.【Results】Cinnamaldehyde can reduce the viability rate of endometrial cancer RL95- 2 cells,which is related to the treatment duration and concentration. Compared with the solvent control group, the apoptosis percentage of RL95- 2 cells in the cinnamaldehyde group (0.29, 0.59, 1.20 mg/mL) was significantly increased after 48 hours(P < 0.01),typical apoptotic bodies were found ,and the expression of Cleaved caspase-3 protein was significantly increased(P < 0.01),there was no significant change in the expression of Caspase 3 protein(P > 0.05),while the expression of NF- κB · p65,IL- 6 and IGF- R protein were significantly increased(P <0.05).【Conclusion】Cinnamaldehyde can reduce the expression of NF-κB·p65,IL-6 and IGF-R proteins in RL95-2 cells and promote the apoptosis of RL95-2 cells,thus playing an anti-endometrial cancer role.
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Objective: To evaluate the association of four single nucleotide polymorphisms (SNPs) in the functional regions, methylation and mRNA expression level of the catechol-Omethyl transferase (COMT) gene with the risk of premature ovarian failure (POF). Methods: According to the POF diagnostic criteria, the participants recruited in this study included 304 patients with POF and 317 healthy women as controls. DNA and RNA were extracted from the peripheral blood. Genotyping of the 4 SNPs was conducted using the SNaPshot method. Methylation and mRNA level was tested by MethylTarget target region methylation sequencing and RT-PCR, respectively. Results: The outcomes showed that the COMT gene rs4680 AA genotype (OR=1.605, 95% CI=1.111-2.319, P=0.011) and A allele (OR=1.277, 95% CI=1.022-1.596, P=0.032) frequencies, methylation level of CpG_8 (t=-2.234, P=0.027) and CpG_10 (t=-2.033, P=0.043) were significantly higher in the POF patients than in the healthy controls. The COMT gene mRNA level was significantly lower in the POF patients than the healthy controls (t=2.071, P=0.041). Conclusion: Our findings indicate that the COMT gene rs4680 A allele, and methylation level of CpG_8 and CpG_10 may be associated with the risk and development of POF by downregulating the COMT gene expression level.
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AIM: To investigate the effect of tumor necrosis factor receptor associated factor 6 (TRAF6) on proliferation, apoptosis and invasion of retinoblastoma Y79 cells. METHODS: The Y79 cells were divided into three groups:blank control group, negative control group and TRAF6 siRNA group. After TRAF6 siRNA transfection, the levels of TRAF6 mRNA and protein in Y79 cells were examined by RT-PCR and Western blotting. MTT assay was used to detect cell proliferation. Flow cytometry was employed to detect changes in cell cycle and apoptosis. Cell invasiveness was detected by the Transwell method. RESULTS: Expression of TRAF6 mRNA and protein in the TRAF6 siRNA group significantly decreased compared with the negative and blank control groups. Following the silencing of TRAF6,cell proliferation was inhibited and the apoptosis rate increased; the cell cycle was arrested at G0/G1 phase; the number of cells in S phase was reduced, while the invasion ability of cancer cells decreased. CONCLUSION: Silencing TRAF6 may inhibit the proliferation of Y79 cells, promote cell apoptosis, arrest the cell cycle at G0/G1 phase and decrease the invasive ability. Thus,TRAF6 may be a potential target in therapy for retinoblastoma.
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We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.
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Adult , Humans , Male , Azoospermia/therapy , Follicle Stimulating Hormone/blood , Microdissection , Oligospermia/pathology , Predictive Value of Tests , Sensitivity and Specificity , Sertoli Cell-Only Syndrome/pathology , Sperm Maturation , Sperm Retrieval , Spermatozoa , Testis/pathology , Threshold Limit ValuesABSTRACT
Calpain activation contributes to hyperglycemia-induced endothelial dysfunction and apoptosis. This study was designed to investigate the role of calpain inhibition in improving diabetic erectile dysfunction (ED) in mice. Thirty-eight-week-old male C57BL/6J mice were divided into three groups: (1) nondiabetic control group, (2) diabetic mice + vehicle group, and (3) diabetic mice + MDL28170 (an inhibitor of calpain) group. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin at 60 mg kg-1 body weight for 5 consecutive days. Thirteen weeks later, diabetic mice were treated with MDL28170 or vehicle for 4 weeks. The erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were collected for measurement of calpain activity and the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) staining was used to evaluate apoptosis. Caspase-3 expression and activity were also measured to determine apoptosis. Our results showed that erectile function was enhanced by MDL28170 treatment in diabetic mice compared with the vehicle diabetic group. No differences in calpain-1 and calpain-2 expressions were observed among the three groups. However, calpain activity was increased in the diabetic group and reduced by MDL28170. The eNOS-NO-cGMP pathway was upregulated by MDL28170 treatment in diabetic mice. Additionally, MDL28170 could attenuate apoptosis and increase the endothelium and smooth muscle levels in corpus cavernosum. Inhibition of calpain could improve erectile function, probably by upregulating the eNOS-NO-cGMP pathway and reducing apoptosis.
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Animals , Male , Mice , Apoptosis/drug effects , Calpain/antagonists & inhibitors , Cyclic GMP/biosynthesis , Diabetes Complications/drug therapy , Diabetes Mellitus, Experimental/complications , Dipeptides/therapeutic use , Endothelium/metabolism , Enzyme Inhibitors/therapeutic use , Erectile Dysfunction/etiology , In Situ Nick-End Labeling , Mice, Inbred C57BL , Muscle, Smooth/metabolism , Nitric Oxide Synthase Type III/biosynthesis , Penis/enzymology , Up-RegulationABSTRACT
This study aimed to assess the relationship of OAS2 rs739901 5'-flanking C/A polymorphisms with the susceptibility to Enterovirus-71 (EV71) infection.We investigated 294 hand-foot-mouth disease (HFMD) Chinese children with EV71 infection (165 mild cases and 129 encephalitis cases).The improved multiplex ligation detection reaction (iMLDR) technique was used to test the genotypes.In EV71-infected patients,the CA genotype distribution (P=0.007),A allele frequency (OR 1.32,95% CI 1.0-1.7,P=0.034)and CA+AA carriage frequency (P=0.003) of OAS2 rs739901 5'-flanking were obviously elevated as compared with controls,but there were no statistically significant differences between mild cases and encephalitis cases.In EV71-infected patients,the counts of white blood cells (P=0.034) and blood glucose concentrations (P=0.042) were raised in A carriers (CA+AA).Among different genotypes of encephalitis cases,the contents of cerebrospinal fluid (CSF) showed no significant differences.IFN-γ levels in EV71-infected patients were higher than those in controls (mild group vs.control group,P<0.01;encephalitis group vs.control group,P<0.001).In encephalitis cases,IFN-γ levels were reduced (P<0.05) in A carriers compared to CC genotype,however,there were no significant differences between genotypes CA and AA (P=0.226).These findings suggest that OAS2 rs739901 5'-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection,and A allele might be a risk factor of the susceptibility to EV-71 infection.
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This study aimed to assess the relationship of OAS2 rs739901 5'-flanking C/A polymorphisms with the susceptibility to Enterovirus-71 (EV71) infection.We investigated 294 hand-foot-mouth disease (HFMD) Chinese children with EV71 infection (165 mild cases and 129 encephalitis cases).The improved multiplex ligation detection reaction (iMLDR) technique was used to test the genotypes.In EV71-infected patients,the CA genotype distribution (P=0.007),A allele frequency (OR 1.32,95% CI 1.0-1.7,P=0.034)and CA+AA carriage frequency (P=0.003) of OAS2 rs739901 5'-flanking were obviously elevated as compared with controls,but there were no statistically significant differences between mild cases and encephalitis cases.In EV71-infected patients,the counts of white blood cells (P=0.034) and blood glucose concentrations (P=0.042) were raised in A carriers (CA+AA).Among different genotypes of encephalitis cases,the contents of cerebrospinal fluid (CSF) showed no significant differences.IFN-γ levels in EV71-infected patients were higher than those in controls (mild group vs.control group,P<0.01;encephalitis group vs.control group,P<0.001).In encephalitis cases,IFN-γ levels were reduced (P<0.05) in A carriers compared to CC genotype,however,there were no significant differences between genotypes CA and AA (P=0.226).These findings suggest that OAS2 rs739901 5'-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection,and A allele might be a risk factor of the susceptibility to EV-71 infection.
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<p><b>OBJECTIVE</b>To investigate the potential relationship between the high-resolution HLA-A,-B,-DRB1 alleles and haplotype polymorphism with actute myeloid leukemia (AML) and chronic myeloid leukemia (CML) of Han people in North China.</p><p><b>METHODS</b>A total of 1241 healthy unrelated Han people's bone marrow donors in North China were used as a control group, 259 patients with myeloid leukemia were genotyped at high-resolution level by means of PCR-SBT, -SSO and -SSP typing methods for HLA-A,-B,-DRB1 loci. The frequencies of HLA allele and haplotype were calculated by software Arleguin 3.5.2. The different distribution of genes and haplotypes was analyzed by case control study, and the odd ratio (OR) of leukemia was also calculated. The structural difference of HLA alleles was analyzed 111by HLA three-dimensional structure modeling and software Swiss-PdbViewer v4.1.</p><p><b>RESULTS</b>χtest and correction showed that an increased frequency of A*02:07 (8.47% vs 5.28%, P' =0.013), A*29:01 (1.85% vs 0.68%, P=0.044), B*07:02 (5.29% vs 3.10%, P=0.029), B*07:05:01G (1.85% vs 0.68%, P=0.044) and B*35:02 (1.06% vs 0.20%, P=0.023) were found in AML patients (n=189) as compared with controls, respectively; whereas A*02:03 was less frequent in AML as compared with controls (0.79% vs 3.10%, P=0.011). The frequency of B*46:01 was lower in CML patients (n=70) as compared with controls (2.86% vs 7.82%, P=0.031). However, the above-mentioned discrepancies were not statistically significant by Bonferroni correction. Through Fisher exact test and Bonferroni correction, the frequency of DRB1*11:28 and its haplotype A*24:02-B*15:01-DRB1*11:28 in CML group were very significantly higher than in controls (1.43% vs 0.00%, Pc=0.015; 1.43% vs 0.00%, P=0.003). Three-dimensional structure modeling of DRB1*11:28 and DRB1*11:01 presented significant structure differentiation (RMSD=0.09 nm) in peptide binding region of the backbone calculated by Swiss-PdbViewer v4.1. The haplotype A*03:01-B*50:01-DRB1*07:01 in AML and A*11:01-B*40:06-DRB1*09:01 in CML patients were significantly higher than that in controls (1.06% vs 0.00%, Pc=0.000; 2.86% vs 0.07%, Pc=0.000), and positively correlated with leukemia (OR=59.66, 95% CI=3.21-1110.39; OR=42.91, 95% CI=7.07-260.32).</p><p><b>CONCLUSION</b>The relationship of HLA-A,-B,-DRB1 alleles and haplotype polymorphism with leukemia at high-resolution level were obtained and unique in north Chinese Han population. AML and CML patients in Northern Han people carry particular susceptible haplotypes. DRB1*11:28, which might not actively present bcr-abl peptide to CD4T cells, and is a susceptibile gene for CML patients of Northern Han people, especially in Shaanxi Province (OR=89.62, 95% CI=4.28-1875.87), as well as correlated with its particular haplotype.</p>
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Objective To study the clinical characteristics of pulmonary invasive fungal infection (IFI) in patients with severe aplastic anemia (SAA) after allogeneic hematopoietic stem cells transplantation (allo-HSCT).Methods The clinical data of 30 SAA patients received allo-HSCT in 307 Hospital of PLA from Jan.2012 to Jan.2015 were analyzed retrospectively.All the SAA patients accepted combined bone marrow with peripheral blood stem cells transplantation,and then the clinical features and outcome of pulmonary IFI after transplantation were analyzed.Results Six (20%) of the 30 SAA patients were complicated by IFI after transplantation,including 4 males and 2 females with average age of 18.3(6-42) years.All the 6 patients showed characteristic imaging changes in pulmonary,of which 3 cases were definitely diagnosed by bronchoscopy or sputum fungal culture,and the other 3 cases by imaging and clinical manifestation.Four cases were cured and 2 cases died after first-line antifungal therapy,the total mortality was 33.3%.Conclusion High incidence of complicated IFI in SAA patients after allo-HSCT may lead to the high mortality,it's necessary to give an empiric antifungal therapy as earlier as possible.
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Synaptic dysplasia induced by gene mutation is one of the most important mechanisms of the development of autism spectrum disorders (ASD).Based on in-depth studies of ASD patients and model organisms,a number of causative genes and signaling pathways have been identified,which have been demonstrated to play crucial roles in the synaptic development and cognitive function in the brain.However,the underlying neural mechanisms of the development of ASD and synaptic dysplasia merit further investigation.Given the latest rapid advances in research on ASD in recent years,we overview and summarize the linkages and potential neural mechanisms about the synaptic dysplasia and ASD in the current review,which focuses on the related crucial molecules,signaling pathways,brain circuits and therapeutic targets in ASD clinical trials in recent years.This review is intended to deepen the understanding of the pathogenesis of neural mechanisms of ASD,and provide new ideas for development of new drugs,prevention and therapy of ASD patients in clinic.
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To explore the medication rules of famous veteran traditional Chinese medicine (TCM) doctors in treatment of chronic bronchitis, a structured medical record database for famous veteran TCM doctors in modern clinical books was established. First, Lantern 3.1.2(Kongmin light) implicit structure analysis software was used to build an implicit structure model and make an implicit interpretation. Then, SAS 9.1 was adopted to mine herb-herb, herb-symptom and herb-syndrome association rules. Through the mining, 1 274 commonly used herbs for chronic bronchitis were found, including liquorice, bitter almond, pinellia, dried tangerine or orange peel, poria cocos. The medicine types included antiasthmatic medicine, qi-tonifying medicine, and heat-phlegm removing medicine. The medicine tastes included sweet, pungent and bitter. The meridian distributions included lung, spleen and stomach channels. The famous commonly used prescriptions included Xiaoqinglong decoction, Maxing Shigan decoction and Erchen decoction. The 147-herb implicit structure model for the first diagnosis was built to get 44 hidden variables, 88 hidden classes, 7 comprehensive clustering models, 9 dual herb associations, 50 triple herb associations and 89 quadruple associations. Totally 297 medical records for the second diagnosis were compared to obtain 24 herb-symptom associations, which reduced ephedra, bitter almond, pinellia and added poria cocos, atractylodes, dangshen, 20 dual herb associations and 8 triple herb associations. A model for the top 83 symptoms and top 96 herbs in the first diagnosis was built to get 50 hidden variables and 101 hidden classes. The commonly used herbs of famous veteran TCM doctors included bitter almond, pinellia, dried tangerine or orange peel, poria cocos, which feature mild property and sweet favor and enter lung, spleen, kidney meridians; the commonly herbal pairs included atractylodes and poria cocos, asarum, fructus schisandrae and pinellia, as well as poria cocos, dangshen, pinellia and dried tangerine or orange peel. The herb-syndrome associations involved ephedra, bitter almond, cassia twig and scanty sputum, pinellia and external cold and internal fluid syndrome, turbid phlegm obstructing lung syndrome and spleen deficiency syndrome, bitter almond and turbid phlegm obstructing lung syndrome, phlegm-heat accumulated in the lung and wind-cold invading the lung. The implicit structure model can be used to quantify tacit knowledge of TCM, extend to the herb and syndrome level for the first time, and quantify the major, minor and compatible statues of different variables in the same data. This study concluded that the medication rules of famous veteran TCM doctors in treatment of chronic bronchitis have certain reference value for the clinical diagnosis and treatment. The data sources, analysis methods and mining results were relatively reliable and objective, and can provide a reference for rules of other disease treatment based on syndrome differentiation.
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<p><b>Objective</b>To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment.</p><p><b>METHODS</b>We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15).</p><p><b>RESULTS</b>The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B ([2.35±0.71] vs [1.83±0.36] cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level ([0.78±0.40] vs [2.71±0.70] ng/ml with Andriol; [0.93±0.44] vs [3.07±0.67] ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm ([11.5±2.3] vs [7.5±2.3] ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either.</p><p><b>CONCLUSIONS</b>Hypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.</p>
Subject(s)
Adult , Humans , Male , Chorionic Gonadotropin , Therapeutic Uses , Follicle Stimulating Hormone , Blood , Hypogonadism , Diagnosis , Therapeutics , Luteinizing Hormone , Blood , Pituitary Neoplasms , Blood , Pathology , Therapeutics , Prolactinoma , Blood , Pathology , Therapeutics , Retrospective Studies , Sella Turcica , Spermatogenesis , Spermatozoa , Testis , Testosterone , Blood , Therapeutic Uses , Tumor BurdenABSTRACT
<p><b>BACKGROUND</b>The absolute lymphocyte counts (ALCs) have been reported as one of worse prognostic factors for hepatocellular carcinoma (HCC) patient after liver transplantation. The aim of this study was to assess the influence of ALCs on the outcomes of patients with hepatitis B virus (HBV)-related HCC within the Milan criteria following liver resection.</p><p><b>METHODS</b>Data of patients with HCC within the Milan criteria who received liver resection between January 2007 and June 2013 were reviewed, and perioperative ALCs were carefully monitored. All potential risk factors were statistically analyzed by uni- and multi-variate analyses. The receiver operating characteristic (ROC) curve was used to determine the optimal ALCs cut-off value to predict HCC recurrence after liver resection.</p><p><b>RESULTS</b>A total of 221 patients were enrolled in the current study. During the follow-up period, 106 patients experienced recurrence, and 38 patients died. Multivariate analysis suggested microvascular invasion (MVI), a tumor grade ≥2, and a low postoperative ALCs in the 1st postoperative month increased the incidence of postoperative recurrence, besides, MVI, intraoperative transfusion, and a low postoperative ALCs in the 1st postoperative month were associated with poor overall survival (OS). An ROC analysis showed that a cut-off value of 1.5 × 109/L for ALCs in the 1st postoperative month predicted postoperative recurrence. The 5-year recurrence-free survival (RFS) and OS rates of patients with low postoperative ALCs were 34.5% and 64.8%, respectively, which were significantly lower than those of patients with high postoperative ALC (58.5% for RFS and 86.5% for OS).</p><p><b>CONCLUSION</b>Low ALCs in the 1st postoperative month may be associated with high recurrence incidence and poor OS for patients with HBV-related HCC within the Milan criteria after liver resection.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , Allergy and Immunology , Mortality , General Surgery , Liver Neoplasms , Allergy and Immunology , Mortality , General Surgery , Lymphocyte Count , Neoplasm Recurrence, Local , Prognosis , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To explore the risk factors and clinical characteristics of non-erosive reflux disease (NERD) based on a prospective single disease database of functional gastrointestinal disease.</p><p><b>METHODS</b>Using a customized case report form, we collected the personal and clinical data of all study participants in an online database for further analysis. High-resolution manometry and multichannel intraluminal impedance-pH monitoring were performed in some cases.</p><p><b>RESULTS</b>A total of 504 NERD cases and 152 control cases were included in our database. The NERD patients consisted of 266 (52.8%) female patients and 238 (47.2%) male patients; 32.7% of the patients were from rural areas and 67.3% from urban areas; 23.1% of the patients worked in the line of business, 19.6% were civil servants, 19.2% were unemployed, and 17.1% were workers; the mean disease duration of the patients was 27.88∓16.33 month. Our analysis showed that adverse events in life (P=0.045, OR=1.954), frequent drinking (P=0.040, OR=3.957), snoring (P=0.002, OR=2.334), late meals (P=0.002, OR=2.752), and anxiety or depression (P=0.003, OR=2.723) were all independent risk factors for NERD. Of these patients, 60.81% had varying degrees of ineffective contraction of the esophageal body. The total liquid reflux events differed significantly between NERD patients with hiatal hernia and those without (P<0.05).</p><p><b>CONCLUSION</b>Unhealthy eating habits and lifestyle, history of adverse events, anxiety and depression, snoring, poor esophageal motor function and hiatal hernia are significant factors contributing to NERD, which is related with occupation and living areas and occurs most commonly at 30-50 years of age.</p>