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5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone, which causes abnormal urogenital sinus development. The aim of this study was to analyze the relationship between genotype-phenotype, surgical selections, and postoperative complications of 5α-reductase 2-deficient patients with hypospadias. We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children's Hospital, Capital Medical University (Beijing, China), from April 2007 to December 2021. A total of 69 patients were included in this study; the mean age at surgery was 34.1 months, and the average follow-up time was 54.1 months. Sixty children were treated with preoperative hormone stimulation (PHS) to promote penile growth. The average penis length and glans width were increased by 1.46 cm and 0.62 cm, respectively. The most frequent mutations were p.R227Q (39.1%, 54/138), p.Q6* (15.2%, 21/138), p.G203S (12.3%, 17/138), and p.R246Q (11.6%, 16/138). In 64 patients who were followed up, 43 had a one-stage operation and 21 had a staged operation, and there were significant differences in external masculinization score (EMS) ( P = 0.008) and the average number of operation required to cure ( P < 0.001) between one-stage and staged operations. PHS had a positive effect ( P < 0.001) on penile development. The p.R227Q mutation was associated with higher EMS and less severe hypospadias. One-stage surgery can be selected if conditions permit. The growth and development of children are acceptable in the long term, but penis growth remains unsatisfactory. Long-term complications of hypospadias should be considered during puberty.
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Male , Humans , Child , Infant , Hypospadias/surgery , Retrospective Studies , Oxidoreductases , Postoperative Complications , Genetic Association StudiesABSTRACT
Aim To investigate the feasibility and mechanism of rhynchophylline in the treatment of in-rhynchophylline flammatory bowel disease (IBD) based on network pharmacology combined with in vivo and in vitro experiments. Methods The target of rhynchophylline-IBD intersection was obtained from the database, and GO and KEGG enrichment analysis were performed. The binding of key target proteins was screened by molecular docking. In vivo the IBD model of mice was induced by sodium dextran sulfate (DSS). After seven days of rhynchophylline intervention, the signs of mice in each group were observed and DAI scores were recorded. The levels of interleukin-1β (3 (IL-1 β), my-eloperoxidase (MPO) and other inflammatory factors in colon tissue of mice were detected by ELISA. The intestinal permeability of each group was detected. In vitro experiments were conducted to establish the inflammatory model of Caco2 cells induced by DSS, and to clarify the regulatory effect of leptosinine on key targets. Results A total of 70 rhynchophylline-IBD intersection targets were screened, and enrichment analysis showed that they were related to the inflammatory prooess, PI3K-Akt and Hippo signaling pathway s. Molecular docking results showed that was most stable in binding with JAK2 and JAK1. In vivo experiment results showed that compared with model group, body weight, colon length and weight of rhynchophylline group significantly increased (P < 0. 05). DAI score, IL-1β, MPO and other inflammatory factors in colon tissue and intestinal permeability significantly decreased (P < 0. 01). In vitro experiment results showed that compared with model group, rhynchophylline group significantly promoted the proliferation of Caco2 cells (P < 0. 05). The levels of IL-6 and NO were significantly reduced (P < 0. 05). Western blot results showed that rhynchophylline could decrease the expressions of JAK2 and JAK1 (P < 0. 05). Conclusion Rhynchophylline may play a role in the treatment of IBD by inhibiting the expression of JAK2 and JAK1 proteins and reducing inflammatory response in body.
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Objective: To explore the risk factors of malnutrition in infants with congenital heart disease within one year after surgery. Methods: This retrospective cohort study selected 502 infants with congenital heart disease who underwent surgical treatment in Guangzhou Women and Children's Medical Center from February 2018 to January 2019. Their basic information and clinical data were analyzed, and their nutrition status after the surgery was followed up by questionnaire survey. Weight-for-age Z score (WAZ)≤-2 one year after operation was defined as malnutrition group, and WAZ>-2 was non-malnutrition group. The perioperative indicators and complementary food advancement were compared between the two groups by chi-square test, t-test, and Kruskal-Wallis test. The risk factors of malnutrition were analyzed by Logistic regression. Results: A total of 502 infants were selected, including 301 males and 201 females, with the age of 4.1 (2.0, 6.8) months. There were 90 cases in malnutrition group and 412 cases in non-malnutrition group. The body length and weight at birth in the malnutrition group were lower than those in the non-malnutrition group ((47.8±3.8) vs. (49.3±2.5) cm, (2.7±0.6) vs.(3.0±0.5) kg, both P<0.001). The proportion of paternal high school education or above and the proportion of family per capita income of 5 000 yuan or above in the malnutrition group were lower than those in the non-malnutrition group ((18.9% (17/90) vs. 30.8% (127/412), 18.9% (17/90) vs. 33.7% (139/412), both P<0.05). Compared to the non-malnutrition group, the proportion of complex congenital heart disease in the malnutrition group was higher (62.2% (56/90) vs. 47.3% (195/412), P<0.05). The postoperative mechanical ventilation time, postoperative intensive care unit (ICU) stay time, postoperative hospital stay, total length of ICU stay and total hospital stay in the malnutrition group were significantly longer than those in non-malnutrition group (all P<0.05). The proportion of egg and fish supplementation over 2 times/week within one year after the surgery was also lower in the malnutrition group (both P<0.05). Logistic regression analysis showed that mother's weight at delivery (OR=0.95,95%CI 0.91-0.99), the pre-operative WAZ≤-2 (OR=6.04, 95%CI 3.13-11.65), the complexity of the cardiac disease (OR=2.23, 95%CI 1.22-4.06), the hospital stay after the surgery over 14 days (OR=2.61, 95%CI 1.30-5.26), the types of complementary food<4 (OR=2.57, 95%CI 1.39-4.76), and the frequency of meat and fish<2 times/week (OR=2.11, 95%CI 1.13-3.93) were the risk factors associated with malnutrition within one year after the surgery. Conclusion: Mother's weight at delivery pre-operative nutritional status, complexity of cardiac disease, postoperative hospital stay, types of daily supplements and frequency of fish are risk factors associated with malnutrition within one year after surgery in children with congenital heart disease.
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Male , Humans , Female , Cardiac Surgical Procedures , Retrospective Studies , Malnutrition/complications , Heart Defects, Congenital/surgery , Risk Factors , Length of Stay , Infant Nutrition Disorders/complicationsABSTRACT
@#Abstract:Objective To analyze the stabilities of neuraminidase(NA)in influenza vaccine at different temperatures and provide a reference for further complete understanding of overall shelf life of vaccines. Methods Monovalent bulks of influenza H1N1,H3N2 and B vaccines were stored at 4(low temperature),25(room temperature)and 37 ℃(changed temperature)for 0. 5,2,7,24 and 48 h separately,using that at 100 ℃(extreme temperature)for 1 h as control,and determined for NA activity by enzyme⁃linked lectin method. Results The NA activities of influenza H1N1 vaccines stored at 25 and 37 ℃ decreased significantly with the increasing of time. No significant decreases were observed in H3N2 and B vaccines even after storage at two non⁃storage temperatures for 48 h. However,all the NA activities of three vaccines decreased at 100 ℃. Conclusion Both H3N2 and B vaccines showed high stability at abnormal storage temperatures not more than 37 ℃,while H1N1 vaccine was relatively sensitive to the temperature for storage.
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Diversity-oriented synthesis is aimed to increase the chemical diversity of target natural products for extensive biological activity evaluation. Indole ring is an important functional group in a large number of drugs and other biologically active agents, and indole-containing natural products have been frequently isolated from marine sources in recent years. In this paper, a series of indole-containing marine natural hyrtioreticulin derivatives, including 19 new ones, were designed, synthesized through a key Pictet-Spengler reaction, and evaluated for their inflammation related activity. Compound 13b displayed the most promising activity by inhibiting TNF-α cytokine release with an inhibitory rate of 92% at a concentration of 20 μmol·L-1. A preliminary structure-activity relationship analysis was also discussed. This research may throw light on the discovery of marine indole alkaloid derived anti-inflammatory drug leads.
Subject(s)
Animals , Anti-Inflammatory Agents/pharmacology , Biological Products/pharmacology , Indole Alkaloids/pharmacology , Porifera , Structure-Activity RelationshipABSTRACT
Lobane-type diterpenoids are not frequently discovered from marine soft corals. In this paper, three new lobane type diterpenes, 13-methoxyloba-8,10,15(16),17(18)-tetraene (1), 8,10,13(15)Z,16E-lobatetraene (2) and 19-hydroxy-lobatetraene (3), and a new natural compound, 17,18-epoxyloba-16-acetoxy-8,10,13(15)-trien (4), co-occurring with a known related diterpenoid, 18-methoxyloba-8,10,13(15),16(17)-tetraene (5), were isolated from the South China Sea soft coral Sinularia polydactyla. The structures of new compounds were determined by extensive spectroscopic analysis and by comparison with those reported in the literature. In bioassay, all the isolates were inactive on antibacterial, PTP1B inhibitory, and immunological activities. This study increased the chemical diversity of marine diterpenoids.
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The chemical constituents of gorgonian Junceella fragilis Ridley, collected from Ximao Island, the South China Sea, were investigated. A new briarane-type diterpenoid, named fragilide Y (1), together with five known compounds (2–6), namely fragilide D (2), cholesterol (3), ergosterol peroxide (4), 2'-deoxythymidine (5) and cis-thyminenol (6), were isolated from the acetone extract of J. fragilis. The structure of the new compound 1 was elucidated by extensive spectroscopic analysis, while the known compounds were identified by comparison with the reported data. In bioassay, none of these compounds displayed obvious anti-inflammatory and cytotoxic effects.
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Objective To investigate the automatic implicit attitude and explicit stigma of mental illness,and the intervention effectiveness on the stigma of mental illness in college students.Methods Single category implicit association test(SC-IAT) and questionnaire survey were used to study the degree of implicit and explicit mental illness stigma among 30 college students of Peking University,and investigated the effect of two strategies,education and contact.Data were analyzed by SPSS 22.0 with t-test and variance analysis.Results The D values of SC-IAT in the three dimensions of cognitive evaluation,emotional response and behavioral tendency of college students were 0.29±0.37,0.24±0.43,and 0.10±0.43.There was a statistically significant difference between the cognitive evaluation dimension,the emotional response dimension and 0(t=4.069,P<0.01;t=2.925,P<0.01).There was no statistically significant difference between the implicit stigma and the 0 in the behavioral tendency dimension (t=1.423,P=0.167).In the explicit stigma,the mercy dimension score(1.94±0.61) was lower than the median,and the difference was statistically significant(t=-12.286,P< 0.01),while the scores of anger dimension (4.62 ± 0.44) and fear dimension (4.55±0.31) were higher than the median (t=13.243,3.200,both P<0.01).There were no significant differences in the values of implicit and external stigma among pre-intervention,education int.ervention and after contact(P>0.05).The correct rates of questions "Which of the following situations do you think are considered mentally unhealthy?" and "Which of the following disorders are mental illnesses" (42± 13)%,(54± 13) %) increased after receiving educational intervention ((49 ± 12) %,(64± 13) %),the difference was statistically significant (F=3.682,P<0.05;F=3.576,P< 0.05).Conclusion College students have implicit mental illness stigma,educational and contact intervention strategies can help improve college students' understanding of relevant knowledge,and cannot improve the level of implicit stigma of college students on mental illness.
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Objective Autophagy serves a role in the pathogenesis of chronic inflammatory diseases. The aim of the present study was to compare the autophagy levels of the peripheral blood mononuclear cells (PBMCs) in patients with chronic obstructive pulmonary disease (COPD) and healthy individuals and to assess the association between autophagy and the clinical parameters of COPD. Methods Samples of peripheral blood from 20 patients with stable COPD and 20 healthy controls were collected. PBMCs were harvested using Ficoll density gradient centrifugation. Levels of the autophagy-associated proteins ubiquitin-binding protein P62 (P62), microtubule-associated proteins 1A/1B light chain 3A (LC3 I/Ⅱ) and beclin-1 in PBMCs were detected by western blotting. Enzyme-linked immunosorbent assay kits were used to detect the serum concentrations of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α. Results Western blotting demonstrated that the protein expression of P62 decreased (P62/GAPDH = 0.212 ± 0.089 vs. 0.378 ± 0.176,P = 0.001 1), but LC3 I/Ⅱ(4.94 ± 1.85 vs. 3.85 ± 1.06, P = 0.024 9) and beclin-1 (Beclin-1/GAPDH = 0.578 ± 0.126 vs. 0.149 ± 0.035, P<0.01) levels increased in patients with COPD compared with healthy controls. Serum levels of IL-6 [(11.96 ± 3.46) ng/L vs. (2.70 ± 1.72) ng/L, P < 0.01], IL-8[(20.38 ± 18.44) ng/L vs. (6.00 ± 4.08) ng/L, P=0.001 6] and TNF-α (29.50 ± 28.18 vs. 11.08 ± 12.07, P=0.010 6) increased in patients with COPD. The extent of PBMC autophagy was negatively correlated with FEV1% predicted, but positively correlated with levels of proinflammatory cytokines. The levels of autophagy in PBMCs in patients with COPD increased and were negatively correlated with FEV1% predicted and positively correlated with circulating levels of pro-inflammatory cytokines. Conclusions Autophagy may serve a role as a biomarker of the severity of COPD or as a therapeutic target for treatment of COPD.
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Objective@#To investigate the automatic implicit attitude and explicit stigma of mental illness, and the intervention effectiveness on the stigma of mental illness in college students.@*Methods@#Single category implicit association test(SC-IAT) and questionnaire survey were used to study the degree of implicit and explicit mental illness stigma among 30 college students of Peking University, and investigated the effect of two strategies, education and contact.Data were analyzed by SPSS 22.0 with t-test and variance analysis.@*Results@#The D values of SC-IAT in the three dimensions of cognitive evaluation, emotional response and behavioral tendency of college students were 0.29±0.37, 0.24±0.43, and 0.10±0.43.There was a statistically significant difference between the cognitive evaluation dimension, the emotional response dimension and 0(t=4.069, P<0.01; t=2.925, P<0.01). There was no statistically significant difference between the implicit stigma and the 0 in the behavioral tendency dimension(t=1.423, P=0.167). In the explicit stigma, the mercy dimension score(1.94±0.61) was lower than the median, and the difference was statistically significant(t=-12.286, P<0.01), while the scores of anger dimension(4.62±0.44) and fear dimension (4.55±0.31) were higher than the median(t=13.243, 3.200, both P<0.01). There were no significant differences in the values of implicit and external stigma among pre-intervention, education intervention and after contact(P>0.05). The correct rates of questions "Which of the following situations do you think are considered mentally unhealthy? " and "Which of the following disorders are mental illnesses" (42±13)%, (54±13)%) increased after receiving educational intervention ((49±12)%, (64±13)%), the difference was statistically significant (F=3.682, P<0.05; F=3.576, P<0.05).@*Conclusion@#College students have implicit mental illness stigma, educational and contact intervention strategies can help improve college students' understanding of relevant knowledge, and cannot improve the level of implicit stigma of college students on mental illness.
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<p><b>OBJECTIVE</b>We aimed to elucidate the rates of repeat HIV testing and incident HIV diagnosis, and baseline CD4+ T cell count among individuals attending HIV voluntary counseling and testing (VCT) clinics in Wuxi, China.</p><p><b>METHODS</b>A repeat HIV testing within 12 months was recorded if individuals had their first test with negative results, during 2013-2014 and retested within 12 months. An incident HIV diagnosis was recorded if individuals had their first test with negative results, during 2013-2015 and had a subsequent positive result at any point by the end of 2015. Data on HIV testing and diagnosis among individuals attending 32 VCT clinics from 2013 to 2015 and HIV diagnosis from other clinical services in Wuxi, China, were retrieved. A multivariate logistic regression model was used to analyze factors associated with repeat HIV testing. Cox regression was used to evaluate factors associated with incident HIV diagnosis.</p><p><b>RESULTS</b>From 2013 to 2014, 11,504 individuals tested HIV negative at their first recorded test, with 655 (5.7%) retesting within 12 months. Higher repeat HIV testing within 12 months was associated with male gender [adjusted odds ratio (aOR) = 1.7, 95% confidence interval (CI): 1.4-2.2], risk behaviors [commercial heterosexual behaviors (aOR = 1.4, CI: 1.1-1.6), male-male sexual behaviors (aOR = 3.7, CI: 2.7-4.9)], injection drug use (aOR = 9.9, CI: 6.5-15.1), and having taken HIV tests previously (aOR = 2.0, CI: 1.6-2.4). From 2013 to 2015, 1,088 individuals tested negative on HIV test at their visit and at ⋝ 2 subsequent tests; of them 30 had incident HIV diagnosis. The overall rate of incident HIV diagnosis among all VCT individuals was 1.6 (95% CI: 1.1-2.1) per 100 person-years. Incident HIV diagnosis was associated with male gender [adjusted hazard ratio (aHR) = 8.5, 95% CI: 1.9-38.1], attending hospital-based VCT clinics (aHR = 7.8, 95% CI: 1.1-58.3), and male-male sexual behavior (aHR = 8.4, 95% CI: 1.5-46.7). Individuals diagnosed at VCT clinics had higher CD4+ T cell count compared with those diagnosed at other clinical services (median 407 vs. 326 copies/mm3, P = 0.003).</p><p><b>CONCLUSION</b>VCT individuals in Wuxi, China, had a low repeat HIV testing rate and high HIV incidence. VCT-clinic-based interventions aimed at increasing repeat HIV testing are needed to detect more cases at an earlier stage, especially among individuals at high risk for HIV infection such as men who have sex with men.</p>
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Objective: To discuss possible ethical and boundary issues when contacting clients through WeChat in different situations. Methods: Self-made questionnaires were utilized to investigate 194 counselors' (18 counselors gave clients their job WeChat ID, 64 counselors gave their private WeChat ID, and 115 counselors do not give WeChat toclients) attitudes and behaviors of encountering multiple relationship issues when using WeChat Results: For WeChat boundary, counselors who had job WeChat ID would post more private photos and videos on the post than counselors with no job ID and without ID(P <0.01). Although 41% of counselors would use WeChat during the counseling and other related activities, only 10% of the counselors had job ID. Counselors with no ID tended to accept clients breaking the boundaries through other ways (P <0.01). Conclusion: The study indicates that counselors have encountered ethic issues of multiple relationships when using WeChat Counselors who only have private WeChat ID should increase their sensitivity of the boundary issues in the use of WeChat.
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Aim To investigate the effects of salidro-side on oxygen glucose deprivation/reoxygenation ( OGD/R) injury in human umbilical vein cells ( HU-VECs ) and the possible mechanism. Methods OGD/R model was built after the density of cell growth reached 80% ~85%. The OGD time point was deter-mined by MTT method to detect cell viability;LDH ac-tivity detection was used to explore the best dosage sol-ubility;NO content assay was applied to determine the best drug solubility, the degree of apoptosis was detec-ted by Annexin V/PI, and the expression of P-selectin was detected by immunohistochemistry. Results MTT detection determined that the time point of OGD was 16 h; LDH activity detection and NO content detection showed that the best efficacy of salidroside was 10μmol · L-1 . Compared with control group, Annexin V/PI detection showed that the apoptotic rate increased significantly ( P <0.01 ) after OGD/R, and the ex-pression of P-selectin in OGD/R group obviously in-creased ( P <0.01 ) . Compared with OGD/R group,the expression of P-selectin obviously declined ( P <0.05 ) , while the cell apoptotic rate increased ( P <0.05) after the administration. Conclusions Salidro-side may protect HUVEC cells from OGD/R injury and its mechanism may be related to related to the down-regulation of P-selectin and the inhibition of the pro-duction of inflammation.
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A new ultrasonic-assisted extraction (UANE) method coupled with solid phase extraction (SPE) using ultrasonic fountain was established for the extraction of eight common ginsenosides from leaves of Panax quinquefolium L. The extraction system has been designed and several experimental parameters,including the type and volume of extraction solvent,pH value and salt concentration of extraction solvent,type and volume of elution solvent,and amount of C18, extraction time were examined and optimized. Under the optimal conditions,the recoveries of ginsenosides were in the range of 96. 3% -110. 6%, the relative standard deviations (RSDs) were in the range of 2.8%-4.3%,indicating that the method has a good performance for the extraction of these ginsenosides. Compared with traditional UANE-SPE method, the modified method simplified the extraction device,shortened the extraction time and improved the extraction efficiency.
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A green, rapid and efficient method was developed for the extraction of 4 kinds of hosenkosides from the seeds of Impatiens balsamina L. The hosenkosides were extracted by ionic liquid, and then enriched by solid phase extraction. The effects of the kinds and volume of ionic liquid, pH value, ultrasonic time, solid phase extractant and eluent on the extraction fields were investigated and optimized. Under the optimum conditions, the recoveries of 4 kinds of hosenkosides were between 92. 1% and 108. 2% , the correlation coefficients were 0. 9945-0. 9975, and the detection limits were 1. 8-4. 5 μg / mL. The RSD values were all less than 3. 9% . The experimental results showed that this method was fast, efficient, environmental protection. This study provided a reference for the extraction and enrichment of trace components in Chinese medicinal herbs.
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This study was to investigate the changes of autonomic nerve function and hemodynamics in patients with vasovagal syncope (VVS) during head-up tilt-table testing (HUT).HUT was performed in 68 patients with unexplained syncope and 18 healthy subjects served as control group.According to whether bradycardia,hypotension or both took place during the onset of syncope,the patients were divided during the test into three subgroups:vasodepressor syncope (VD),cardioinhibitory syncope (CI) and mixed syncope (MX) subgroups.Heart rate,blood pressure,heart rate variability (HRV),and deceleration capacity (DC) were continuously analyzed during HUT.For all the subjects with positive responses,the normalized low frequency (LFn) and the LF/HF ratio markedly decreased whereas normalized high frequency (HFn) increased when syncope occurred.Syncopal period also caused more significant increase in the power of the DC in positive groups.These changes were more exaggerated compared to controls.All the patients were indicative of a sympathetic surge in the presence of withdrawal vagal activity before syncope and a sympathetic inhibition with a vagal predominance at the syncopal stage by the frequency-domain analysis of HRV.With the measurements ofDC,a decreased vagal tone before syncope stage and a vagal activation at the syncopal stage were observed.The vagal tone was higher in subjects showing cardioinhibitory responses at the syncopal stage.DC may provide an alternative method to understand the autonomic profile of VVS patients.
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In recent years,health economics developed quickly,which attracted both international academic and public interested.Compared with the developed countries,although the study of health economics in China started relatively slow,it has already attracted more and more attention by the academic along with the rapidly social development.With the support from international organizations and academic institutions,China had gradually established its health economics research net from 1990s,the research system had been improved and a serious of research achievements had already playedmore important role in the procedure of government decision making.It summarized the research progress in the field of international and China's health economics so as to provide references for research and policies.
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Objective:To describe health service use and trend of treatment and rehabilitation rates among people with psychiatric disability from 2007 to 2013.Methods:Data collected by the 2006 Second China National Sample Survey and the 2007-2013 National Disability Monitoring Survey were utilized and analyzed.The 2006 National Sample Survey on Disabilities investigated 2 526 145 non-institutionalized representative civilians in 734 counties across mainland China.Psychiatric disability was diagnosed by clinical psychiatrists according to ICD-10 and WHO DAS Ⅱ criteria.The 2007 to 2013 National Disability Monitoring Survey selected 1 to 2 study sites among each of the 734 study counties that had been investigated by the Second China National Sample Survey.Information on living conditions,health service use,education and employment were recorded.Results:The data showed that treatment and rehabilitation rates for people with psychiatric disability had largely increased from 2007 to 2013 among adults aged 18 years or older,with the treatment and rehabilitation rates from 49.52% and 21.8% to 66.9% and 58.7% respectively,and the rates among those with 17 years or younger from 23.5% to 43.9%.However,with regard to the effect of the treatment and rehabilitation services,a much larger proportion of people with psychiatric disability reported that the effect was soso instead of good or very good.In addition,among those who received rehabilitation service,most received day care or psychotherapy service,only less than 8% participated work therapy,farming therapy or working skill trainings.Conclusion:The results suggest treatment and rehabilitation rates among people with psychiatric disability are largely increased from 2007 to 2013,while the quality of the service needs further attention.
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Objective To introduce the application experience of Leica CM1950 automatic constant temperature freezing microtome in frozen section.Methods Cooling time and temperature were determined based on the natures of submitted masses,and some techniques were involved in the rapid section staining and diagnosis.Results The submitted masses after using this microtome gained advantages in freezing speed,few ice crystal,easy operation and high quality,and facilitated accurate pathologic diagnosis.Conclusion Leica CM1950 automatic constant temperature freezing microtome has double compressor and semiconductor refrigeration units,can set corresponding freezing temperature for different organizations and provide high-quality frozen section for accurate and rapid intraoperative pathological diagnosis.
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Objective:To illustrate the effect and mechanism of ibrutinib,a Bruton's tyrosine kinase(BTK)inhibitor that inhibits diffuse large B-cell lymphoma(DLBCL)cell survival.Methods:DLBCL cell lines SUDHL-10 and HBL-1 were treated with ibrutinib at different concentrations.A MTT assay was used to detect the inhibition of cell proliferation.Cell apoptosis was analyzed by Annexin V-binding assay,as well as flow cytometry and DAPI staining.The expression of phosphorylated BTK,AKT and ERK was detected by Western blot. DLBCL cells were co-cultured with MSC.The inhibitory effect of ibrutinib on DLBCL cells in tumor microenvironment was assessed in clonogenicity in vitro and in a tumor-bearing non-obese diabetic/severe combined immunodeficient mice in vivo.Results:Up to 2.5 μmol/L and high concentrations of ibrutinib significantly inhibited the proliferation of DLBCL cells in a dose-dependent manner.Approx-imately 1 and 2.5 μmol/L ibrutinib was added on SUDHL-10 cells for 24 h,and the cell apoptotic rates were(21.73±3.64)% and(34.71± 2.36)%,respectively.Both were superior to that of the control group(3.55±1.89)%(P<0.05).Both two DLBCL cell lines pretreated with 5 and 10 μmol/L ibrutinib for 24 h and exhibited nuclear shrinkage at 5 μmol/L and nuclear fragmentation at 10 μmol/L.The expres-sion of phosphorylated BTK,AKT,and ERK decreased significantly after ibrutinib treatment.Ibrutinib inhibited clonogenicity in vitro(P<0.01)and cell proliferation and growth in vivo of DLBCL cells in co-culture system.The differences were statistically significant.Conclu-sion:Ibrutinib can inhibit the proliferation and induce apoptosis of SUDHL-10 and HBL-1 cell lines through a mechanism of blocking the AKT and ERK signaling pathways,as well as the proliferation of DLBCL cells in tumor microenvironment.This finding can significant-ly benefit DLBCL treatment.