[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

[Development of Risk Assessment Index System on HIV infection among young students based on Delphi method].

Objective: To develop a Risk Assessment Index System (RAIS) on HIV infection among young students based on Delphi method and to provide individual HIV infection risk assessment, targeted prevention and control measures. Methods: Delphi method was applied to determine the index system and weight of the assessment tool through three rounds of expert consultation and overall consideration of opinions and suggestions from 19 experts. Results: The positivity coefficients of three rounds of expert consultation were 100%. The authority coefficient of experts was between 0.887 and 0.945. The Kendall's W coefficients through first, second and third round specialist consultation was 0.379, 0.329 and 0.248, respectively (all P<0.001). The coefficients of variation in the third round were all less than 0.25, indicating that experts' opinion tend to be consistent and the results are highly reliable. The HIV infection risk assessment index system among young students consisted of 7 first grade indices and 54 second grade indices, of which weight was calculated. Conclusions: The RAIS on HIV infection for young students was initially established based on Delphi method, and could be used in the development of HIV infection risk assessment tools for personalized prevention and intervention among young students. However, the reliability, validity and effect of this assessment index system need to be further evaluated.

[Cluster analysis on survey of sexual health characteristics and health education demands in young students].

Objective: To explore the difference of sexual health characteristics and demands in students in different groups, and provide the basis for targeted sexual health eduction for AIDS prevention in young students. Methods: A survey was conducted based on the requirement of health education about sexual health and AIDS prevention in young students by the education department of Guangdong province. A two-step cluster analysis was performed on the survey data obtained by convenient sampling, the variables and number of clusters included were determined by combination of analysis results and professional knowledge. The demographic characteristics, the content and form of sexual health education needed were compared among different groups. Results: Survey data of 3 884 students were collected, and six variables were used for classification: cognition or occurrence masturbation, sexual behavior, frequency of sexual information acquisition, number of acceptable sex partners and AIDS knowledge awareness rate. By these variables, the students were classified into three levels of risk groups: high risk group (46.6%), medium risk group (39.9%) and low risk group (13.5%). As for demographic characteristics, high risk group, with a median age of 19 years, had the highest proportions of boys (65.9%), students with non-heterosexuality orientation (15.2%), urban residents (58.2%), only children (30.8%) and undergraduates (54.7%). Medium risk group, with a median age of 19 years, had the highest proportions of girls (82.7%) and vocational college students (34.0%). Low risk group, with a median age of 18 years, had the highest proportions of rural residents (52.4%), non-only child (80.6%), senior high school students (41.3%), non-boarding students (17.5%) and students without internship and part-time job experience (43.2%). In terms of health education demands, high risk group had a higher demand of information about self-identity, sexual safety, sexual decision making, contraception, abortion, and sexually transmitted disease or AIDS prevention. Medium risk group paid more attention to value on love and marriage, sexual assault. Low risk group showed a higher demand of adolescent physiology knowledge. Compared with low risk group, high risk group had a higher demand of peer education, Internet/multimedia, anonymous counseling and other forms of sexual health education. The differences were significant. Conclusion: The characteristics, sexual knowledge awareness, attitude and behavior, and health education demands of young students in different groups are different, so health education materials and methods should be developed according to the characteristics of different groups to enhance the acceptance and enthusiasm of students and improve the quality of sexual health education.

[Analysis on influencing factors of HIV testing services utilization in students with self-assessed high risk of HIV infection based on Andersen's model].

Objective: To analyze the influencing factors for HIV testing services utilization in students with self-assessed high risk of HIV infection. Methods: The research framework of the influencing factors for HIV testing services utilization in students was developed based on Andersen's health services utilization behavioral model and related literature. A cross-sectional survey was performed in students with self-assessed high risk of HIV infection by an online HIV infection risk assessment tool from March to April 2019. Multiple logistic regressions were applied with hierarchical model. Results: A total of 526 students were included in the study (age: 19.30±1.19 years old), in whom 96.2% agreed that HIV testing should be received after high-risk behavior. 56.7% (298/526) had sexual behavior and the HIV testing rate was 11.0% (58/526). The HIV testing rates in students who had and had no sex behavior were 13.42%(40/298) and 7.89% (18/228), respectively. According to the results from multivariate logistic regression analysis, non-heterosexual (compared with heterosexual, OR=7.88, 95%CI: 3.98-15.61) and higher score of AIDS knowledge awareness (compared with lower score, OR=2.05, 95%CI: 1.07-3.93) in propensity factor module, and having risk sexual behavior (compared with having no risk sexual behavior, OR=2.66, 95%CI: 1.41-5.03) and having diagnosis of STD infection in hospital (compared with having no such diagnosis, OR=6.35, 95%CI: 2.21-18.27) in demand factor module, and receiving health education about AIDS prevention in the past year (compared with receiving no such health education, OR=0.29, 95%CI: 0.11-0.76) and receiving health education about AIDS testing service in the past year (compared with receiving no such health education, OR=3.67, 95%CI: 1.71-7.90) in ability factor module were the influencing factors for utilization of HIV testing services. Conclusions: The acceptance of HIV testing in students needs to be improved urgently. Propensity factors, such as their AIDS knowledge awareness and sexual orientation, and demand factors, such as having risk sexual behavior and STD infection, have obvious impacts on the utilization of HIV testing services. However, health education about AIDS prevention and HIV testing service can play a more important role in facilitating the utilization of HIV testing in students. In the future, we should further strengthen the publicity of voluntary HIV counseling and testing service in students with particular attention to girls and those with risk sexual behaviors.

[Influence of self-categorized deviation in knowledge, attitude and practice for sexual health on the willingness to seek help for corresponding problems among young students].

Objective: To evaluate the effect of "self-categorization" on decision of health preference and the influence of self-categorized deviation in knowledge, attitude and practice (KAP) on the willingness of seeking help for sexual health among young students. Methods: From March to April 2019, young students who used a WeChat applet for sexual health and HIV infection risk assessment, which is called "Detective Bear" were recruited and investigated. According to the consistency between the self-categorization of KAP for sexual health and the systematic categorization from their honest answers, the participants were allocated into three groups: consistent, low or high status, according to their judgment on sexual information acquisition, sexual attitude, and the actual number of sexual experiences. Logistic regression was used to analyze the differences in the willingness to seek help for sexual health problems between the three groups. Results: 2 009 students with an average age of (19.2±1.1) were included. 54.7% (1 099/2 009) were female, and 98.4% (1 976/2 009) were college, undergraduate or postgraduate students. 49.0% (984/2 009) were in the consistent group, 10.9% (219/2 009) had a lower self-categorization, 40.1% (806/2 009) had a higher self-categorization. Compared with the consistent group, students with lower self-categorization of KAP for sexual health were less likely to assess HIV voluntary counseling and testing (aOR=0.65, 95%CI: 0.43-0.99). However, students with higher self-categorization seemed to dislike seeking help for sexually transmitted diseases (aOR=0.76, 95%CI: 0.59-0.98). Conclusions: Deviation in self-categorization of KAP for sexual health will reduce the young students' willingness to seek help for related problems. Especially those with lower self-categorization, lack of risk consciousness, and refuse to assess counseling and testing may increase the HIV/AIDS epidemic among this population. It is necessary to strengthen the capacity of self-assessment for young students while promoting sex education.

[Design and analysis of testing results of a WeChat applet for sexual health and HIV infection risk assessment in young students].

Objective: To summarize the design and analysis of testing results of a WeChat applet, which is called "Detective Bear", for sexual health and HIV infection risk assessment in young students, and evaluate its feasibility and effectiveness. Methods: Based on self-categorization theory, by using cluster analysis and Delphi expert consulting method, the framework of WeChat applet, risk assessment index system and preventive intervention content were determined. Young students were recruited by student associations for the application test, the results of the repeated tests and the satisfaction survey were collected and analyzed. Results: The study included 393 participants who repeated the test twice and 750 participants who volunteered to participate in the satisfaction questionnaire survey. The applet contains five modules: self-role judgment, self-test, risk assessment, assessment report generation and background management. The risk assessment module contains 6 first-level indicators and 55 second-level indicators. Assessment report generation module includes role diagnosis type, radar chart of HIV sexual health KAP and intervention prescription. In 393 students who repeated the test, the awareness of AIDS to be a serious sexually transmitted disease, the epidemic trend in young students in China, with active seeking HIV testing services and caring the infected improved. The satisfaction survey showed that 75.7% of students (568/750) accepted the applet, 86.5% (649/750) agreed the evaluation report, 83.1%(623/750) thought that there were some problems, but it was easy to use, 93.3% (700/750) said they can learn something from the applet and 84.1% (631/750) satisfied with the page design. Some students thought the questionnaire was too long and somewhat difficult to complete (P<0.05), and some reported that more can be learned (P<0.05). Conclusions: The applet integrates AIDS prevention related knowledge and practice into a challenging, interesting, interactive game and provide individualized, concrete risk assessment and self-intervention for young students, which can effectively help students to improve the awareness of AIDS related knowledge and get links for access to condoms, testing and other intervention services. However, its large-scale application and long-term effect need to be further tested.

[Status quo and characteristic analysis among MSM-users of the "Internet Plus-based AIDS Comprehensive Prevention Service System" in Guangzhou].

Objective: To analyze the characteristics of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM who frequently using the Internet in Guangzhou. Methods: An online survey was conducted among MSM who were recruited through gay-website portals between August and September, 2018 in Guangzhou, to collect information regarding the use of and attitudes on the "Interner Plus-based AIDS Comprehensive Prevention Service System" . Logistic regression was used to explore the association between the use of Internet intervention tools and related behavioral characteristics. Information on the awareness of AIDS, HIV testing, and condomless anal sex behavior were compared between the core or non-core services users. Results: A total of 777 Internet-based MSM were recruited as participants including 638 men (82.1%) as core service users. MSM were satisfied in using the the "Interner Plus-based AIDS Comprehensive Prevention Service System" while more than 80.0% of the users felt that the tools were helpful in: increasing the HIV awareness, promoting test uptake, and reducing those related risk behavior. Comparing with those who did not use the tools, the users showed higher rates in practising condomless anal intercourse (1.50-1.86 times), commercial sex with men (11.60-21.21 times), and unprotected vaginal intercourse (13.62-20.67 times), in the last 6 months. Proportions of core service users appeared as: [96.6% vs. 74.8%, aOR (95%CI): 8.80 (4.85-15.97)] on HIV testing, [56.4% vs. 22.3%, aOR (95%CI): 4.54 (2.94-7.02)] on regular HIV testing and [86.2% vs. 80.6%, aOR (95%CI): 1.75 (1.06-2.89)] on awareness of HIV knowledge respectively, which were all significantly higher than the non-core service users. Conclusions: The frequent Internet using MSM in Guangzhou claimed to have had high acceptance and satisfaction on the local Internet HIV intervention service tools. The "Internet Plus-based AIDS Comprehensive Prevention Service System" had effectively reached the high-risk subgroups of MSM, increasing the awareness on related risk and promoting testing on HIV.

[Characteristic analysis among MSM-users of the "Online HIV Acquisition Risk Assessment System" in Guangzhou].

Objective: To analyze the characteristics of levels related to the risk through self-evaluation system, among MSM users in Guangzhou, between 2015 and 2017. Methods: Between 2015 and 2017, data was collected from the users of a self-evaluation system network related to HIV infection, based on the previous 'HIV health risk appraisal model'. Information on risk factors was collected to calculate the scores and levels of risks and to estimate the incidence of HIV. Taking the reference of R value on risks as (R=0.9-1.1) in general population. The ones with very low risk, with low risk, moderate risk, high risk and very high risk were set as R≤0.5, 0.52.0, respectively. The scores of modifiable risk factors were compared with different subgroups of MSM. Results: A total of 4 601 MSM were involved in this study, with the following features presented as: aged 16-64 (28.38±7.11) years, proportions of residence from Guangzhou, Guangdong province or other provinces as 38.6%(1 776/4 601)、35.4%(1 629/4 601) and 26.0%(1 197/4 601), 59.6%(2 742/4 601) received bachelor or above degrees. 81.3%(3 741/4 601) of them claimed as having homosexual orientation. R values of risk level on very low risk, low risk level, moderate risk, high risk and very high risk appeared as 12.9%(594/4 601), 50.9%(2 342/4 601), 17.0%(783/4 601), 14.8%(682/4 601) and 4.3%(200/4 601), respectively. Scores of modifiable risk factors decreased year by year (P<0.05), among MSM in this study. In either of the groups that experiencing insertive or receptive sex, the ones with heterosexual orientation presented the highest scores of modifiable risk factors (P<0.05). Conclusions: The risk levels on HIV infections called for special attention among the users of the self-evaluation network system. Among the MSM that carrying either insertive or receptive sex role, the ones with heterosexual orientation had the highest risk levels and scores of modifiable risk factors in Guangzhou. Further study should be explored to better understand the causes of related risks.

[Applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou].

Objective: This article was to evaluate the applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou. Hopefully, the results could be used to improve the existing HIV testing services and to support the implementation and scale-up of HIV self-testing programs. Methods: Data were collected from a survey on HIV testing preferences among the Internet-using MSM in April to June, 2015. Univariate and multivariate logistic regression analysis were applied to identify factors associated with the use of HIV self-testing service provided by Lingnanzhun. Information related to the users of Lingnanzhun during September 2014 and December 2018 was also collected. Results: 769 MSM were recruited as participants. Of them, age distribution was 16-77(28.6±6.8) years old, 88.3%(679/769) were unmarried, 42.2%(325/769) were registered residents of Guangzhou, 82.1%(631/769) had university or college education. Among them, 195 (25.4%) used the HIV self- testing program of Lingnanzhun while 574 (74.6%) using the clinic service. Compared with the clinic service users, the Lingnanzhun users showed the following characteristics: longer experience in the MSM community ≥10 years (32.8% vs. 20.9%, 64/195 vs. 120/574); having male casual sexual partners ≥2 (42.1% vs. 29.6%, 82/195 vs. 170/574); having group sex (6.2% vs. 2.6%, 12/195 vs. 15/574) and having commercial sex with men (13.8% vs. 3.0%, 27/195 vs. 17/574). Data from the Lingnanzhun users showed that a total of 3 000 users had practised 5 038 times of self HIV-testings. 11.4% (343/3 000) of the Lingnanzhun users had never been tested. Conclusions: It was applicable and feasible to provide Internet-based HIV self-testing service to MSM as a significant complement to the traditional facility-based HIV testing services. It was also useful in accessing those who were having higher risk or had never received HIV testing so as to increase the testing uptake and the frequency.

[Effectiveness of the "Internet Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou].

Objective: To evaluate the effectiveness of the "Internet Plus-based AIDS Comprehensive Prevention Service System" among men who have sex with men in Guangzhou. Methods: Data through case-reporting and follow-up programs on MSM HIV/AIDS in Guangzhou was collected from the China Information System for Disease Control and Prevention, which including those from the referral and follow-up treatment compliance programs in 2008-2014 (pre-treatment) and 2017-2018 (post-treatment). According to the types of care services, three groups were set as: with "Internet Plus" service, with 'HIV counseling/testing service' or with 'routine medical service'. General Estimating Equation (GEE) was used to analyze the follow up situation of HIV/AIDS cases, annually. Cox proportional hazard regression model was used to analyze the proportions of treatment referral, within the 30 days of diagnosis. Results: Before the implementation of immediate treatment after HIV diagnosis, 90.6% (707/780) of the HIV/AIDS cases received the first follow up program including the CD(4)(+) T cells counts (CD(4)) test service within 90 days of diagnosis, in the "Internet Plus-based HIV/AIDS care service" group presented 1.19 times (95%CI: 1.14-1.25) of the routine medical service group. The implementation of immediate treatment after HIV diagnosis, compared with the routine medical service group, the "Internet Plus" service group presented 1.71 times (95%CI: 1.03- 2.83) more treatment referrals within the 30 days of diagnosis, when the first testing CD(4) was ≤200 cells/µl. Compared with the routine medical service group, the HIV counseling and testing service group showed 1.37 times (95%CI: 1.20-1.56) more of the treatment referrals within the 30 days of HIV diagnosis, after the first testing CD(4) counts as >200 cells/µl. Conclusion: Standardized care and follow-up service should be promoted as soon as the referral and treatment programs were set after the diagnosis was made, under the "Internet Plus-based AIDS Comprehensive Prevention Service System" for the MSM population, in Guangzhou.

[Prevention effectiveness of the "Internet Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou: a dynamic model of infectious disease].

Objective: To evaluate the effect of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou, during 2010-2017, using a dynamic compartmental model. Methods: A dynamic compartmental model was developed to describe the HIV situation among MSM in Guangzhou. This model was parameterized on data from published literature or surveillance programs from the Guangzhou CDC. The Matlab 7.0 software was used for coding and analysis on collected data. HIV prevalence was analyzed among MSM under the status quo data and estimated the impact by the "Internet Plus" AIDS prevention services project. Results: HIV prevalence would have increased to 22.75% in 2017, and the total number of new HIV infections would have been 11 038, from 2010 to 2017, using the data status quo. Under the Guangzhou "Internet Plus" AIDS prevention services project, the prevalence of HIV among MSM from 2010 to 2017 was estimated to be 8.44%, 9.68%, 10.65%, 11.34%, 11.73%, 11.83%, 11.71% and 11.43% in Guangzhou, which were similar to the surveillance data. The total number of new infections in the past 8 years under the "Internet Plus" scenario was estimated to be 4 009. The "Internet Plus" program would have prevented 7 029 (63.68%) new infections during 2010-2017 as compared to the number, status quo. Conclusions: The fitting result of dynamic compartmental model seemed more reasonable, which was applicable to predict HIV epidemic among MSM in Guangzhou, suggesting that the increase of HIV prevalence had been curbed since the "Internet Plus" project which was launched in 2010, and the "Interner Plus-based AIDS Comprehensive Prevention Service System" had achieved the purpose as planned, epidemiologically.

[Effects and safety of quadratus lumborum block in analgesia after hip arthroplasty].

Objective: To evaluate the efficacy of ultrasound guided quadratus lumborum block combined with non-steroidal anti-inflammatory drugs for postoperative analgesia in patients undergoing total hip arthroplasty. Methods: From January to June 2017, sixty American Society of Anesthesiologists (ASA) physical status Ⅰ to Ⅲ patients, aged 55-75 yr, scheduled for total hip arthroplasty, were randomly divided into control group(group N) and quadratus lumborum block (group R). Ultrasound guided quadratus lumborum block was implemented on the affected side at the end of operation.Then 30 ml 0.33% ropivacaine were administrated in group R, while the control group did not receive the same block. A sufentanil patient-controlled analgesia pump was connected to the patient. The rest visual analogue score (VAS) were recorded at 0 h(T(0)), 3 h(T(1)), 6 h (T(2)), 12 h(T(3)), 24 h (T(4)), 36 h (T(5)) and 48 h(T(6)) after sugery, the VAS scores on movement were evaluated at T(4), T(5) and T(6) time points.The consumption of sufentanil within each period time were recorded.The maximal flexion and abduction degrees of the hip joint were evaluated at 12, 24, 36 and 48 h after operation. The number of patients for rescue pain relief by intravenous analgesia pump during 24 h and 48 h after surgery were counted in both groups. The postoperative adverse effects and overall satisfaction in the two groups were recorded. Results: The VAS at rest in group R were 0.8±0.4, 1.0±0.3, 1.2±0.5, 2.0±0.5, 1.7±0.4 , 1.6±0.5 at T(1), T(2), T(3), T(4), T(5), T(6) respectively, and those in group N were 3.0±0.7, 3.5±0.9, 3.8±0.9, 3.3±1.1, 3.3±0.7, 3.0±0.7 at the same time points. The VAS at rest were lower in group R than those in control group at all time points (F=203.090, 216.354, 203.956, 35.548, 96.332, 80.577, all P<0.01). The VAS on movement in group R were 2.7±0.9, 2.9±0.7 , 2.0±0.6 at T(4), T(5), T(6) respectively , and those in group N were 6.0±1.5, 5.8±1.1, 4.5±1.0. The VAS on movement were also lower in group R than those in control group(F=154.561, 143.224, 141.479, all P<0.01). The maximum flexion degrees in group R were (61±12)degrees, (64±10)degrees, (69±15)degrees and(78±19)degrees at 12, 24, 36, 48 h after operation, and those were (45±11) degrees, (49±10)degrees, (52±12)degrees and(60±14)degrees at the same time points. The maximum flexion degrees in group R were increased more than control group at 12, 24, 36, 48 h after operation(F=34.981, 35.575, 52.106, 41.681, all P<0.01). The abduction degrees in group R were(22±6)degrees, (26±6)degrees, (27±8)degrees and(28±7)degrees at 12, 24, 36, 48 h after surgery, and those in group N were (14±5) degrees, (17±6)degrees, (20±6)degrees and(20±5)degrees. The abduction degrees in group R were increased more than those in group N(F=58.974, 33.402, 19.151, 20.575, all P<0.01). The rates of rescue analgesia for pain relief were 10% and 16.7% at 24 h and 48 h after operation respectively in group R, and those were 100% and 100% in group N. Compared to group N, the rates of rescue analgesia for pain relief in group R were significantly decreased (χ(2)=49.091, 42.857, all P<0.01). The incidences of postoperative nausea and vomiting, pruritus in group R were 3.3% and 3.3% respectively, and those in group N were 23.3% and 20.0%. The incidences of nausea and vomiting, pruritus in group R were lower than those in group N (χ(2)=5.192, 4.875, all P<0.01). The overall satisfaction scores in group R (3.7 ± 1.0 ) were higher than those (1.9±0.7) in the group N(t=7.841, P<0.01). Conclusion: The quadratus lumborum block combined with parecoxib sodium for multimodal analgesia after total hip arthroplasty is effective and provides satisfactory analgesia.

Gastrodin suppresses BACE1 expression under oxidative stress condition via inhibition of the PKR/eIF2α pathway in Alzheimer's disease.

The expression of ß-site APP-cleaving enzyme 1 (BACE1) is increased in the brain of late-onset sporadic Alzheimer's disease (AD) and oxidative stress may be the potential cause of this event. The phenolic glucoside gastrodin (Gas), a main component of a Chinese herbal medicine Gastrodia elata Blume, has been demonstrated to display antioxidant activity and suppresses BACE1 expression. However, the mechanisms by which Gas suppresses BACE1 expression are not clear. Morris water maze test was performed to assess the effect of Gas treatment on memory impairments in Tg2576 mice. The level of oxidative stress in the brain of Tg2576 mice was determined by measuring the superoxide dismutase (SOD) activity, catalase (CAT) activity, and the levels of malondialdehyde (MDA) and ROS. In vivo and in vitro, we detected the expression levels of BACE1, pPKRThr446, PKR, pPERKThr981, PERK, peIF2αSer51, and eIF2α using western blot analysis. We found that Gas improved learning and memory abilities of Tg2576 transgenic mice and attenuated intracellular oxidative stress in hippocampi of Tg2576 mice. We discovered that the expression levels of BACE1, activated PKR (pPKRThr446) and activated eIF2α (peIF2αSer51) were elevated in the brains of Tg2576 mice and hydrogen peroxide (H2O2)-stimulated SH-SY5Y cells. Moreover, peptide PKR inhibitor (PRI) and Gas down-regulated BACE1 expression in Tg2576 mice and H2O2-stimulated SH-SY5Y cells by inhibiting activation of PKR and eIF2α. Gas alleviates memory deficits in mice and suppresses BACE1 expression by inhibiting the protein kinase/Eukaryotic initiation factor-2α (PKR/eIF2α) pathway. The research suggested that Gas may develop as an drug candidate in neurodegenerative diseases.

I148M variant of PNPLA3 increases the susceptibility to non-alcoholic fatty liver disease caused by obesity and metabolic disorders.

BACKGROUND: The patatin-like phospholipase 3 (PNPLA3) rs738409 gene polymorphism is an important genetic determinant of non-alcoholic fatty liver disease (NAFLD). However, the associations between liver fat and metabolic traits in rs738409 G allele carriers and the allelic influence on this association have not been fully studied. AIM: To investigate the influence of the PNPLA3 gene polymorphism on the association of liver fat with serum metabolic factors and carotid atherosclerosis. METHODS: Liver fat was measured by quantitative ultrasound in 4300 subjects in the Shanghai Changfeng community and analysed for its association with obesity and metabolic factors in individuals with the PNPLA3 CC, CG and GG genotypes. RESULTS: Non-alcoholic fatty liver disease occurred in 37.9% and 28.8% of the subjects with the GG and CC genotypes respectively (P < 0.001). Liver fat was significantly associated with body mass index, waist circumference, serum triglycerides, high-density lipoprotein cholesterol, fasting blood glucose and insulin in the PNPLA3 rs738409 G allele carriers (P < 0.001). Compared with the CC homozygotes, the GG homozygotes presented higher liver fat and liver fibrosis scores despite their better metabolic status (comparison of regression line slopes, P < 0.05). An increase in liver fat was accompanied by a significant increase in the average and maximum carotid intima-media thickness in subjects with the PNPLA3 CC genotype but not in those with the GG genotype. CONCLUSIONS: PNPLA3 rs738409 G allele carriers were found to be more susceptible to the metabolic-related hepatic steatosis, and developed NAFLD and liver fibrosis despite presenting relatively better metabolic statuses and lower risks for carotid atherosclerosis.

Expression levels of urotensin II are associated with endoplasmic reticulum stress in patients with severe preeclampsia.

Hypertensive disorders in pregnancy remain a leading cause of maternal and perinatal mortality and morbidity. We aim to study urotensin II (UII) and its association with the markers of endoplasmic reticulum stress (ERS) in placentas of patients with severe preeclampsia (SPE). Thirty-three patients with hypertensive disorders in pregnancy and twenty-two healthy pregnant women designated as healthy controls were recruited. Expression levels of UII, UII receptor (GPR14) and the markers of ERS in placenta specimens of patients were performed. Plasma and urinary UII levels were measured by radioimmunoassay method. Our study showed that the plasma levels of UII in patients with hypertensive disorders during pregnancy were significantly higher than that of the healthy control group. However, the urinary levels of UII had no difference in two groups. The expression level of mRNA and protein of UII, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulation protein 78 in placentas of SPE was significantly increased. Immunohistochemical analyses show that the expression levels of UII and ERS markers were mainly located in the cytoplasm of placental trophoblastic cells. Moreover, expression level of UII mRNA and protein was positively correlated with that of the markers of ERS. The positive correlation between UII and ERS markers expression level also corresponded with the level of patient's systolic blood pressure and proteinuria. In conclusion, we first verify that expression of UII is associated with ERS in patients with SPE. Our results indicate that UII may trigger ERS in placental trophoblastic cells in patients with preeclampsia.

Congenital hydrocephalus and hemivertebrae associated with de novo partial monosomy 6q (6q25.3→qter).

This study was conducted to describe a prenatal case of congenital hydrocephalus and hemivertebrae with a 6q terminal deletion and to investigate the possible correlation between the genotype and phenotype of the proband. We performed an array-based comparative genomic hybridization (aCGH) analysis on a fetus diagnosed with congenital hydrocephalus and hemivertebrae. The deletion, spanning 10.06 Mb from 6q25.3 to 6qter, was detected in this fetus. The results of aCGH, karyotype and fluorescent in situ hybridization (FISH) analyses in the healthy parents were normal, which confirmed that the proband's copy-number variant (CNV) was de novo. This deleted region encompassed 97 genes, including 28 OMIM genes. We discussed four genes (TBP, PSMB1, QKI and Pacrg) that may be responsible for hydrocephalus while the T gene may have a role in hemivertebra. We speculate that five genes in the 6q terminal deletion region were potentially associated with hemivertebrae and hydrocephalus in the proband.

Transcriptional regulation of CD4 gene expression in porcine kidney epithelial cells by virus-like double-stranded RNA and DNA methyltransferase inhibitor.

The effects of virus-like double-stranded RNA (dsRNA, PolyI:C) and DNA methyltransferase inhibitor (Aza-CdR) on CD4 gene expression were investigated in a porcine kidney cell line (PK15). We found that expression levels of TLR3 and IFNαwere significantly upregulated by PolyI:C, compared to the untreated PK15 cells, which shows that PolyI:C successfully mimics viral infection in PK15 cells. We also found that PolyI:C (10 µg/ml) and/or Aza-CdR (5 µM) significantly induces DNA demethylation of porcine CD4, promoting the binding of NF-κB to the CpG site on the CD4 promoter and activating expression of CD4. These data help clarify the regulatory mechanism of DNA methylation of the CD4 gene in non-immune cell response to virus replication. Further study is warranted to identify CD4 gene expression regulated by DNA methylation and live virus infection.

Cloning, expression and characterization of four serpin-1 cDNA variants from the spruce budworm, Choristoneura fumiferana.

Four cDNAs (Cfserpin-1a, Cfserpin-1b, Cfserpin-1c and Cfserpin-1d) of the Choristoneura fumiferana serpin-1 gene were cloned from an epidermis cDNA library. Analysis of the deduced amino acid sequences indicated that the cloned cDNAs encode four different proteins displaying identical N- but distinct C-termini, the latter region containing the inhibitory loop. The entire CfSerpin-1 gene is transcribed while the variants are generated. Antibodies generated against the purified recombinant serpins cross-reacted with the other three. Each of the four Cfserpin-1 cDNA variants was transcribed throughout larval development, from the 4th to the 6th instar, but transcript levels during the intermolt phases were generally higher than during the molting phase. The epidermis and fat body had higher levels of Cfserpin-1 transcripts than the midgut. Cfserpin-1 proteins, detected with the Cfserpin-1a antibody, were found in the epidermis, midgut, fat body, plasma and molting fluid of 6th instar larvae and pre-pupae. Prepupal and pupal insects had higher levels of the proteins than the 6th instar feeding larvae, despite a drop in transcript levels. Cfserpin-1a could bind with the serine proteinase elastase and form a complex in vitro. We hypothesize that the cloned serpins could be involved in the regulation of cuticle degradation during the insect molting cycle.

1H-NMR signal assignments and secondary structure analysis of martentoxin.

Martentoxin is a peptide of 37 amino acid residues purified from the venom of the Chinese scorpion Buthus martensi Karch, which has been demonstrated to be an inhibitor of voltage-dependent sodium channel and voltage-dependent delayed rectifier potassium channel. To elucidate the molecular mechanism of this interaction, the structure of martentoxin was studied by 2D-NMR. The secondary structure of martentoxin consists of a triple-stranded beta-sheet connected to a alpha-helical structure. This helix encompasses 10 residues from Ser11 to Lys20. The three strands of beta-sheet probably comprise residues Gly2-Asp5, Q27-N30 and Glu33-Cys36, Cys30-Asn33 with a type I'beta turn centered on Asn31-Asn32. The results indicate that martentoxin possesses the conserved beta alpha beta beta structure of all the potassium channel toxins.

Cytochalasin D from Hypocrella bambusae.

Cytochalasin D which shows marked cytotoxic effects on multi-tumor cells was newly isolated at high content(5.28 mg/g, dry weight) from Fungus Hypocrella bambusae(B.et Br.) Sacc. Its structure was elucidated by spectroscopic methods. Two-dimensional NMR techniques were applied to make complete assignment for the 1H- and 13C-NMR chemical shifts of this compound.