Investigating the nexus of metabolic syndrome, serum uric acid, and dementia risk: a prospective cohort study.

BACKGROUND: The global dementia prevalence is surging, necessitating research into contributing factors. We aimed to investigate the association between metabolic syndrome (MetS), its components, serum uric acid (SUA) levels, and dementia risk. METHODS: Our prospective study comprised 466,788 participants without pre-existing MetS from the UK Biobank. We confirmed dementia diagnoses based on the ICD-10 criteria (F00-03). To evaluate the dementia risk concerning MetS, its components, and SUA levels, we applied Cox proportional hazards models, while adjusting for demographic factors. RESULTS: Over a median follow-up of 12.7 years, we identified 6845 dementia cases. Individuals with MetS had a 25% higher risk of all-cause dementia (hazard ratio [HR] = 1.25, 95% confidence interval [CI] = 1.19-1.31). The risk increased with the number of MetS components including central obesity, dyslipidemia for high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides. Particularly for those with all five components (HR = 1.76, 95% CI = 1.51-2.04). Dyslipidemia for HDL cholesterol, hypertension, hyperglycemia, and dyslipidemia for triglycerides were independently associated with elevated dementia risk (p < 0.01). MetS was further linked to an increased risk of all-cause dementia (11%) and vascular dementia (VD, 50%) among individuals with SUA levels exceeding 400 µmol/L (all-cause dementia: HR = 1.11, 95% CI = 1.02-1.21; VD: HR = 1.50, 95% CI = 1.28-1.77). CONCLUSIONS: Our study provides robust evidence supporting the association between MetS, its components, and dementia risk. These findings emphasize the importance of considering MetS and SUA levels in assessing dementia risk, offering valuable insights for prevention and management strategies.

A nomogram of preoperative indicators predicting lymph vascular space invasion in cervical cancer.

PURPOSE: To develop predictive nomograms of lymph vascular space invasion (LVSI) in patients with early-stage cervical cancer. METHODS: We identified 403 patients with cervical cancer from the Affiliated Hospital of Jiangnan University from January 2015 to December 2019. Patients were divided into the training set (n = 242) and the validation set (n = 161), with patients in the training set subdivided into LVSI (+) and LVSI (-) groups according to postoperative pathology. Preoperative hematologic indexes were compared between the two subgroups. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for LVSI, from which a nomogram was constructed using the R package. RESULTS: LVSI (+) was present in 94 out of 242 patients in the training set, accompanied by a significant increase in the preoperative squamous cell carcinoma antigen (SCC), white blood cells (WBC), neutrophil (NE), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and tumor size (P < 0.05). Univariate analysis showed that SCC, WBC, NE, NLR, PLR, SII, and tumor size were correlated with LVSI (P < 0.05), and multivariate analysis showed that tumor size, SCC, WBC, and NLR were independent risk factors for LVSI (P < 0.05). A nomogram was correspondingly established with good performance in predicting LVSI [training: ROC-AUC = 0.845 (95% CI: 0.731-0.843) and external validation: ROC-AUC = 0.704 (95% CI: 0.683-0.835)] and high accuracy (training: C-index = 0.787; external validation: C-index = 0.759). CONCLUSION: The nomogram based on preoperative tumor size, SCC, WBC, and NLR had excellent accuracy and discriminative capability to assess the risk of LVSI in early-stage cervical cancer patients.

Phenyldivinylsulfonamides for the construction of antibody-drug conjugates with controlled four payloads.

Phenyldivinylsulfonamides emerged from a series of divinylsulfonamides, demonstrating their ability to effectively re-bridge disulfide bonds. This kind of linkers was attached to monomethyl auristatin E (MMAE) and further conjugated with a model antibody, trastuzumab. After optimization, the linker 20 can deliver stable and highly homogenous DAR (Drug-to-Antibody Ratio) four antibody-drug conjugates (ADCs). The method was also applicable for other IgG1 antibodies to obtain ADCs with controlled four payloads. Moreover, the MMAE-bearing ADC is potent, selective and efficacious against target cell lines.

Site-specific construction of triptolide-based antibody-drug conjugates.

Antibody-drug conjugates (ADCs) have emerging as efficient agents to target deliver cytotoxic drugs and reduce their off-target side effects. Triptolide has attracted attention to be used in ADC development. Herein, three rationally designed triptolide drug-linkers have been synthesized for use in site-specific construction of ADCs. Carbamates that were supposed to be more stable than carbonates were introduced to attach triptolide to the linkers. PEG and discrete PEG chains were incorporated to improve the hydrophilicity of drug-linkers. The ADCs were finally site-specifically prepared by conjugation of the drug-linkers to trastuzumab through disulfide re-bridging approach. The preliminary anti-tumor activities of these ADCs were evaluated and they displayed high potencies against HER2-targeted cancer in vitro and in vivo.

Lumbar muscles biomechanical characteristics in young people with chronic spinal pain.

BACKGROUND: The prevalence of low back pain is rising among the young adult population. Altered lumbar muscle tone was suggested to be associated with underlying pathologies and symptoms. To date, there is minimum information available on the repeatability of lumbar spine muscle mechanical properties in the young adults who experienced low back pain. This study aimed to assess the reproducibility of mechanical properties of lumbar spinal muscle in young adults with spinal pain by myotonometer and explored the difference in reproducibility when different number of indentations was used. METHODS: Participants who aged between 18 to 25 and reported chronic LBP were recruited. Lumbar muscle tone (Hz) and stiffness (N/m) were assessed by myotonometer on one occasion by two assessors. Parameters were recorded by triple scans and 5-scans mode. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Bland and Altman analysis were used to assess agreement between two measurements. The relationship between muscle mechanical properties and pain score and disability level were assessed by Spearman's rank correlation coefficient. RESULTS: The results of ICCs indicated excellent repeatability in triple scans and 5-scans mode for each lumbar level bilaterally (ICC > 0.75). SEM and SRD were smaller in triple scans than 5-scans mode for most levels. Bland and Altman analysis revealed no systematic bias. Spearman's rank correlation analysis indicated significant high correlations between muscle tone and disability level (r = 0.80, p < 0.05), and between muscle stiffness and disability level (r = 0.81, p < 0.05). CONCLUSIONS: This study found that lumbar spinal muscle tone and stiffness were repeatable parameters when measured by myotonometer. The reproducibility of muscle mechanical parameters did not appear to differ between the two scanning modes with different number of indentations. Muscle tone and stiffness measured by myotonometer may therefore be reliable as outcome measures to assess intervention induced changes. The lack of significant association between intensity of pain and mechanical properties of paraspinal muscles may suggest that muscle properties measured at rest might not be related to pain level at rest but more related to pain elicited during movement.

The Human Immunodeficiency Virus Care Continuum in China: 1985-2015.

Background: Human immunodeficiency virus (HIV) care continuum attrition is a major global public health challenge. Few studies have examined this problem in resource-limited settings. We aimed to assess cumulative, current, and historical achievement along China's HIV continuum of care. Methods: A nationwide, serial cross-sectional study of all individuals with HIV infection diagnosed in China between 1 January 1985 and 31 December 2015 was conducted using data from China's HIV/AIDS information systems. Biennial estimates of the number of persons living with HIV were also used. We defined 7 steps in HIV care continuum as infected (estimated), diagnosed, linked, retained, enrolled, receiving antiretroviral therapy (ART), and virally suppressed. Cumulative, 30-year performance, and biennial performance during the most recent 10 years were examined. Results: A total of 573529 persons diagnosed with HIV infection were included. Cumulatively, 94% were linked, 88% were retained, 73% were enrolled, 67% were receiving ART, and 44% were suppressed. Greatest attrition was observed for adolescents, minorities, and those who reported injecting drug use as their route of infection. Improvement was observed from 2005 to 2015. As of the end of 2015, 68% among those infected were diagnosed, 67% among diagnosed were receiving ART, and 65% among those receiving ART were virally suppressed. After adjusting for those without viral load testing, the proportion suppressed increased to 89%. Conclusions: Despite dramatic improvements, China faces serious challenges in achieving the Joint United Nations Programme on HIV/AIDS 90-90-90 targets, because of substantial attrition along its continuum of HIV care.

"Late for testing, early for antiretroviral therapy, less likely to die": results from a large HIV cohort study in China, 2006-2014.

BACKGROUND: Timely HIV testing and initiation of antiretroviral therapy are two major determinants of survival for HIV-infected individuals. Our study aimed to explore the trend of late HIV/AIDS diagnoses and to assess the factors associated with these late diagnoses in China between 2006 and 2014. METHODS: We used data from the Chinese Comprehensive Response Information Management System of HIV/AIDS (CRIMS). All individuals who tested positive for HIV between 2006 and 2014 in China and were at least 15 years of age were included. A late diagnosis was defined as an instance in which an individual was diagnosed as having AIDS or WHO stage 3 or 4 HIV/AIDS, or had a CD4 cell count less than 200 cells/mm3 at the time of diagnosis. RESULTS: Among the 528,234 individuals (≥15 years old) newly diagnosed with HIV between 2006 and 2014, 179,700 (34.0%) people were considered to have received late diagnoses. The late diagnosis rate decreased from 33.9% in 2006 to 29.7% in 2014 (P < 0.01). Late diagnoses were more likely to be found among those who were 45-54 years old (adjusted odds ratio [aOR]: 3.25, 95% confidence interval [CI]: 3.17-3.34) or 55+ years old (OR: 2.94, 95% CI: 2.86-3.02), male (aOR: 1.15, 95% CI: 1.13,1.17), employed as a farmer or rural laborer (aOR: 1.13, 95% CI: 1.11-1.14), infected through blood or plasma transfusion (aOR: 4.18, 95% CI: 4.02, 4.35), diagnosed at hospitals (OR: 1.17, 95% CI: 1.15, 1.19), of Han ethnicity (aOR: 1.30, 95% CI: 1.28, 1.32), and married (OR: 1.12, 95% CI: 1.11,1.13). Of those people living with HIV (PLHIV) who received late diagnoses, 7.4%(8637) and 46.1%(28,462) ultimately died with or without receiving antiretroviral therapy within a year of diagnosis, respectively. CONCLUSION: A large proportion of individuals with HIV/AIDS receive late diagnoses, and this proportion has witnessed a slight decline in recent years. Expanded testing is needed to increase early HIV diagnosis and antiretroviral therapy should be recommended to all diagnosed individuals as early as possible to reduce AIDS-related death.

Care cascade structural intervention versus standard of care in the diagnosis and treatment of HIV in China: a cluster-randomized controlled trial protocol.

BACKGROUND: The high rate of attrition along the care cascade of infection with human immunodeficiency virus (HIV) results in lost opportunities to provide timely antiretroviral therapy (ART) and to prevent unnecessarily high mortality. This study aims to assess the effectiveness of a structural intervention, the one-stop ("One4All") strategy that streamlines China's HIV care cascade with the intent to improve testing completeness, ART initiation, viral suppression, and mortality. METHOD: A two-arm, cluster-randomized controlled trial was implemented in twelve county hospitals in Guangxi China to test the effectiveness of the One4All strategy (intervention arm) compared to the current standard of care (SOC; control arm). The twelve study hospitals were selected for homogeneity and allocated one-to-one to the intervention and control arms. All patients screening HIV positive in study hospitals were enrolled. Target study enrollment was 180 participants per arm, 30 participants per hospital. Basic demographic information was collected as well as HIV risk behavior and route of infection. In intervention hospitals, patients then went on to receive point-of-care CD4 testing and in-parallel viral load (VL) testing whereas patients in control hospitals progressed through the usual SOC cascade. The primary outcome measure was testing completeness within 30 days of positive initial HIV screening result. Testing completeness was defined as receipt of all tests, test results, and post-test counseling. The secondary outcome measure was ART initiation (receipt of first ART prescriptions) within 90 days of positive initial HIV screening result. Tertiary outcome measures were viral suppression (≤200 copies/mL) and all-cause mortality at 12 months. DISCUSSION: We expect that this first-ever, cluster-randomized controlled trial of a bundle of interventions intended to streamline the HIV care cascade in China (the One4All strategy) will provide strong evidence for the benefit of accelerating diagnosis, thorough clinical assessment, and ART initiation via an optimized HIV care cascade. We furthermore anticipate that this evidence will be valuable to policymakers looking to elevate China's overall HIV/AIDS response to meet the UNAIDS 90-90-90 targets and the broader, global goal of eradication of the HIV/AIDS epidemic. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02084316 . (Registered on March 7, 2014).

Simplified HIV Testing and Treatment in China: Analysis of Mortality Rates Before and After a Structural Intervention.

BACKGROUND: Multistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality. METHODS AND FINDINGS: In the "pre-intervention 2010" (from January 2010 to December 2010) and "pre-intervention 2011" (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the "post-intervention 2012" (from July 2012 to June 2013) and "post-intervention 2013" (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6-18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27-141)/43 d (IQR 15-113) to 5 d (IQR 2-12)/5 d (IQR 2-13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239-0.620] and 0.380 [95% CI 0.233-0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226-0.603] and 0.361 [95% CI 0.221-0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52. CONCLUSIONS: Our results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART.

[Analysis of factors associated with antiretroviral therapy intiation and its timeliness among HIV sero-discordant couples in high HIV prevalence regions, China].

OBJECTIVE: To analyze factors associated with antiretroviral therapy (ART) initiation and its timeliness among HIV sero-discordant couples in high HIV prevalence regions in China. METHODS: Data from the national HIV epidemiology and treatment databases by Dec 31, 2013 were used to collect HIV serodiscordant couples' baseline and follow-up informations in 40 counties which had reported 200 HIV cases cumulatively from Yunnan, Guangxi, Sichuan, Henan, and Xinjiang. Positive couples were divided into ART group and Non-ART group based on their ART initiation status. Sero-discordant couples that were reported between January 1, 2012 and October 31, 2013 and initiated ART treatment by 2013, were classified into two categories: 'having initiated ART within two months of receiving their HIV diagnosis', and not accessing timely treatment as 'having not initiated ART within two months of receiving their HIV diagnosis'. Multivariate logistic regressions were used to analyze potential factors associated with ART initiation and serodiscordant couples' timeliness to treatment. Odds ratios (95% confidence internal) were used to measure the associations. RESULTS: A total of 10 213 HIV-positive individuals were included in this study, among whom 73.9% (7 550/10 213) were males and 26.1% (2 663/10 213) were females, 66.4% (6 780/10 213) had initiated ART and 33.6% (3 433/10 213) had not. There were 1 733 serodiscordant couples who were reported during January 1, 2012 to October 31, 2013 had initiated ART. Among those 64.9% (1 125/1 733) had successfully initiated ART within two months of receiving their HIV diagnosis and 35.1% (608/1 733) had not. Multivariate logistic regression analysis showed that those being male were 0.81(0.71-0.92) less likely to initiate ART, as compared with those being female. Those being Yi ethnicity were 0.29(0.25-0.35) less likely to initiate ART, as compared with those being Han ethnicity. Those being Uygur ethnicity were 1.57 (1.28-1.93) times more likely to initiate ART, as compared with those being Han ethnicity. Those engaging the other jobs were 0.85(0.75-0.96) less likely to initiate ART, as compared with those being peasant. Those being diagnosed in medical institutions were 0.61 (0.53-0.71) less likely to initiate ART, as compared with those being diagnosed in VCT. Those having CD4⁺ T cells of 250-349, 350-550 and > 550 were 0.75 (0.64-0.89), 0.17 (0.14-0.19), 0.10 (0.08-0.11) less likely to initiate ART, respectively, as compared with those having CD4⁺ T cells of < 250. Those having duration of follow-up of 13-36 months and ≥ 37 months were 0.55(0.48-0.63) and 0.32 (0.28-0.37) less likely to initiate ART respectively, as compared with those having duration of follow-up of ≤ 12 months. Multivariate logistic regression analysis showed that those being Yi and Uygur ethnicity were 0.63 (0.44-0.91) and 0.40(0.29-0.56) less likely to initiate ART timely respectively, as compared with those being Han ethnicity. Those being infected through injecting drug use were 0.64 (0.47-0.86) less likely to initiate ART timely, as compared with those being infected through heterosexual intercourse. Those being diagnosed in other institutions were 0.58(0.43-0.78) less likely to initiate ART timely, as compared with those being diagnosed in VCT. Those having CD4⁺T cells of 250-349, 350-550 and > 550 were 0.75(0.56-1.00), 0.44(0.34-0.58), and 0.31(0.22-0.45) less likely to initiate ART timely respectively, as compared with those having CD4⁺ T cells of < 250. CONCLUSION: Being males, being Yi ethnicity, engaging other jobs, being diagnosed in medical institutions, having high CD4⁺ T cells and having long duration of follow-up were risk factors for initiating ART among serodiscordant couples.Being Yi and Uygur ethnicity, being infected through injecting drug use, and having CD4⁺ T cells were risk factors for initiating ART timely among serodiscordant couples.

Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study.

BACKGROUND: On the basis of the results of the randomised clinical trial HPTN 052 and observational studies, WHO has recommended that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether or not such a public health approach is feasible and the outcomes are sustainable at a large scale and in a developing country setting has not previously been assessed. METHODS: In this retrospective observational cohort study, we included treated and treatment-naive HIV-positive individuals with HIV-negative partners of the opposite sex who had been added to the national HIV epidemiology and treatment databases between Jan 1, 2003 and Dec 31, 2011. We analysed the annual rate of HIV infection in HIV-negative partners during follow-up, stratified by treatment status of the index partner. Cox proportional hazards analyses were done to examine factors related to HIV transmission. FINDINGS: Based on data from 38,862 serodiscordant couples, with 101,295·1 person-years of follow-up for the seronegative partners, rates of HIV infection were 2·6 per 100 person-years (95% CI 2·4-2·8) among the 14,805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per µl [IQR 314-590]) and 1·3 per 100 person-years (1·2-1·3) among the 24,057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per µl [62-269]). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0·74, 95% CI 0·65-0·84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0·64, 0·54-0·76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0·76, 0·59-0·99) or heterosexual intercourse (0·69, 0·56-0·84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0·98, 0·71-1·36). INTERPRETATION: Antiretroviral therapy for HIV-positive individuals in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale in a developing country context. The durability and generalisability of such protection, however, needs to be further studied. FUNDING: Chinese Government's 12th Five-Year Plan, the National Natural Science Foundation of China, and the Canadian International Development Research Centre.

Impact of Cooking Methods on Phenolic Acid Composition, Antioxidant Activity, and Starch Digestibility of Chinese Triticale Porridges: A Comparative Study between Atmospheric Pressure and High Pressure Boiling.

Water boiling under atmospheric pressure (CAP) and water boiling under high pressure (CHP) are two popular domestic cooking methods for Chinese porridge making. In this study, we aimed to evaluate the effects of these two methods on the phenolic acid composition, antioxidant activity, and starch digestibility of triticale porridges. The contents of total free and total bound phenolic acids in the CHP sample were 1.3 and 1.6 times higher than those in the CAP counterpart, respectively, although the DPPH and ABTS values of these two samples were comparable. CAP induced more small pieces of starch than CHP, and the gelatinization enthalpy was 19% higher in the CHP sample than that in the CAP. Both cooking methods increased the starch digestibility, while the CHP sample (58.84) showed a lower GI than the CAP (61.52). These results may promote the application of triticale in health-promoting staple foods.

Effectiveness of Frequent Viral Load Testing Plus Additional Interventions to Prevent HIV Transmission in Heterosexual, Serodiscordant Couples - Yunnan Province, China, 2019-2021.

What is already known about this topic?: HIV transmission among serodiscordant couples remains a persistent issue in China. However, the practice of combining counseling with antiretroviral therapies (ART) to enhance ART adherence is not widely implemented or recommended in Chinese health guidelines. What is added by this report?: This randomized controlled trial suggests that increased follow-up, counseling, and awareness of HIV risk can enhance ART compliance, thereby maximizing treatment efficacy. What are the implications for public health practice?: Early testing and counseling of serodiscordant couples, following the identification of a human immunodeficiency virus (HIV) positive spouse, is crucial for initiating ART and reducing the risk of seroconversion in the uninfected partner. Implementing a combination of ART and adjunct counseling in China is advisable.

HIV and syphilis prevalence among men who have sex with men: a cross-sectional survey of 61 cities in China.

BACKGROUND: Human immunodeficiency virus (HIV) has rapidly spread among men who have sex with men (MSM) in China in recent years; the magnitude of the epidemic is unclear. We sought to test 3 hypotheses: (1) The prevalence of both HIV and syphilis among MSM in China is high, (2) the 2 epidemics each have unique geographical distributions, and (3) demographic and sexual behavior characteristics are different among segments of the MSM population in China. METHODS: A total of 47 231 MSM from 61 cities in China participated in a cross-sectional survey conducted from February 2008 to September 2009. Demographic and behavioral data were collected and analyzed and blood samples tested for HIV and syphilis. Three subgroups among the broader MSM sample were described. Main outcome measures were HIV and syphilis prevalence. RESULTS: An overall prevalence of 4.9% (2314/47 231; 95% confidence interval [CI], 4.7%-5.1%) for HIV and 11.8% (5552/47 231; 95% CI, 11.5%-12.0%) for syphilis was found. Syphilis-positive MSM had the highest HIV prevalence, 12.5% (693/5552; 95% CI, 11.6%-13.4%). However, correlations between HIV and syphilis prevalence were found in only 3 of 6 geographical regions (Northwest: r = 0.82, P = .0253; East: r = 0.78, P = .0004; and South-central: r = 0.63, P = .0276). Three subgroups-nonlocal MSM, Internet-using MSM, and female-partnering MSM-were found to have different profiles of characteristics and behaviors. CONCLUSIONS: HIV and syphilis prevalences among MSM in China are high and the 2 epidemics are largely separate geographically. Three segments of the Chinese MSM population each have different demographic and sexual risk "profiles" that suggest high potential for bridging infection across geographies, generations, and sexes.

Frontoparietal regions may become hypoactive after intermittent theta burst stimulation over the contralateral homologous cortex in humans.

Brain injury to the dorsal frontoparietal networks, including the posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (DLPFC), commonly cause spatial neglect. However, the interaction of these different regions in spatial attention is unclear. The aim of the present study was to investigate whether hyperexcitable neural networks can cause an abnormal interhemispheric inhibition. The Attention Network Test was used to test subjects following intermittent theta burst stimulation (iTBS) to the left or right frontoparietal networks. During the Attention Network Test task, all subjects tolerated each conditioning iTBS without any obvious iTBS-related side effects. Subjects receiving real-right-PPC iTBS showed significant enhancement in both alerting and orienting efficiency compared with those receiving either sham-right-PPC iTBS or real-left-PPC iTBS. Moreover, subjects exposed to the real-right-DLPFC iTBS exhibited significant improvement in both alerting and executive control efficiency, compared with those exposed to either the sham-right-DLPFC or real-left-DLPFC conditioning. Interestingly, compared with subjects exposed to the sham-left-PPC stimuli, subjects exposed to the real-left-PPC iTBS had a significant deficit in the orienting index. The present study indicates that iTBS over the contralateral homologous cortex may induce the hypoactivity of the right PPC through interhemispheric competition in spatial orienting attention.

Translation and concurrent validity, sensitivity and specificity of Chinese version of Short Orientation Memory Concentration Test in people with a first cerebral infarction.

Purpose: This study aimed to translate the English version of the Short Orientation-Memory-Concentration (SOMC) test into a Chinese version, denoted the C-SOMC test, and to investigate the concurrent validity, sensitivity, and specificity of the C-SOMC test against a longer and widely used screening instrument in people with a first cerebral infarction. Methods: An expert group translated the SOMC test into Chinese using a forward-backward procedure. Eighty-six participants (67 men and 19 women, mean age = 59.31 ± 11.57 years) with a first cerebral infarction were enrolled in this study. The validity of the C-SOMC test was determined using the Chinese version of Mini Mental State Examination (C-MMSE) as the comparator. Concurrent validity was determined using Spearman's rank correlation coefficients. Univariate linear regression was used to analyze items' abilities to predict the total score on the C-SOMC test and the C-MMSE score. The area under the receiver operating characteristic curve (AUC) was used to demonstrate the sensitivity and specificity of the C-SOMC test at various cut-off values distinguishing cognitive impairment from normal cognition. Results: The total score for the C-SOMC test and the score for item 1 on this test exhibited moderate-to-good correlations with the C-MMSE score, with respective ρ-values of 0.636 and 0.565 (P < 0.001). The scores for each of items 2, 4, 5, 6, and 7 yielded fair correlations with C-MMSE score, with ρ-value from 0.272 to 0.495 (P < 0.05). The total score on the C-SOMC test and the item score were good predictors (adjusted R2 = 0.049 to 0.615) of the C-MMSE score, and six items were good predictors (adjusted R2 = 0.134 to 0.795) of the total score. The AUC was 0.92 for the C-SOMC test. A cut-off of 17/18 on the C-SOMC test gave optimal performance: correct classification of 75% of participants, with 75% sensitivity and 87.9% specificity. Conclusion: The C-SOMC test demonstrated good concurrent validity, sensitivity and specificity in a sample of people with a first cerebral infarction, demonstrating that it could be used to screen for cognitive impairment in stroke patients.

Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma.

B7-H3 (immunoregulatory protein B7-homologue 3) is overexpressed in many cancer cells with limited expression in normal tissues, considered to be a promising target for tumor therapeutics. Clinical trials of antibody-drug conjugates (ADCs) against different targets for glioblastoma have been investigated and showed potent efficacies. In this study, we developed a homogeneous ADC 401-4 with a drug-to-antibody ratio (DAR) of 4, which was prepared by conjugation of Monomethyl auristatin E (MMAE) to a humanized anti-B7-H3 mAb 401, through a divinylsulfonamide-mediated disulfide re-bridging approach. In vitro studies, 401-4 displayed specific killing against B7-H3-expressing tumors and was more effective in cells with higher levels of B7-H3 for different glioblastoma cells. 401-4 was furthered labeled with Cy5.5 to yield a fluorescent conjugate 401-4-Cy5.5. The in vivo imaging studies showed that the conjugate accumulated in tumor regions and exhibited the ability to target-specific delivery. In addition, significant antitumor activities for 401-4 was observed against U87-derived tumor xenografts in a dose dependent manner.

Gradient boosting DD-MLP Net: An ensemble learning model using near-infrared spectroscopy to classify after-stroke dyskinesia degree during exercise.

This study aims to develop an automatic assessment of after-stroke dyskinesias degree by combining machine learning and near-infrared spectroscopy (NIRS). Thirty-five subjects were divided into five stages (healthy, patient: Brunnstrom stages 3, 4, 5, 6). NIRS was used to record the muscular hemodynamic responses from bilateral femoris (biceps brachii) muscles during passive and active upper (lower) limbs circular exercise. We used the D-S evidence theory to conduct feature information fusion and established a Gradient Boosting DD-MLP Net model, combining the dendrite network and multilayer perceptron, to realize automatic dyskinesias degree evaluation. Our model classified the upper limb dyskinesias with high accuracy: 98.91% under the passive mode and 98.69% under the active mode, and classified the lower limb dyskinesias with high accuracy: 99.45% and 99.63% under the passive and active modes, respectively. Our model combined with NIRS has great potential in monitoring the after-stroke dyskinesias degree and guiding rehabilitation training.

[Analysis on late diagnosis reasons of newly diagnosed HIV/AIDS patients].

OBJECTIVE: To understand the characteristics of HIV/AIDS patients with late diagnosis and find the factors associated with late HIV detection. METHODS: HIV late diagnosed patients and early diagnosed patients, which were identified and classified by definition in advance, were selected from the case reporting database of HIV/AIDS Comprehensive Response Information Management System in eight counties of four provinces (Zhumadian, Nanyang, and Zhoukou of Hennan province; Liuzhou and Lingshan county of Guangxi autonomous region; Guangzhou and Shenzhen of Guangdong province; Dehong of Yunnan province) between January 1, 2009 and June 30, 2010. A total of 3912 eligible patients were investigated, including 2496 late diagnosis and 1416 early diagnosis. The structured questionnaires were used to obtain information on behaviors, HIV detection history and reason of late detection for all eligible HIV/AIDS patients. Late diagnosed patients were defined by CD4 T-cell counts less than 200 cells/mm(3) or diagnosis as AIDS within the reported year after the first HIV positive test. The univariate and multivariate logistic regression methods were used to analyze the characteristics of HIV/AIDS late diagnosed patients. RESULTS: Only 14.2% (350/2469) of them have ever had the awareness of "to go for HIV testing", 68.8% (150/218)of which did not put it into practice within one month because of discrimination and stigma. Among those HIV late diagnosed patients without the awareness of "to go for HIV testing", the proportions of "never worried about HIV infection" or "never heard of AIDS" were 69.7% (1476/2116) and 18.1% (383/2116), respectively. When those HIV late diagnosed patients visited health settings because of AIDS related symptoms, only 40.0% (590/1475) of them received the HIV testing service. Furthermore, 54.5% (322/590) of those received HIV testing were not informed the results. Compared with early diagnosed patients, patients with late diagnosis were over 50 years old (OR = 4.14, 95%CI: 3.09 - 5.55), primary school education (OR = 1.29, 95%CI: 1.10 - 1.52) and illiteracy (OR = 2.15, 95%CI: 1.25 - 2.82), Routes of transmission from former illegal blood or plasma (OR = 2.91, 95%CI: 2.27 - 3.74) and transfusion of blood/blood products (OR = 2.79, 95%CI: 2.11 - 3.68). Late diagnosed patients were identified mainly from voluntary counseling and testing (45.4%, 1130/1528) and medical institutions (38.3%, 954/1469). CONCLUSION: The main reasons for late diagnosis of HIV infection are low initiative of HIV testing and discrimination and stigma. Furthermore, the low awareness of medical institutions to actively provide HIV testing affects the early diagnosis of HIV infections.

Is Static Alignment a Good Predictor of Dynamic Alignment after Total Knee Arthroplasty?

BACKGROUND: Total knee arthroplasty (TKA) is the only effective treatment of end-stage knee osteoarthritis (OA). Lower limb neutral alignment has been a criterion to predict prosthesis life; however, there has been recent controversy over this. Some researchers believe that lower limb static alignment does not significantly affect prosthesis life and some researchers have found that dynamic mechanical alignment may affect prosthesis life, which needs to be further studied. METHODS: Eighty-seven patients with knee OA were evaluated by a three-dimensional (3D) gait analysis system before TKA and six months after TKA, dynamic mechanical alignment and basic gait parameters were then calculated. Based on the static alignment of the lower limb on the postoperative X-radiographs, they were divided into a neutral alignment group (58 cases), varus alignment group (20 cases), and valgus alignment group (9 cases). Simple linear regression was used to assess the correlation between static and dynamic alignment. One-way analysis of variance (ANOVA) was used to compare the differences in gait parameters between and within groups. RESULTS: Eighty-seven patients were followed up for an average of six months after the operation. There was no significant difference in all gait parameters among the three groups after TKA. There was no correlation found between static alignment and dynamic alignment/knee adduction moment (KAM) after TKA, although patients showed a significant linear correlation before operation. There was a significant linear correlation between dynamic alignment and KAM before and after the operation. CONCLUSIONS: Static alignment has no significant effect on postoperative gait function. Static alignment is no longer an effective predictor of the dynamic alignment or KAM six months after TKA, although they are correlated before TKA. The dynamic alignment allows for better prediction of KAM, which may be a risk factor for the life of the prosthesis.