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Introduction: Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21.Methods: In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection in vivo. Twenty cynomolgus monkeys were injected subcutaneously with different doses of FGF-21 for 86 days. Serum samples were collected at eight different time points (0, 0.5, 1.5, 3, 5, 8, 12, and 24 h) on day 1, 37 and 86 for toxicokinetic analysis. The serum concentrations of FGF-21 were measured using a double sandwich Enzyme-linked immunosorbent assay. Blood samples were collected on day 0, 30, 65, and 87 for blood and blood biochemical tests. Necropsy and pathological analysis were performed on d87 and d116 (after recovery for 29 days).Results: The average AUC(0-24h) values of low-dose FGF-21 on d1, d37, and d86 were 5253, 25268, and 60445 μg h/L, and the average AUC(0–24h) values of high-dose FGF-21 on d1, d37, and d86 were 19964, 78999, and 1952821 μg h/L, respectively. Analysis of the blood and blood biochemical indexes showed that prothrombin time and AST content in the high-dose FGF-21 group increased. However, no significant changes in other blood and blood biochemical indexes were observed. The anatomical and pathological results showed that continuous subcutaneous injection of FGF-21 for 86 days did not affect organ weight, the organ coefficient, and histopathology in cynomolgus monkeys.Discussion: Our results have guiding significance for the preclinical research and clinical use of FGF-21.

Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21. In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection in vivo. Twenty cynomolgus monkeys were injected subcutaneously with different doses of FGF-21 for 86 days. Serum samples were collected at eight different time points (0, 0.5, 1.5, 3, 5, 8, 12, and 24 h) on day 1 (d1), d37, and d86 for toxicokinetic analysis. The serum concentrations of FGF-21 were measured using a double sandwich ELISA. Necropsy and pathological analysis were performed on d87 and d116 (after recovery for 29 days). The average AUC(0-24h) values of low-dose FGF-21 on d1, d37, and d86 were 5253, 25268, and 60445 μg·h/L, and the average AUC(0-24h) values of high-dose FGF-21 on d1, d37, and d86 were 19964, 78999, and 1952821 μg·h/L, respectively. The peak concentrations (Cmax) of low-dose FGF-21 on d1, d37, and d86 were 621.1, 2767.9, and 4182.0 μg/L, respectively. The Cmax values of high-dose FGF-21 on d1, d37, and d86 were 2196.8, 6637.5, and 13430.4 μg/L, respectively. The elimination half-lives (t1/2z) of low- and high-dose FGF-21 on d1, d37, and d86 were 3.1–4.8, 4.2–6.7, and 6.2–8.8 h, respectively. The anatomical and pathological results showed that continuous subcutaneous injection of FGF-21 for 86 days did not affect organ weight, the organ coefficient, and histopathology in cynomolgus monkeys. Our results have guiding significance for the preclinical research and clinical use of FGF-21.

Objective This study examined the reliability and validity of a Shame and Stigma Scale (SSS) and assessed shame and stigma among patients with facial disfigurement from nasopharyngeal carcinoma (NPC). Methods Data were collected from 218 patients with NPC through a cross-sectional survey between January 14, 2020, and December 1, 2020. The original SSS is a 20-item scale with four dimensions (i.e., shame with appearance, sense of stigma, regret, and social/speech concern). We used Cronbach’s alpha and McDonald’s omega to assess reliability and exploratory factor analysis (EFA) to assess the factor structure. We also used Pearson correlation analysis to examine the relationship between each item and total score of scale items and convergent validity. Results The final 18-item SSS had a Cronbach’s alpha coefficient of .89. The EFA revealed that the SSS has a four-factor structure: sense of stigma, social/speech concern, shame with appearance, and regret. These factors showed satisfactory reliability, with McDonald’s omega coefficients of .87, .77, .86, and .79, respectively. The scale showed significant relationship between each item and total score of scale items with respect to item–total correlations, item–subscale correlations, and item–other-subscale correlations. Convergent validity was supported by the significant positively correlated with the total scores for depression and anxiety. Conclusion The SSS is valid and reliable in assessing shame and stigma and monitoring treatment compliance among patients with NPC.

Background This study aimed to determine whether the disclosure of same-sex behavior to health care providers (HCPs) is associated with higher rates of prior human immunodeficiency virus (HIV) testing experience and greater awareness of immediate antiretroviral therapy (ART), Undetectable = Untransmittable (U=U), and pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM). Methods We conducted a cross-sectional survey among 689 adult males in Chengdu, China who self-reported having had anal intercourse with at least one man in the past 6 months. We measured same-sex behavior disclosure to three types of HCPs (hospital clinicians, community-based organization peer educators, and Center for Disease Control and Prevention public health specialists), and the awareness of immediate ART, U=U, and PrEP. Results Of the 689 enrolled participants, 31.4% had disclosed their same-sex behavior to some or all of the clinicians, 83.9% had done so to the peer educators, and 56.8% had done so to the public health specialists. Approximately four in five (82.1%) of the participants had ever been tested for HIV. The awareness rate was 84.8% for immediate ART, 20.2% for U=U, and 50.7% for PrEP. After controlling for significant background variables, same-sex behavior disclosure to clinicians was associated with greater awareness of PrEP (adjusted odds ratio [AOR] = 1.64; 95% confidence interval [CI]: 1.08–2.48), but similar findings were not reported regarding disclosure to peer educators or public health specialist. Same-sex behavior disclosure to any types of HCPs was not associated with HIV testing experience, and awareness of immediate ART or U=U. Conclusions The rates of same-sex behavior disclosure varied with different types of HCPs. Disclosure to clinicians was associated with greater awareness of PrEP, but not awareness of immediate ART or U=U.

Given the recent evidence on “Undetectable = Untransmittable” (U=U) and pre-exposure prophylaxis (PrEP), the present study aimed to investigate HIV disclosure behaviors and their associations with sexual risk behaviors and U=U and PrEP awareness among men who have sex with men (MSM) in China. A cross-sectional survey was conducted among 689 MSM recruited through a gay-friendly non-governmental organization located in Chengdu, China in 2018–2019. Information was collected by a structured self-administrated questionnaire. The enrolled sample included 554 (80.4%) participants who were HIV-negative and 135 (19.6%) participants with an unknown HIV status. In terms of disclosure, 41.4% of participants informed all partners about their HIV status all the time (informing behavior), while 30.4% asked all partners about their HIV status all the time (asking behavior). Only one-fifth knew about U=U, but this was not statistically associated with either informing or asking behavior. Half (50.5%) had heard of PrEP but this was not statistically associated with either informing or asking behavior. Common barriers to informing and asking behaviors were lower risk perception of HIV infection, a history of sexually transmitted infections, engagement in receptive sex, and a history of sex with casual partners. We found that both U=U and PrEP awareness and HIV serostatus disclosure were infrequent and not associated in this study of Chinese MSM. These data indicate huge information gaps among MSM in China.

Open source development, to a great extent, is a type of social movement in which shared ideologies play critical roles. For participants of open source development, ideology determines how they make sense of things, shapes their thoughts, actions, and interactions, enables rich social dynamics in their projects and communities, and hereby realizes profound impacts at both individual and organizational levels. While software engineering researchers have been increasingly recognizing ideology's importance in open source development, the notion of "ideology" has shown significant ambiguity and vagueness, and resulted in theoretical and empirical confusion. In this article, we first examine the historical development of ideology's conceptualization, and its theories in multiple disciplines. Then, we review the extant software engineering literature related to ideology. We further argue the imperatives of developing an empirical theory of ideology in open source development, and propose a research agenda for developing such a theory. How such a theory could be applied is also discussed., To be published in CHASE 2021

Background The prevalence of HIV among men who have sex with men (MSM) in southwest China is still increasing. This study aimed to investigate the trend in HIV incidence and its associated risk factors among MSM in Chengdu, China. Method Incidence data were collected from the largest local non-governmental organization (NGO) serving MSM in Chengdu between 2012 and 2018, while information on sexual behaviors was collected from 2014. All MSM who received voluntary counseling and testing services (VCT) in the collaborating NGO at least twice during the study period were included. We calculated the HIV incidence density among MSM every 2 years and the overall incidence rate. A Cox proportional hazards regression model was employed to identify risk factors for HIV infection. Result A total of 4578 HIV-negative participants were included in the cohort. The total incidence density was 5.95 (95% CI: 5.37–6.56)/100 person-years (PYs) between 2012 and 2018. The segmented incidence density was 9.02 (95% CI: 7.46–10.78), 5.85 (95% CI: 4.86–6.97), 5.43 (95% CI: 4.53–6.46), and 3.09 (95% CI: 2.07–4.41)/100 PYs in 2012–2013, 2014–2015, 2016–2017, and 2018, respectively. After adjusting for sociodemographic characteristics, compared to participants without sexual partners within 6 months, MSM with one fixed partner (Adjusted Hazard Ratio, AHR = 1.18, 95% CI: 0.44–3.19) and more than five partners (AHR = 2.24, 95% CI: 0.81–6.20) had increased risk of HIV infection. MSM who used condom inconsistently had a higher risk of HIV infection (AHR = 1.87, 95% CI: 1.46–2.38) compared to consistent condom users. Conclusion The decreased HIV incidence density among MSM was potentially related to the successful comprehensive HIV prevention strategies in Chengdu. Multiple male sexual partnerships and inconsistent condom use during anal intercourse were risk factors associated with HIV occurrence.

Background: The 2019 novel Coronavirus (COVID-19) emerged in Wuhan, China in December 2019 and has been spreading rapidly in China. Decisions about its pandemic threat and the appropriate level of public health response depend heavily on estimates of its basic reproduction number and assessments of interventions conducted in the early stages of the epidemic. Methods: We conducted a mathematical modeling study using five independent methods to assess the basic reproduction number (R0) of COVID-19, using data on confirmed cases obtained from the China National Health Commission for the period 10th January – 8th February. We analyzed the data for the period before the closure of Wuhan city (10th January – 23rd January) and the post-closure period (23rd January – 8th February) and for the whole period, to assess both the epidemic risk of the virus and the effectiveness of the closure of Wuhan city on spread of COVID-19. Findings: Before the closure of Wuhan city the basic reproduction number of COVID-19 was 4.38 (95% CI: 3.63 – 5.13), dropping to 3.41 (95% CI: 3.16 – 3.65) after the closure of Wuhan city. Over the entire epidemic period COVID-19 had a basic reproduction number of 3.39 (95% CI: 3.09 – 3.70), indicating it has a very high transmissibility. Interpretation: COVID-19 is a highly transmissible virus with a very high risk of epidemic outbreak once it emerges in metropolitan areas. The closure of Wuhan city was effective in reducing the severity of the epidemic, but even after closure of the city and the subsequent expansion of that closure to other parts of Hubei the virus remained extremely infectious. Emergency planners in other cities should consider this high infectiousness when considering responses to this virus. Funding Statement: JL is supported by the National Natural Science Foundation of China (grant ID 81803334) and China Medical Board (grant ID 18-301). JG is supported by the National Natural Science Foundation of China (grant ID 71774178). CH is supported by the National Natural Science Foundation of China (grant ID 71974212). YH is supported by the National Natural Science Foundation of China (grant ID 81973150) and the National Science and Technology Major Project of China (grant ID 2018ZX10715004). Declaration of Interests: The authors have no conflict of interests to declare.

Traditional Chinese Medicine (TCM) is an outstanding representative among Chinese civilization, and is widely recognized by people in many countries for its unique advantages in disease prevention, treatment and rehabilitation. TCM is the crystallization of the Chinese civilization, the treasure of ancient Chinese science and a carrier of traditional culture. Through literature review, combined with actual life, the advantages of TCM and its future development methods are comprehensively analyzed. It is precisely because of its increasingly important influence on Western countries that we should pay more attention to its development and make it stand firmly on the world stage.

IntroductionIn the past three decades, China has made great strides in the prevention and treatment of tuberculosis (TB). However, the TB burden remains high. In 2019, China accounted for 8.4% of global incident cases of TB, the third highest in the world, with a higher prevalence in rural areas. The Healthy China 2030 highlights the gate-keeping role of primary healthcare (PHC). However, the impact of PHC reforms on the future TB burden is unclear. We propose to use mathematical models to project and evaluate the impacts of different gate-keeping policies.Methods and analysisWe will develop a deterministic, population-level, compartmental model to capture the dynamics of TB transmission within adult rural population. The model will incorporate seven main TB statuses, and each compartment will be subdivided by service providers. The parameters involving preference for healthcare seeking will be collected using discrete choice experiment (DCE) method. We will solve the deterministic model numerically over a 20-year (2021–2040) timeframe and predict the TB prevalence, incidence and cumulative new infections under the status quo or various policy scenarios. We will also conduct an analysis following standard protocols to calculate the average cost-effectiveness for each policy scenario relative to the status quo. A numerical calibration analysis against the available published TB prevalence data will be performed using a Bayesian approach.Ethics and disseminationMost of the data or parameters in the model will be obtained based on secondary data (eg, published literature and an open-access data set). The DCE survey has been reviewed and approved by the Ethics Committee of the School of Public Health, Sun Yat-sen University. The approval number is SYSU [2019]140. Results of the study will be disseminated through peer-reviewed journals, media and conference presentations.

To deliver chemotherapeutic drugs simultaneously, using drug carriers is a feasible strategy for a better synergetic effect. We have constructed hollow silica nanoparticles (HSNPs) sealed with ZnO quantum dots (QDs) as a pH-sensitive nanocarrier, where the HSNPs have large hollow interiors for delivering hydrophobic camptothecin (CPT) and a mesoporous structure for delivering hydrophilic doxorubicin (DOX·HCl). This cooperative drug loading has largely increased the drug encapsulation efficiency of both CPT and DOX up to 89.28% and 44.98%, respectively. Meanwhile, the ZnO QD lids in this drug delivery system are found to be rapidly dissolved in the acidic intracellular compartments to trigger pH-sensitive drug release. The co-delivery of multi-drugs with different anticancer mechanisms in the same nanocarrier enables the intracellular release of the drug combinations to greatly enhance chemotherapeutic efficacy and overcome multidrug resistance (MDR).

ObjectivesThis study aimed to examine the urban–rural disparity in health-related quality of life (HRQoL) of the Chinese elderly and to explore the mediating roles of socioeconomic status (SES) and frequency of contact with children in the relationship between urban/rural areas and HRQoL.MethodsThis cross-sectional study used data from China Health and Retirement Longitudinal Study for 2015–2016, involving 12 369 Chinese aged 45 years and over. HRQoL of respondents was measured by three-level EuroQol five dimensions (EQ-5D-3L). SES, based on principal components analysis, was combined by the individual possessions of durable consumer goods and houses. Frequency of contact with children was derived from the responses to whether they live with children and how often they contact with them. Mediation analyses were performed to examine the mediating effects of SES and frequency of contact in the relationship between urban/rural areas and HRQoL.ResultsUrban respondents had higher scores of HRQoL than rural respondents (pConclusionsThere was a significant difference in HRQoL between urban and rural middle-aged and elderly participants, which was partially mediated by urban–rural disparities in SES and frequency of contact with children. Higher SES and frequency of contact with children contributed to higher health status in the Chinese elderly.