A non-canonical role of endothelin converting enzyme 1 (ECE1) in promoting lung cancer development via directly targeting protein kinase B (AKT).

BACKGROUND: Lung cancer is the second most common malignancy in the world, and lung adenocarcinoma (LUAD) in particular is the leading cause of cancer death worldwide. Endothelin converting enzyme 1 (ECE1) is a membrane-bound metalloprotease involved in endothelin-1 (ET-1) processing and regulates vasoconstriction. However, very few studies have reported the involvement of ECE1 in regulating tumor cell proliferation, and the mechanism remains poorly understood. Therefore, we aimed to determine the role of ECE1 in lung cancer development. METHODS: The Cancer Genome Atlas database and Kaplan-Meier plotter were used to assess the association between ECE1 and lung cancer. The expression of ECE1 was detected using immunohistochemistry staining and western blotting. A variety of in vitro assays were performed to evaluate the effects of ECE1 on the colony formation, proliferation, migration and invasion using ECE1 knockdown lung cancer cells. The gene expression profiles regulated by ECE1 were investigated by RNA sequencing. An immunoprecipitation assay and immunofluorescence assay were used to evaluate the mechanism underlying the regulatory effect of ECE1 on protein kinase B (AKT). The effect of ECE1 on tumor development was assessed by xenografted lung cancer cells in either C57BL/6 mice or nude mice. RESULTS: ECE1 was upregulated in LUAD and correlated with the poor prognosis of patients with LUAD. Functional studies showed that knockdown of ECE1 retarded the progression of tumors formed by lung cancer cells at least partly by inhibiting tumor cell proliferation. Moreover, ECE1 accelerated tumor cell proliferation through promoting AKT activation dispensable of its canonical target ET-1. Mechanically, ECE1 interacted with the pleckstrin homology (PH) domain of AKT and facilitated its translocation to the plasma membrane for activation. Furthermore, the inhibition of AKT activity counteracted the lung cancer cell growth inhibition observed both in vitro and in xenografts caused by ECE1 suppression. CONCLUSIONS: The present study reveals a non-canonical function of ECE1 in regulating AKT activation and cell proliferation, which provides the basis for the development of a novel strategy for the intervention of cancer including LUAD by abrogating ECE1-AKT signaling.

Mycobacterium tuberculosis suppresses APLP2 expression to enhance its survival in macrophage.

Mycobacterium tuberculosis (M.tb), the most successful pathogen responsible for approximately 1.6 million deaths in 2021, employs various strategies to evade host antibacterial defenses, including mechanisms to counteract nitric oxide (NO) and certain cytokines. While Amyloid ß (A4) precursor-like protein 2 (Aplp2) has been implicated in various physiological and pathological processes, its role in tuberculosis (TB) pathogenesis remains largely uncharted. This study unveils a significant reduction in Aplp2 levels in TB patients, M.tb-infected macrophages, and mice. Intriguingly, Aplp2 mutation or knockdown results in diminished macrophage-mediated killing of M.tb, accompanied by decreased inducible nitric oxide synthase (iNOS) expression and reduced cytokine production, notably interleukin-1ß (Il-1ß). Notably, Aplp2 mutant mice exhibit heightened susceptibility to mycobacterial infection, evident through aggravated histopathological damage and increased lung bacterial loads, in contrast to Mycobacterium bovis BCG-infected wild-type (WT) mice. Mechanistically, the cleaved product of APLP2, AICD2, generated by γ-secretase, translocates to the nucleus, where it interacts with p65, culminating in enhanced the nuclear factor κB (NF-κB) transcriptional activity. This interaction triggers the upregulation of Il-1ß and iNOS expression. Collectively, our findings illuminate Aplp2's pivotal role in safeguarding against mycobacterial infections by promoting M.tb clearance through NO- or IL-1ß-mediated bactericidal effects. Therefore, we unveil a novel immune evasion strategy employed by M.tb, which could potentially serve as a target for innovative TB interventions.

TAK1 is an essential kinase for STING trafficking.

The translocation of stimulator of interferon genes (STING) from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC) enables its activation. However, the mechanism underlying the regulation of STING exit from the ER remains elusive. Here, we found that STING induces the activation of transforming growth factor beta-activated kinase 1 (TAK1) prior to STING trafficking in a TAK1 binding protein 1 (TAB1)-dependent manner. Intriguingly, activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation. Importantly, activation of TAK1 by monophosphoryl lipid A, a TLR4 agonist, boosts cGAMP-induced antitumor immunity dependent on STING phosphorylation in a mouse allograft tumor model. Taken together, TAK1 was identified as a checkpoint for STING activation by promoting its trafficking, providing a basis for combinatory tumor immunotherapy and intervention in STING-related diseases.

Public health engagement: new opportunities and challenges in 60 years of China's health aid to Africa.

Along with China's active engagement in global affairs over the past decade, China's public health engagement (CPHE) has become an essential element of China's 60th anniversary of health aid and cooperation with Africa. Through analysis, we found that CPHE in Africa reflects a new shift in the content and form of China's foreign health aid. Compared with China's medical teams which only involve bilateral cooperation, CPHE has a number of substantive characteristics, mainly including the construction of public health infrastructure, malaria control, participation in public health emergencies and the provision of global public goods. This complexity necessitates that CPHE be implemented in a different form from China's medical teams, by adopting inclusive multiparty cooperation involving African and international partners. However, CPHE in Africa still faces a number of challenges in its practices. In particular, these challenges arise from the cross-cultural practice process, the African sociocultural context, the experience of public health and its participants. While the reasons for these challenges are diverse, this study argues that the main reason is the lack of multidisciplinary engagement in the Africanisation of the Chinese experience that corresponds to cross-cultural practice. On the Chinese side, a systematic strategy is needed to critically refine these challenges.

HIV-Related Knowledge and Sexual Behaviors among Teenagers: Implications for Public Health Interventions.

Background: Teenagers are at a turning point in people's physical and psychological maturity and are also in a critical period in reproductive and sexual health. It is reported that the initial age at first sexual behavior is younger than decades ago, which implies that the risky sexual behavior among teenagers may be on the rise. However, it is unclear about the changes of sexual knowledge and behaviors in recent years. Methods: Based on the national sentinel surveillance survey in 2011-2021 among students in Hangzhou, we selected out teenagers aged 10-19 years as our study sample. Demographic characteristics (gender, age, marital status, etc.), knowledge of HIV and sexual behaviors were collected. The sexual knowledge score and sexual behaviors were analyzed, and their influencing factors were explored. Results: In total, 1355 teenagers were incorporated in this study; the awareness rates of sexual knowledge in 2011, 2013, 2014 and 2021 were 74.9%, 71.8%, 89.3% and 95.8%, respectively, which showed an overall upward trend. The results of binary logistic regression showed that the survey year, whether students had received and participated in HIV-related publicity services and whether they had sexual behaviors, had a significant influence on whether the awareness rate ≥ 75%. The survey year and whether the awareness rate ≥ 75% had a significant influence on whether students had sexual behaviors. Conclusions: Both the average scores and awareness rates of teenagers' sexual knowledge showed an overall upward trend from 2011 to 2021. Teenagers' initial sexual behavior was at a low age, and the proportion of teenagers who had fixed, temporary and commercial heterosexual sex was still relatively high despite no significant increasing. Therefore, we should further strengthen health education on the risks of sexual behaviors from schools, families and health-related institutions to ensure teenagers receive HIV-related publicity services.

The Vulnerability of International Floating Populations to Sexually Transmitted Infections: A Qualitative Study.

With the rapid development of the global economy, along with globalisation, the health of international floating populations (especially their sexual health) has become a problem that cannot be ignored. This study explored the potential vulnerability of international floating populations to sexually transmitted infections (STIs) from the points of view of society, religion, culture, migration, community environment, and personal behaviours. In-depth exploratory interviews with 51 members of the international floating population living in China were conducted in June and July 2022. A qualitative thematic analysis methodology was used to analyse the content of these interviews. We found that a conservative culture orientated around religion leads to a lack of sex education, resulting in insufficient personal knowledge as well as a lack of the motivation and awareness required to encourage condom use during sexual contact. Additionally, both geographical isolation and reduced social supervision have expanded personal space, which has led to social isolation and marginalisation, in addition to challenges for coping with STI risk. These factors have increased the possibility of individuals engaging in risky behaviours.

Migration experiences and reported commercial and non-commercial sexual behaviors among newly diagnosed HIV infections in China: a cross-sectional study.

BACKGROUND: Migration is known to influence human health. China has a high migration rate and a significant number of people who are HIV-positive, but little is known about how these factors intersect in sexual risk behaviors. OBJECTIVE: This study aimed to explore sexual risk behaviors between migrants and non-migrants among newly diagnosed HIV infections, and assess the changes of sexual risk behaviors with length of stay in the current city of migrants. METHODS: A cross-sectional questionnaire was conducted among people newly diagnosed with HIV from July 2018 to December 2020 who lived in Zhejiang Province. In the study, sexual risk behaviors included having multiple sexual partners and unprotected sexual behaviors (in commercial sexual behaviors, non-commercial sexual behaviors, heterosexual behaviors, and homosexual behaviors). Binary logistic regression models were employed to explore the influencing factors of sexual risk behaviors, measured by multiple sexual partners and unprotected sexual partners. RESULTS: A total of 836 people newly diagnosed with HIV/AIDS were incorporated in the study and 65.31% (546) were migrants. The percentages of non-commercial sexual behaviors among migrants were statistically higher than those of non-migrants. Commercial heterosexual behavior was higher among non-migrants compared with migrants. The proportion of study participants having unprotected sexual behaviors and multiple sexual partners with commercial/non-commercial partners was both higher among migrants compared with non-migrants. Among migrants, the likelihood of sexual risk behaviors in both commercial and non-commercial sex increased in the first 3 years and reduced after 10 years. Compared with non-migrants, migrants were statistically associated with multiple sexual partners [P = .007, odds ratio (OR) = 1.942]. However, migrants did not exhibit a significant difference in unprotected sexual behaviors compared with non-migrants. In addition, migrants aged between 18 and 45 years who relocated to the current city in the past 2-3 years tended to have multiple sexual partners (P < .05). CONCLUSIONS: People newly diagnosed with HIV engaged in different sexual risk behaviors among migrants and non-migrants and more attention should be paid to migrants. For non-migrants, it is urgent to promote the prevention of commercial sexual behaviors. For migrants, prevention of non-commercial sexual behaviors and universal access to health care especially for new arrivals who migrated to the current city for 2-3 years are needed. Moreover, sexual health education and early HIV diagnosis are necessary for the entire population.

Determinants of Bangladeshi patients' decision-making process and satisfaction toward medical tourism in India.

Objectives: The aims are to explore the factors influencing Bangladeshi patients' decision-making process and their satisfaction level toward medical tourism in India. Methods: The study used a quantitative research approach with a cross-sectional survey. Data were collected from the patients or their relatives (N = 388) who would have decided to travel to India for medical and treatment purposes at the Chittagong Indian visa center (IVAC). Data were collected using a structured, pre-tested, and facilitator-administered questionnaire, which mainly included the social demographic characteristics, health status, medical tourism information and medical tourism index. Hierarchical regression analysis was performed to explore the factors influencing their satisfaction level toward medical tourism in India. Results: More than three-fourths of the participants had visited India for self-treatment. Of the participants, 14% were cardiology patients, and 13% suffered from cancer. The relatives were the key source of information regarding medical tourism for more than one-fourth of the respondents. India's availability of well-experienced doctors, hospital/medical facilities with high standards, well-trained doctors, reputable doctors, and quality treatments and medical materials were top-ranked items. Regression results depict that facility and services appeared as the strongest factor (ß = 0.24, t = 4.71, p < 0.001) followed by tourism destination factor (ß = 0.16, t = 3.11, p = 0.002), medical tourism costs factor (ß = 0.16, t = 3.24, p = 0.001) and country environment factor (ß = 0.15, t = 2.69, p = 0.007). Conclusions: We found that the factor related to facility and services is one of the strongest predictors in our models. Therefore, home countries must strengthen the health care providers' advanced professional training, including service attitudes. Moreover, it is important to lessen the language barrier, reduce the airfare for medical tourists, and make the treatment cost more affordable for patients.

Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity.

Enhancing chemosensitivity is one of the largest unmet medical needs in cancer therapy. Cyclic GMP-AMP synthase (cGAS) connects genome instability caused by platinum-based chemotherapeutics to type I interferon (IFN) response. Here, by using a high-throughput small-molecule microarray-based screening of cGAS interacting compounds, we identify brivanib, known as a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor, as a cGAS modulator. Brivanib markedly enhances cGAS-mediated type I IFN response in tumor cells treated with platinum. Mechanistically, brivanib directly targets cGAS and enhances its DNA binding affinity. Importantly, brivanib synergizes with cisplatin in tumor control by boosting CD8+ T cell response in a tumor-intrinsic cGAS-dependent manner, which is further validated by a patient-derived tumor-like cell clusters model. Taken together, our findings identify cGAS as an unprecedented target of brivanib and provide a rationale for the combination of brivanib with platinum-based chemotherapeutics in cancer treatment.

Vulnerability to HIV Infection Among International Immigrants in China: Cross-sectional Web-Based Survey.

BACKGROUND: The rising number of migrants worldwide, including in China given its recent rapid economic development, poses a challenge for the public health system to prevent infectious diseases, including sexually transmitted infections (STIs) caused by risky sexual behaviors. OBJECTIVE: The aim of this study was to explore the risky sexual behaviors of international immigrants living in China to provide evidence for establishment of a localized public health service system. METHODS: Risky sexual behaviors were divided into multiple sexual partners and unprotected sexual behaviors. Basic characteristics, sexual knowledge, and behaviors of international immigrants were summarized with descriptive statistics. Multivariate logistic regression analyses were used to identify factors associated with risky sexual behaviors, and the associations of demographic characteristics and risk behaviors with HIV testing and intention to test for HIV. RESULTS: In total, 1433 international immigrants were included in the study, 61.76% (n=885) of whom had never heard of STIs, and the mean HIV knowledge score was 5.42 (SD 2.138). Overall, 8.23% (118/1433) of the participants had been diagnosed with an STI. Among the 1433 international immigrants, 292 indicated that they never use a condom for homosexual sex, followed by sex with a stable partner (n=252), commercial sex (n=236), group sex (n=175), and casual sex (n=137). In addition, 119 of the international immigrants had more than three sex partners. Individuals aged 31-40 years were more likely to have multiple sexual partners (adjusted odds ratio [AOR] 2.364, 95% CI 1.149-4.862). Married participants were more likely to have unprotected sexual behaviors (AOR 3.096, 95% CI -1.705 to 5.620), whereas Asians were less likely to have multiple sexual partners (AOR 0.446, 95% CI 0.328-0.607) and unprotected sexual behaviors (AOR 0.328, 95% CI 0.219-0.492). Women were more likely to have taken an HIV test than men (AOR 1.413, 95% CI 1.085-1.841). Those who were married (AOR 0.577, 95% CI 0.372-0.894), with an annual disposable income >150,000 yuan (~US $22,000; AOR 0.661, 95% CI 0.439-0.995), considered it impossible to become infected with HIV (AOR 0.564, 95% CI 0.327-0.972), and of Asian ethnicity (AOR 0.330, 95% CI 0.261-0.417) were less likely to have an HIV test. People who had multiple sexual partners were more likely to have taken an HIV test (AOR 2.041, 95% CI 1.442-2.890) and had greater intention to test for HIV (AOR 1.651, 95% CI 1.208-2.258). CONCLUSIONS: International immigrants in China exhibit risky sexual behaviors, especially those aged over 30 years. In addition, the level of HIV-related knowledge is generally low. Therefore, health interventions such as targeted, tailored programming including education and testing are urgently needed to prevent new HIV infections and transmission among international immigrants and the local population.

Polo-like Kinase 4: the Variation During Therapy and its Relation to Treatment Response and Prognostic Risk Stratification in Childhood Acute Lymphoblastic Leukemia Patients.

Polo-like kinase 4 (PLK4) plays an essential role in the tumorigenesis of some blood malignancies; consequently, we hypothesized that PLK4 might serve as a potential biomarker in childhood acute lymphoblastic leukemia (ALL) patients. Therefore, this study investigated the expression of PLK4 and its clinical relevance in childhood ALL patients. Bone marrow specimens were collected from 95 childhood ALL patients and 20 primary immune thrombocytopenia patients (as controls), and their PLK4 expression (reverse transcription-quantitative polymerase chain reaction) was measured after enrollment. Besides, the PLK4 expression in childhood ALL patients was also determined at day 15 after the initiation of induction therapy (D15). PLK4 was increased in childhood ALL patients compared with controls (2.830 (interquartile range (IQR): 1.890-3.660) versus 0.976 (IQR: 0.670-1.288), P ≤0.001). PLK4 at diagnosis was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients ( P =0.027). Besides, PLK4 at diagnosis was positively linked with the Chinese Medical Association risk stratification ( P =0.016), but not with prednisone response ( P =0.077) or bone marrow response ( P =0.083). In addition, PLK4 was decreased at D15 after treatment compared with at diagnosis ( P ≤0.001). Interestingly, PLK4 at D15 (P=0.033) was elevated in T cell acute lymphoblastic leukemia patients than in B cell acute lymphoblastic leukemia patients. Furthermore, increased PLK4 at D15 was associated with poor prednisone response ( P =0.018), poor bone marrow response ( P =0.034), and increased the Chinese Medical Association risk stratification ( P =0.015). In terms of prognosis, high PLK4 was associated with shorter event-free survival ( P =0.020), whereas it was not related to the overall survival ( P =0.135). In conclusion, PLK4 has the potential as a biomarker for treatment response and prognostic risk stratification of childhood ALL patients.

HIV Detection and Delayed Diagnosis: A Time Series Analysis in China.

BACKGROUND: Insufficient HIV detection and late presentation to antiretroviral therapy (ART) pose significant public health challenges. In China, universal access to HIV testing is available now. Under this background, we aim to analyze the trends of HIV detection and the prevalence of delayed HIV diagnosis (DHD) in order to provide evidence for HIV prevention and treatment in China. METHODS: Data of HIV tests in Hangzhou city between 2007 and 2018 were collected from the Chinese National HIV/AIDS Comprehensive Response Information Management System (CRIMS). Descriptive statistics were used to describe the characteristics of HIV testing and detection and the prevalence of DHD among newly diagnosed HIV cases. Non-parametric tests were employed to examine the prevalence of DHD among newly diagnosed HIV cases. Moreover, logistic regression models were employed to explore the influencing factors of DHD. RESULTS: Testing rates doubled from 14.1% in 2007-2010 to 28.2% in 2016-2018. The total positive rate of HIV tests was 5.3 per 10,000. Preoperative testing was the predominant pathway for HIV tests, accounting for 41.9%, followed by testing for health screening, maternal examination and other patients, accounting for 18.4%, 13.2% and 11.8%, respectively. Meanwhile, the predominant pathway for HIV case detection was also preoperative testing, accounting for 29.1%, followed by testing for other patients, testing at STD clinics and VCT, with the proportions of 18.8%, 15.8% and 13.6%, respectively. MSM (men who have sex with men) contact was the main transmission route, accounting for 55.3%, followed by heterosexual contact, accounting for 41.6%. Overall, DHD occurred in 29.0% of the newly diagnosed cases, and this rate had not improved over the years. A higher prevalence of DHD was found in those diagnosed through a pre-test for receiving blood/products [OR (95%CI): 5.42(2.95-9.97)], detection of other patients [OR (95%CI): 2.08(1.64-2.63)], preoperative testing [OR (95%CI): 1.83(1.44-2.32)] and spouse or sexual partner testing in positive person [OR (95%CI): 1.93(1.34-2.78)] compared with those diagnosed at a VCT clinic. Heterosexuals [OR (95%CI): 1.20(1.06-1.36)] had a higher risk of DHD than MSM. Diagnosis at a CDC [OR (95%CI): 0.68(0.55-0.83)] and community health centers [OR (95%CI): 0.54(0.39-0.75)] had a lower risk of DHD than in hospitals. Older age, males, being single/divorced or widowed and floating population were also associated with DHD. CONCLUSIONS: In China, DHD had not improved in the last 10 years, although HIV testing had been expanded. Therefore, it is important for continued efforts to promote early diagnosis of HIV to prevent transmission, morbidity and early mortality in HIV infection.

Identification of phosphorylation site on PARP1 mediating its cytosolic translocation in virus-infected HeLa cells.

Poly (ADP-ribose) polymerase 1 (PARP1) localization is controlled by its phosphorylation state. Here, we describe a protocol to monitor PARP1 subcellular localization in HSV-1-infected HeLa cells using immunofluorescence microscopy and cytoplasmic/nuclear fractionation. We detail steps to identify phosphorylation sites on PARP1 using conserved motif analysis and mass spectrometry. This protocol can be applied to the study of other protein phosphorylation events in other cell types. For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).

Primary Health Institutions and Service Quality in China: Implications for Health Policy.

BACKGROUND: To protect and improve the health of populations, the important role of primary health institutions has been strengthened through a series of health policies, especially the implementation of a national hierarchical diagnosis and treatment system. In this light, we aim to evaluate the development of primary health institutions between 2013, before the implementation of the hierarchical diagnosis and treatment system, and 2020 as well as people's perception of the quality of primary healthcare services. METHOD: The national-level data (e.g., the numbers of primary health institutions, personnel, beds, visits, and hospitalizations) regarding primary health institutions were collected from the Health Statistics Yearbook, and the perceptions of the quality of primary healthcare services were collected by a web-based questionnaire survey using an internationally recognized assessment tool (i.e., PCAT-AE). In total, 10,850 persons were surveyed, and 10,419 participants were incorporated into the final analysis after removing invalid questionnaires. A descriptive statistical analysis (i.e., frequency and percentage) was used to analyze the national-level characteristics of primary health institutions and people's perceptions of the quality of primary healthcare services. Moreover, a logistic regression model was used to analyze the factors influencing the perceptions of the quality of primary healthcare services. RESULTS: From the macro perspective, the number of primary health institutions, beds, and personnel per 10 thousand residents slightly increased from 2013 to 2020, especially in the eastern and central areas. However, the average number of visits and the hospitalization rate in primary health institutions showed a decrease, especially in central and eastern areas. Among participants, 92.2% (9606/10,419) of them had previously sought healthcare services in primary health institutions, and most were seeking general outpatient services (57.06-63.45%), followed by medicine purchasing (16.49-21.51%), physical examinations (9.91-11.49%), preventive health services (5.11-6.48%), and hospitalization services (3.17-5.67%). The total perception scores on the quality of primary healthcare services reported by the participants were 26.19 and 27.00 for rural and urban areas, respectively, which accounted for 65.5% and 67.5% of the total score, respectively, and 26.62, 26.86, and 25.89 for the eastern, central, and western areas, respectively, with percentages of 66.6%, 67.2%, and 64.7%. The perception score on the quality among people contracted with a family doctor (29.83, 74.58%) was much higher than those who were not (25.25, 63.13%), and the difference was statistically significant (p < 0.001). Moreover, people who were female, married, had higher incomes, and were diagnosed with various diseases had better perceptions of the primary healthcare services compared to their counterparts (p < 0.05). CONCLUSION: Improvements were seen for primary health institutions, especially in terms of hardware resources such as beds and personnel. However, the service utilization in primary health institutions did not improve between 2013 and 2020. The perception score on the quality of primary healthcare was moderate to low in rural and urban as well as eastern, central, and western areas, but it was significantly higher among people contracted with a family doctor than those who were not. Therefore, it is important for policy makers to take or adjust measures focusing on quality improvement and increasing the service utilization in primary health institutions with good first contact, accessibility, continuity, comprehensiveness, and coordination, such as raising the enrollment rate of family doctors and promoting the provision of high-quality services.

Risky sexual behaviour and HIV testing uptake among male college students: a cross-sectional study in China.

OBJECTIVE: To understand the sexual behaviours and HIV testing uptake of sexually experienced male college students in China. DESIGN: A cross-sectional study was conducted between September and November of 2020 among male college students. SETTING: Hangzhou, China. PARTICIPANTS: Male students who had sexual experience in the previous year were investigated. OUTCOME MEASURES: Sexual risk behaviour was defined as having multiple sexual partners or having unprotected sex. RESULTS: More than half of the sexually experienced male students (556, 53.2%) had their first sexual intercourse under the age of 18 years old. Among participants, 32.82% (343/1045) had causal sex in the last 6 months; 4.21% (44/1045) had paid sex; 37.32% (390/1045) had sex with other men and had two or more sexual partners in last half year; and 33.33% (130/390) used psychoactive drugs during same-sex intercourse. Only 33.5% (350/1045) of male students had undertaken an HIV test before. CONCLUSION: Male college students especially men who have sex with men were at risk because they tended to be sexually adventurous, have sex at an early age, have sex with multiple sexual partners and practice unprotected sex. Furthermore, they had a low HIV testing uptake. This highlights the importance of carrying out targeted and timely HIV risk education towards college students.

Family planning knowledge, attitude and practice among Rohingya women living in refugee camps in Bangladesh: a cross-sectional study.

BACKGROUND: Considering the high risk of maternal morbidity and mortality, increased risks of unintended pregnancy, and the unmet need for contraceptives prevalent among the Rohingya refugees, this study aims to explore the knowledge, attitude, and practice (KAP) of family planning (FP) and associated factors among Rohingya women living in refugee camps in Bangladesh. METHODS: Four hundred Rohingya women were interviewed. Data were collected using a structured and pretested questionnaire, which included study participants' socio-demographic characteristics, access to FP services, knowledge, attitude, and practice of FP. Linear regression analysis was performed to identify the influencing factors of FP-KAP. RESULTS: Of the 400 Rohingya refugee women, 60% were unaware that there was no physical harm brought by using a permanent method of birth control. Half of the women lack proper knowledge regarding whether a girl was eligible for marriage before the age of 18. More than two-thirds of the women thought family planning methods should not be used without the husband's permission. Moreover, 40% were ashamed and afraid to discuss family planning matters with their husbands. Of the study participants, 58% had the opinion that a couple should continue bearing children until a son is born. Linear regression analyses found that study participants' who have a profession, have less children, whose primary source of FP knowledge was through a physician/nurse, have had FP interventions in the camp, and talk with a health care provider on FP were found to have better FP-KAP. CONCLUSION: The study showed that Rohingya refugee women are a marginalized population in terms of family planning and their comprehensive FP-KAP capability was low. Contraceptives among the Rohingyas were unpopular, mainly due to a lack of educational qualifications and family planning awareness. In addition, family planning initiatives among Rohingya refugees were limited by a conservative culture and religious beliefs. Therefore, strengthening FP interventions and increasing the accessibility to essential health services and education are indispensable to improving improve maternal health among Rohingya refugees.

Considering the high risk of maternal morbidity and mortality, increased risks of unintended pregnancy, and the unmet need for contraceptives prevalent among the Rohingya refugees, this study aims to explore the knowledge, attitude and practice (KAP) of family planning (FP) and associated factors among Rohingya women living in the refugee camps in Cox's Bazar, Bangladesh. Four hundred Rohingya women participated in the study. We found that Rohingya refugee women were a marginalized population in family planning and their comprehensive FP-KAP status was low. Contraceptive uptake among the Rohingya women was low due to a lack of education and family planning awareness. In addition, family planning initiatives among Rohingya refugees were limited by various traditional cultural and religious beliefs. Therefore, strengthening FP interventions and increasing accessibility to essential health services and education are indispensable to improving maternal health among refugees.

The Effects of Internet Exposure on Sexual Risk Behavior Among Sexually Experienced Male College Students in China: Cross-sectional Study.

BACKGROUND: As a young subgroup, college students have become the main users of mobile social networks. Considering that people can indiscriminately access explicit sexual content on the internet, coupled with the increase of HIV infections in male college students, the role of the internet in meeting sexual partners and its correlation to risky sexual behavior has become an important topic. OBJECTIVE: The aim of this study is to explore the effects of internet exposure on sexual partners and sexual risk behavior among sexually experienced male college students. METHODS: An institution-based cross-sectional study design was used to collect data through a paper-based questionnaire administered to male college students recruited from colleges and gay organizations in Hangzhou, Zhejiang Province, China. A total of 1045 sexually experienced male students were incorporated in our analysis, with the following information collected: sociodemographic characteristics, sexual intercourse-related behaviors, and sexually transmitted disease (STD) knowledge. Mann-Whitney U and Kruskal-Wallis tests were used to examine differences regarding basic characteristics and sexual risk behaviors between male college students who meet sexual partners via the internet and those who do not. Sequential logistic regression models were employed to examine the influence of meeting sexual partners via the internet on risky sexual behaviors after controlling for other factors. RESULTS: The mean age of the sexually experienced male students was 21.6 (SD 2.0) years. The likelihood of risky sexual behavior was varied, yet it was the highest for those who aim to meet paid sexual partners (145/192, 75.5% to 19/22, 86.4%), followed by those seeking partners for love or romance (258/435, 59.3%). Compared to non-internet partner seekers, internet partner seekers tended to have more casual intercourse (292/542, 53.9% versus 51/503, 10.1%), paid intercourse (32/542, 5.9% versus 12/503, 2.4%), and intercourse with same-sex partners (349/542, 64.4% versus 41/503, 8.2%); they were also more likely to use psychoactive drugs (125/349, 35.8% versus 5/41, 12.2%) and have more than 2 partners. With the increase of HIV and STD knowledge, the probability of having unprotected intercourse decreased for non-internet partner seekers. However, it increased for internet partner seekers with a rising HIV knowledge score. Sequential logistic regression showed that meeting sexual partners on the internet was statistically associated with sexual risk behaviors with multiple sexual partners (odds ratio 4.434; P<.001). CONCLUSIONS: Meeting sexual partners via the internet is a common behavior among sexually experienced male college students, and those who meet partners on the internet exhibited higher levels of risky sexual behaviors although they had sufficient HIV and STD knowledge; this is especially true for students who aimed to find partners for sexual intercourse. Thus, more attention should be paid to young adults to address the risky sexual behaviors that may contribute to STD spread among this population.

Cytoplasmic PARP1 links the genome instability to the inhibition of antiviral immunity through PARylating cGAS.

Virus infection modulates both host immunity and host genomic stability. Poly(ADP-ribose) polymerase 1 (PARP1) is a key nuclear sensor of DNA damage, which maintains genomic integrity, and the successful application of PARP1 inhibitors for clinical anti-cancer therapy has lasted for decades. However, precisely how PARP1 gains access to cytoplasm and regulates antiviral immunity remains unknown. Here, we report that DNA virus induces a reactive nitrogen species (RNS)-dependent DNA damage and activates DNA-dependent protein kinase (DNA-PK). Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. Mechanistically, cytoplasmic PARP1 interacts with and directly PARylates cyclic GMP-AMP synthase (cGAS) on Asp191 to inhibit its DNA-binding ability. Together, our findings uncover an essential role of PARP1 in linking virus-induced genome instability with inhibition of host immunity, which is of relevance to cancer, autoinflammation, and other diseases.

CDK inhibitor Palbociclib targets STING to alleviate autoinflammation.

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases.

The Service Capability of Primary Health Institutions under the Hierarchical Medical System.

BACKGROUND: Primary health institutions (PHIs) are the foundation of the whole health system and the basic link to achieve the goal of all people enjoying primary health care. However, the service capability of primary health institutions is not under the hierarchical medical system. METHOD: Data were collected from the China Health Statistics Yearbook between 2014 and 2020. PHIs included community health centres, community health stations, and township hospitals in our study. The service capability of primary health institutions was analysed from the perspective of structure, process, and results. Structure capability was evaluated using the number of beds, number of personnel, number of health technicians, and proportion of the number of personnel in PHIs accounting for the total number of health personnel. Process capability was evaluated using the number of general practitioners. The number of outpatients and inpatients, medical income, the proportion of drug income, and the average number of patients and beds served by physicians in PHIs per day were employed to evaluate the resulting capability. RESULTS: From 2014 to 2020, the number of community health service centres/stations increased, while the number of township health centres decreased. In the aspect of structure capability, the total number of personnel and health technicians in community health centres/stations and township hospitals both increased during 2014 and 2020. However, the increasing rate in PHIs was a little bit less than that of general medical institutions. The proportion of male health technicians in community health centres and township hospitals both decreased, while the proportion of female technicians in both increased. From 2014 to 2020, the number of beds in PHIs also increased from 138.12 × 104 to 164.94 × 104. However, the proportion of beds in PHIs accounting for the total number of beds in medical institutions decreased. For the resulting capability, from 2014 to 2019, the proportion of diagnosis and treatment times in PHIs decreased from 57.41% to 51.96%, although it increased in 2020. The proportion of inpatients in PHIs decreased from 20.03% to 16.11%. From 2014 to 2020, the utilisation rate of hospital beds in PHIs decreased (from 55.6% to 34% for community health centres and 60.5% to 53.6% for township hospitals). The average daily bed days of doctors in township hospitals was higher than that of doctors in community health service centres. However, the average medical cost of outpatients and the per capita medical cost of inpatients in community health service centres were higher than in township hospitals. CONCLUSION: In recent years, although the service capability showed an increasing trend in PHIs, the growth rate was lower than the general health institutions. The utilisation rates of PHIs, including beds and physicians, were decreased. Among PHIs, the utilisation in township hospitals was higher than in community health centres with a relatively low price. Under the hierarchical medical system and normalisation period of the COVID-19 epidemic, it is important to improve the service capability to achieve its goal of increasing PHI utilisation and decreasing secondary and tertiary hospital utilisation.