Urea cycle promotion via ammonia-upregulated CPS1 is involved in arsenite-induced pulmonary fibrosis through enhancing collagen synthesis.

Arsenic exposure is connected with lung toxicity and is related to lung fibrotic changes. Idiopathic pulmonary fibrosis (IPF) is characterized by extracellular matrix (ECM) deposition. Various genetic mechanisms and environmental factors induce or exacerbate pulmonary fibrosis. Collagen synthesis induced by sodium arsenite (NaAsO2) is closely associated with IPF. Fibroblasts tend to fine-tune their metabolic networks to support their synthetic requirements in response to environmental stimuli. Alterations in metabolism have an influential role in the pathogenesis of IPF. However, it is unclear how arsenic affects the metabolism in IPF. The urea cycle (UC) is needed for collagen formation, which provides adequate levels of proline (Pro) for biosynthesis of collagen. Carbamoyl phosphate synthetase 1 (CPS1) converts the ammonia to carbamoyl phosphate, which controls the first reaction of the UC. We show that, in arsenite-exposed mice, high amounts of ammonia in the lung microenvironment promotes the expression levels of CPS1 and the Pro metabolism. Reduction of ammonia and CPS1 ablation inhibit collagen synthesis and ameliorate IPF phenotypes induced by arsenite. This work takes advantage of multi-omics data to enhance understanding of the underlying pathogenic mechanisms, the key molecules and the complicated cellular responses to this pollutant, which provide a target for the prevention of pulmonary fibrosis caused by arsenic.

Characteristics of men who have casual sex with men among Chinese university students: A cross-sectional study.

OBJECTIVES: The characteristics of men who have sex with men (either exclusively or with both men and women; MSM) who engaged in casual sex among Chinese male university students have not been compared with the characteristics of men who have sex with only women (MSW). This information is important for tailoring targeted behavioral interventions to prevent human immunodeficiency virus (HIV)/sexually transmitted infection (STI) transmission in this subgroup of MSM. METHODS: Data were derived from a large cross-sectional electronic questionnaire survey conducted at 13 universities in Zhejiang Province, China, in 2018. Bivariate analyses were used to compare demographic, HIV-related psychosocial, and behavioral characteristics between MSM and MSW students who engaged in casual sex during the previous year. Proportion differences between the two groups and their 95% confidence intervals were analyzed. RESULTS: Among the 583 sexually active male students who engaged in casual sex during the previous year, 128 and 455 were MSM and MSW, respectively. Compared with MSW students, larger proportions of MSM students reported knowing that male-to-male sexual behavior was the main mode of HIV transmission among Chinese students (62.5% vs. 45.5%), consenting to commercial sex (67.2% vs. 53.4%), wanting to know the HIV serostatus of partners before casual sex (65.8% vs. 51.3%), feeling at risk of HIV infection (40.5% vs. 11.8%), high condom-decision scale scores (55.3% vs. 42.6%), engaging in sex with ≥ 5 casual sex partners (44.6% vs. 25.9%), searching for casual partners online (89.2% vs. 51.3%), consuming alcohol before casual sex (64.8% vs. 45.0%), engaging in sex with regular partners (83.1% vs. 67.0%), engaging in commercial sex (54.2% vs. 26.4%), and visiting a clinic for voluntary counselling and testing (VCT) (16.4% vs. 8.4%). However, compared with MSW students, smaller proportions of MSM students reported knowing that consistent condom use could prevent HIV transmission (80.5% vs. 95.2%) and that VCT should be actively sought after risky sexual behavior (78.9% vs. 93.8%), using condoms sometimes/often (26.4% vs. 44.3%), and consistently using condoms (28.9% vs. 40.1%) while engaging in sex with casual partners. CONCLUSIONS: MSM students who engaged in casual sex were at a greater risk of HIV/STI transmission, compared with MSW students. Comprehensive interventions to address the risks of unprotected male-to-male sex, searching for casual sex partners online, and non-use of HIV testing services are needed to reduce the burden of HIV/STI transmission among this subgroup of MSM.

Factors associated with voluntary HIV counseling and testing among young students engaging in casual sexual activity: a cross-sectional study from Eastern China.

OBJECTIVES: To investigate the factors associated with voluntary HIV counseling and testing (VCT) among young students engaging in casual sexual activity and to establish a scientific rationale for developing targeted intervention strategies for preventing HIV/AIDS in this population. METHODS: Stratified cluster sampling was used to conduct a survey using questionnaires to collect demographic and behavioral information for statistical analysis. RESULTS: Data from 611 young students, who reported engaging in casual sexual activity, were included in the statistical analysis. Among these, 68 (11.13%) students underwent the VCT. Among young students who engaged in casual sexual activity, those who were non-Zhejiang residents (adjusted odds ratio [aOR]: 2.11; 95% Confidence Interval [CI]: 1.17-3.80), those who had received AIDS-themed lectures or health education courses from the school in the past year (aOR = 3.96, 95% CI = 1.49-10.50), those who had received HIV risk self-assessment conducted by the school in the past year (aOR = 2.31, 95% CI = 1.17-4.59), and those who had engaged in commercial sex activity in the past year (aOR = 1.98, 95% CI = 1.07-3.66) were more inclined to have undergone VCT. Male students (aOR = 0.37, 95% CI = 0.18-0.77) and those who used condoms consistently during casual sexual activity (aOR = 0.45, 95% CI = 0.21-0.97) were less likely to undergo VCT. CONCLUSION: Casual sexual activity was relatively prevalent among young students, posing a potential risk for HIV transmission. These findings will be instrumental in the development more effective HIV prevention and control strategies for young students. Additionally, it highlights the necessity of promoting and popularizing VCT among young students without Zhejiang province residency, who are involved in commercial sexual activity, and/or those who lacking HIV education. Moreover, additional research and implementation of refined HIV behavioral interventions specifically tailored to young students are necessary to enhance their awareness and knowledge of HIV prevention.

Factors associated with the choice of having multiple sexual partners among male college students with casual heterosexual sex in Zhejiang Province, Eastern China.

BACKGROUND: Young students infected with HIV have become a significant public health issue in China, this study aimed to understand the factors influencing the choice of having multiple sexual partners among male college students who had casual heterosexual sex in Zhejiang Province and to scientifically justify developing HIV/AIDS intervention strategies among them. METHODS: A stratified cluster sampling method was used for the survey of students from 13 colleges or universities in Zhejiang Province between October and November 2018. The questionnaire collected information on general demographic characteristics, knowledge of HIV/AIDS prevention and treatment, sexual attitudes and risk awareness, sexual behavioural characteristics, and acceptance of interventions. The univariable and multivariable analyses were conducted in this study. RESULTS: Study participants included 362 male college students who exhibited casual heterosexual sex and were aware of the number of sexual partners they had. Among them, 222 students engaged in casual heterosexual sex with multiple sexual partners (61.33%). The results of the multivariable analysis revealed several factors associated with male students' choice to have multiple sexual partners: monthly living expenses greater than or equal to 1501 CNY (adjusted OR = 2.24, 95% CI = 1.21-4.16), sexual behavior after consuming alcohol (adjusted OR = 2.19, 95% CI = 1.32-3.63), whose casual partner types were non-student (adjusted OR = 2.51, 95% CI = 1.45-4.22), and those who discussed using condoms during sexual intercourse (adjusted OR = 0.50, 95% CI = 0.28-0.89). CONCLUSION: The choice to engage in casual heterosexual sex with multiple partners was found to be associated with several factors among male college students, including economic status, engaging in sexual behavior after consuming alcohol, the type of the casual partner, and using condoms. These findings highlight the significance of implementing targeted interventions and comprehensive sexual health education programs within college settings in order to encourage safer sexual practices among students.

Factors Associated with HIV Testing among Male Students Who Have Engaged in Sexual Behaviour in Zhejiang Province, China.

Objective: This study aimed to estimate the prevalence of human immunodeficiency virus (HIV) testing, identify factors associated with HIV testing among male students who have engaged in sexual behaviour in Zhejiang province, and provide a scientific basis for the prevention and control of HIV infection on campus. Methods: Stratified cluster random sampling analysis was performed, which included general characteristics, sexual attitudes, sexual behaviours, information on HIV testing, and self-risk assessment for HIV infection. Univariate and multivariate logistic regression analyses were conducted to identify the influencing factors. Results: Among 2734 male students who have engaged in sexual behaviour, 319 (11.7%) had undergone HIV antibody testing in the previous year. The results of multivariate analysis demonstrated that the participants who were in the junior grade level (adjusted odds ratio (AOR) = 1.59, 95% confidence interval (95% CI): 1.10-2.30) exhibited acceptance to male homosexual behaviour (AOR = 1.73, 95% CI: 1.19-2.52), had been exposed to testing publicity in the previous year (AOR = 1.51, 95% CI: 1.06-2.15), had been exposed to self-risk assessment for HIV infection (AOR = 2.66, 95% CI: 1.99-3.55), had male or bisexual partners (AOR = 1.60, 95% CI: 1.05-2.46), had a score for the scale indicating awareness of different testing methods between 2 and 5 (AOR = 2.19, 95% CI: 1.51-3.16) or greater than 6 (AOR = 1.49, 95% CI: 1.01-2.66), and had a score for the scale indicating knowledge of different testing facilities between 3 and 5 (AOR = 1.63, 95% CI: 1.00-2.66) were inclined to engage in HIV testing. Conclusions: In this study, the proportion of HIV-testing among male students who have engaged in sexual behaviour was low. This study revealed that students who exhibited acceptance to male homosexual behaviours had been exposed to publicity for HIV testing or a self-risk assessment for HIV infection which were more inclined to engage in HIV testing. Our study underscores the urgent need to enhance educational interventions concerning HIV risks and warnings as part of the health education curriculum on campus. The graveness of the AIDS epidemic among students necessitates this emphasis. Moreover, we recommend deploying condom-dispensing machines or HIV testing facilities across the campus for easy access to preventive and testing services for HIV.

Correlates of condom use among male university students from eastern China who engage in casual sex.

Consistent condom use with casual partners is critical for preventing the transmission of human immunodeficiency virus (HIV) among male university students. This study aimed to determine the level of consistent condom use and explore the correlates of condom use consistency in male university students in eastern China. A descriptive cross-sectional survey was conducted in 13 universities in Zhejiang Province, which involved the recruitment of 31,674 students by stratified random sampling. Among them, 545 male students who engaged in casual sex in the year prior to this study were included. Adjusted and unadjusted logistic regression models were used to examine the correlates associated with consistent condom use. Among the 545 male university students, only 205 (37.6%) consistently used condoms in the previous year. The following correlates were associated with higher rates of consistent condom use: 1) Knowledge, specifically, the number of correct answers to "HIV infection can be determined by appearance" (AOR: 2.06, 95% CI: 1.21-3.49); 2) never finding casual partners on the internet during the past over the prior year (AOR: 0.63; 95% CI: 0.40-0.99); 3) never drinking alcohol before casual sex during the last over the prior year (AOR: 0.30; 95% CI: 0.20-0.46); 4) never engaging in commercial sex (AOR: 0.57; 95% CI: 0.34-0.96); and 5) high condom self-efficacy score (AOR: 2.55; 95% CI: 1.44-4.49). The study found a low level of consistent condom use among male university students. Promoting condom self-efficacy, reducing web-based casual sex, drinking before sex, and commercial sex are essential to improving the level of consistent condom use among male university students to reduce the transmission of HIV.

Analysis of Multiple Sexual Partners among 2665 Male College Students Who Have Sexual Behaviour in Zhejiang Province, China.

Objective: The objective of this study was to understand multiple sexual partners and related factors among male college students who exhibited sexual behaviour to provide a scientific basis for formulating HIV/AIDS prevention measures among college students. Methods: A stratified cluster random sampling method was conducted among 2665 male students who had sexual behaviour and were informed of the number of sexual partners from 13 colleges/universities in 11 cities in Zhejiang Province in 2018. Demographic characteristics, sexual attitudes, sexual behaviour, interventions, and related information were collected using a homemade online questionnaire. The chi-square test or univariate logistic regression in different groups was conducted for multiple sexual partners, and a logistic regression model was used in the related factor analysis. Results: A total of 2665 college students who engaged in sexual behaviour were involved in the research; among them, 485 students (18.20%) had multiple sexual partners. The results of multivariate analysis showed that the participants whose sexual orientation was homosexual (adjusted OR = 4.10, 95%CI = 2.89 - 5.80), those who had received school education about HIV testing in the previous year (adjusted OR = 1.55, 95%CI = 1.20 - 1.99), those who had accepted one-night stands (adjusted OR = 3.29, 95%CI = 2.43 - 4.47), those who had accepted commercial sex (adjusted OR = 1.89, 95%CI = 1.44 - 2.48), and those who were very confident in a condom use measure of self-efficacy (adjusted OR = 1.78, 95%CI = 1.31 - 2.41) were more likely to have multiple sexual partners. The participants who were senior students (adjusted OR = 0.51, 95%CI = 0.31 - 0.84), those whose monthly living expenses were 1001-1500 renminbi (adjusted OR = 0.69, 95%CI = 0.51 - 0.93), those who had known that "daily life and study contact cannot spread HIV" (adjusted OR = 0.59, 95%CI = 0.43 - 0.80), and those who knew that the CDC provides HIV testing (adjusted OR = 0.66, 95%CI = 0.46 - 0.95) were less likely to have multiple sexual partners. Conclusion: Multiple sexual partners were quite common among male college students who engaged in sexual behaviour. They had a separation of HIV/AIDS knowledge and action and a low rate of HIV testing. Further health education and intervention, including informing friends of strategies, are needed to guide students in correct sexual attitudes, safe sexual behaviour, and prevention of the spread of disease.

Factors Associated with Commercial Sex Behavior among Male College Students Who Engaged in Temporary Heterosexual Behavior in Zhejiang Province, China.

Objective: This study explored the characteristics and associated factors of commercial sex behavior among male college students who engaged in temporary heterosexual behaviors in Zhejiang Province, China. Methods: The participants were male college students with temporary heterosexual behaviors. We developed an online questionnaire to collect information on demographic characteristics, sexual attitudes, sexual behaviors, and HIV/AIDS interventions through stratified cluster sampling. Chi-square (χ 2) tests were performed for the different groups of participants. The occurrence of commercial sex behavior among participants was taken as the dependent variable, and logistic regression was used to analyze the factors associated with the participants' commercial sex behavior. Results: This study investigated the temporary heterosexual behavior of 424 male college students. Among them were 112 students who reported commercial sex behavior (26.42%), whose average age was 20.25 ± 1.27 years, and whose household registration of Zhejiang Province accounted for 63.39%. The results of the multivariate logistic regression analysis indicated that acceptance of commercial sex behavior (Adjusted (a) OR = 3.53, 95% CI = 1.94~6.40) and feeling at risk of contracting HIV (aOR = 6.44, 95% CI = 2.98~13.94), seeking temporary sexual partners through the Internet (aOR = 2.58, 95% CI = 1.27~5.25), consistently using condoms during sex (aOR = 0.34, 95% CI = 0.16~0.70), or using condoms sometimes/frequently during sex (aOR = 0.30, 95% CI = 0.13~0.68) were independent factors associated with male college students with temporary heterosexual behavior engaging in commercial sex behavior. Conclusion: Open sexual attitudes, seeking temporary sexual partners through the Internet, high awareness of HIV infection risk, and low condom use are associated factors for male college students engaging in commercial sex behavior. For college students' HIV/AIDS prevention and education interventions, it is necessary to strengthen the prevention of network influence, increase peer education, increase teacher participation in education, enhance college students' risk awareness, advocate for the use of condoms, and promote HIV/AIDS prevention and treatment.

SWOT analysis of HIV control strategy in key areas of Zhejiang Province / 预防医学

Objective @#To analyze the problems in the AIDS control strategy in key areas of Zhejiang Province, so as to provide insights into the improvement of the control strategy.@*Methods @#The AIDS control data were collected from 10 key counties (districts) in Zhejiang Province, and the AIDS control strategy was comprehensively evaluated using a SWOT analysis.@*Results @#The strengths of the AIDS control strategy in key counties (districts) of Zhejiang Province included distinct working objectives, well-organized leadership, and effective control measures, the weaknesses included large number of HIV-infected cases, high burden of disease, difficulty in management of AIDS transmission and insufficient AIDS control capability, and the opportunities included the AIDS control in key counties (districts) conforming to the current status of AIDS control, strong support of innovative strategies and technical support from professional teams, while the threats included insufficient working mechanisms for AIDS control, the gap between the effectiveness of AIDS control and the target goal and unverified scientific evidence of the control strategy. Supported policies should be fully used, working mechanisms need to be improved, control strategies need to be innovated, and assessments need to be implemented for AIDS control in key counties (districts). @*Conclusions @#There are both opportunities and challenges for AIDS control in key counties (districts) of Zhejiang Province. Optimization of the working mechanisms, promotion of precision interventions, and search for repeatable control strategy in other disease-affected regions are required for AIDS control.

Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors.

In recent years, immune checkpoint inhibitors (ICIs) have become the standard treatment option for tumors. With the widespread application of ICIs, immune-related adverse events (irAEs) have gradually attracted the attention of researchers. Owing to the characteristics of ICIs, irAEs can affect each organ of the human body. Thromboembolism is uncommon in cancer patients receiving ICIs, but it may affect their survival. Most thromboembolic events do not cause serious effects after early prediction and treatment, but life-threatening toxic reactions are also observed. This condition should not be ignored because of vague and atypical symptoms, which make early diagnosis more challenging. This article focuses on the high-risk factors, underlying mechanisms, incidence, and prognosis of thromboembolism in patients using ICIs and briefly describes the intervention and treatment measures. This information would allow patients to effectively manage the side effects of thromboembolism during Immune checkpoint inhibitors treatment, ensuring the efficacy of ICIs and reducing mortality.

Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-ß1/smad2/ROS/caspase-3 pathway.

Scutellarin plays an anti-tumor role in A549 lung cancer cells, but the underlying mechanism is unclear. In this study, scutellarin was used to treat A549 cells for 12, 24, and 48 h, followed by the addition of Tempo, a selective scavenger of mitochondrial reactive oxygen species (ROS) and SB431542, a transforming growth factor (TGF)-ß1 receptor inhibitor. A dihydroethidium fluorescence probe was used to measure the intracellular ROS level, Cell Counting Kit-8 (CCK-8) was used to detect cell viability, and flow cytometry was performed to examine apoptosis. Western blots were used to detect the total protein level of TGF-ß1, p-smad2, and cleaved caspase-3 in A549 cells. The results showed that scutellarin significantly inhibited cell viability and increased apoptosis. Scutellarin also promoted intracellular ROS production, TGF-ß1/smad2 signaling pathway activation, and cleaved caspase-3 expression, which was partly reversed by Tempo. Moreover, scutellarin-induced intracellular ROS production and cleaved caspase-3 expression were inhibited by blocking the TGF-ß1/smad2 pathway with SB431542. In conclusion, scutellarin promoted apoptosis and intracellular ROS accumulation, which could be abrogated by Tempo and SB431542 treatment in A549 cells. Our study indicated that scutellarin induced A549 cell apoptosis via the TGF-ß1/smad2/ROS/caspase-3 pathway.

Analysis of homosexual behavior characteristics and influencing factors of male college students in Zhejiang Province.

ABSTRACT: The purpose of this study was to understand the homosexual behavior characteristics and influencing factors of male college students and to provide scientific evidence for the prevention of HIV infection in college students.A self-made online questionnaire was used to collect information on demographic characteristics, sexual attitudes, sexual behaviors, and interventions of the respondents. The χ2 test was performed on the constituent ratios of different groups, and whether homosexual behavior occurred was the dependent variable. Logistic regression was subsequently used to analyze the influencing factors of male homosexual behavior.A total of 2665 students were surveyed, including 219 men who have sex with men, accounting for 8.22% of the sample population. Multivariate analysis revealed the following independent influencing factors of homosexual behavior among male college students: the student's household registration was Zhejiang Province, the hometown was in the city, accepted male homosexual sex, had temporary sex in the last year, and awareness that the correct use of condoms can reduce the spread and risk of acquired immunodeficiency syndrome.Various measures should be enacted to promote human immunodeficiency virus/acquired immunodeficiency syndrome education and intervention among college students, especially emphasizing making friends and advocating safe sex to prevent the spread of the disease.

Analysis of factors influencing casual sexual behavior among male college students in Zhejiang Province, China.

OBJECTIVE: The purpose of this study was to explore the situations and factors influencing casual sexual behavior among male college students, in order to provide scientific evidences and measures of the prevention and control for HIV/AIDS. METHOD: Using the stratified cluster sampling method, male college students who self-reported sexual behavior were selected as survey subjects in 13 colleges and universities in 11 cities of Zhejiang Province from October to November 2018. We used a custom online questionnaire to collect information on the demographic characteristics, sexual attitudes, sexual behaviors, and HIV interventions of the respondents. The χ2 test was performed on the composition ratios between different groups. With the occurrence of casual sexual behavior as the dependent variable, logistic regression was used to analyze the factors influencing casual male sexual behavior. RESULTS: A total of 2734 male college students were surveyed, aged 20.20±1.41 years, of which 595 had casual sex, accounting for 21.7%. The rate of HIV prevention awareness among the participants was 85.1%. Multivariate analysis showed that receiving a self-assessment of HIV risk conducted by the school (Ajusted OR = 1.45, 95% CI = 1.14-1.84), knowing that HIV self-test kits were available at school (Ajusted OR = 2.02, 95% CI = 1.56-2.62), accepting one-night stands (Ajusted OR = 2.82, 95% CI = 2.18-3.66), accepting commercial sex (Ajusted OR = 1.95, 95% CI = 1.53-2.48), being a man who has sex with men (Ajusted OR = 1.81, 95% CI = 1.37-2.39), being a senior (Ajusted OR = 0.46, 95% CI = 0.30-0.71), having knowledge of HIV/AIDS prevention and treatment (Ajusted OR = 0.66, 95% CI = 0.51-0.86), and knowing that the CDC provides HIV testing services (Ajusted OR = 0.56, 95% CI = 0.41-0.77) were factors influencing male college students' casual sexual behavior. CONCLUSION: Male college students who have causal sexual behaviors have a high degree of openness in sexual attitudes, insufficient knowledge of AIDS prevention, and knowledge of HIV testing-related information but low testing rates. For male college students' HIV prevention education intervention, it is necessary to emphasize the establishment of correct sexual attitudes and concepts and promote safe sexual behaviors to prevent the spread of HIV.

The first 90: Progress in HIV detection in Zhejiang Province, 2008-2018.

To analyze the results of HIV screening and the HIV-positive rate based on different HIV detection strategies in Zhejiang Province, China. Data were downloaded from the AIDS Prevention and Control Information System on May 1, 2019. HIV screening, prevalence, and incidence data were analyzed from 2008 to 2018. The incidence of HIV was calculated from the results of BED testing. SPSS software (ver. 19.0) was used for the analysis. The number of people screened for HIV increased by 229.7% from 2008 to 2018, while the incidence of HIV increased from 1.14‱ (2010) to 1.67‱ (2018), peak by 2015 (2.28‱). The proportion of people screened for HIV in medical institutions increased from 62.0% in 2008 to 67.1% in 2018, while of all positive tests, 47.9% were conducted at medical institutions in 2008, which increased to 63.2% in 2018. VCT and STD clinic attendees, who had only 4.5% of all those undergoing HIV tests, accounted for 23.7% of all HIV positive in 2018. The rate of HIV-positive people and incidence of HIV both increased in Zhejiang Province between 2008 and 2015. The most effective strategy for detecting HIV new cases is screening visitors to VCT and STD clinics.

Prognostic Value of Neoantigen Load in Immune Checkpoint Inhibitor Therapy for Cancer.

Immune checkpoint inhibitors (ICIs) have made great progress in the field of tumors and have become a promising direction of tumor treatment. With advancements in genomics and bioinformatics technology, it is possible to individually analyze the neoantigens produced by somatic mutations of each patient. Neoantigen load (NAL), a promising biomarker for predicting the efficacy of ICIs, has been extensively studied. This article reviews the research progress on NAL as a biomarker for predicting the anti-tumor effects of ICI. First, we provide a definition of NAL, and summarize the detection methods, and their relationship with tumor mutation burden. In addition, we describe the common genomic sources of NAL. Finally, we review the predictive value of NAL as a tumor prediction marker based on various clinical studies. This review focuses on the predictive ability of NAL's ICI efficacy against tumors. In melanoma, lung cancer, and gynecological tumors, NAL can be considered a predictor of treatment efficacy. In contrast, the use of NAL for urinary system and liver tumors requires further research. When NAL alone is insufficient to predict efficacy, its combination with other indicators can improve prediction efficiency. Evaluating the response of predictive biomarkers before the treatment initiation is essential for guiding the clinical treatment of cancer. The predictive power of NAL has great potential; however, it needs to be based on more accurate sequencing platforms and technologies.

Ursolic acid inhibits the invasiveness of A498 cells via NLRP3 inflammasome activation.

Renal cell cancer is a common malignant tumor of the urinary system. Ursolic acid (UA) serves an important antitumor role in certain types of cancer, such as lung cancer, breast cancer and hepatocellular carcinoma; however, to the best of our knowledge, the effect of UA on renal cancer has not yet been investigated. In the present study, A498 cells were treated with different concentrations of UA for 12, 24 and 48 h, and then MCC950, an inhibitor of the NLR family pyrin domain-containing 3 (NLRP3) receptor, was added to block NLRP3 signaling. The proliferation of A498 cells was analyzed using an MTS assay and invasiveness was analyzed using a Transwell assay. The expression levels of NLRP3, cleaved caspase-1, IL-1ß and MMP-2 were detected using western blotting. The present results demonstrated that the invasiveness of A498 cells was significantly decreased following UA treatment (P<0.05), while expression levels of NLRP3, cleaved caspase-1 and IL-1ß were significantly increased, and MMP-2 expression was decreased following UA stimulation (P<0.05). This was reversed by MCC950 treatment (P<0.05), with the exception of NLRP3. In conclusion, the present results indicated that UA exposure decreased the proliferation and invasiveness of A498 cells. Additionally, UA exposure significantly decreased MMP-2 production and induced the activation of NLRP3 inflammasome, which was reversed by MCC950 treatment, indicating that NLRP3 activation may be involved in UA inhibition of A498 cell invasiveness.

Significant benefits of pembrolizumab in treating refractory advanced pulmonary sarcomatoid carcinoma: A case report.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC), a rare subtype of non-small cell lung cancer (NSCLC), is poorly differentiated and highly aggressive. Treatment is limited, and the prognosis is poor. Pembrolizumab is an anti-programmed death (PD)-1 antibody with good efficacy in NSCLC. Recent studies have demonstrated that PD-ligand 1 (PD-L1) overexpression is common in PSCs, which suggests that anti-PD-L1 treatment is an ideal option. However, the response to pembrolizumab in PSC has not been studied. CASE SUMMARY: We present a PSC case with PD-L1 overexpression that significantly benefited from pembrolizumab. A 73-year-old Chinese male was detected with a right lung lesion. Pathological analysis of the right upper lobectomy confirmed PSC. The PD-L1 test revealed overexpression (TPS: 90%). Multiple metastases occurred 1 mo after surgery, representing stage IV PSC. Neither first-line chemotherapy nor second-line antiangiogenic agents showed any benefit. Radiotherapy (1200 cGy) was administered to relieve chest wall pain. The patient received the PD-1 inhibitor pembrolizumab (100 mg) as third-line therapy; however, because of fever and severe infection, he refused to receive immunotherapy any longer. Thus, only one dose of pembrolizumab was administered. Deep sustained remission of most of the metastases was achieved except for lesions in the right adrenal gland, which first shrank and then progressed. The patient died because of disease progression in the right adrenal gland. He achieved a progression-free survival time of 8 mo and an overall survival time of 9 mo with third-line pembrolizumab. CONCLUSION: Our findings highlight and offer direct evidence of the efficacy of pembrolizumab in PD-L1-overexpressing PSCs. Combined radiotherapy and immunotherapy may enhance treatment efficacy.

Assessment on the third round of Zhejiang Comprehensive AIDS Response program / 预防医学

Objective@#To evaluate the third round of Zhejiang Comprehensive AIDS Response (CARES) program (nine national areas and three provincial areas) and the control effect of AIDS, so as to provide reference for AIDS prevention and control. @*Methods@#According to the final assessment protocol of the third round of China CARES, the data of 23 assessment items which were collected from online database and field investigation for 12 response areas of Zhejiang in 2014 and 2018 were evaluated. The endemic situation and detection of AIDS in CARES areas was compared with those in non-CARES areas, in order to evaluate the achievement of Zhejiang CARES areas.@*Results@#The rates of reaching the standard ranged from 91.30% to 100.00% in 12 CARES areas. Six indexes in leadership and innovation, fifteen (seventeen in total) indexes in HIV/AIDS control and prevention reached the standard. The items that failed included the awareness rates of AIDS and indicators in “prevention and intervention”. The rates of of reaching the standard in “publicity and education”, “monitoring and testing”, “prevention and intervention”, and “treatment and follow-up” increased from 55.56%, 79.17%, 79.76% and 65.00% in 2014 to 91.67%, 100.00%, 90.48% and 100.00% in 2018, respectively. The proportion of HIV testing people in permanent residents was 30.94% in CARES areas in 2018, which was significantly higher than 20.70% in non-CARES areas (P<0.05). The proportion of new reported HIV/AIDS in CARES areas was 50.87%, and the average increase was 4.48%, which was lower than 9.95% in non-CARES areas.@*Conclusion@#The third round of Zhejiang CARES program has remarkable achievement and plays a positive role in the prevention and control of AIDS.

Prototype of integrated pseudo-dynamic crosstalk network for cancer molecular mechanism.

In this study, we attempted to solve two important challenges in systems biology. First, although the Michaelis-Menten (MM) model provides local kinetic information, it is hard to generalize MM models to model a large system because increasingly large amounts of experimental data are necessary for the parameter identification. In addition, it is not possible to develop an MM model that provides information about the strength of the interactions in the system. Second, although the dynamic simulation of various signal transduction pathways is important in cancer research, it is impossible to theoretically derive a mathematical model to describe the cancer molecular mechanism. Predictive computational approaches can be used to analyze the dynamics of a system and to determine the dysfunction of a regulatory process. In this report, we first propose a pseudo-dynamic pathway to describe protein interactions in an MM system. We then discuss the dynamic behavior of two large-scale systems (antigrowth-signal-induced cell cycle and apoptotic-signal-transduction mechanism). These two systems were constructed through the in-series and organic integration, respectively, of MM modules with Petri net modules; moreover, more than 30% additional reactions were added during this integration step. We then described an extremely large multi-stream system (growth signal transduction); however, the analysis of this system to obtain dynamic predictions is critical but appears impossible. Thus, we introduced a fuzzy concept that can be used to develop a physically realizable model prototype. In the future, through step-by-step in vivo modifications, researchers will be able to develop a complete model of cancer metabolism to achieve accurate predictions.