A case report and literature review on respiratory failure with immune checkpoint inhibitors: a life-threatening adverse event.

Neuromuscular associated respiratory failure is a rare toxicity of immunotherapy for malignant tumors. In most cases, it may overlap with the symptoms of the primary disease or myocarditis, myositis and myasthenia gravis, resulting in difficult etiological diagnosis. Early detection and optimal treatment are still topics that need attention. Here, a case of 51-year-old male lung cancer patient with sintilimab-associated myasthenia gravis, myositis, and myocarditis overlap syndrome involving the diaphragm who developed severe type II respiratory failure was reported. After high-dose methylprednisolone, immunoglobulin and pyridostigmine intravenous injection with non-invasive positive pressure ventilation, the patient's symptoms improved significantly and was discharged. One year later, the patient received immunotherapy again due to tumor progression. After 53 days, he developed dyspnea again. Chest X-ray demonstrated marked elevation of the diaphragm, and the electromyogram demonstrated dysfunction of diaphragm. With rapid diagnosis and timely treatment, the patient was finally discharged safely. A comprehensive search of PubMed, EMBASE was performed to identify all previously reported cases of immune checkpoint inhibitors-associated respiratory failure. The potential mechanisms of respiratory failure caused by ICI-associated diaphragmatic dysfunction may be related to T cell-mediated immune disturbances and we proposed possible diagnostic processes. For patients with unexplained respiratory failure who are receiving immunotherapy, standardized diagnostic strategies should be implemented immediately on admission before deciding whether to conduct a more invasive diagnostic procedure or empirical treatment.

R-Phycoerythrin Induces SGC-7901 Apoptosis by Arresting Cell Cycle at S Phase.

R-Phycoerythrin (R-PE), one of the chemical constituents of red algae, could produce singlet oxygen upon excitation with the appropriate radiation and possibly be used in photodynamic therapy (PDT) for cancer. Documents reported that R-PE could inhibit cell proliferation in HepG2 and A549 cells, which was significative for cancer therapy. This is due to the fact that R-PE could kill cancer cells directly as well as by PDT. However, little is known about the cytotoxicity of R-PE to the SGC-7901 cell. In this study, it has been found that R-PE could inhibit SGC-7901 proliferation and induce cell apoptosis, which was achieved by arresting the SGC-7901 cell at S phase. CyclinA, CDK2 and CDC25A are proteins associated with the S phase, and it was found that R-PE could increase the expression of cyclin A protein and decrease the expression of CDK2 and CDC25A proteins. Thus, it was concluded that R-PE reduced the CDK2 protein activated through decreasing the CDC25A factor, which reduced the formation of Cyclin-CDK complex. The reduction of Cyclin-CDK complex made the SGC-7901 cells arrest at the S phase. Therefore, R-PE induced apoptosis by arresting the SGC-7901 cell at S phase was successful, which was achieved by the expression of the CDC25A protein, which reduced the CDK2 protein actived and the formation of Cyclin-CDK complex.

A static precise single-point positioning method based on carrier phase zero-baseline self-differencing.

Satellite navigation positioning has become an indispensable component of everyday life, where precise pinpointing and rapid convergence are crucial in delivering timely and accurate location information. However, due to the damping of integer ambiguities and system residual errors, the rapid convergence of Precise Point Positioning (PPP) implementation is a significant challenge. To address this, this paper proposes a novel Carrier Phase Zero-Baseline Self-Differencing Precise Point Positioning (CZS-PPP) technique and its ionosphere-free fusion model. By employing the proposed CZS-PPP approach in separate scenarios involving BDS-3, GPS, and dual-system settings, we systematically validate the efficacy of the method. The experimental results indicate that the convergence time of the method is less than 4 min in a single-system scenario. Furthermore, in a dual-system scenario, the method can achieve rapid convergence in less than 3 min. The CZS-PPP technique presented demonstrates the elimination of integer ambiguities and the effective suppression of system residuals, in comparison to the conventional method. The proposed approach has demonstrated remarkable performance across different systems, offering a promising new pathway for achieving PPP fast convergence in BDS/GNSS.

Coexistence of a novel SRBD1-ALK, ALK-CACNA1D double-fusion in a lung adenocarcinoma patient and response to alectinib: A case report.

A Chinese male patient with advanced lung adenocarcinoma experienced disease progression one and a half years after receiving first-line immunochemotherapy. The second biopsy was performed and tissue immunohistochemistry revealed Anaplastic lymphoma kinase (ALK) expression in the cytoplasm of tumor cells, so he began to receive Alectinib treatment. Then the next generation sequencing found double fusion variants of S1 RNA binding domain 1 (SRBD1)- ALK and ALK- Calcium voltage-gated channel subunit alpha1 D (CACNA1D). After continuous Alectinib treatment for 7 months, almost complete response (CR) was achieved. The patient is currently taking Alectinib for 13 months, the condition is stable, and is waiting for the next cycle of efficacy evaluation.

Network Pharmacology Analysis on the Mechanism of Xihuangwan in Treating Rectal Cancer and Radiation Enteritis.

BACKGROUND: Recent studies have shown that XihuangWan (XHW) is a kind of Chinese medicine with significant anti-tumor and anti-inflammatory activities. However, its mechanism for preventing and treating radiation proctitis in rectal cancer patients during radiotherapy remains unclear. METHODS: This study employed the network pharmacology to establish a "drug-active ingredient-target genedisease" network via using TCMSP, SymMap, GeneCard, and OMIM databases. The PPI network was conducted by the String tool. The core targets of XHW in the treatment of rectal cancer and radiation enteritis were identified by topological analysis, and the functional annotation analysis and pathway enrichment analysis were performed. RESULTS: A total of 61 active ingredients of XHW ingredients, 4607 rectal cancer-related genes, 5803 radiation enteritis-related genes, and 68 common targets of XHW in the treatment of rectal cancer and radiation enteritis were obtained. PTGS1 and NR3C2, as identified potential targets, were significantly associated with OS of colorectal cancer patients. GO and KEGG enrichment analysis showed that bioinformatics annotation of these common genes was mainly involved in DNA-binding transcription factor, PI3K/Akt, TNF, HIF-1 signaling pathway, and colorectal cancer pathway. CONCLUSION: The active ingredients of XHW, mainly including Quercetin, Ellagic acid, and Stigmasterol, might act on common targets of rectal cancer and radiation enteritis, such as PTGS1, NR3C2, IL-6, EGFR, HIF-1A, CASP3, BCL2, ESR1, MYC, and PPARG, and regulate multiple signaling pathways like PI3K-Akt, TNF, and HIF-1 to inhibit tumor proliferation, tumor angiogenesis, inflammatory responses, and oxidative stress, thereby achieving prevention and treatment of radiation enteritis in rectal cancer patients during radiotherapy. It provided an important reference for further elucidating the anti-inflammation and anti-tumor mechanism and clinical application of XHW.

Network pharmacology in combination with bibliometrics analysis on the mechanism of compound Kushen injection in the treatment of radiation pneumonia and lung cancer.

Radiation pneumonia is a common adverse reaction during radiotherapy in lung cancer patients, which negatively impacts the quality of life and survival of patients. Recent studies have shown that compound Kushen injection (CKI), a traditional Chinese medicine (TCM), has great anti-inflammatory and anticancer potential, but the mechanism is still unclear. We used CiteSpace, the R package "bibliometrix," and VOSviewers to perform a bibliometrics analysis of 162 articles included from the Web of Science core collection. A network pharmacology-based approach was used to screen effective compounds, screen and predict target genes, analyze biological functions and pathways, and construct regulatory networks and protein interaction networks. Molecular docking experiments were used to identify the affinity of key compounds and core target. The literature metrology analysis revealed that over 90% of the CKI-related studies were conducted by Chinese scholars and institutions, with a predominant focus on tumors, while research on radiation pneumonia remained limited. Our investigation identified 60 active ingredients of CKI, 292 genes associated with radiation pneumonia, 533 genes linked to lung cancer, and 37 common targets of CKI in the treatment of both radiation pneumonia and lung cancer. These core potential targets were found to be significantly associated with the OS of lung cancer patients, and the key compounds exhibited a good docking affinity with these targets. Additionally, GO and KEGG enrichment analysis highlighted that the bioinformatics annotation of these common genes mainly involved ubiquitin protein ligase binding, cytokine receptor binding, and the PI3K/Akt signaling pathway. Our study revealed that the main active components of CKI, primarily quercetin, luteolin, and naringin, might act on major core targets, including AKT1, PTGS2, and PPARG, and further regulated key signaling pathways such as the PI3K/Akt pathway, thereby playing a crucial role in the treatment of radiation pneumonia and lung cancer. Moreover, this study had a certain promotional effect on further clinical application and provided a theoretical basis for subsequent experimental research.

The prognostic impact of severe grade immune checkpoint inhibitor related pneumonitis in non-small cell lung cancer patients.

Objective: To compare the prognostic differences between non-small cell lung cancer (NSCLC) patients with mild and severe checkpoint inhibitor-associated pneumonitis (CIP), and explore the causes of death and prognostic risk factors in NSCLC patients with severe CIP. Methods: A retrospective study of a cohort of 116 patients with unresectable stage III or IV NSCLC with any grade CIP from April 2016 to August 2022 were conducted. To analyze the clinical characteristics of patients with different CIP grades, patients were divided into mild CIP group (grade 1-2, n=49) and severe CIP group (grade 3-5, n=67) according to the grade of CIP. To explore the OS-related risk factors in the severe CIP group, the patients were divided into a good prognosis (GP) group (≥ median OS, n=30) and a poor prognosis (PP) group (< median OS, n=37) based on whether their overall survival (OS) were greater than median OS. Baseline clinical and laboratory data were collected for analysis. Results: The median OS of all NSCLC patients combined with CIP was 11.4 months (95%CI, 8.070-16.100), The median OS for mild CIP and severe CIP was 22.1 months and 4.4 months respectively (HR=3.076, 95%CI, 1.904-4.970, P<0.0001). The results showed that the most common cause of death among severe CIP patients in the PP group was CIP and the most common cause in the GP group was tumor. The univariate regression analysis showed that suspension of antitumor therapy was a risk factor for poor prognosis (OR=3.598, 95%CI, 1.307-9.905, p=0.013). The multivariate logistic regression analysis showed that suspension of anti-tumor therapy (OR=4.24, 95%CI, 1.067-16.915, p=0.040) and elevated KL-6 (OR=1.002, 95%CI, 1.001-1.002, p<0.001) were independent risk factors for poor prognosis. Conclusion: In conclusion, patients with severe CIP had a poor prognosis, especially those with elevated KL-6, and the main cause of death is immune checkpoint inhibitor-associated pneumonitis complicated with infection. In addition, anti-tumor therapy for severe CIP patients should be resumed in time and should not be delayed for too long.

Syphilis-related perceptions not associated with risk behaviors among men who have sex with men having regular male sex partner(s) in Nanjing, China.

The prevalence of HIV among men who sex with men (MSM)has been increasing sharply in China. The prevalence of unprotected anal intercourse (UAI)among them is very high, especially when male regular sex partners are involved. Many MSM having regular sex partners are engaged in multiple sex partnerships, which often involved UAI. This study interviewed 168 MSM in Nanjing, China, having had anal intercourse with at least one male regular sex partner in the last six months. Amongst the participants, 52.4% reported having had UAI with male regular sex partners whilst 50.0% reported multiple male sex partnerships in the last six months. Multivariate analysis showed that monthly personal income higher than 2000 RMB (multivariate OR = 0.49, 95% CI: 0.26-0.96), HIV antibody testing in the last year (multivariate OR = 0.19, 95% CI: 0.06-0.60), sexual position being both insertive and receptive during anal sex with male sex partners in general (multivariate OR = 0.43, 95% CI: 0.18-0.99; reference group: with receptive position only) were associated with lower likelihoods of UAI. Syphilis-related perceptions, including knowledge, cognitions (perceived susceptibility, perceived severity, self-efficacy in avoiding syphilis infection and perceived infectivity and perceived syphilis-related norms among MSM in general)were not associated with risk behaviors (UAI and multiple male sex partnerships). Our sampled MSM are exposed to very high risk of HIV/STD transmission. We found no association between syphilis-related perceptions and the two types of risk behaviors. Future studies are warranted to understand such associations in the context of sexual intercourse with non-regular sex partners among MSM.

[Chemoinformatics study on antibacterial activity of traditional Chinese medicine compounds].

OBJECTIVE: The structure-activity relationship between traditional Chinese medicine (TCM) compounds and antibacterial activity was studied by chemoinformatics approach. METHOD: Cytoscape and its plug-in ChemViz were applied to compute the 2D chemical structure similarity and topological parameter TPSA (topological molecular polar surface area), which measures cell permeability of chemicals, between TCM compounds and clinical antibacterials. The overall degree of structure similarity was then calculated and represented by E-value for the eight categories of TCM compounds and the known antibacterials. RESULT: Our results indicated that flavonoids showed good structural similarity with antibacterials and appropriate cell permeability, compared with those of the TCM compounds of the other categories. As flavonoids were featured by good drug safety, it suggested that they can be regarded as the preferred lead compounds skeleton structure source for further antibacterials synthesis. CONCLUSION: The application of chemoinformatics helps explore the structure-activity relationship between TCM compounds and the antibacterial activity and search for suitable antibacterial lead compounds skeleton structure source.

Successful management of Epstein­Barr virus­associated severe checkpoint inhibitor­related pneumonitis: A case report.

A novel current treatment, immunotherapy, is normally effective for pulmonary lymphoepithelial carcinoma (pLELC). However, it is frequently accompanied by responses such as immune checkpoint inhibitor-associated pneumonitis (CIP), a rare immune adverse reaction that may be fatal in severe cases. pLELC is known to be linked to Epstein-Barr virus (EBV), while associations between EBV and CIP in clinical settings have rarely been reported. A 57-year-old male patient with pLELC presented at our hospital with cough, expectoration, fever and dyspnea following his third course of immunotherapy at another hospital. Diagnosis of grade 4 CIP was confirmed. Simultaneously, a rapid increase in the EBV titer and response of CIP to corticosteroids were observed. The corticosteroids and antiviral drugs were then increased. In spite of his severe condition, the patient recovered within eight days. After discontinuing antiviral drugs, chest computed tomography indicated rapid lesion progression and significantly increased bilateral multiple metastases. To our knowledge, the present study was the first to report a case of CIP caused by EBV during immune checkpoint inhibitor treatment. It indicates that EBV may be associated with CIP development. As immunotherapy has off-target effects, clinicians should remain aware of combined corticosteroids and antivirals in similar cases.

Case report: Spontaneous remission in lung carcinoma with a late relapse after adjuvant immunotherapy: Exceptional tumor micro-environment.

Spontaneous remission (SR) of local recurrence after adjuvant immunotherapy has rarely been reported, and the underlying mechanism is poorly understood. Herein, we reported a patient with stage cT2aN2M0 squamous cell lung carcinoma who received neoadjuvant and adjuvant treatment with nivolumab plus chemotherapy. The patient experienced a late relapse in the subcarinal lymph node seven months after the last dosage of treatment but achieved SR in the next three months without additional antitumor therapy. The complete response lasted for eleven months and counting. Notably, high copies of pathogenic microorganisms were detected in the patient's bronchoalveolar lavage fluid along with the recurrence but disappeared after SR. The patient also experienced a lymph node puncture-induced fever but had no other symptoms. A longitudinal analysis of infiltrated immune cells in the recurrent lymph node was performed by multiplex immunofluorescence and whole transcriptome sequencing, which revealed that CD8+ T cells were recruited during the initial relapse, specifically in the stromal area, then migrated into the tumor tissue, and continued to increase after elimination of tumor cells. Meanwhile, the initial recruitment of CD8+ T cells was coupled with a higher proportion of B cells, and the abundant neutrophil population was synchronous with the infiltration of CD8+ T cells into tumor cells. This is the first report on an Non-small cell lung cancer (NSCLC) patient with a late relapse after adjuvant immune checkpoint inhibitor (ICI) therapy who achieved SR. Our case highlights the complexity and plasticity of antitumor immunity and is expected to help find efficient strategies against the resistance of ICI treatment.

Evaluating the effect of the plan of national syphilis control in controlling the syphilis epidemic in Jiangsu, China 2010-2020.

Background: Starting in 2010, the Chinese government initiated a 10-year syphilis control plan, called the national syphilis control plan (NSCP), to address the emerging threat of syphilis. We aimed to evaluate the effect of the NSCP plan on syphilis control in Jiangsu, China. Methods: The temporal trends of syphilis incidence, prevalence and rate of condom use were estimated by Joinpoint regression with average annual percent change (APC) and average annual percentage (APPC). A Chi-square test was conducted to analyze the outcomes in different subgroups. ArcGIS was used to analyze the spatiotemporal distribution of syphilis incidence. Results: Geographically, early and congenital syphilis incidence decreased significantly in all areas of the province during the period of NSCP. Early syphilis incidence decreased from 21.1 to 8.8 (APC: -7.5, 95%CI: -8.6, -6.5, p < 0.001) per 100,000 people, and congenital syphilis decreased from 63.6 to 4.1 (APC: -14.8, 95%CI: -20.8, -8.4, p < 0.01) per 100,000 newborns from 2010 to 2020. Also, syphilis prevalence reduced from 13.4 to 3.8% (APC: -8.7, 95%CI: -12.1, -5.0, p = 0.001) among men who have sex with men, from 5.3 to 1.7% (APC: -7.9, 95%CI: -11.7, -3.8, p = 0.002) among female sex workers and remained under 1.0% with slight variations among pregnant women (APC: 0.3, 95%CI: -4.3, 5.1, p = 0.877) from 2010 to 2020. 0.2% (2,436) of pregnant women who received free syphilis testing during pregnancy were diagnosed with current syphilis infection, and 97.0% (2,555) of newborns in the province were delivered to women diagnosed with syphilis. 91.8% (2,346) of live babies and about 90% of diagnosed patients received complete standard syphilis diagnosis and treatment services. Conclusion: Trends of early syphilis incidence and syphilis prevalence show a considerable decreasing trend among almost all the key populations after implementing NSCP. Congenital syphilis has significantly decreased as well and hence, the NSCP program should be sustained and strengthened to control the syphilis epidemic in China further.

A Risk-Scoring Model for Severe Checkpoint Inhibitor-Related Pneumonitis: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Checkpoint inhibitor-related pneumonitis (CIP) is one of the most common serious and fatal adverse events associated with immune checkpoint inhibitors (ICIs). The study sought to identify risk factors of all-grade and severe CIP and to construct a risk-scoring model specifically for severe CIP. METHODS: This observational, retrospective case-control study involved 666 lung cancer patients who received ICIs between April 2018 and March 2021. The study analyzed patient demographic, preexisting lung diseases, and the characteristics and treatment of lung cancer to determine the risk factors for all-grade and severe CIP. A risk score for severe CIP was developed and validated in a separate patient cohort of 187 patients. RESULTS: Among 666 patients, 95 patients were afflicted with CIP, of which 37 were severe cases. Multivariate analysis revealed age ≥ 65 years, current smoking, chronic obstructive pulmonary disease, squamous cell carcinoma, prior thoracic radiotherapy, and extra-thoracic radiotherapy during ICI were independently associated with CIP events. Five factors, emphysema (odds ratio [OR] 2.87), interstitial lung disease (OR 4.76), pleural effusion (OR 3.00), history of radiotherapy during ICI (OR 4.30), and single-agent immunotherapy (OR 2.44) were independently associated with severe CIP and were incorporated into a risk-score model (score ranging 0-17). The area under the model receiver operating characteristic curve for the model was 0.769 in the development cohort and 0.749 in the validation cohort. CONCLUSIONS: The simple risk-scoring model may predict severe CIP in lung cancer patients receiving ICIs. For patients with high scores, clinicians should use ICIs with caution or strengthen the monitoring of these patients.

A randomized controlled trial to evaluate the relative efficacy of enhanced versus standard voluntary counseling and testing on promoting condom use among men who have sex with men in China.

The randomized controlled trial investigated the relative efficacy of an enhanced (EVCT) versus standard (SVCT) voluntary counseling and testing in reducing unprotected anal intercourse (UAI) among men who have sex with men (MSM) in China. 295 participants who recruited by respondent driven sampling methods were randomly allocated to the two arms. In addition to the SVCT, the EVCT group watched a theory-based video narrated by a HIV positive MSM, received enhanced counseling and a reminder gift. As compared to the SVCT group, the EVCT group reported lower prevalence of UAI with any male sex partners (48.4% versus 66.7%, RR = 0.7, ARR = -18.3%, p = 0.010) and with regular male sex partners (52.2% versus 68.9%, RR = 0.8, ARR = -16.7%, p = 0.043) at Month 6, whilst baseline between-group differences were statistically non-significant. Between-group differences in HIV/syphilis incidence were statistically non-significant. Translational research should be conducted to integrate non-intensive enhancements such as the EVCT into regular testing services.

Myocardial infarction and stroke risks in multiple sclerosis patients: A two-sample Mendelian randomization study.

Observational studies indicated multiple sclerosis (MS) patients may have a higher risk of myocardial infarction (MI) and stroke than the general population, whereas the previously reported findings were inconsistent. Using two-sample Mendelian randomization (MR) analysis with genetic data from large-scale genome-wide association studies (International Multiple Sclerosis Genetics Consortium containing 14,498 MS cases, Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics consortium containing 43,676 MI cases and 40,585 stroke cases), we found that MS was causally associated with an increased risk of MI (OR = 1.03; 95%CI 1.00-1.06; P = 0.0243), directionally consistent in the weighted median, MR-Egger, and the MR-PRESSO methods. No causal association between MS and stroke was observed (OR = 1.01; 95%CI 0.99-1.04; P = 0.2974). Therefore, timelier and more effective measures should be conducted among MS patients to decrease the burden of both diseases.

Zebrafish Model-Based Assessment of Indoxyl Sulfate-Induced Oxidative Stress and Its Impact on Renal and Cardiac Development.

Kidney disease patients may have concurrent chronic kidney disease-associated mineral bone disorder and hypertension. Cardiovascular disease (CVD) and neuropathy occur due to kidney failure-induced accumulation of uremic toxins in the body. Indoxyl sulfate (IS), a product of indole metabolism in the liver, is produced from tryptophan by the intestinal flora and is ultimately excreted through the kidneys. Hemodialysis helps renal failure patients eliminate many nephrotoxins, except for IS, which leads to a poor prognosis. Although the impacts of IS on cardiac and renal development have been well documented using mouse and rat models, other model organisms, such as zebrafish, have rarely been studied. The zebrafish genome shares at least 70% similarity with the human genome; therefore, zebrafish are ideal model organisms for studying vertebrate development, including renal development. In this study, we aimed to investigate the impact of IS on the development of zebrafish embryos, especially cardiac and renal development. At 24 h postfertilization (hpf), zebrafish were exposed to IS at concentrations ranging from 2.5 to 10 mM. IS reduced survival and the hatching rate, caused cardiac edema, increased mortality, and shortened the body length of zebrafish embryos. In addition, IS decreased heart rates and renal function. IS affected zebrafish development via the ROS and MAPK pathways, which subsequently led to inflammation in the embryos. The results suggest that IS interferes with cardiac and renal development in zebrafish embryos, providing new evidence about the toxicity of IS to aquatic organisms and new insights for the assessment of human health risks. Accordingly, we suggest that zebrafish studies can ideally complement mouse model studies to allow the simultaneous and comprehensive investigation of the physiological impacts of uremic endotheliotoxins, such as IS, on cardiac and renal development.

The incidence of syphilis, HIV and HCV and associated factors in a cohort of men who have sex with men in Nanjing, China.

OBJECTIVE: This study investigated the incidence of syphilis, HIV and hepatitis C virus (HCV), as well as factors associated with syphilis seroconversion among men who have sex with men (MSM) in Nanjing, China. METHODS: A cohort of MSM was recruited by respondent-driven sampling methods. Those who were syphilis-, HIV- and HCV-seronegative at the baseline were invited to be retested at month 6. A Poisson regression analysis was performed. RESULTS: Of the 416 participants in the study, 348 participants were HIV-, syphilis- and HCV-negative at the baseline, 250 (71.84%) of whom returned for retesting at month 6. Nine of these 250 participants had seroconverted to syphilis-positive (incidence=7.58 per 100 person-years (PY); 95% CI 2.63 to 12.53 per 100 PY), and five had seroconverted to HIV-positive (incidence=4.17 per 100 PY; 95% CI=0.52 to 7.83 per 100 PY). No HIV and syphilis coinfection and no HCV seroconversion were found. Multivariate analysis identified four statistically significant factors predicting syphilis seroconversion, including currently single marital status (RR=0.32, 95% CI 0.16 to 0.65, p<0.01), monthly income >US$300 (RR=2.68, 95% CI 1.28 to 5.61, p<0.01), self-reported homosexual orientation (RR=0.48, 95% CI 0.24 to 0.96, p<0.05) and recruitment of male sex partners mostly from gay saunas (RR=6.72, 95% CI 2.88 to 15.68, p<0.01). CONCLUSIONS: The high incidence of syphilis and HIV reflects the seriousness and urgency of the HIV and sexually transmitted diseases (STD) epidemics among MSM in China. Effective interventions of syphilis treatment and prevention should target MSM with characteristics reflecting the aforementioned risk factors.

Genetically predicted circulating homocysteine, vitamin B12, and folate levels and risk of multiple sclerosis: evidence from a two-sample Mendelian randomization analysis.

The association between homocysteine and risk of multiple sclerosis (MS) remains unclear. We implemented a two-sample Mendelian randomization (MR) analysis to comprehensively investigate the causal relationships between circulating homocysteine, vitamin B12 (VitB12), and folate levels and MS with data from large-scale genome-wide association studies. MR results demonstrated an inverse association between genetically predicted higher circulating homocysteine levels (per 1 standard deviation (SD) increase) and risk of MS (OR 0.78, 95% CI 0.64-0.94, p = 0.0106). No significant causal relationships between genetically determined higher VitB12 and folate levels and MS were observed. Further studies are warranted to elucidate the potential mechanisms.

Univariable and Multivariable Two-Sample Mendelian Randomization Investigating the Effects of Leisure Sedentary Behaviors on the Risk of Lung Cancer.

Leisure sedentary behaviors (LSB) are widespread, and observational studies have provided emerging evidence that LSB play a role in the development of lung cancer (LC). However, the causal inference between LSB and LC remains unknown. Methods: We utilized univariable (UVMR) and multivariable two-sample Mendelian randomization (MVMR) analysis to disentangle the effects of LSB on the risk of LC. MR analysis was conducted with genetic variants from genome-wide association studies of LSB (408,815 persons from UK Biobank), containing 152 single-nucleotide polymorphisms (SNPs) for television (TV) watching, 37 SNPs for computer use, and four SNPs for driving, and LC from the International Lung Cancer Consortium (11,348 cases and 15,861 controls). Multiple sensitivity analyses were further performed to verify the causality. Results: UVMR demonstrated that genetically predisposed 1.5-h increase in LSB spent on watching TV increased the odds of LC by 90% [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.44-2.50; p < 0.001]. Similar trends were observed for squamous cell lung cancer (OR, 1.97; 95%CI, 1.31-2.94; p = 0.0010) and lung adenocarcinoma (OR, 1.64; 95%CI 1.12-2.39; p = 0.0110). The causal effects remained significant after adjusting for education (OR, 1.97; 95%CI, 1.44-2.68; p < 0.001) and body mass index (OR, 1.86; 95%CI, 1.36-2.54; p < 0.001) through MVMR approach. No association was found between prolonged LSB spent on computer use and driving and LC risk. Genetically predisposed prolonged LSB was additionally correlated with smoking (OR, 1.557; 95%CI, 1.287-1.884; p < 0.001) and alcohol consumption (OR, 1.010; 95%CI, 1.004-1.016; p = 0.0016). Consistency of results across complementary sensitivity MR methods further strengthened the causality. Conclusion: Robust evidence was demonstrated for an independent, causal effect of LSB spent on watching TV in increasing the risk of LC. Further work is necessary to investigate the potential mechanisms.

HIV incidence and associated factors in a cohort of men who have sex with men in Nanjing, China.

BACKGROUND: Many surveys conducted in recent years reported the increasing trend of HIV infection among men who have sex with men (MSM), but limited data exists on HIV incidence by cohort study in China. METHODS: A 6-month prospective cohort study was conducted. A total of 397 MSM found HIV seronegative at baseline study were followed-up for 6 months starting from May 2007 and re-evaluated seroconversions of HIV at 6 months. Questionnaire interviews were conducted to collect information about risk behaviors. RESULTS: Of the 397 MSM who were found seronegative at the baseline study, 286 (72.0%) received the HIV antibody testing at month 6; 7 of them showed HIV seroconversions, yielding an incidence of 5.12 per 100 person-years. Significant predictors of seroconversion (Poisson regression analyses) included duration being MSM >10 years (relative risks [RR] = 3.08, 95% CI: 1.53-6.20), recruiting male sex partner mostly at saunas (RR = 2.35, 95% CI:1.09-5.08), positive syphilis diagnosis made at the baseline study (RR = 2.82, 95% CI: 1.31-6.09), having multiple male sex partners in the last 6 months (RR = 2.54, 95% CI: 1.18-5.49), having at least 1 casual male sex partner in the last 6 months (RR = 2.17, 95% CI: 1.00-4.70), and having unprotected anal sex with a regular male sex partner in the last 6 months (RR = 2.22, 95% CI: 1.10-4.49). CONCLUSIONS: The incidence of HIV among MSM is very high; many new infections would hence occur in China. Effective interventions are warranted. The risk factors reported in this study give some insights for designing relevant prevention programs.