Considerations when treating influenza infections with oseltamivir.

INTRODUCTION: Since the coronavirus disease 2019-mandated social distancing policy has been lifted worldwide, the circulation of influenza is expected to resume. Currently, oseltamivir is approved as the first-line agent for influenza prevention and treatment. AREAS COVERED: This paper reviews the updated evidence in the pharmacology, resistance mechanisms, clinical pharmacy management, and real-world data on oseltamivir for influenza. EXPERT OPINION: Oseltamivir is an oral prodrug of oseltamivir carboxylate, an influenza A and B neuraminidase inhibitor. Recently, the therapeutic efficacy of oseltamivir has been demonstrated in several trials. Oseltamivir is generally well-tolerated but may lead to neuropsychiatric events and bleeding. Oseltamivir-resistant influenza virus has been associated with the H275Y mutation in the influenza A(H1N1)pdm09 virus, while most strains are still sensitive to oseltamivir. Dose adjustment for oseltamivir should be based on creatinine clearance and body weight in pediatric patients with renal failure. According to real-world data from Nanfang Hospital, the annual number of patients prescribed oseltamivir declined from 35,711 in 2019 to 8,971 in 2020, with marked increases in 2022 (20,213) and 2023 (18,071). Among the 206 inpatients, children aged < 6 years who were treated with oseltamivir had the shortest duration to defervescence.

Integrin αvß6 mediates the immune escape through regulation of PD-L1 and serves as a novel marker for immunotherapy of colon carcinoma.

The immune escape of colon cancer and its role in the response to immunotherapies such as PD-1/PD-L1 checkpoint inhibitors have long been of great interest. The positive outcomes of immunotherapy are limited by the immunosuppressive nature of the tumor microenvironment. Integrin αvß6, which can regulate the progression of colon cancer, was recently reported to be involved in the immune suppression of colon cancer. In the present study, we explored the correlation between αvß6 and PD-L1 expression by immunohistochemistry of colon cancer tissues. Then, the regulation of PD-L1 signaling by αvß6 in colon cancer cells was demonstrated. We constructed an in vivo model and performed immunophenotyping experiments to analyze further the regulation of the immune response by αvß6. The role of αvß6 in the response to anti-PD-1 therapy in colon cancer was also verified. αvß6-positive tissues exhibited increased PD-L1 expression. Inhibition of αvß6 not only downregulated constitutive PD-L1 expression but also decreased IFN-γ-induced PD-L1 expression. In addition, αvß6-induced PD-L1 expression was suppressed by the ERK inhibitor PD98059, and knockdown of the ß6-ERK2 binding site had the equivalent effect. αvß6 decreased CD8+ T cell infiltration and granzyme B expression in CD8+ T cells in colon cancer patients. Furthermore, mice engrafted with αvß6-expressing colon cancer cells exhibited an unsatisfactory response to anti-PD-1 therapy, and anti-PD-1-induced increases in CD4+ and CD8+ T cell infiltration could be inhibited by αvß6. These results indicate that αvß6 mediates immune escape in colon cancer by upregulating PD-L1 through the ERK/MAPK pathway. Moreover, αvß6 could serve as a marker for the efficacy of anti-PD-1 therapy in colon cancer.

Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Dynamic role of CUL4B in radiation-induced intestinal injury-regeneration.

CUL4B, a crucial scaffolding protein in the largest E3 ubiquitin ligase complex CRL4B, is involved in a broad range of physiological and pathological processes. While previous research has shown that CUL4B participates in maintaining intestinal homeostasis and function, its involvement in facilitating intestinal recovery following ionizing radiation (IR) damage has not been fully elucidated. Here, we utilized in vivo and in vitro models to decipher the role of CUL4B in intestinal repair after IR-injury. Our findings demonstrated that prior to radiation exposure, CUL4B inhibited the ubiquitination modification of PSME3, which led to the accumulation of PSME3 and subsequent negative regulation of p53-mediated apoptosis. In contrast, after radiation, CUL4B dissociated from PSME3 and translocated into the nucleus at phosphorylated histones H2A (γH2AX) foci, thereby impeding DNA damage repair and augmenting p53-mediated apoptosis through inhibition of BRCA1 phosphorylation and RAD51. Our study elucidated the dynamic role of CUL4B in the repair of radiation-induced intestinal damage and uncovered novel molecular mechanisms underlying the repair process, suggesting a potential therapeutic strategy of intestinal damage after radiation therapy for cancers.

LATS2 degradation promoted fibrosis damage and rescued by vitamin K3 in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients. METHODS: In this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN. RESULTS: Restoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo. CONCLUSION: In summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.

Application of Bioinformatics in Predicting the Efficacy of Digestive Tumour Immunotherapy Target TIM-3 and its Inhibitors.

Background: Our main objective is to apply bioinformatics in predicting the efficacy of digestive tumour immunotherapy target TIM-3 and its inhibitors. Methods: Our study used the gene expression omnibus (GEO) database to identify datasets associated with digestive tumours and the action of TIM-3. The GSE427729 dataset based on the GPL10192 platform. The dataset consisted of six samples of total RNA derived from TIM-3 control and knockdown RAW 264.7 cells. We used GEO2R tool to identify DEGs before performing Gene Ontology and identifying the kyoto encyclopedia of genes and genomes (KEGG) pathways. Lastly, we determined the PPI networks to identify hub genes. Results: Our study identified 57 differentially expressed genes based on an adjusted p-value of less than 0.05 and a log2 fold change of 2.0. There were 26 down-regulated genes with 31 up-regulated genes while 22, 404 genes were non-significant. The DEGs were enriched in biological pathways such as activating leukocytes, cells, and development of the immune system. Additionally, we identified four significant KEGG pathways that were implicated in digestive tumour immunotherapy and TIM-3; pathways of pancreatic cancer, NF-Kappa B signalling pathway, Toll-like receptor signalling pathway and C-type lectin receptor signalling pathway. The PPI networks identified 10 hub genes that were implicated in digestive tumour immunotherapy target TIM-3 (Myd88, Traf6, Irf7, Cdk4, Ccnd2, Mapkap1, Prr5, Mpp3, Serpinb6b and Pvrl3). Conclusion: Targeting these biological pathways, KEGG pathways, molecular functions and cellular processes can lead to novel therapeutic treatment and management in digestive tumours based on TIM-3 immunotherapy.

Internal Carotid Artery Dissecting Aneurysm Associated with Persistent Trigeminal Artery: A Case Report.

BACKGROUND: Persistent trigeminal artery (PTA) is the most common vascular anastomosis between the carotid artery and vertebrobasilar systems. We report a very rare case of dissecting aneurysm in the right internal carotid artery (ICA) with ipsilateral PTA and discuss its clinical importance. CASE REPORT: A 38-year-old male presented to the emergency department with paroxysmal dysphasia for 6h. Brain magnetic resonance (MR) imaging showed acute cerebral infarction of the right corona radiata and right parietal lobe. Three-dimensional time-of-flight MR angiography (3D TOF MRA) revealed severe stenosis of the petrous segment (C1 portion) of the right internal carotid artery and a PTA originating from the right ICA cavernous segment (C4 portion), with a length of approximately 1.8cm and a diameter of approximately 0.2cm. The ICA segments are all named according to the Bouthilier classification. The basilar artery (BA) under union was well developed. The bilateral posterior communicating arteries were also present. One day later, the high-resolution vessel-wall MR demonstrated a dissecting aneurysm in the C1 portion of the right ICA. The length of the dissecting aneurysm is approximately 4.4cm, the diameter of the true lumen at the most severe stenosis is approximately 0.2cm, and the diameter of the false lumen is approximately 0.8cm. Subsequent digital subtraction angiography (DSA) confirmed a dissecting aneurysm in the C1 portion of the right ICA. The patient was treated conservatively and did not undergo interventional surgery. Four months later, head and neck MRA showed that the right ICA blood flow was smooth and that the dissecting aneurysm had disappeared. The Ethics Committee of Liaocheng People's Hospital approved the research protocol in compliance with the Helsinki Declaration. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article. CONCLUSION: Flow alteration with PTA may have influenced the formation of ICA dissection in this patient. Awareness of this is crucial in clinical practice because it can influence treatment options and intervention procedures.

Changing trends in Chlamydia and gonorrhea infections among female sex workers in Southern China: a surveillance data analysis spanning 2019 to 2022.

BACKGROUND: Female sex workers (FSW) are particularly vulnerable to chlamydia and gonorrhea infections. However, there were few studies that detail the evolving patterns of chlamydia and gonorrhea among Chinese FSW. Therefore, our study endeavors to assess the prevalence of chlamydia and gonorrhea epidemics within FSW, investigate their changing trends and scrutinize associated factors. METHODS: In 2019, China instituted a sentinel surveillance network focused on FSW in Guangdong Province. This network conducted an annual serial cross-sectional survey spanning from April to August. All analyses are predicated on surveillance data accumulated between 2019 and 2022. RESULTS: The prevalence of chlamydia increased from 10.1 to 12.3%, exhibiting an annual percentage shift of 6.8%. Conversely, the prevalence of gonorrhea dwindled from 2.0 to 1.3%, marking an annual percentage decline of 13.4% (P < 0.001). After adjusting for covariates, chlamydia exhibited associations with having household registration in other provinces (adjusted odds ratio (aOR = 0.55)), displaying symptoms of sexually transmitted infections (STIs) (aOR = 1.65) and infected with gonorrhea (aOR = 5.68). In parallel, gonorrhea demonstrated associations with providing oral sex to clients (aOR = 3.74), manifesting STIs symptoms (aOR = 4.27) and those infected with chlamydia (aOR = 5.43). CONCLUSIONS: Our observations underscore the imperative to implement a comprehensive intervention strategy concentrating on chlamydia, while simultaneously fortifying endeavors to expand the scope of gonorrhea prevention services.

Relationship between cancer stem cell-related SNPs and survival outcomes in patients with primary lung cancer.

BACKGROUND: Cancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients. METHODS: The SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0). RESULTS: Stratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death. CONCLUSION: Rs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.

Mediating immunosuppressive functions: a new perspective on the complex immunological properties of SEMA4D in the tumor microenvironment.

Semaphorin 4D (SEMA4D) is considered a new antitumor target closely related to immune cells. However, understanding the role of SEMA4D in the tumor microenvironment (TME) is limited. In this study, we explored the expression and immune cell infiltration patterns of SEMA4D using multiple bioinformatics datasets and analyzed the relationship between SEMA4D expression with immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI) and immune function. We detected that SEMA4D is overexpressed in many tumors types, widely enriched in immune cells, and closely associated with TILs, MSI, TMB, as well as T-cell exhaustion-associated immune checkpoints, and thus can broadly affect the immune microenvironment. We further verified the overexpression of SEMA4D in tumor and its distribution in TME by immunohistochemistry, RT-qPCR and flow cytometry, and confirmed that decreased expression of SEMA4D can lead to recovery of T cell exhaustion. In conlusion, this study provides a more comprehensive perspective of SEMA4D regulation of tumor immunity, which provide a new option for cancer immunotherapy.

KLF5 and p53 comprise an incoherent feed-forward loop directing cell-fate decisions following stress.

In response to stress, cells make a critical decision to arrest or undergo apoptosis, mediated in large part by the tumor suppressor p53. Yet the mechanisms of these cell fate decisions remain largely unknown, particularly in normal cells. Here, we define an incoherent feed-forward loop in non-transformed human squamous epithelial cells involving p53 and the zinc-finger transcription factor KLF5 that dictates responses to differing levels of cellular stress from UV irradiation or oxidative stress. In normal unstressed human squamous epithelial cells, KLF5 complexes with SIN3A and HDAC2 repress TP53, allowing cells to proliferate. With moderate stress, this complex is disrupted, and TP53 is induced; KLF5 then acts as a molecular switch for p53 function by transactivating AKT1 and AKT3, which direct cells toward survival. By contrast, severe stress results in KLF5 loss, such that AKT1 and AKT3 are not induced, and cells preferentially undergo apoptosis. Thus, in human squamous epithelial cells, KLF5 gates the response to UV or oxidative stress to determine the p53 output of growth arrest or apoptosis.

Optimization, and biological evaluation of 3-O-ß-chacotriosyl betulinic acid amide derivatives as novel small-molecule Omicron.

SARS-CoV-2 Omicron viruses possess a high antigenic shift, and the approved anti-SARS-CoV-2 drugs are extremely limited, which makes the development of new antiviral drugs for the clinical treatment and prevention of SARS-CoV-2 outbreaks imperative. We have previously discovered a new series of markedly potent small-molecule inhibitors of SARS-CoV-2 virus entry, exampled by the hit compound 2. Here, we report a further study of bioisosteric replacement of the eater linker at the C-17 position of 2 with a variety of aromatic amine moieties, followed by a focused structure-activity relationship study, leading to the discovery of a series of novel 3-O-ß-chacotriosyl BA amide derivatives as small-molecule Omicron fusion inhibitors with improved potency and selectivity index. Particularly, our medicinal chemistry efforts have resulted in a potent, and efficacious lead compound S-10 with appreciable pharmacokinetic properties, which exhibited broad-spectrum potency against Omicron and other variants with EC50 values ranging from 0.82 to 5.45 µM. Mutagenesis studies confirmed that inhibition of Omicron viral entry was mediated by the direct interaction with S in the prefusion state. These results reveal that S-10 is suitable for further optimization as Omicron fusion inhibitors, with the potential to be developed as therapeutic agents for the treatment and control of SARS-CoV-2 ant its variants infections.

Identification of N- and C-3-Modified Laudanosoline Derivatives as Novel Influenza PAN Endonuclease Inhibitors.

Influenza PAN inhibitors are of particular importance in current efforts to develop a new generation of antiviral drugs due to the growing emergence of highly pathogenic influenza viruses and the resistance to existing antiviral inhibitors. Herein, we design and synthesize a set of 1,3-cis-N-substituted-1,2,3,4-tetrahydroisoquinoline derivatives to enhance their potency by further exploiting the pockets 3 and 4 in the PAN endonuclease based on the hit d,l-laudanosoline. Particularly, the lead compound 35 exhibited potent and broad anti-influenza virus effects with EC50 values ranging from 0.43 to 1.12 µM in vitro and good inhibitory activity in a mouse model. Mechanistic studies demonstrated that 35 could bind tightly to the PAN endonuclease of RNA-dependent RNA polymerase, thus blocking the viral replication to exert antiviral activity. Overall, our study might establish the importance of 1,2,3,4-tetrahydroisoquinoline-6,7-diol-based derivatives for the development of novel PAN inhibitors of influenza viruses.

PB@PDA nanocomposites as nanolabels and signal reporters for separate-type cathodic photoelectrochemical immunosensors in the detection of carcinoembryonic antigens.

Photoelectrochemical (PEC) immunoassays exhibiting high sensitivity and decent operability have considerable potential in areas such as cancer diagnostics. In particular, cathodic PEC configurations can prevent interference from reductive substances, which can occur in biological samples; however, challenges remain in terms of sensitivity and operability. In this study, separate-type PEC immunoassays were developed for carcinoembryonic antigen (CEA) by combining microplate-based immune recognition and off-on cathodic PEC detection. Polydopamine (PDA)-coated Prussian blue (PB) nanoparticles (PB@PDA NPs) were used as signal tags to label the detection antibody. The PB NPs and PDA captured on the microplates both disassembled under strongly alkaline conditions to generate redox-active electron acceptors. The disassembled products were quantitatively transferred to PEC detection cells and synergistically enhanced the PEC current with microstructured BiOI, which operated as a cathodic semiconductor electrode. As proof of principle, carcinoembryonic antigen (CEA) was applied to elucidate the potential application of PEC immunoassay in clinical diagnosis, and the obtained linear range of the sensor was 0.001-100 ng mL-1 with the detection limit of 54.9 fg mL-1 (S/N = 3). The proposed separate-type off-on PEC strategy showed high sensitivity and decent operability for CEA detection, indicating its potential for the identification of other tumor markers.

Discovery and structural optimization of 3-O-ß-Chacotriosyl betulonic acid saponins as potent fusion inhibitors of Omicron virus infections.

The recent global Omicron epidemics underscore the great need for the development of small molecule therapeutics with appropriate mechanisms. The trimeric spike protein (S) of SARS-CoV-2 plays a pivotal role in mediating viral entry into host cells. We continued our efforts to develop small-molecule SARS-CoV-2 entry inhibitors. In this work, two sets of BA derivatives were designed and synthesized based on the hit BA-1 that was identified as a novel SARS-CoV-2 entry inhibitor. Compound BA-4, the most potent one, showed broad inhibitory activities against pOmicron and other pseudotyped variants with EC50 values ranging 2.73 to 5.19 µM. Moreover, pSARS-CoV-2 assay, SPR analysis, Co-IP assay and the cell-cell fusion assay coupled with docking and mutagenesis studies revealed that BA-4 could stabilize S in the pre-fusion step to interfere with the membrane fusion, thereby displaying promising inhibition against Omicron entry.

TRPV4 channel is involved in HSV-2 infection in human vaginal epithelial cells through triggering Ca2+ oscillation.

Herpes simplex virus (HSV) infection induces a rapid and transient increase in intracellular calcium concentration ([Ca2+]i), which plays a critical role in facilitating viral entry. T-type calcium channel blockers and EGTA, a chelate of extracellular Ca2+, suppress HSV-2 infection. But the cellular mechanisms mediating HSV infection-activated Ca2+ signaling have not been completely defined. In this study we investigated whether the TRPV4 channel was involved in HSV-2 infection in human vaginal epithelial cells. We showed that the TRPV4 channel was expressed in human vaginal epithelial cells (VK2/E6E7). Using distinct pharmacological tools, we demonstrated that activation of the TRPV4 channel induced Ca2+ influx, and the TRPV4 channel worked as a Ca2+-permeable channel in VK2/E6E7 cells. We detected a direct interaction between the TRPV4 channel protein and HSV-2 glycoprotein D in the plasma membrane of VK2/E6E7 cells and the vaginal tissues of HSV-2-infected mice as well as in phallic biopsies from genital herpes patients. Pretreatment with specific TRPV4 channel inhibitors, GSK2193874 (1-4 µM) and HC067047 (100 nM), or gene silence of the TRPV4 channel not only suppressed HSV-2 infectivity but also reduced HSV-2-induced cytokine and chemokine generation in VK2/E6E7 cells by blocking Ca2+ influx through TRPV4 channel. These results reveal that the TRPV4 channel works as a Ca2+-permeable channel to facilitate HSV-2 infection in host epithelial cells and suggest that the design and development of novel TRPV4 channel inhibitors may help to treat HSV-2 infections.

Emerging antiviral therapies and drugs for the treatment of influenza.

INTRODUCTION: Both vaccines and antiviral drugs represent the mainstay for preventing and treating influenza. However, approved M2 ion channel inhibitors, neuraminidase inhibitors, polymerase inhibitors, and various vaccines cannot meet therapeutic needs because of viral resistance. Thus, the discovery of new targets for the virus or host and the development of more effective inhibitors are essential to protect humans from the influenza virus. AREAS COVERED: This review summarizes the latest progress in vaccines and antiviral drug research to prevent and treat influenza, providing the foothold for developing novel antiviral inhibitors. EXPERT OPINION: Vaccines embody the most effective approach to preventing influenza virus infection, and recombinant protein vaccines show promising prospects in developing next-generation vaccines. Compounds targeting the viral components of RNA polymerase, hemagglutinin and nucleoprotein, and the modification of trusted neuraminidase inhibitors are future research directions for anti-influenza virus drugs. In addition, some host factors affect the replication of virus in vivo, which can be used to develop antiviral drugs.

Sexual uses of drug and alcohol among men who have sex with men in China: implications for HIV prevention.

BACKGROUND: Sexual uses of alcohol and drugs are pervasive among men who have sex with men (MSM) and associated with increased risk of HIV infection. However, there are limited studies related to sexual uses of alcohol and drugs among MSM in China. This study aims to describe the pattern of alcohol use, drug use, and multi-drug use during sex among Chinese MSM and to examine the association between condomless anal intercourse, group sex, commercial sex and HIV infection. METHODS: We conducted an online cross-sectional survey in China. Characteristics on social-demographic, sexual behaviors, and sexual uses of alcohol and drugs were collected. The associations with high-risk sexual behaviors and HIV infection were analyzed with multivariable logistic regression. RESULTS: A total of 699 MSM were included in this study. About 39.5% (230/582) of men reported sexual alcohol use in the past three months and 50.8% (355/699) reported sexual drug use. Of those reporting sexual drug use, around 10.7% (38/355) reported having multi-drug use. Factors associated with both sexual uses of alcohol and drugs included: reporting more male sexual partners (alcohol: adjusted odds ratio [aOR] = 1.77; drug: aOR = 2.12), reporting condomless anal intercourse in the past three months (alcohol: aOR = 2.08; drug: aOR = 2.08), having ever engaged in group sex (alcohol: aOR = 2.04; drug: aOR = 5.22; multi-drug: aOR = 3.52) and commercial sex (alcohol: aOR = 4.43; drug: aOR = 4.22 multi-drug: aOR = 5.07). Sexual drug use was also correlated with reported HIV-positive status (drug: aOR = 2.53, 95% CI:1.31-4.90). CONCLUSION: Sexual uses of alcohol and drugs are prevalent among Chinese MSM. Interventions to reduce the sexual use of alcohol and other drugs may be warranted among MSM in China.

An Automatic Defect Detection System for Petrochemical Pipeline Based on Cycle-GAN and YOLO v5.

Defect detection of petrochemical pipelines is an important task for industrial production safety. At present, pipeline defect detection mainly relies on closed circuit television method (CCTV) to take video of the pipeline inner wall and then detect the defective area manually, so the detection is very time-consuming and has a high rate of false and missed detections. To solve the above issues, we proposed an automatic defect detection system for petrochemical pipeline based on Cycle-GAN and improved YOLO v5. Firstly, in order to create the pipeline defect dataset, the original pipeline videos need pre-processing, which includes frame extraction, unfolding, illumination balancing, and image stitching to create coherent and tiled pipeline inner wall images. Secondly, aiming at the problems of small amount of samples and the imbalance of defect and non-defect classes, a sample enhancement strategy based on Cycle-GAN is proposed to generate defect images and expand the data set. Finally, in order to detect defective areas on the pipeline and improve the detection accuracy, a robust defect detection model based on improved YOLO v5 and Transformer attention mechanism is proposed, with the average precision and recall as 93.10% and 90.96%, and the F1-score as 0.920 on the test set. The proposed system can provide reference for operators in pipeline health inspection, improving the efficiency and accuracy of detection.

Microwave-induced steam distillation (MISD) remediation in petroleum hydrocarbon-contaminated sites: From process improvement to pilot application.

The process improvement, a pilot remediation test and the decontamination mechanism of microwave-induced steam distillation (MISD) for petroleum hydrocarbons (PHs) removal were conducted. Processes of multistage steam distillation and carbon reinforcement were compared to determine the best remediation process. Pilot project was then carried out to explore the applicability of MISD in site-scale remediation. The remediation efficiency, procedures and influencing factors of site-scale MISD project were studied by monitoring variations of soil moisture, temperature and PHs concentrations. Furthermore, the decontamination mechanisms of PHs were clarified based on kinetic analysis. The results showed that the multistage steam distillation could improve 10%∼15% remediation efficiency, and the carbon reinforcement could shorten remediation duration of each steam distillation stage by 50%. Pilot MISD project adopted multistage steam distillation process and went through four (initial, rapid heating-up, gentle heating-up and quasi-equilibrium) remediation stages (overall temperature ≤100 °C). The final PHs removal rate was about 60%, which would get better with greater proportion of low boiling points components and stronger vapor extraction. Kinetic studies showed that PHs was removed by steam stripping and limited by intraparticle diffusion in the "steam distillation zone", while local high temperature (＞100 °C) greatly improved PHs volatilization and provided activation energy for PHs desorbed and degraded in the "selective heating zone".