Phytochemical determination and mechanistic investigation of Polygala tenuifolia root (Yuanzhi) extract for bronchitis: UPLC-MS/MS analysis, network pharmacology and in vitro/in vivo evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE: Bronchitis is a respiratory disease characterized by a productive cough. Polygala tenuifolia Willd., commonly known as Yuan zhi, is a traditional Chinese herbal medicine used for relieving cough and removing phlegm. Despite its historical use, studies are lacking on the effectiveness of P. tenuifolia in treating bronchitis. Furthermore, the molecular mechanisms underlying the action of its bioactive compounds remain unknown. AIM OF THE STUDY: This study aims to identify the main bioactive compounds responsible for the effects of P. tenuifolia liquid extract (PLE) in treating bronchitis and to elucidate the associated molecular mechanisms. MATERIALS AND METHODS: The main chemical compounds in PLE were identified and determined using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The antitussive, expectorant and anti-inflammatory activities of PLE were evaluated in an ammonia-induced mouse cough model, a tracheal phenol red excretion mouse model, and a xylene-induced ear swelling mouse model, respectively. A network pharmacology analysis was conducted to investigate the associated gene targets, gene ontology, and KEGG pathways related to the main bio-actives in PLE targeting bronchitis. PLE and its five bioactive compounds were assessed for their potential anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Western blot analysis was conducted to elucidate the associated molecular mechanisms. RESULTS: Thirty-seven compounds in PLE were identified, and twelve main compounds were further quantified in PLE using UPLC-MS/MS. PLE oral gavage administrations (0.6 and 0.12 mg/kg) for 7 days markedly reduced cough frequency, prolonged latency period of cough, reduced phlegm and inflammation in mice. The network pharmacology analysis identified 57 gene targets of PLE against bronchitis. The PI3K/AKT and MAPK signalling pathways were the top two modulated pathways. In RAW264.7 cells, PLE (12.5-50 µg/mL) significantly reduced cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. PLE downregulated LPS-elevated protein targets in both PI3K/AKT and MAPK signaling pathways. In PLE, tenuifolin, polygalaxanthone ⅠⅠⅠ, polygalasaponin ⅩⅩⅤⅢ, tenuifoliside B, and 3,6'-Disinapoyl sucrose, were identified as the top five core components responsible for treating bronchitis. These compounds were also found to modulate the protein targets in the PI3K/AKT and MAPK signalling pathways. CONCLUSIONS: This study demonstrated the potential therapeutic effects of PLE on bronchitis by reducing cough, phlegm and inflammation. The anti-inflammatory action and molecular mechanisms of the 5 main bioactive compounds in PLE were partly validated through the in vitro assays. The findings provide valuable insights into the mechanisms underlying the traditional use of PLE for bronchitis.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Investigation on the efficiency of lentinan for injection combining cisplatin on treating malignant pleural effusion based on systematic review and meta-analysis.

BACKGROUND: Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is beneficial for improving patients' quality of life and prolonging their survival. The purpose of this meta-analysis is to evaluate the efficacy and safety of LNT combining cisplatin in the treatment of MPE. METHODS: Randomized controlled trials (RCTs) of LNT combining cisplatin in the treatment of MPE were searched in 6 literature databases from the establishment time of each database by 2 researchers. According to the inclusion criteria, 2 researchers independently screened studies, assessed the risk of bias and conducted subgroup analyses for different outcome indicators according to the specific characteristics of the included literature. Analyzing the data by Revman software, and evaluating the stability of the results by Stata software. RESULTS: A total of 52 RCTs were included. The results showed that combined use of LNT and cisplatin could improve the treatment effect, and the difference between groups was statistically significant (RR = 1.40, 95%CI: 1.33 ~ 1.46, P < .001). And the combined use of LNT could increase the quality of life (RR = 1.45, 95%CI: 1.35 ~ 1.56, P < .001). The using of LNT could significantly decrease the incidence of gastrointestinal reactions (RR = 0.86, 95%CI: 0.78 ~ 0.94, P < .001). Sensitivity analysis results showed that there were no qualitative changes in the indicator, and suggested the possibility of publication bias. CONCLUSIONS: Available evidence suggested the combined use of LNT and cisplatin showed better efficacy in treating MPE without increasing ADR incidence than using cisplatin alone. LNT is an ideal treatment for MPE, which has high clinical application value.

Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/ß-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity.

Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, ß-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/ß-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.

Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages.

BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan parasite that causes severe threats to humans and livestock. Macrophages are the cell type preferentially infected by T. gondii in vivo. Protein phosphorylation is an important posttranslational modification involved in diverse cellular functions. A rapidly accelerated fibrosarcoma kinase (A-Raf) is a member of the Raf family of serine/threonine protein kinases that is necessary for MAPK activation. Our previous research found that knockout of A-Raf could reduce T. gondii-induced apoptosis in porcine alveolar macrophages (3D4/21 cells). However, limited information is available on protein phosphorylation variations and the role of A-Raf in macrophages infected with T. gondii. METHODS: We used immobilized metal affinity chromatography (IMAC) in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile changes in phosphorylation in T. gondii-infected 3D4/21 and 3D4/21-ΔAraf cells. RESULTS: A total of 1647 differentially expressed phosphorylated proteins (DEPPs) with 3876 differentially phosphorylated sites (DPSs) were identified in T. gondii-infected 3D4/21 cells (p3T group) when compared with uninfected 3D4/21 cells (pho3 group), and 959 DEPPs with 1540 DPSs were identified in the p3T group compared with infected 3D4/21-ΔAraf cells (p3KT group). Venn analysis revealed 552 DPSs corresponding to 406 DEPPs with the same phosphorylated sites when comparing p3T/pho3 versus p3T/p3KT, which were identified as DPSs and DEPPs that were directly or indirectly related to A-Raf. CONCLUSIONS: Our results revealed distinct responses of macrophages to T. gondii infection and the potential roles of A-Raf in fighting infection via phosphorylation of crucial proteins.

Pineal cysts may promote pubertal development in girls with central precocious puberty: a single-center study from China.

Introduction: Pineal cysts have long been considered a benign intracranial variation. However, in our clinical practice, it has been observed that some children with central precocious puberty (CPP) who have pineal cysts experience rapid progression in adolescent development. In recent years, there has been a significant increase in the prevalence of CPP in girls, leading to more diagnoses of CPP among children with pineal cysts. Despite this, there is no consensus regarding whether pineal cysts contribute to CPP as one of its organic factors. This study aimed to analyze the clinical characteristics of pineal cysts in children with CPP and explore the potential effects of pineal cysts on puberty development. Methods: This single-center study retrospectively analyzed clinical data from girls aged 3 to 10 years who underwent head/pituitary magnetic resonance imaging at the Children's Hospital Affiliated to Zhengzhou University between 2019 and 2022. The study categorized the detection rates of pineal cysts based on systematic disease classification and compared the rates of cyst detection between girls diagnosed with CPP and those without CPP. Subsequently, CPP-diagnosed girls with pineal cysts were examined. Among CPP-diagnosed girls meeting the study's criteria, those with pineal cysts formed the 'cyst group,' while those without cysts were matched in a 1:1 ratio based on age and body mass index to form the 'non-cyst group.' Comparative analyses were conducted to assess the clinical characteristics between these two groups. CPP-diagnosed girls with cysts were further subdivided into three groups according to cyst size (≤5 mm, 5.1-9.9 mm, and ≥10 mm) to investigate potential differences in clinical characteristics among these subgroups. The study involved an analysis of clinical data from girls diagnosed with CPP and included imaging follow-ups to explore the progression of pineal cysts over time. Results: Among the 23,245 girls who underwent head/pituitary magnetic resonance imaging scans, the detection rate of pineal cysts was 3.6% (837/23,245), with most cases being associated with endocrine diseases. The detection rate of pineal cysts in CPP patients was 6.4% (262/4099), which was significantly higher than the 3.0% (575/19,146) in patients without CPP. In comparison to the non-cyst group, the cyst group exhibited statistically significant increases in estradiol levels, peak luteinizing hormone (LH) levels, peak LH/follicle-stimulating hormone (FSH) ratios, uterine body length, and cervix length (P < 0.001). As cyst size increased, there were significant rises in LH peak, peak LH/FSH ratio, uterine body length, and cervical length (P < 0.01). Estradiol levels and left ovarian volume also showed an increasing trend (P < 0.05). Among girls who underwent follow-up imaging, 26.3% (5/19) exhibited an increase in cyst size. Conclusion: Pineal cysts are relatively common in children with CPP. They may affect the pubertal development process, with larger cysts correlating to faster pubertal development. Therefore, the authors hypothesize that pineal cysts may trigger CPP in some cases, especially when the cysts are larger than 5 mm in size, as indicated by our data.

Paraptosis: a non-classical paradigm of cell death for cancer therapy.

Due to the sustained proliferative potential of cancer cells, inducing cell death is a potential strategy for cancer therapy. Paraptosis is a mode of cell death characterized by endoplasmic reticulum (ER) and/or mitochondrial swelling and cytoplasmic vacuolization, which is less investigated. Considerable evidence shows that paraptosis can be triggered by various chemical compounds, particularly in cancer cells, thus highlighting the potential application of this non-classical mode of cell death in cancer therapy. Despite these findings, there remain significant gaps in our understanding of the role of paraptosis in cancer. In this review, we summarize the current knowledge on chemical compound-induced paraptosis. The ER and mitochondria are the two major responding organelles in chemical compound-induced paraptosis, which can be triggered by the reduction of protein degradation, disruption of sulfhydryl homeostasis, overload of mitochondrial Ca2+, and increased generation of reactive oxygen species. We also discuss the stumbling blocks to the development of this field and the direction for further research. The rational use of paraptosis might help us develop a new paradigm for cancer therapy.

Phylogeny and molecular evolution of the first local monkeypox virus cluster in Guangdong Province, China.

The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies.

The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions.

Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson's disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design.

Global patterns and trends in Kaposi sarcoma incidence: a population-based study.

BACKGROUND: Kaposi sarcoma is a rare, possibly angioproliferative, tumour. Kaposi sarcoma is one of the most common cancers in people living with HIV and poses a serious public health challenge in regions with high HIV burden. We aim to describe global patterns and population-wide trends in the burden of Kaposi sarcoma. METHODS: In this population-based study, the incidence and mortality estimates of Kaposi sarcoma from 185 countries and regions in 2020 were extracted from the GLOBOCAN 2020 database. The time trends in Kaposi sarcoma incidence were evaluated using the cancer registry data from Cancer Incidence in Five Continents plus from 1998 to 2012. We did not apply any inclusion or exclusion criteria to the data used in this study. Joinpoint regression was used to evaluate the average annual percentage change (AAPC) to quantify trends in the age-standardised incidence rate (ASIR) of Kaposi sarcoma. Correlation analysis was used to evaluate the relationship between the ASIR or age-standardised mortality rate (ASMR) and Human Development Index (HDI). FINDINGS: In 2020, the global estimated ASIR of Kaposi sarcoma was 0·39 (per 100 000 people), with an estimated 34 270 newly diagnosed cases (23 413 males and 10 857 females). An estimated 15 086 Kaposi sarcoma deaths were reported (9929 males and 5157 females), corresponding to an ASMR of 0·18 (per 100 000 people). In 2020, Africa accounted for 73·0% (25 010 of 34 270) of the incidence and 86·6% (13 066 of 15 086) of the deaths from Kaposi sarcoma worldwide. There was a significant correlation between the ASIR or ASMR and HDI. The incidence of Kaposi sarcoma increased in males in both Türkiye and the Netherlands. The AAPC was 11·5% (95% CI 3·2-20·4) for males in Türkiye and 2·5% (1·1-3·9) for males in the Netherlands from 1998 to 2012. The incidence of Kaposi sarcoma decreased in White Americans, Israel, Uganda, Costa Rica, Colombia, Canada, and Denmark, from 1998 to 2012. INTERPRETATION: Kaposi sarcoma is a relatively rare cancer worldwide but is endemic in some countries in southern and eastern Africa. Addressing disparities in health-care resource allocation and improving HIV/AIDS care across different HDI regions might contribute to the prevention of Kaposi sarcoma. FUNDING: The Natural Science Foundation of China Excellent Young Scientists Fund and the Natural Science Foundation of China International/Regional Research Collaboration Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Changes in HPV prevalence, incidence, and clearance following the use of HIV pre-exposure prophylaxis (PrEP) among MSM in Xinjiang, China: An observational cohort study.

The association between HIV pre-exposure prophylaxis (PrEP) and the natural history of human papillomavirus (HPV) has not been well documented. Our objective was to evaluate the impact of PrEP on the prevalence, incidence, and clearance of anal HPV among men who have sex with men (MSM). Sexually active, HIV-negative MSM aged 18 years and older in Xinjiang, China since September 1, 2016, were enrolled in an ongoing observational cohort study of HPV. At baseline and every 6 months, an anal swab was taken to test for HPV and a questionnaire on sociodemographic characteristics and sexual behaviors was collected. Those who consented to receive PrEP were enrolled in an open-label PrEP intervention study from November 1, 2019, to June 30, 2021. This study analyzed data from participants present in the HPV cohort between November 1, 2019, and June 30, 2021. We compared the prevalence, incidence, and clearance of anal HPV between men who received PrEP (PrEP users) and those who did not (non-PrEP users), and compared men before and after initiating PrEP. We calculated prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for both comparisons. Of the 870 participants present in the HPV cohort during the period between November 1, 2019, and June 30, 2021, 859 had adequate ß-globin for HPV genotype testing and were included in our study. Among them, 429 were PrEP users, while 430 were non-PrEP users. Median age was 32 years (interquartile range [IQR]: 26-38). Among PrEP users, 217 were tested for anal HPV before PrEP initiation. PrEP users had lower prevalence of HPV 45, 51, and 54 (PRs: 0.27 [95% CI: 0.09-0.80], 0.42 [0.21-0.85], and 0.41 [0.17-0.99], respectively) and lower clearance of HPV 16 (CRR: 0.31 [0.10-0.91]) compared with non-PrEP users. PrEP users exhibited lower prevalence of HPV 51 (PR: 0.31 [0.12-0.84]), lower incidence of HPV 6, 11, 16, 39 and 61 (IRRs: 0.34 [0.13-0.90], 0.26 [0.08-0.87], 0.44 [0.21-0.91], 0.21 [0.05-0.93], and 0.19 [0.04-0.82], respectively), as well as higher clearance of HPV 52 (CRR: 2.17 [1.08-4.35]) after PrEP initiation. PrEP use may lower the risk of HPV infection among MSM in Xinjiang, China. Our findings further extend the knowledge of the impact of PrEP on sexually transmitted infections.

Artificial intelligence in orthodontics and orthognathic surgery: a bibliometric analysis of the 100 most-cited articles.

BACKGROUND: The application of artificial intelligence (AI) in orthodontics and orthognathic surgery has gained significant attention in recent years. However, there is a lack of bibliometric reports that analyze the academic literature in this field to identify publishing and citation trends. By conducting an analysis of the top 100 most-cited articles on AI in orthodontics and orthognathic surgery, we aim to unveil popular research topics, key authors, institutions, countries, and journals in this area. METHODS: A comprehensive search was conducted in the Web of Science (WOS) electronic database to identify the top 100 most-cited articles on AI in orthodontics and orthognathic surgery. Publication and citation data were obtained and further analyzed and visualized using R Biblioshiny. The key domains of the 100 articles were also identified. RESULTS: The top 100 most-cited articles were published between 2005 and 2022, contributed by 458 authors, with an average citation count of 22.09. South Korea emerged as the leading contributor with the highest number of publications (28) and citations (595), followed by China (16, 373), and the United States (7, 248). Notably, six South Korean authors ranked among the top 10 contributors, and three South Korean institutions were listed as the most productive. International collaborations were predominantly observed between the United States, China, and South Korea. The main domains of the articles focused on automated imaging assessment (42%), aiding diagnosis and treatment planning (34%), and the assessment of growth and development (10%). Besides, a positive correlation was observed between the testing sample size and citation counts (P = 0.010), as well as between the time of publication and citation counts (P < 0.001). CONCLUSIONS: The utilization of AI in orthodontics and orthognathic surgery has shown remarkable progress, particularly in the domains of imaging analysis, diagnosis and treatment planning, and growth and development assessment. This bibliometric analysis provides valuable insights into the top-cited articles and the trends of AI research in this field.

Effectiveness and cost-effectiveness of human papillomavirus vaccination strategies among men who have sex with men in China: a modeling study.

Introduction: The health and economic benefits of human papillomavirus (HPV) vaccination targeted at men who have sex with men (MSM) in developing settings have been rarely assessed. This study aimed to evaluate the effectiveness and cost-effectiveness of different HPV vaccination strategies among MSM in China. Methods: A Markov model was developed to simulate HPV transmission dynamics among a total of 30.73 million MSM in China. The corresponding natural history included 6 states: susceptible, infected with low-risk subtypes, high-risk subtypes, anogenital warts and anal cancer, and deaths from anal cancer. MSM were divided into three age groups with cut-off points of 27 and 45 years. Alternative vaccination strategies were built by allocating bivalent, quadrivalent, nine-valent, or no vaccine to each of the groups. We generated the prevented infections and deaths by vaccination compared with baseline (no vaccination) and calculated incremental cost-effectiveness ratios (ICERs) to determine the optimal strategy. Results: The model showed that in 10 years, at baseline, the existing cases of anogenital warts would reach 5,464,225 (IQR, 4,685,708-6,174,175); that of anal cancer would reach 1,922.95 (1,716.56-2,119.93), resulting in 940.55 (732.27-1,141.87) deaths. Under 50% vaccination coverage among one age group, the prevented cases of anogenital warts were maximized with quadrivalent vaccines allocated to MSM aged 27-45 years; that of anal cancer were maximized when offering nine-valent vaccines to the same group. Under 50% vaccination coverage among all groups, the lowest ICER (34,098.09 USD/QALY, 31,146.54-37,062.88) was reached when only quadrivalent vaccines were provided. Based on this strategy, when the annual vaccination rate increased by 30%, the ICER (33,521.75 USD/QALY, 31,040.73-36,013.92) would fall below three times China's per capita GDP. When the vaccine price decreased by 60%, the ICER was reduced to 7,344.44 USD/QALY (4,392.89-10,309.23), indicating good cost-effectiveness taking China's per capita GDP as a threshold. Conclusions: HPV vaccination can effectively reduce the prevalence and mortality of related diseases among MSM in China, especially quadrivalent vaccines for anogenital warts and nine-valent vaccines for anal cancer. MSM aged 27-45 years were the optimal group for vaccination. Annual vaccination and appropriate adjustment of vaccine price are necessary to further improve the cost-effectiveness.

Corrigendum: Incidence, persistence, and clearance of anogenital human papillomavirus among men who have sex with men in Taiwan: a community cohort study.

[This corrects the article DOI: 10.3389/fimmu.2023.1190007.].

Changes in human papillomavirus prevalence, incidence, and clearance among men who have sex with men in Xinjiang, China after implementation of nonpharmaceutical interventions to control COVID-19: An interrupted time series analysis.

OBJECTIVES: This study aimed to assess the effects of COVID-19 nonpharmaceutical interventions (NPIs) on the human papillomavirus (HPV) epidemic among men who have sex with men (MSM) in Xinjiang, China. METHODS: In our cohort study, we enrolled and followed HIV-negative MSM in Xinjiang, China, between 2016 and 2022. Anal swab samples were collected to test for HPV DNA. We used interrupted time series analysis to characterize the temporal trends in HPV prevalence, incidence, and clearance before (September 01, 2016, to July 16, 2020) and during the implementation of COVID-19 NPIs in Xinjiang (July 17, 2020, to March 31, 2022). We used binomial segmented regression models to estimate the impact of COVID-19 NPIs on HPV prevalence, incidence, and clearance. RESULTS: We recruited 1296 MSM who contributed to a total of 5374 HPV tests in our study. COVID-19 NPIs were associated with a 37.9% decrease in the prevalence (prevalence ratio, 0.621; 95% confidence interval, 0.465-0.830), 52.2% decrease in the incidence (risk ratio, 0.478; 0.377-0.606), and 40.4% increase in the clearance (risk ratio, 1.404; 1.212-1.627) of HPV of any genotype after the implementation of COVID-19 NPIs in Xinjiang. CONCLUSION: COVID-19 NPIs may lead to lower transmission and higher clearance of HPV among MSM. Future studies are needed to clarify the longer-term impact of COVID-19 on the transmission and natural history of HPV among MSM.

Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals diagnostic and prognostic signatures and immunoinfiltration in gastric cancer.

BACKGROUND: Early diagnosis and prognostic predication of gastric cancer (GC) pose significant challenges in current clinical practice of GC treatments. Therefore, our aim was to explore relevant gene signatures that can predict the prognosis of GC patients. METHODS: Here, we established a single-cell transcriptional atlas of GC, focusing on the expression of T-cell-related genes for cell-cell communication analysis, trajectory analysis, and transcription factor regulatory network analysis. Additionally, we conducted validation and prediction of immune-related prognostic gene signatures in GC patients using TCGA and GEO data. Based on these prognostic gene signatures, we predicted the immune infiltration status of GC patients by grouping the patient samples into high or low-risk groups. RESULTS: Based on 10 tumor samples and corresponding normal samples from GC patients, we selected 18,416 cells for subsequent analysis using single-cell sequencing. From these, we identified 3,284 T-cells and obtained 641 differentially expressed genes related to T-cells from 5 different T-cell subtypes. By integrating bulk RNA sequencing data, we identified prognostic signatures associated with T-cells. Stratifying patients based on these prognostic signatures into high-risk or low-risk groups allowed us to effectively predict their survival rates and the immunoinfiltration status of the tumor microenvironment. CONCLUSION: This study explored prognostic gene signatures associated with T-cells in GC patients, providing insights into predicting patients' survival rates and immunoinfiltration levels.

Self-designed three-dimensional printed skeletal anchorage titanium device for orthopaedic traction in a growing Class III patient.

Maxillary retrusion in a growing skeletal class III patient can be treated with growth modification by facemask therapy with skeletal anchorage. A 12-year-old boy presented with Skeletal Class III relationship, retrognathic maxilla and paranasal deficiency. Cone beam computer tomography (CBCT) was taken for the design of the customized skeletal anchorage device with a 3D planning computer software. Two pairs of skeletal anchorage surgical guides and plates were designed with the correct vector and location, and to avoid tooth roots in the fixation. The plates were printed with titanium and fixed onto the patient for the facemask therapy. CAD-CAM technology allows customization and precise execution of the skeletal anchorage for the facemask therapy. Self-designed 3D printed skeletal anchorage device, with the advantages of increased rigidity, ease of placement and accuracy of force application, can be a valid alternative to stock titanium plates.

Incidence, persistence, and clearance of anogenital human papillomavirus among men who have sex with men in Taiwan: a community cohort study.

Background: Men who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection. This study aimed to assess the incidence, persistence, and clearance of anogenital HPV infections among MSM and the correlates in a 3-year community cohort study. Methods: From 2015 to 2019, MSM were recruited and followed up at 6, 12, 24, and 36 months in Taiwan. Questionnaires and anogenital swabs were collected at baseline and each follow-up visit. Thirty-seven HPV genotypes were tested and genotyped using the linear array HPV genotyping test. The incidence, persistence, and clearance rates of anogenital HPV infection and 95% confidence intervals (CIs) were estimated through Poisson regression. Correlates of the incidence and clearance rates were examined using a generalized estimating equations (GEE) model. Results: A total of 201 MSM were retained in the cohort study with a median age of 27 years (interquartile range [IQR]: 24-32) at baseline. The incidence, persistence, and clearance rates of any anal HPV infection among MSM were 43.6 (95% CI: 33.7-55.6), 23.4 (17.7-30.2), and 58.3 (45.1-74.1) per 1,000 person months (pms), respectively. The incidence, persistence, and clearance rates of any penile HPV infection among MSM were 26.8 (20.1-34.9), 13.4 (8.0-20.9), and 51.5 (37.8-68.5) pms, respectively. MSM who did not consistently use a condom in receptive sex (adjusted odds ratio [AOR]: 2.06, 95% CIs: 1.14-3.72) were more likely to acquire any anal HPV infection. Age at recruitment (1.05, 1.01-1.09) was positively associated with any penile HPV incidence. MSM with over one sex partner in receptive anal sex (0.53, 0.30-0.94) were less likely to clear any anal HPV infection. MSM who were unemployed/students (0.55, 0.30-0.98) were less likely to clear any penile HPV infection. Conclusion: High incidence and low clearance of anogenital HPV infection among MSM in the study serve as a reminder that this population needs to be targeted for HPV vaccination. It is essential for MSM to scale up HPV screening and adhere to safe sex.

Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid.

Breast cancer is the leading cause of cancer-related death in women. Among breast cancer types, triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers with aggressive tumor behavior. By using bioinformatic approaches, we observed that the microRNA-708 promoter is highly methylated in breast carcinomas, and this methylation is linked to a poor prognosis. Moreover, microRNA-708 expression correlates with better clinical outcomes in TNBC patients. Combination treatment with the hypomethylating agent decitabine and synthetic glucocorticoid significantly increased the expression of microRNA-708, reactivated DNMT-suppressed pathways, and decreased the expression of multiple metastasis-promoting genes such as matrix metalloproteinases (MMPs) and IL-1ß, leading to the suppression of breast cancer cell proliferation, migration, and invasion, as well as reduced tumor growth and distant metastasis in the TNBC xenograft mouse model. Overall, our study reveals a therapeutic opportunity in which a combined regimen of decitabine with glucocorticoid may have therapeutic potential in treating TNBC patients.

Voluntary Medical Male Circumcision and Incident HIV Infection Among Men Who Have Sex With Men in China (The CoM Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Systematic reviews and meta-analyses based on observational studies have shown voluntary medical male circumcision (VMMC) may reduce HIV risk among men who have sex with men (MSM). There is a lack of randomized controlled trial (RCT) data assessing the efficacy of VMMC. OBJECTIVE: The primary objective of this study was to assess the efficacy of VMMC for preventing HIV acquisition among MSM who primarily engage in insertive anal sex. METHODS: A multicenter RCT will be conducted among MSM in 8 cities in China. Eligible participants are men aged 18-49 years who self-report ≥2 male sex partners in the past 6 months, predominantly practice insertive anal sex, and are willing to undergo circumcision. Interested men who satisfy inclusion criteria will be tested for HIV 1 month before enrollment and at enrollment, and only those who are HIV negative will be enrolled. At baseline, all enrolled participants will be asked to report sociodemographic characteristics and sexual behaviors; provide a blood sample for HIV, syphilis, and herpes simplex virus type 2 testing; and provide a penile swab for human papillomavirus testing. Participants will be randomly assigned to the intervention or control group. Those in the intervention group will receive VMMC and undergo a web-based weekly follow-up assessment of postsurgery healing for 6 consecutive weeks. All participants will be tested for HIV at 3-, 6-, 9-, and 12-month follow-ups. All participants will also be asked to report sexual behaviors and undergo repeat herpes simplex virus type 2 and human papillomavirus testing at 6- and 12-month follow-ups. The primary end point is HIV seroconversion. Secondary end points are the safety and satisfaction with VMMC and the changes in sexual behaviors after VMMC. The grouped censored data will be analyzed by intention-to-treat approach. RESULTS: Recruitment for the RCT began in August 2020 and continued through July 2022. Data collection is expected to be completed by July 2023, and full data analysis is going to be completed by September 2023. CONCLUSIONS: This study will be the first RCT to assess the efficacy of VMMC in preventing HIV infection among MSM. Results from this trial will provide preliminary evidence for the potential efficacy of VMMC to reduce incident HIV infection among MSM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000039436; https://www.chictr.org.cn/showproj.html?proj=63369. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47160.