An NIR-responsive hydrogel loaded with polydeoxyribonucleotide nano-vectors for enhanced chronic wound healing.

Chronic diabetic wounds are difficult to treat due to imbalanced inflammatory responses, high blood glucose levels, and bacterial infections. Novel therapeutic approaches based on nucleic acid analogues have been proposed, with unique advantages in improving angiogenesis, increasing collagen synthesis, and exerting anti-inflammatory effects. However, the inherent electronegativity of nucleic acids makes them less susceptible to cellular uptake. In this paper, a kind of near infrared (NIR)-responsive nanocomposite hydrogel loaded with nucleic acid vectors was proposed for promoting wound healing. The redox system composed of molybdenum disulphide nanosheets (MoS2 NSs) initiated the copolymerization of quaternized chitosan containing double bonds and N-isopropylacrylamide (NIPAAm) to form the matrix. In addition, MoS2 NSs with photothermal conversion performance endow the nanocomposite hydrogel to have NIR-response property and act as physical crosslinking points in the matrix. Polydeoxyribonucleotides (PDRN), which have the effect of promoting wound healing, were made into nucleic acid vectors, and loaded into the NIR-responsive hydrogel. MoS2 NSs can convert NIR irradiation into heat, causing phase transitions of temperature-sensitive segments that trigger volume contraction of the hydrogel to extrude the nucleic acid vector. Promoting angiogenesis, slowing inflammation, and guiding tissue regeneration were demonstrated in the diabetic wound model treated with the NIR-responsive nanocomposite hydrogel.

Transplacental transfer of perfluorinated and poly-fluorinated substances in maternal-cord serum and association with birth weight: a birth cohort study, China.

Although the effects of traditional perfluorinated and polyfluorinated substances (PFASs) exposure have been extensively explored, research on novel PFASs remains limited, and there is a lack of data regarding their placental transfer and fetal impact. Herein, we aimed to examine maternal and fetal PFASs exposure levels, placental transfer efficiency (TTE), and the consequences of prenatal exposure on birth weight. The study included 214 mother-child pairs recruited in Wuxi birth cohort from 2019 to 2021. Twenty-three PFASs were quantified in maternal serum during the second trimester and umbilical serum during delivery. Median concentrations of ∑23PFASs in maternal and cord sera were 9.34 and 6.88 ng/mL, respectively. The novel alternatives exhibited elevated levels of maternal and fetal exposure, such as perfluorovaleric acid (PFPeA, 2.00 ng/mL and 1.66 ng/mL, respectively) and perfluorohexane sulfonate (PFHxS, 1.77 and 1.14 ng/mL, respectively). With increasing carbon chain length, the TTE of perfluorocarbonic acid (PFCAs) displayed a pattern of initially decreasing before subsequently increasing, with novel alternatives exhibiting a relatively high TTE. Multiple linear regression showed that exposure to perfluorobutane sulfonate (PFBS) and PFPeA in cord serum positively correlated with the birth weight of female infants (ß= 231.04 g, 95% confidence interval [CI]: 21.73-440.36; ß= 121.26 g, 95% CI: 29.51-213.00). No nonlinear relationship was observed between cord serum PFASs and birth weight. The weighted quantile sum (WQS) regression analysis has reaffirmed that PFPeA and PFBS were predominant contributors to the positive correlation observed between the mixture of PFASs and birth weight. Our findings suggest that novel PFASs may exhibit a heightened susceptibility for transplacental transfer and that exposure to PFBS and PFPeA during pregnancy could be linked to increased birth weight.

Progress of Nanomaterials Based on Manganese Dioxide in the Field of Tumor Diagnosis and Therapy.

As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.

Delving deeper into the mechanisms fundamental to HIV-associated immunopathology using single-cell sequencing techniques: A scoping review of current literature.

Human immunodeficiency virus (HIV) infection has evolved into an established global pandemic over the past four decades; however, despite massive research investment globally, the precise underlying mechanisms which are fundamental to HIV-related pathogenesis remain unclear. Single cell ribonucleic acid (RNA) sequencing methods are increasingly being used for the identification of specific cell-type transcriptional changes in HIV infection. In this scoping review, we have considered information extracted from fourteen published HIV-associated single-cell RNA sequencing-related studies, hoping to throw light on the underlying mechanisms of HIV infection and pathogenesis, and to explore potential candidate biomarkers for HIV disease progression and antiviral treatment. Generally, HIV positive individuals tend to manifest disturbances of frequency of multiple cellular types, and specifically exhibit diminished levels of CD4+ T-cells and enriched numbers of CD8+ T-cells. Cell-specific transcriptional changes tend to be linked to cell permissiveness, hyperacute or acute HIV infection, viremia, and cell productivity. The transcriptomes of CD4+ T-cell and CD8+ T-cell subpopulations are also observed to change in HIV-positive diabetic individuals, spontaneous HIV controllers, individuals with high levels of HIV viremia, and those in an acute phase of HIV infection. The transcriptional changes seen in B cells, natural killer (NK) cells, and myeloid dendritic cells (mDCs) of HIV-infected individuals demonstrate that the humoral immune response, antiviral response, and immune response regulation, respectively, are all altered following HIV infection. Antiretroviral therapy (ART) plays a crucial role in achieving immune reconstitution, in improving immunological disruption, and in mitigating immune system imbalances in HIV-infected individuals, while not fully restoring inherent cellular transcription to levels seen in HIV-negative individuals. The preceding observations not only illustrate compelling advances in the understanding of HIV-associated immunopathogenesis, but also identify specific cell-type transcriptional changes that may serve as potential biomarkers for HIV disease monitoring and therapeutic targeting.

Composite scattering characteristics analysis of micro-ellipsoidal periodic structure optical surface and microdefects.

In order to adjust and detect micro-nano periodic structure optical surface accurately and efficiently, the problem of composite scattering between micro-ellipsoidal periodic structure optical surface and pore defects is studied use the multi-resolution time domain (MRTD) approach. A calculation model is established for the intensity distribution of composite scattering, which is modulated by the micro-ellipsoidal periodic structure optical surface and microdefects. Results are in good agreement with those obtained using CST Microwave Studio software and the finite-different time-domain (FDTD) approach, which demonstrates the effectiveness of the calculation model and method. By combining the field distribution of the micro-ellipsoidal periodic structure optical surface containing microdefects with the optical response at different wavelengths, it is necessary to study the influence of various parameters of the micro-ellipsoidal structure and microdefects on the optical system of metamaterials. The effects of the parameters such as roughness, structure of micro-ellipsoidal unit, defect sizes and buried depths on the composite scattering characteristics are analyzed numerically. The results provide technical support for the fields of functional surface design, ultrasensitive detection, scattering peak orientation and frequency selection.

Cardiac magnetic resonance imaging-derived pathophysiology and prognosis of diabetes mellitus with acute myocardial infarction after revascularization: a prospective cohort study.

BACKGROUND: Little is known about the underlying factors contributing to unfavourable clinical outcomes in patients with diabetes mellitus (DM) complicated by new-onset acute myocardial infarction (AMI). The aim of this study was to investigate the impact of DM on the pathophysiologic features and prognosis of patients with new-onset AMI following successful revascularization by utilizing cardiac magnetic resonance (CMR). METHODS: Consecutive patients diagnosed with new-onset AMI between June 2022 and January 2024 were included. All patients underwent culprit vessel revascularization upon admission and CMR imaging 3-7 days later. The primary clinical endpoint of this study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), for which the average follow-up was 10 months. RESULTS: A total of 72 patients were divided into a DM group (n = 23) and a non-DM group (n = 49). Multivariate logistic regression analysis revealed that DM was an independent risk factor for the occurrence of microvascular obstruction. Multivariate linear regression analysis found that DM was the influencing factor of global radial strain (B = -4.107, t = -2.328, p = 0.023), while fasting blood glucose influenced infarct segment myocardial radial strain (B = -0.622, t = -2.032, p = 0.046). DM independently contributed to the risk of MACCEs following successful revascularization in patients with AMI (p < 0.05). CONCLUSION: Comprehensive phenotypic characterization of myocardial injury and microcirculatory status could enable reliable identification of high-risk MACCEs in DM patients with new-onset AMI following successful revascularization.

Association of waist-to-hip ratio adjusted for body mass index with cognitive impairment in middle-aged and elderly patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. METHODS: A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. RESULTS: WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261-1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032-4.371, P for trend < 0.001). CONCLUSIONS: Our study illustrated that higher WHRadjBMI is likely to be associated with an increased risk of CI among patients with T2DM. These findings support the detrimental effects of excess visceral fat accumulation on cognitive function in middle-aged and elderly T2DM patients.

An investigation of CO generation path upon loading coal from perspective of macromolecular simulation.

CO is a hazardous and pollutant gas that can be produced in many scenarios of coal-related operations. The study mainly investigated CO production process and mechanism when coal is subject to external forces. The effects of coal type, particle size, temperature, and inlet atmosphere on CO production from coal body fragmentation were investigated through coal loading experiments. Materials Studio software was used to carry out coal macromolecular mechanics simulation and molecular dynamics simulation, and the gas production mechanism of coal under loading was explored at the molecular level. It was found that under air atmosphere, the low degree of deterioration, small particle size, and elevated temperature are all more likely to cause coal samples to fragment and decompose to produce CO. The carbonyl group in the molecular structure of coal is shed or broken free radical fragments react with oxygen which may lead to CO formation.

Mechano-triggered eradication of dentinal tubule biofilm via in situ generation of nanoscale sonosensitizer by the tailored irrigation formulation.

The efficient elimination of bacteria within the dentinal tubules has been hindered by the poor deposition and short residence of disinfecting agents. Meanwhile, the current irrigant (e.g., NaClO, 5.25 %) shows severe adverse effects on the surrounding soft tissues because of its inherent high irritancy. To address this issue, this work reports an in situ generated sonosensitizer to handle the biofilm in dentinal tubules with minimal adverse effects. The production of nanoscale sonosensitizer involves the concurrent delivery of H2O2 (0.01 %), ferrocene derivative (Fc), and indocyanine green (ICG). With ultrasound treatment, the reaction between H2O2 and Fc liberated Fe3+ that was further complexed with ICG to generate the nanoscale sonosensitizer in situ, followed by singlet oxygen production for potent disinfecting action. Because the above cascade reactions occur within the confined dentinal tubules, the generated ICG-Fe3+ nanosensitizer would show prolonged retention therein. The anti-bacterial potency of nanosensitizer was demonstrated in petrodish and ex vivo biofilm models. Meanwhile, the transmission electron microscope imaging of biofilm and cytotoxicity assay in L929 fibroblast cells proved the superiority of nanosensitizer against NaClO regarding adverse effects. The current work opens new avenues of biofilm elimination in dentinal tubules, showing a high translation potential.

MicroRNAs: pioneering regulators in Alzheimer's disease pathogenesis, diagnosis, and therapy.

This article delves into Alzheimer's disease (AD), a prevalent neurodegenerative condition primarily affecting the elderly. It is characterized by progressive memory and cognitive impairments, severely disrupting daily life. Recent research highlights the potential involvement of microRNAs in the pathogenesis of AD. MicroRNAs (MiRNAs), short non-coding RNAs comprising 20-24 nucleotides, significantly influence gene regulation by hindering translation or promoting degradation of target genes. This review explores the role of specific miRNAs in AD progression, focusing on their impact on ß-amyloid (Aß) peptide accumulation, intracellular aggregation of hyperphosphorylated tau proteins, mitochondrial dysfunction, neuroinflammation, oxidative stress, and the expression of the APOE4 gene. Our insights contribute to understanding AD's pathology, offering new avenues for identifying diagnostic markers and developing novel therapeutic targets.

Neutrophil-to-lymphocyte ratio and prognostic nutritional index in predicting composite endpoint of early safety following transcatheter aortic valve replacement.

BACKGROUND: The incidence of composite endpoint of early safety (CEES) after transcatheter aortic valve replacement (TAVR) has been a topic of focus within the cardiovascular field due to its impact on long-term patient outcomes. Timely prophylactic interventions are crucial for patients identified as high risk for CEES through preoperative risk stratification. OBJECTIVES: This study aimed to explore the connection between inflammatory and nutritional markers, specifically the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI), and CEES occurrence. MATERIAL AND METHODS: A cohort of 134 patients undergoing TAVR in a single center was studied. The study endpoint was the occurrence of CEES, which was defined according to the Valve Academic Research Consortium 3. RESULTS: The CEES was reached in 25.4% of patients at 30 days. A high NLR was associated with a 5.55-fold increased risk of CEES (95% confidence interval (95% CI): 1.52-20.29; p < 0.05), while a low PNI was linked to a 4.43-fold increased risk (95% CI: 1.55-12.65; p < 0.01). Combining NLR and PNI provided additional risk stratification for high-risk patients (hazard ratio (HR), 95% CI: 2.24-43.37; p < 0.005). CONCLUSIONS: A high NLR and low PNI were shown to be significant predictors of CEES following TAVR. These findings underscore the significance of NLR and PNI in the risk assessment of TAVR patients, offering valuable insights for preventive measures.

Region of Interest Detection in Melanocytic Skin Tumor Whole Slide Images-Nevus and Melanoma.

Automated region of interest detection in histopathological image analysis is a challenging and important topic with tremendous potential impact on clinical practice. The deep learning methods used in computational pathology may help us to reduce costs and increase the speed and accuracy of cancer diagnosis. We started with the UNC Melanocytic Tumor Dataset cohort which contains 160 hematoxylin and eosin whole slide images of primary melanoma (86) and nevi (74). We randomly assigned 80% (134) as a training set and built an in-house deep learning method to allow for classification, at the slide level, of nevi and melanoma. The proposed method performed well on the other 20% (26) test dataset; the accuracy of the slide classification task was 92.3% and our model also performed well in terms of predicting the region of interest annotated by the pathologists, showing excellent performance of our model on melanocytic skin tumors. Even though we tested the experiments on a skin tumor dataset, our work could also be extended to other medical image detection problems to benefit the clinical evaluation and diagnosis of different tumors.

Amelioration of nonalcoholic fatty liver disease by inhibiting the deubiquitylating enzyme RPN11.

Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation nonalcoholic steatohepatitis (NASH), is a global public health challenge. Here, we explore the role of deubiquitinating enzyme RPN11 in NAFLD and NASH. Hepatocyte-specific RPN11 knockout mice are protected from diet-induced liver steatosis, insulin resistance, and steatohepatitis. Mechanistically, RPN11 deubiquitinates and stabilizes METTL3 to enhance the m6A modification and expression of acyl-coenzyme A (CoA) synthetase short-chain family member 3 (ACSS3), which generates propionyl-CoA to upregulate lipid metabolism genes via histone propionylation. The RPN11-METTL3-ACSS3-histone propionylation pathway is activated in the livers of patients with NAFLD. Pharmacological inhibition of RPN11 by Capzimin ameliorated NAFLD, NASH, and related metabolic disorders in mice and reduced lipid contents in human hepatocytes cultured in 2D and 3D. These results demonstrate that RPN11 is a novel regulator of NAFLD/NASH and that suppressing RPN11 has therapeutic potential for the treatment.

Targeting the Skin: The Study of a Bottlebrush Polymer-Antisense Oligonucleotide Conjugate in a Psoriasis Mouse Model.

The investigation of gene regulation therapeutics for the treatment of skin-related diseases is rarely explored in part due to inefficient systemic delivery. In this study, a bottlebrush polymer-antisense oligonucleotide (ASO) conjugate, termed pacDNA, designed to target IL-17 receptor A (IL-17RA), which is involved in psoriasis pathogenesis is presented. Systemic administration of pacDNA led to its accumulation in epidermis, dermis, and hypodermis of mouse skin, reduced IL-17RA gene expression in skin, and significantly reversed the development of imiquimod (IMQ)-induced psoriasis in a mouse model. These findings highlight the potential of the pacDNA as a promising nanoconstruct for systemic oligonucleotide delivery to the skin and for treating psoriasis and other skin-related disorders through systemic administration.

Maternal vitamin D status during pregnancy and infant's gut microbiota: a prospective cohort study.

Objectives: To prospectively explore the association of maternal serum 25(OH)D levels with the infant's gut microbiota in Chinese populations, and to evaluate its potential influence on the dynamic change patterns of offspring's gut microbiota from 1 to 6 months old. Methods: Eighty-seven mother-infant dyads (vitamin D insufficient group vs. normal group = 59 vs. 28) were included in this longitudinal study. Two fecal samples were collected for the included infant at home by the parents at 1 month of age ("M1 phase") and 6 months of age ("M6 phase"). Gut microbiota were profiled by 16S rRNA gene sequencing. We performed mixed effects models on alpha diversity metrics, PERMANOVA tests on beta diversity distances, and linear discriminant analysis (LDA) to identify differently abundant taxa. Results: We observed significantly lower Pielou's evenness and Shannon diversity in the vitamin D insufficient group in the M6 phase (p = 0.049 and 0.015, respectively), but not in the M1 phase (p > 0.05), and the dynamic changes in alpha diversity from 1 to 6 months old were significantly different according to maternal vitamin D status (p < 0.05). There were also significant differences in gut microbiota composition between the vitamin D insufficient group and normal group, both in the M1 and M6 phases (LDA score > 2.0, p < 0.05). Moreover, among the predicted metagenome functions, pathways related to amino acid biosynthesis, starch degradation, and purine nucleotides biosynthesis were enriched in the vitamin D insufficient group. Conclusion: Our findings highlight that maternal vitamin D status plays a pivotal role in shaping the early-life gut microbiota of the next generation.

Enantioselective SN1-type reaction via electrochemically generated chiral α-Imino carbocation intermediate.

Electrochemical reactions via carbocation intermediates remain fundamental transformations that build up molecular functionality and complexity in a sustainable manner. Enantioselective control of such processes is a great challenge in a highly ionic electrolyte solution. Here, we report an anodic generation of chiral α-imino carbocation intermediates by enamine catalysis. The chiral carbocation intermediates can be intercepted by a variety of nucleophiles such as alcohols, water and thiols with high stereoselectivity. The key SN1 step proceeds via a tertiary amine-mediated proton shuttle that facilitates facial selection in reacting with carbocation.

Quercetin Increases Growth Performance and Decreases Incidence of Diarrhea and Mechanism of Action in Weaned Piglets.

This study aimed to investigate the mechanism of quercetin increasing growth performance and decreasing incidence of diarrhea in weaned piglets. Forty-eight Duroc × Landrace × Large White weaned piglets with similar body weight (7.48 ± 0.20 kg, 28 days of age) were randomly divided into four treatments (control, 250 mg/kg quercetin, 500 mg/kg quercetin, and 750 mg/kg quercetin treatments) and fed with basal diet or experimental diet supplemented with quercetin. Performance, diarrhea rate and index, and content of serum anti-inflammatory factors were determined and calculated in weaned piglets; colonic flora and signaling pathways related to anti-inflammation were measured using 16S rDNA sequencing and RNA-seq, respectively. The results showed that compared with control, feed-to-gain ratio and content of serum interferon gamma (IFN-γ) were significantly decreased in the 500 and 750 mg/kg quercetin treatments (P < 0.05); quercetin significantly decreased diarrhea rate and diarrhea index (P < 0.05) and significantly increased the content of serum transforming growth factor (TGF-ß) in weaned piglets (P < 0.05); the content of serum NF-κB was significantly decreased in the 750 mg/kg quercetin treatment (P < 0.05); moreover, quercetin significantly increased diversity of colonic flora (P < 0.05), and at the phylum level, the relative abundance of Actinobacteria in the 500 and 750 mg/kg treatments was significantly increased (P < 0.05), and the relative abundance of Proteobacteria in the three quercetin treatments were significantly decreased (P < 0.05) in the colon of weaned piglets; at the genus level, the relative abundance of Clostridium-sensu-stricto-1, Turicibacter, unclassified_f_Lachnospiraceae, Phascolarctobacterium, and Family_XIII _AD3011_group was significantly increased (P < 0.05); the relative abundance of Subdollgranulum and Blautia was significantly decreased in the 500 and 750 mg/kg treatments (P < 0.05); the relative abundance of Eschericha-Shigella, Terrisporobacter, and Eubacterium-coprostanoligenes was significantly increased (P < 0.05); the relative abundance of Streptocococcus, Sarcina, Staphylococcus, and Ruminococcaceae_UCG-008 was significantly decreased in the three quercetin treatments (P < 0.05); the relative abundance of Ruminococcaceae_UCG_014 was significantly increased in the 250 mg/kg quercetin treatment in the colon of weaned piglets (P < 0.05). The results of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differentially expressed genes (DEGs) from the quercetin treatments were significantly enriched in nuclear transcription factor-κB (NF-κB) signal pathway (P < 0.05); mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1R1 (IL-1R1), conserved helix-loop-helix ubiquitous kinase (CHUK), toll-like receptor 4 (TLR4), and IL-1ß from quercetin treatments were significantly decreased in colonic mucosa of weaned piglets (P < 0.05). In summary, quercetin increased feed conversion ratio and decreased diarrhea through regulating NF-κB signaling pathway, controlling the balance between anti-inflammatory and proinflammatory factors, and modulating intestinal flora, thus promoting the absorption of nutrients in weaned piglets. These results provided the theoretical foundation for applying quercetin in preventing weaning piglets' diarrhea and animal husbandry practices.

Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Age at first sexual intercourse, age at menarche, and age at menopause: a mendelian randomization study on lung cancer risk.

Background: There is increasing evidence that sex hormones are involved in the development of lung cancer, but the correlation between the reproductive behavior that changes sex hormone levels and lung cancer is not yet clear. Many previous studies have investigated the association between reproductive factors and lung cancer risk, but the results have been inconsistent. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential relationship between age at first sexual intercourse (AFS), age at menarche, and age at menopause, and lung cancer. Methods: We performed a MR analysis of the data from the genome-wide association study (GWAS) of European ancestry to evaluate the independent effects of three reproductive behaviors on lung cancer overall (LUCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small cell lung cancer (SCLC). We mainly used the inverse-variance weighting method for the MR analysis. Sensitivity was determined by a MR-pleiotropy residual sum and outlier analysis, a weighted median analysis, a MR-Egger analysis, and a leave-one-out analysis. Results: The MR analysis results revealed that older AFS had a causal relationship with LUCA [odds ratio (OR) =0.6283, 95% confidence interval (CI): 0.4959-0.7961, P=0.0001), LUAD (OR =0.7042, 95% CI: 0.4967-0.9984, P=0.049), and LUSC (OR =0.6231, 95% CI: 0.4386-0.8853, P=0.0083). Conclusions: Our results revealed a causal relationship between older AFS and a lower risk of lung cancer. Our findings emphasize the importance of providing sex education, as early sexual intercourse may have undesirable effects. In addition, early psychological treatment is also essential.