Pharmacokinetics and pharmacodynamics of intravenous delafloxacin in healthy subjects: model-based dose optimization.

Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC0-24h in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant Staphylococcus aureus (MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC90 of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.

16S rRNA gene sequencing reveals altered gut microbiota in young adults with schizophrenia and prominent negative symptoms.

BACKGROUND: Gut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH-N) in young adults have been poorly elucidated. METHODS: Stool samples were obtained from 30 young adults with SCH-N, 32 SCH patients with prominent positive symptoms (SCH-P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). RESULTS: There is a significant difference in ß-diversity but not α-diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH-N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia-Shigella, Dorea, and Butyricicoccus) that can distinguish SCH-N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH-N and SCH-P is much less than that between SCH-N and the HC, and SCH-N and SCH-P cannot be effectively distinguished by gut microbiota. CONCLUSION: The composition of gut microbiota was changed in the patients with SCH-N, which may help in further understanding of pathogenesis in young adults with SCH-N.

Decoding Fujian's cervical HPV landscape: unmasking dominance of non-16/18 HR-HPV and tailoring prevention strategies at a large scale.

Background: Persistent HR-HPV causes cervical cancer, exhibiting geographic variance. Europe/Americas have higher HPV16/18 rates, while Asia/Africa predominantly have non-16/18 HR-HPV. This study in Fujian, Asia, explores non-16/18 HR-HPV infections, assessing their epidemiology and cervical lesion association for targeted prevention. Methods: A total of 101,621 women undergoing HPV screening at a hospital in Fujian Province from 2013 to 2019 were included. HPV genotyping was performed. A subset of 11,666 HPV-positive women with available histopathology results were analyzed to characterize HPV genotype distribution across cervical diagnoses. Results: In 101,621 samples, 24.5% tested positive for HPV. Among these samples, 17.3% exhibited single infections, while 7.2% showed evidence of multiple infections. The predominant non-16/18 high-risk HPV types identified were HPV 52, 58, 53, 51, and 81. Single HPV infections accounted for 64.1% of all HPV-positive cases, with 71.4% of these being non-16/18 high-risk HPV infections. Age-related variations were observed in 11,666 HPV-positive patients with pathological results. Cancer patients were older. In the cancer group, HPV52 (21.8%) and HPV58 (18.6%) were the predominant types, followed by HPV33, HPV31, and HPV53. Compared to single HPV16/18 infection, non-16/18 HPV predominated in LSIL. Adjusted odds ratios (OR) for LSIL were elevated: multiple HPV16/18 (OR 2.18), multiple non-16/18 HR-HPV (OR 2.53), and multiple LR-HPV (OR 2.38). Notably, solitary HPV16/18 conferred higher odds for HSIL and cancer. Conclusion: Our large-scale analysis in Fujian Province highlights HPV 52, 58, 53, 51, and 81 as predominant non-16/18 HR-HPV types. Multiple HPV poses increased LSIL risks, while solitary HPV16/18 elevates HSIL and cancer odds. These findings stress tailored cervical cancer prevention, highlighting specific HPV impacts on lesion severity and guiding region-specific strategies for optimal screening in Asia, emphasizing ongoing surveillance in the vaccination era.

Evaluation of cutout factors with small and narrow fields using various dosimetry detectors in electron beam keloid radiotherapy.

BACKGROUND: The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. OBJECTIVE: To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. METHOD: The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. RESULTS: The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. CONCLUSION: The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3 cm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.

Experimental study of different dehydration methods in the process of preparing frozen brain sections.

This study aimed to provide a recommendable protocol for the preparation of brain cryosections of rats to reduce and avoid ice crystals. We have designed five different dewatering solutions (Scheme 1: dehydrate with 15%, 20%, and 30% sucrose-phosphate-buffered saline solution; Scheme 2: 20% sucrose and 30% sucrose; Scheme 3: 30% sucrose; Scheme 4: 10%, 20%, and 30% sucrose; and Scheme 5: the tissue was dehydrated with 15% and 30% sucrose polyacetate I until it sank to the bottom, followed by placement in 30% sucrose polyacetate II) to minimize the formation of ice crystals. Cryosections from different protocols were stained with Nissl staining and compared with each other by density between cells and the distance of intertissue spaces. The time required for the dehydration process from Scheme 1 to Scheme 5 was 24, 23, 24, 24, and 33 h, respectively. Density between cells gradually decreased from Scheme 1 to Scheme 5, and the distance of intertissue spaces was differentiated and irregular in different schemes according to the images of Nissl staining. We recommend the dewatering method of Scheme 4 (the brain tissues were dehydrated in 10%, 20% and 30% sucrose solution in turn until the tissue samples were completely immersed in the solution and then immersed in the next concentration solution for dehydration).

miR-29a-5p rescues depressive-like behaviors in a CUMS-induced mouse model by facilitating microglia M2-polarization in the prefrontal cortex via TMEM33 suppression.

BACKGROUND: Depression accounts for a high proportion of neuropsychiatric disorders and is associated with abnormal states of neurons in specific brain regions. Microglia play a pivotal role in the inflammatory state during depression development; however, the exact mechanism underlying chronic mood states remains unknown. Thus, the present study aimed to determine whether microRNAs (miRNAs) alleviate stress-induced depression-like behavior in mice by regulating the expression levels of their target genes, explore the role of neuroinflammation induced by microglial activation in the pathogenesis and progression of depression, and determine whether the role of the miR-29a-5p/transmembrane protein 33 (TMEM33) axis. METHODS: In this study, chronic unpredictable mild stress (CUMS) mouse depression model, various behavioral tests, western blotting, dual-luciferase reporter assay, enzyme-linked immunosorbent assay, real-time quantitative reverse transcription PCR, immunofluorescence and lentivirus-mediated gene transfer were used. RESULTS: After exposure to the CUMS paradigm, miR-29a-5p was significantly down-regulated. This downregulation subsequently promoted the polarization of microglia M1 by upregulating the expression of TMEM33, resulting in enhanced inflammatory chemokines affecting neurons. Conversely, the upregulation of miR-29a-5p within the prefrontal cortex (PFC) suppressed TMEM33 expression, facilitated microglia M2-polarization, and ameliorated depressive-like behavior. LIMITATIONS: Only rodent models of depression were used, and human samples were not included. CONCLUSIONS: The results of this study suggest that miR-29a-5p deficits within the PFC mediate microglial anomalies and contribute to depressive-like behaviors. miR-29a-5p and TMEM33 may, therefore, serve as potential therapeutic targets for the treatment of depression.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden.

BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. RESULTS: The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. CONCLUSION: The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

Molecular and immunological characteristics of postoperative relapse in lymph node-positive esophageal squamous cell cancer.

BACKGROUND: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. METHODS: A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. RESULTS: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). CONCLUSION: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.

Anti-inflammatory and antinociceptive effects, toxicity, and phytochemical analysis of Beaumontia grandiflora Wall.

Preliminary pharmacological studies revealed that the EtOAc fraction (BGEA) might be the main active fraction with anti-inflammatory and antinociceptive effects in Beaumontia grandiflora Wall. Further assays on BGEA at doses of 200, 400, and 800 mg/kg using four animal models showed that it could inhibit the xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced writhing and prolong the latency time in the hot-plate test. ELISA analysis revealed that the anti-inflammatory activity of BGEA might be associated with the decrease of TNF-α, IL-1ß, and IL-6 levels and the increase of the IL-10 level. The acute toxicity test showed that except for the n-BuOH fraction, the LD50 values of the extract and other three fractions were higher than 2000 mg/kg bw. Finally, 14 compounds were identified from BGEA by LC-MS. This research provides some basis for the folk use of B. grandiflora in the treatment of inflammation and pain-related diseases.

To identify important MRI features to differentiate hepatic mucinous cystic neoplasms from septated hepatic cysts based on random forest.

OBJECTIVE: To identify important MRI features to differentiate hepatic mucinous cystic neoplasms (MCN) from septated hepatic cysts (HC) using random forest and compared with logistic regression algorithm. METHODS: Pathologically diagnosed hepatic cysts and hepatic MCNs with pre-operative contrast-enhanced MRI in our hospital from 2010 to 2023 were collected and only septated lesions on enhanced MRI were enrolled. A total of 21 septated HC and 18 MCNs were included in this study. Eighteen MRI features were analyzed and top important features were identified based on random forest (RF) algorithm. The results were evaluated by the prediction performance of a RF model combining the important features and compared with the performance of the logistic regression (LR) algorithm. Finally, for each identified feature, diagnostic probability, sensitivity, and specificity were calculated and compared. RESULTS: Four variables, i.e., the septation arising from wall without indentation, multiseptate, intracapsular cyst sign, and solitary lesion were extracted as top important features with significance for MCNs by the random forest algorithm. The RF model using these variables had an AUC of 0.982 (0.95CI, 0.950-1.000), compared with the LR model based on two identified features with AUC of 0.931 (0.95CI, 0.846-1.000), p = 0.202. Among the four important features, multiseptate had the highest specificity (95.2%) and good sensitivity (72.2%, lower than the septation from wall without indentation, 94.4%) to diagnose MCNs. CONCLUSION: Four out of 18 MRI features were extracted as reliably important factors to differ hepatic MCNs from septated HC. The combination of these four features in a RF model could achieve satisfactory diagnostic efficacy.

The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

Revealing genes associated with cervical cancer in distinct immune cells: A comprehensive Mendelian randomization analysis.

Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from different immune cell types in cervical cancers remains limited. Therefore, the primary objective of our study was to investigate the potential causal relationships between specific immune cell genes and the development of cervical cancers. By accessing expression quantitative trait loci datasets of 14 distinct immune cell types and genome wide association study of cervical cancers, we employed the summary data-based Mendelian randomization (SMR) along with multi-single nucleotide polymorphism (SNP)-based SMR to identify significant genes associated with cervical cancers. Colocalization analysis was further conducted to explore the shared genetic causality. A total of 10 genes across 11 immune cell types (26 significant gene-trait associations) were found to be associated with cervical cancers after false discovery rate correction. Notably, the ORMDL3, BRK1 and HMGN1 gene expression levels showed significant association with cervical cancer in specific immune cell types, respectively. These associations were supported by strong evidence of colocalization analyses. Our study has identified several genes in different immune cells that were associated with cervical cancer. However, further research is necessary to confirm these findings and provide more comprehensive insights into the association between these gene expressions and cervical cancer risk.

A novel clinical nomogram for predicting cancer-specific survival in patients with non-serous epithelial ovarian cancer: A real-world analysis based on the Surveillance, Epidemiology, and End Results database and external validation in a tertiary center.

BACKGROUND: Currently, there is a lack of prognostic evaluation methods for non-serous epithelial ovarian cancer (EOC). METHOD: We collected patients with non-serous EOC diagnosed between 2010 and 2017 from the Surveillance, Epidemiology, and End Results (SEER) database into a training cohort (n = 2078) and an internal validation cohort (n = 891). Meanwhile, patients meeting the criteria were screened from the Fujian Provincial Maternal and Child Health Hospital from 2013 to 2022 as an external validation cohort (n = 56). Univariate and multivariable logistic regression were used to determine the independent prognostic factors of cancer-specific survival (CSS) to construct the nomogram. The nomogram was validated by the concordance index (C-index), receiver operating characteristics (ROC) curve and calibration curves. RESULT: Age, laterality, preoperative CA125 status, histologic type, tumor grade, AJCC stage, surgery lesion, number of lymph nodes examined, residual lesion size, and bone metastasis were identified as independent prognostic factors to construct the nomogram. The nomogram showed better predictive ability than FIGO stage through internal and external cohorts validation. The C-index of the nomogram in the training cohort, validation cohort, and external validation cohort were 0.831, 0.835 and 0.944 higher than those of the Federation International of Gynecology and Obstetric (FIGO) stage, P<0.05. The Area Under Curve (AUC) values results indicated great clinical usefulness of the nomogram. The calibration curve indicated good agreement between the nomogram prediction and actual survival. CONCLUSION: We developed a nomogram with high predictive accuracy to predict survival in patients with non-serous EOC.

Facile introduction of coordinative Fe into oxygen-enriched graphite carbon nitride for efficient photo-Fenton degradation of tetracycline.

Tetracycline (TC) antibiotics have been widely used over the past decades, and their massive discharge led to serious water pollution. Photo-Fenton process has gained ever-increasing attention for its excellent oxidizing ability and friendly solar energy utilization ability in TC polluted water treatment. This work introduced coordinative Fe into oxygen-enriched graphite carbon nitride (OCN) to form FeOCN composites for efficient photo-Fenton process. Hemin was chosen as the source to provide the source of coordinative Fe-Nx groups. The degradation efficiency of TC reached 82.1 % within 40 min of irradiation, and remained 76.9 % after five runs of reaction. The degradation intermediates of TC were detected and the possible degradation pathways were gained. It was found that h+, OH, and O2- played major roles in TC degradation. Notably, the photo-Fenton performance of FeOCN was stable in highly saline water or strong acid/base environment (pH 3.0-9.0). Besides, H2O2 can be generated in-situ in this photo-Fenton process, which is favorable for practical application. It can be anticipated that the coordinative FeOCN composites will promote the application of photo-Fenton oxidation process in TC polluted water treatment.

Carbonaceous Materials-Based Photothermal Process in Water Treatment: From Originals to Frontier Applications.

The photothermal process has attracted considerable attention in water treatment due to its advantages of low energy consumption and high efficiency. In this respect, photothermal materials play a crucial role in the photothermal process. Particularly, carbonaceous materials have emerged as promising candidates for this process because of exceptional photothermal performance. While previous research on carbonaceous materials has primarily focused on photothermal evaporation and sterilization, there is now a growing interest in exploring the potential of photothermal effect-assisted advanced oxidation processes (AOPs). However, the underlying mechanism of the photothermal effect assisted by carbonaceous materials remains unclear. This review aims to provide a comprehensive review of the photothermal process of carbonaceous materials in water treatment. It begins by introducing the photothermal properties of carbonaceous materials, followed by a discussion on strategies for enhancing these properties. Then, the application of carbonaceous materials-based photothermal process for water treatment is summarized. This includes both direct photothermal processes such as photothermal evaporation and sterilization, as well as indirect photothermal processes that assisted AOPs. Meanwhile, various mechanisms assisted by the photothermal effect are summarized. Finally, the challenges and opportunities of using carbonaceous materials-based photothermal processes for water treatment are proposed.

Hypoxia-Responsive Tetrameric Supramolecular Polypeptide Nanoprodrugs for Combination Therapy.

Despite the intense progress of photodynamic and chemotherapy, however, they cannot prevent solid tumor invasion, metastasis, and relapse, along with inferior efficacy and severe side effects. The hypoxia-responsive nanoprodrugs integrating photodynamic functions are highly sought to address the above-mentioned problems and overcome the tumor hypoxia-reduced efficacy. Herein, a hypoxia-responsive tetrameric supramolecular polypeptide nanoprodrug (SPN-TAPP-PCB4) is constructed from the self-assembly of tetrameric porphyrin-central poly(l-lysine-azobenzene-chlorambucil) (TAPP-(PLL-Azo-CB)4) and an anionic water-soluble [2]biphenyl-extended-pillar[6]arene (AWBpP6) via the synergy of hydrophobic, π-π stacking, and host-guest interactions. Upon laser irradiation, the central TAPP can convert oxygen to generate single oxygen (1 O2 ) to kill tumor cells. Furthermore, under the acidic and PDT-aggravated hypoxia tumor cell microenvironment, SPN-TAPP-PCB4 is rapidly disassembled, and then efficiently releases activated CB through the hypoxic-responsive cleavage of azobenzene linkages. Both in vitro and in vivo biological studies showcase synergistic cancer-killing actions between photodynamic therapy (PDT) and chemotherapy (CT) with negligible toxicity. Consequently, this supramolecular polypeptide nanoprodrug offers an effective strategy to design a hypoxia-responsive nanoprodrug for a potential combo PDT-CT transition.

Associations of multi-human papillomavirus infections with expression of p16 in a cohort of women who underwent colposcopy: a retrospective study of 5165 patients.

Objective: Investigate HPV types in cervical specimens, their correlation with p16 expression in lesions, and diagnostic value for cervical lesions. Enhance clinical diagnosis reliability. Methods: Retrospective cross-sectional study at Fujian Maternity and Child Health Hospital's Cervical Disease Center (Jun 2019-Dec 2021). Patients with abnormal cervical screening underwent colposcopy and conization. Pathological diagnosis based on colposcopy, cervical biopsy, ECC, and conization. Analyzed HPV genotyping (18 HR-HPV, 5 LR-HPV) and p16 expression correlation. Statistical analysis used R software. Results: he expression of p16 is significantly associated with the infection of high-risk HPV types, such as 16, 33, 52, and 58, with an increased risk of 1.4 times or higher (OR=1.91, 3.14, 1.40, and 1.78, respectively). The risk of p16 expression increased 4-fold for multiple high-risk HPV types [adjusted OR (95% CI) = 4 (2.92~5.5), P-value <0.001]. Compared to the p16(-) group, the p16(+) group had a higher association with cervical lesions worse than HSIL (High-grade Squamous Intraepithelial Lesions).In the group with multiple Human Papillomavirus Infections with types 16, 33, 52, and 58, the risk of cervical lesions worse than HSIL increased by up to 660-fold compared to the negative group (adjusted OR=660.62, 95% CI: 91.39~4775.53, P<0.001), indicating that this combination of HPV types posed the greatest risk for cervical lesions above HSIL. Conclusions: p16 plays a crucial role in cervical lesion progression, linked to high-risk HPV. Combining p16 with HPV screening improves cervical cancer detection. Studying multiple HPV infections will enhance prevention and management.

Causal effect of gut microbiota on DNA methylation phenotypic age acceleration: a two-sample Mendelian randomization study.

The causal relationship between gut microbiota and DNA methylation phenotypic age acceleration remains unclear. This study aims to examine the causal effect of gut microbiota on the acceleration of DNA methylation phenotypic age using Mendelian randomization. A total of 212 gut microbiota were included in this study, and their 16S rRNA sequencing data were obtained from the Genome-wide Association Study (GWAS) database. The GWAS data corresponding to DNA methylation phenotypic age acceleration were selected as the outcome variable. Two-sample Mendelian randomization (TSMR) was conducted using R software. During the analysis process, careful consideration was given to address potential biases arising from linkage disequilibrium and weak instrumental variables. The results from inverse-variance weighting (IVW) analysis revealed significant associations (P < 0.05) between single nucleotide polymorphisms (SNPs) corresponding to 16 gut microbiota species and DNA methylation phenotypic age acceleration. Out of the total, 12 gut microbiota species exhibited consistent and robust causal effects. Among them, 7 displayed a significant positive correlation with the outcome while 5 species showed a significant negative correlation with the outcome. This study utilized Mendelian randomization to unravel the intricate causal effects of various gut microbiota species on DNA methylation phenotypic age acceleration.

[Short-term nitrogen deposition changes chemical composition of litter and soil organic matter in a Moso bamboo forest]. / 短期氮沉降改变毛竹林凋落物和土壤有机质化学组成.

To investigate the effects of short-term nitrogen (N) deposition on organic matter composition of litter and soil in Moso bamboo (Phyllostachys edulis) forests, we established a N-addition treatments (50 kg N·hm-2·a-1) to simulate the ambient and N deposition in a subtropical Moso bamboo forest from July 2020 to January 2022. We analyzed the organic matter composition of Moso bamboo leaf/root litter and soil by using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) technique. The results showed that short-term N deposition significantly increased the relative content of soil phenols by 50.9%, while significantly decreased fatty acids by 26.3%. The rela-tive content of alkanes & alkenes and lignin in leaf litter was significantly increased by 51.9% and 33.5%, respectively, while that of phenols and polysaccharides significantly decreased by 52.2% and 56.3%. In root litter, eleva-ted N significantly decreased the relative content of polycyclic aromatic hydrocarbons by 16.6%. Moreover, the relative content of fatty acids in soil organic matter was significantly positively correlated with the relative content of poly-saccharides in leaf litter. The relative content of phenols in soil organic matter was significantly positively correlated with the relative content of lignin, and negatively correlated with the relative content of polysaccharides in leaf litter. Our results demonstrated that short-term N deposition did not change the concentration of total organic carbon, total nitrogen, and C/N of the soil, leaf litter, and root litter, but significantly altered the chemical composition of organic matter. In addition, the changes in chemical composition of organic matter in soil under short-term N deposition were affected by the composition of organic matter in leaf litter.