Optimizing the development of contaminated land in China: Exploring machine-learning to identify risk markers.

Often available for use, previously developed land, which includes residential and commercial/industrial areas, presents a significant challenge due to the risk to human health. China's 2018 release of health risk assessment standards for land reuse aimed to bridge this gap in soil quality standards. Despite this, the absence of representative indicators strains risk managers economically and operationally. We improved China's land redevelopment approach by leveraging a dataset of 297,275 soil samples from 352 contaminated sites, employing machine learning. Our method incorporating soil quality standards from seven countries to discern patterns for establishing a cost-effective evaluative framework. Our research findings demonstrated that detection costs could be curtailed by 60% while maintaining consistency with international soil standards (prediction accuracy = 90-98%). Our findings deepen insights into soil pollution, proposing a more efficient risk assessment system for land redevelopment, addressing the current dearth of expertise in evaluating land development in China.

Interactions between microbiota and cervical epithelial, immune, and mucus barrier.

The female reproductive tract harbours hundreds of bacterial species and produces numerous metabolites. The uterine cervix is located between the upper and lower parts of the female genital tract. It allows sperm and birth passage and hinders the upward movement of microorganisms into a relatively sterile uterus. It is also the predicted site for sexually transmitted infection (STI), such as Chlamydia, human papilloma virus (HPV), and human immunodeficiency virus (HIV). The healthy cervicovaginal microbiota maintains cervical epithelial barrier integrity and modulates the mucosal immune system. Perturbations of the microbiota composition accompany changes in microbial metabolites that induce local inflammation, damage the cervical epithelial and immune barrier, and increase susceptibility to STI infection and relative disease progression. This review examined the intimate interactions between the cervicovaginal microbiota, relative metabolites, and the cervical epithelial-, immune-, and mucus barrier, and the potent effect of the host-microbiota interaction on specific STI infection. An improved understanding of cervicovaginal microbiota regulation on cervical microenvironment homeostasis might promote advances in diagnostic and therapeutic approaches for various STI diseases.

Analysis of the related factors of atypical squamous cells of undetermined significance (ASC-US) in cervical cytology of post-menopausal women.

Introduction: Atrophy of the reproductive tract mucosa caused by the decrease of estrogen may increase the detection rate of ASC-US in cervical cytology of post-menopausal women. In addition, other pathogenic infections and inflammation can change the cellular morphology and increase the detection rate of ASC-US. However, further studies are needed to elucidate whether the high detection rate of ASC-US in post-menopausal women leads to the high referral rate of colposcopy. Methods: This retrospective study was conducted to document ASC-US in cervical cytology reports at the Department of Cytology at Gynecology and Obstetrics, Tianjin Medical University General Hospital between January 2006 and February 2021. We then analyzed 2,462 reports of women with ASC-US at the Cervical Lesions Department. A total of 499 patients with ASC-US and 151 cytology with NILM participants underwent vaginal microecology tests. Results: The average reporting rate of ASC-US in cytology was 5.7%. The detection rate of ASC-US in women aged > 50 years (7.0%) was significantly higher than that in women aged ≤50 years (5.0%) (P<0.05). The CIN2+ detection rate was significantly lower in the post- (12.6%) than in pre-menopausal (20.5%) patients with ASC-US (P <0.05). The prevalence of abnormal reporting rate of vaginal microecology was significantly lower in the pre-menopausal group (56.2%) than that in the post-menopausal group (82.9%) (P<0.05). The prevalence of bacterial vaginosis (BV) (19.60%) was relatively high in the pre-menopausal group, but the abundance of bacteria-inhibiting flora (40.79%) was mainly an abnormality in the post-menopausal group. The vaginal microecological abnormality rate of the women with HR-HPV (-) of ASC-US was 66.22%, which was significantly higher than that of the HR-HPV (-) and the NILM group (52.32%; P<0.05). Discussion: The detection rate of ASC-US in women aged > 50 years was higher than that ≤50 years, but the detection rate of CIN2+ was lower in the post-menopausal women with ASC-US. However, vaginal microecological abnormalities may increase the false-positive diagnosis rate of ASC-US. The vaginal microecological abnormalities of the menopausal women with ASC-US are mainly attributed to infectious diseases such as BV, and it mainly occurs in the post-menopausal women was bacteria-inhibiting flora. Therefore, to avoid the high referral rate for colposcopy, more attention should be paid to the detection of vaginal microecology.

Leveraging 16S rRNA data to uncover vaginal microbial signatures in women with cervical cancer.

Microbiota-relevant signatures have been investigated for human papillomavirus-related cervical cancer (CC), but lack consistency because of study- and methodology-derived heterogeneities. Here, four publicly available 16S rRNA datasets including 171 vaginal samples (51 CC versus 120 healthy controls) were analyzed to characterize reproducible CC-associated microbial signatures. We employed a recently published clustering approach called VAginaL community state typE Nearest CentroId clAssifier to assign the metadata to 13 community state types (CSTs) in our study. Nine subCSTs were identified. A random forest model (RFM) classifier was constructed to identify 33 optimal genus-based and 94 species-based signatures. Confounder analysis revealed confounding effects on both study- and hypervariable region-associated aspects. After adjusting for confounders, multivariate analysis identified 14 significantly changed taxa in CC versus the controls (P < 0.05). Furthermore, predicted functional analysis revealed significantly upregulated pathways relevant to the altered vaginal microbiota in CC. Cofactor, carrier, and vitamin biosynthesis were significantly enriched in CC, followed by fatty acid and lipid biosynthesis, and fermentation of short-chain fatty acids. Genus-based contributors to the differential functional abundances were also displayed. Overall, this integrative study identified reproducible and generalizable signatures in CC, suggesting the causal role of specific taxa in CC pathogenesis.

Interaction Patterns between Climate Action and Air Cleaning in China: A Two-Way Evaluation Based on an Ensemble Learning Approach.

China will attempt to achieve its simultaneous goals in 2060, whereby carbon neutrality will be accomplished and the PM2.5 (fine particulate matter) level is expected to remain below 10 µg/m3. Identifying interaction patterns between air cleaning and climate action represents an important step to obtain cobenefits. Here, we used a random sampling strategy through the combination of chemical transport modeling and machine learning approach to capture the interaction effects from two perspectives in which the driving forces of both climate action and air cleaning measures were compared. We revealed that climate action where carbon emissions were decreased to 1.9 Bt (billion tons) could lead to a PM2.5 level of 12.4 µg/m3 (95% CI (confidence interval): 10.2-14.6 µg/m3) in 2060, while air cleaning could force carbon emissions to reach 1.93 Bt (95% CI: 0.79-3.19 Bt) to achieve net carbon neutrality based on the potential carbon sinks in 2060. Additional controls targeting primary PM2.5, ammonia, and volatile organic compounds were required as supplements to overcome the partial lack of climate action. Our study provides novel insights into the cobenefits of air-quality improvement and climate change mitigation, indicating that the effect of air cleaning on the simultaneous goals might have been underestimated before.

Mixed Vaginitis in the Third Trimester of Pregnancy Is Associated With Adverse Pregnancy Outcomes: A Cross-Sectional Study.

Mixed vaginitis is a complex vaginal dysbiosis that differs from single vaginitis. Vaginitis in the third trimester may lead to adverse maternal and neonatal outcomes. The clinical characteristics, microbiological characteristics, and adverse pregnancy outcomes of mixed vaginitis in late pregnancy are worth studying. Therefore, this study investigated the clinical and microbiological characteristics of vaginitis and adverse pregnancy outcomes of patients with mixed vaginitis. We studied 1,674 women in late pregnancy who attended the Tianjin Medical University General Hospital from November, 2019 to October, 2021. We administered standardized questionnaires, performed vaginal examination and sampling plus microscope examinations, and assessed follow-up pregnancy outcomes. We cultured the vaginal discharge of the patients with mixed vaginitis to isolate pathogens and performed antimicrobial susceptibility tests of the isolated pathogens. For the patients with peripartum infection, we collected a sample to isolate pathogens. Among the 1,674 women, 66 (3.9%) had mixed vaginitis. The independent risk factor for mixed vaginitis in late pregnancy was a history of vaginitis during early and middle pregnancy (OR = 5.637, 95% CI: 3.314-9.580). The signs of vaginal erythema (63.6% vs. 42.0%), yellow discharge (81.8% vs. 59.6%), and malodor (31.8% vs. 18.8%) (P <0.05) were significantly higher in patients with mixed vaginitis than in patients with single vaginitis. Bacterial isolates of the vaginal secretions of patients with mixed bacterial vaginitis were mainly the pathogens of aerobic vaginitis and bacterial vaginosis, such as Gardnerella vaginalis, Streptococcus anginosus, and Staphylococcus epidermidis. Pathogen isolation of the vaginal secretions of patients with mixed fungus and bacteria vaginitis mainly included Candida albicans, followed by S. anginosus, Enterococcus faecalis, Staphylococcus hemolyticus, Staphylococcus aureus, Streptococcus agalactiae and Staphylococcus simulans. Women with mixed vaginitis had an increased incidence and risk of peripartum infections (6.1% vs. 1.4%, P <0.05; OR = 3.985, 95% CI:1.214-13.079). Escherichia coli is the main pathogen that causes peripartum infection. Mixed vaginitis in late pregnancy is characterized by a severe and complex phenotype, complex vaginal dysbiosis, and a long course of vaginal dysbiosis. This can lead to an increased incidence and risk of peripartum infection. Therefore, more attention should be paid to patients with mixed vaginitis in the third trimester of pregnancy.

Aerobic Vaginitis Diagnosis Criteria Combining Gram Stain with Clinical Features: An Establishment and Prospective Validation Study.

Wet-mount microscopy aerobic vaginitis (AV) diagnostic criteria need phase-contrast microscopy and keen microscopists, and the preservation of saline smears is less common in clinical practice. This research work developed new AV diagnostic criteria that combine Gram stain with clinical features. We enrolled 325 AV patients and 325 controls as a study population to develop new AV diagnostic criteria. Then, an independent group, which included 500 women, was used as a validation population. AV-related microscopic findings on Gram-stained and wet-mount smears from the same participants were compared. The accuracy of bacterial indicators from the two methods was verified by bacterial 16S rRNA V4 sequencing (n = 240). Logistic regression was used to analyse AV-related clinical features. The screened clinical features were combined with Gram-stain microscopic indicators to establish new AV diagnostic criteria. There were no significant differences in the leukocyte counts or the parabasal epitheliocytes (PBC) proportion between the Gram-stain and wet-mount methods (400×). Gram stain (1000×) satisfied the ability to identify bacteria as verified by 16S rRNA sequencing but failed to identify toxic leukocytes. The new criteria included: Lactobacillary grades (LBG) and background flora (Gram stain, 1000×), leukocytes count and PBC proportion (Gram stain, 400×), and clinical features (vaginal pH > 4.5, vagina hyperemia, and yellow discharge). These criteria satisfied the accuracy and reliability for AV diagnosis (Se = 86.79%, Sp = 95.97%, and Kendall's W value = 0.899) in perspective validation. In summary, we proposed an alternative and valuable AV diagnostic criteria based on the Gram stain, which can make it possible to diagnose common vaginitis like AV, BV, VVC, and mixed infections on the same smear and can be available for artificial intelligence diagnosis in the future.

Recent Advances in Presentation, Diagnosis and Treatment for Mixed Vaginitis.

Mixed vaginitis is the simultaneous presence of at least two types of vaginitis, contributing to an abnormal vaginal milieu and leading to vaginal symptoms and signs. However, associations between symptoms and the type of mixed vaginitis have not been clearly elucidated, and research on mixed vaginitis is still in the preliminary stage. Therefore, the pathogenic mechanism of mixed vaginitis remains understudied. Mixed vaginitis generally involves the formation of mixed biofilms. The study of polymicrobial interactions and mixed biofilms will provide a new idea for the understanding of mixed vaginitis. Moreover, this review summarizes some effective management and laboratory diagnosis of mixed vaginitis to avoid inappropriate therapy, recurrence, and reinfection. It is of high clinical importance to obtain relevant clinical data to improve clinical knowledge about mixed vaginitis.

Unraveling Heterogeneity of Tumor Cells and Microenvironment and Its Clinical Implications for Triple Negative Breast Cancer.

Objective: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, characterized by extensive intratumoral heterogeneity. We aimed to systematically characterize the tumor heterogeneity of TNBC. Methods: Single-cell RNA sequencing (scRNA-seq) of TNBC cells were obtained from the GSE118389 and GSE75688 datasets. After integration of the two datasets, cell clustering analysis was performed using the Seurat package. According to the marker genes of cell cycle, cell cycle of each cell cluster was determined. Then, function enrichment analysis of marker genes in each cell cluster was performed, followed by ligand-receptor signaling network analysis. CIBERSORT was used to estimate the proportion of 22 immune cells in each sample based on RNA-seq data of 58 normal adjacent tissues and 101 TNBC tissues. After that, prognostic value of immune cells was assessed. Results: In the integrated datasets, five cells types including B cells, myeloid cells, stromal cells, T cells, and tumor cells were clustered. Functional enrichment analysis revealed the functional heterogeneity of genes in each cell. Intercellular communication networks were conducted based on ligand-receptor pairs. The heterogeneity in the fractions of 22 immune cells was found in TNBC tissues. Furthermore, there was a significant difference in the fractions of these immune cells between adjacent normal tissues and TNBC tissues. Among them, M2 macrophages and neutrophils were significantly associated with clinical outcomes of TNBC. Moreover, the fractions of T cells CD4 memory resting, monocytes, neutrophils, M1 macrophages, and T cells CD4 memory activated were significantly correlated with clinical characteristics of TNBC. As shown in PCA results, these immune cells could significantly distinguish TNBC tissues into adjacent normal tissues. Conclusion: Our findings characterized the tumor heterogeneity of TNBC, which deepened the understanding of the complex interactions between tumor cells and their microenvironment, especially immune cells.

How to apply O3 and PM2.5 collaborative control to practical management in China: A study based on meta-analysis and machine learning.

Constant increase of atmospheric O3 concentration is a barrier for the further air quality improvement in China. Given that PM2.5 is still controlled as a key pollutant, managements for the collaborative reduction of O3 and PM2.5 are urgently required in China. In the current work, monitoring data of O3 and PM2.5 from 2015 to 2016 in 1464 monitoring sites (MS) was collected and cleaned. Additionally, 7 anthropogenic emission reductions were jointed with the corresponding monitoring data. According to the O3 and PM2.5 variation, a meta-analysis was conducted and divided regions into 4 categories via the effect size, region I: O3 and PM2.5 collaborative reduction, region II: PM2.5 decreased and O3 increased, region III: O3 decreased and PM2.5 increased, regions IV: both O3 and PM2.5 increased. Then, based on the region labels, machine learning was used to identify the pattern between region label and its precursor reductions. The findings were as follows: (1) Principal component analysis showed that NH3 was not focused on. (2) Random forest had a well performance on region classification with the accuracy of 80.40% and the importance of the 7 precursors was in the sequence of VOCs>NH3 > PM2.5 > OC > SO2 > NOX > Coarse PM. (3) Polytomous logistic regression evaluated the critical factors that influenced the region label, which showed that the reductions of VOCs, NH3 and PM2.5 could achieve the collaborative reduction in a short time in most of cities in China. Based on the statistical results above, a kinetic management system including evaluation and policy-making sections was finally established, which filled the gap of the collaborative reduction in environmental management in China.

Identification by Comprehensive Bioinformatics Analysis of KIF15 as a Candidate Risk Gene for Triple-Negative Breast Cancer.

BACKGROUND: Previous studies have shown that kinesin family proteins (KIFs) play an indispensable roles in several types of cancer. However, the expression and clinical significance of KIFs in triple-negative breast cancer remain unclear. METHODS: In this study, the role of KIF15, including gene expression analysis, methylation characteristic, CNV characteristic, and miRNA target regulation, was evaluated using multiple bioinformatic tools based on TCGA database. Quantitative real-time PCR and Western blot were used to determine the expression level of KIF15 in triple-negative breast cancer cell lines. Then, functional experiments were employed to explore the effects of KIF15 on tumor growth and metastasis in triple-negative breast cancer. RESULTS: Our data showed that KIF15 was significantly upregulated in triple-negative breast cancer (TNBC). Functionally, downregulation of KIF15 significantly facilitated apoptosis and G2/M phase arrest, and inhibited the migration and invasion of TNBC cells. The mechanism of action of KIF15 was closely related to DNA replication checkpoint and cell cycle regulation in TNBC based on GSEA. In addition, bioinformatics analysis demonstrated that high expression of KIF15 in TNBC was correlated with copy number aberration and DNA methylation levels. CONCLUSION: Our findings suggest that KIF15 is a novel oncogene in TNBC and provide us a strong evidence that it might be served as a potential clinical target and biomarker in triple-negative breast cancer.

Hormonal therapy in uterine sarcomas.

Uterine sarcomas (USs) are a group of rare but aggressive uterine malignancies, accounting for only 1% of the malignant tumors of female reproductive organs. Due to the high rate of recurrence and metastasis, the prognosis of USs is poor. Given the high mortality rate and limited clinical benefit of surgery and adjuvant chemoradiotherapy, hormonal therapy has shown good prospects in recent years. Hormonal agents include progestins, aromatase inhibitors (AIs), and gonadotropin-releasing hormone analogue (GnRH-a). According to the literature, hormonal therapy has been confirmed effective for recurrent, metastatic or unresectable low-grade endometrial stromal sarcoma (LGESS) and hormone receptor positive (ER+/PR+) uterine leiomyosarcoma (uLMS) with favorable tolerance and compliance. Besides, hormonal therapy can also be used in patients with early-staged disease who desire to preserve fertility. However, due to the rarity of USs, the rationale of hormonal therapy is generally extrapolated from data of hormone-sensitive breast cancer, and present studies of hormonal therapy in USs were almost limited to case reports and small-sized retrospective studies. Therefore, further systematic researches and standardized clinical trials are needed to establish the optimal hormonal therapy regimen of USs. Herein, we reviewed the existing studies related to the hormonal therapy in USs in order to provide reference for clinical management in specific settings.

Risk factors, microbiology and management of infected lymphocyst after lymphadenectomy for gynecologic malignancies.

OBJECTIVE: To evaluate risk factors, microbiology and management of infected lymphocysts in patients undergoing systemic lymphadenectomy for gynecological cancer. METHODS: Patients with gynecological cancer who developed postoperative lymphocysts after lymphadenectomy were enrolled between January 2009 and June 2017. The clinical data of infected lymphocysts were analyzed and compared with non-infected lymphocysts. Multivariate analysis of risk factors, the microbiology and therapeutic strategies for infected lymphocysts were also evaluated. RESULTS: A total of 115 patients out of 619 developed postoperative lymphocysts, the incidence of infected lymphocysts was 4.36%. Infected lymphocysts were more frequently found in patients with combined pelvic and para aortic lymphadenectomy, higher number of resected pelvic lymph nodes, lower level of postoperative serum hemoglobin and higher proportion of neutropenia. The median diameter of infected lymphocysts was significantly larger than non-infected (71.89 vs 38.47 mm, P < 0.001) and a large size (diameter over 60 mm) was identified as an independent risk factor for infected lymphocysts (OR = 3.933, P = 0.017). The microbiology of infected lymphocysts includes gram-positive cocci, gram-negative bacillus and anaerobic bacteria. Percutaneous catheter drainage was successfully performed in 20 patients with infected lymphocysts. 16 of 19 patients with large lymphoceles received combined antibiobics and PCD therapy and showed clinical remission in all cases. Patients with large size infected lymphocysts who received combined therapy experienced a significantly shorter treatment period and lower recurrent rate than those with only antibiotics (P = 0.046, P = 0.018). CONCLUSIONS: The current study demonstrated that a diameter over 60 mm was an independent risk factor for infected lymphocysts. The predominant bacteria originated from the urogenital or skin flora. The combination of PCD with appropriate antibiotics was a convenient and effective therapeutic strategy resulting in a high success rate.

Ovarian cancer presenting with hypercalcemia: two cases with similar manifestations but different mechanisms.

Hypercalcemia presenting in ovarian cancer is uncommon in the clinic. Here, two cases of ovarian epithelial carcinoma that presented with severe hypercalcemia were reported, with a review of the literature. The laboratory findings and stepwise clinical investigations of these two cases differed, indicating distinct underlying causes of hypercalcemia. In case one, the serum levels and immunostaining for parathyroid hormone-related protein (PTHrP) verified humoral hypercalcemia of malignancy (HHM). In case two, the high level of parathyroid hormone (PTH) and the scintigraphy scan showing parathyroid gland adenoma confirmed primary hyperparathyroidism-induced hypercalcemia. Both patients received optimal cytoreductive operation and adjuvant chemotherapy but showed different outcomes respectively. This article focused on differential diagnosis of ovarian cancer-associated hypercalcemia, by stepwise imaging and laboratory investigation, and the appropriate therapy should be considered based on the different etiologies.

Bioinformatics analysis of key differentially expressed genes in well and poorly differentiated endometrial carcinoma.

Endometrial carcinoma (EC) is one of the most common gynecological malignancies. The malignant degree increases between grade (G)1 and G3, and EC of G3 usually presents a high recurrence rate and poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in EC. The microarrays GSE17025, GSE24537 and GSE35784, representing data of Type I EC samples of G1 and G3, were downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) and differentially expressed micro (mi)RNAs (DEMs) were identified, followed by functional enrichment analyses and interaction network construction. In total, 83 upregulated and 130 downregulated DEGs with the same expression trends in two mRNA datasets were screened. The upregulated DEGs were primarily enriched in 'mitotic cell cycle process', 'cell cycle process' and 'mitotic cell cycle'; while the downregulated DEGs were enriched in 'cellular component assembly involved in morphogenesis', 'cell projection organization' and 'microtubule­based movement'. From the protein­protein interaction network, DNA topoisomerase IIα, kinesin family member 11, cyclin B1 and BUB1 mitotic checkpoint serine/threonine were identified as foremost hub genes. One module was extracted and involved in 'mitotic cell cycle process' and 'cell cycle process'. Based on the analysis of DEMs and the miRNA­target regulatory network, miRNA­9 may be the most important upregulated DEM, and the DEGs forkhead box P1 and cyclin E1 may serve vital roles in the differentiation of EC. In conclusion, principal genes were identified that may be determinants of the carcinogenesis of poorly differentiated EC, which may facilitate the examination of potential molecular mechanisms. These genes may additionally help identify candidate biomarkers and novel therapeutic targets for poorly differentiated EC.

Preliminary clinical application of an aromatase inhibitor and a gonadotropin-releasing hormone agonist combination for inoperable endometrial cancer patients with comorbidities: case report and literature review.

Background: Endometrial cancer (EC) occurs most commonly after menopause. A proportion of patients present with advanced age and comorbidities, and become ineligible for surgery. The optimal treatment strategy of these patients remains a clinical challenge. Aromatase inhibitor (AI) combined with Gonadotropin-releasing hormone agonist (GnRH-a) possesses profound effect in suppressing the estrogen level, has become a valid treatment in the breast cancer. However, the combined use of an AI and a GnRH-a in EC has rarely been studied. Case presentation: Herein, we report the combination of an AI and a GnRH-a in the treatment of three patients with advanced age or comorbidities who were ineligible for surgery. The disease remained stable for two years in patients who received the combination treatment as an initial approach without any adverse effects. Moreover, an AI combined with a GnRH-a also effective as salvage treatment of recurrent patients. Further, we provide a brief review of the literature. Conclusion: The combination of an AI and a GnRH-a presents satisfactory therapeutic effect and provides an optimal option for inoperable EC patients.