Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

A Morpholine Derivative N-(4-Morpholinomethylene)ethanesulfonamide Induces Ferroptosis in Tumor Cells by Targeting NRF2.

Small molecule drugs containing morpholine-based moieties have become crucial candidates in the tumor targeted therapy strategies, but the specific molecular mechanisms of these drugs causing tumor cell death require further investigation. The morpholine derivative N-(4-morpholinomethylene)ethanesulfonamide (MESA) was used to stimulate prostate and ovarian cancer cells and we focused on the ferroptosis effects, including the target molecule and signal pathways mediated by MESA. The results showed that MESA could induce ferroptosis to cause the proliferation inhibition and apoptosis effects of tumor cells according to the identification of ferroptosis inhibitor fer-1 and other cell death inhibitors. Further MESA could significantly increase the intracellular malondialdehyde (MDA), reactive oxygen species (ROS) and Fe2+ levels in tumor cells and mediate the dynamic changes of ferroptosis-relative molecules GPX4, nuclear factor erythroid2-related factor 2 (NRF2), ACSL4, SLC7A11 and P62-Kelch-like ECH-associated protein 1 (KEAP1)-NRF2-antioxidant response element (ARE) signal pathways. Further, NRF2 overexpression could reduce the tumor cell death and ROS levels exposure to MESA. Most importantly, it was confirmed that MESA could bind to NRF2 protein through molecular docking and thermal stability assays and NRF2 was a target molecule of MESA for inducing ferroptosis effects in tumor cells. Collectively, our findings indicated the ferroptosis effects of the morpholine derivative MESA in prostate and ovarian cancer cells and its function mechanism including targeted molecule and signal pathways, which would be helpful for developing MESA as a prospective small molecule drug for cancer therapy based on cell ferroptosis.

PAX1 and SEPT9 methylation analyses in cervical exfoliated cells are highly efficient for detecting cervical (pre)cancer in hrHPV-positive women.

Studies have investigated PAX1 and SEPT methylation were closely associated with cervical cancer. For this study, we verified the expressions of PAX1 and SEPT9 methylation in 236 hrHPV women cervical exfoliated cells by using quantitative methylation-specific PCR and we further explored their diagnostic value in cervical (pre)cancer detection. Our results identified that the methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71-0.83) and the AUC of SEPT9 methylation was 0.86 (95% CI 0.81∼0.90). Analyses of the PAX1 and SEPT9 methylation statuses alone or combined with commonly used tests can efficiently identify cervical (pre)cancer. In particular, SEPT9 methylation might serve as an effective and powerful biomarker for the diagnosis of cervical (pre)cancer and as an alternative triage test in HPV-based cervical (pre)cancer screening programs.Impact StatementWhat is already known on this subject? This subject showed that PAX1 and SEPT9 methylation were closely associated with cervical cancer. The methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity and reached a peak in cervical cancer exfoliated cells. We further assessed the diagnostic performances of PAX1 and SEPT9 methylation in cervical cancer screening. In detecting cervical (pre)cancer, the sensitivity values of PAX1 and SEPT9 methylation were up to 61.18% and 82.35%, respectively, and the specificity values of PAX1 and SEPT9 methylation were up to 95.36% and 86.75%, respectively. Moreover, the ROC curve analysis showed AUC values of 0.77 for PAX1 methylation and 0.86 for SEPT9 methylation tests, which were significantly superior to other commonly used tests. These findings suggest that PAX1 and SEPT9 methylation detection may have great clinical potential in cervical cancer screening.What the results of this study add? The rates and levels of PAX1 and SEPT9 methylation increased with the severity of the cervical lesions. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71-0.83), and the sensitivity and specificity values were 61.18% and 95.36%, respectively. The AUC value of the SEPT9 methylation was 0.86 (95% CI 0.81 ∼ 0.90), and the sensitivity and specificity values were 82.35% and 86.75%, respectively. Compared with the various tests we conducted, the PAX1 methylation showed the highest specificity (95.36%), and the SEPT9 methylation demonstrated the highest accuracy(86.00%).What the implications are of these findings for clinical practice and/or further research? The methylation levels of PAX1 and SEPT9 had a certain predictive effect on the severity of cervical lesions in hrHPV-positive women. In addition, SEPT9 methylation analysis performs better than PAX1 methylation analysis and commonly used tests in cervical exfoliated cells for detecting cervical (pre)cancer in hrHPV-positive women. SEPT9 methylation analysis merits consideration as an effective and objective, alternative triage test in HPV-based cervical (pre)cancer screening programs.

Septin9 DNA methylation as a promising biomarker for cervical cancer.

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statementWhat is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction.What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg.What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.

Circ_0025033 deficiency suppresses paclitaxel resistance and malignant development of paclitaxel-resistant ovarian cancer cells by modulating the miR-532-3p/FOXM1 network.

BACKGROUND: Ovarian cancer (OC) is the main cause of cancer-related death in women, and drug resistance is a leading cause of treatment failure. Recently, the involvement of circular RNAs (circRNAs) in cancer progression has become an area of increased investigation. The objective of this study is to uncover the function and regulatory mechanism of circ_0025033 in paclitaxel (PTX)-resistant OC cells. METHODS: The expression of circ_0025033, FOXM1 and miR-532-3p was investigated using quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression of FOXM1 was quantified by western blot. Cell biological functions, including cell viability, migration/invasion and apoptosis, were explored using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays, transwell assays and flow cytometry assays. The interaction between miR-532-3p and circ_0025033 or FOXM1 predicted by bioinformatics analysis was validated by pull-down assay and dual-luciferase reporter assay. Exosomes were isolated to determine the further function of circ_0025033. RESULT: Circ_0025033 and FOXM1 were highly expressed, while miR-532-3p was poorly expressed in OC tissues and cells, and the expression pattern was greater in PTX-resistant OC cells. Circ_0025033 knockdown lessened PTX resistance, suppressed migration/invasion and promoted apoptosis of PTX-resistant cells. With respect to mechanism, circ_0025033 upregulated the expression of FOXM1 by targeting miR-532-3p, and circ_0025033 knockdown blocked the malignant activities of PTX-resistant OC cells by enriching miR-532-3p and suppressing FOXM1. Exosomes derived from PTX-resistant cells with circ_0025033 knockdown also could repress the malignant actions of PTX-resistant OC cells. CONCLUSION: Circ_0025033 downregulation impaired PTX resistance and malignant activities of PTX-resistant OC cells by regulating the miR-532-3p/FOXM1 network.

Second-generation sequencing assistance in the diagnosis of Pasteurella multocida empyema: A case report. / 二代测序协助诊断多杀巴斯德菌脓胸1例.

Pasteurella multocida empyema is rare and easy to be misdiagnosed. An 81-year-old male patient showed symptoms with cough, sputum, and fever for 3 days. Community-acquired pneumonia was diagnosed firstly. After anti-infection treatment, the patient was still in fever. Chest radiography showed pleural effusion, closed thoracic drainage was performed and the reddish-brown fluid was drained out. The second-generation sequencing was performed on pleural fluid and Pasteurella multocida was detected. Pasteurella multocida has strict requirements for growth conditions and it difficult to cultivate. The application of second-generation sequencing is helpful to diagnose the pathogen rapidly.

Artificial intelligence-assisted cytology for detection of cervical intraepithelial neoplasia or invasive cancer: A multicenter, clinical-based, observational study.

OBJECTIVE: Artificial intelligence (AI) could automatedly detect abnormalities in digital cytological images, however, the effect in cervical cancer screening is inconclusive. We aim to evaluate the performance of AI-assisted cytology for the detection of histologically cervical intraepithelial lesions (CIN) or cancer. METHODS: We trained a supervised deep learning algorithm based on 188,542 digital cytological images. Between Mar 13, 2017, and Oct 20, 2018, 2145 referral women from organized screening were enrolled in a multicenter, clinical-based, observational study. Cervical specimen was sampled to generate two liquid-based slides: one random slide was allocated to AI-assisted reading, and the other to manual reading conducted by skilled cytologists from senior hospital and cytology doctors from primary hospitals. HPV testing and colposcopy-directed biopsy was performed, and histological result was regarded as reference. We calculated the relative sensitivity and relative specificity of AI-assisted reading compared to manual reading for CIN2+. This trial was registered, number ChiCTR2000034131. RESULTS: In the referral population, AI-assisted reading detected 92.6% of CIN 2 and 96.1% of CIN 3+, significantly higher than or similar to manual reading. AI-assisted reading had equivalent sensitivity (relative sensitivity 1.01, 95%CI, 0.97-1.05) and higher specificity (relative specificity 1.26, 1.20-1.32) compared to skilled cytologists; whereas higher sensitivity (1.12, 1.05-1.20) and specificity (1.36, 1.25-1.48) compared to cytology doctors. In HPV-positive women, AI-assisted reading improved specificity for CIN1 or less at no expense of reduction of sensitivity compared to manual reading. CONCLUSIONS: AI-assisted cytology may contribute to the primary cytology screening or triage. Further studies are needed in general population.

Investigations on the mechanism of progesterone in inhibiting endometrial cancer cell cycle and viability via regulation of long noncoding RNA NEAT1/microRNA-146b-5p mediated Wnt/ß-catenin signaling.

Progesterone is often used to protect the endometrium and prevent endometrial cancer. An intensive study on its molecular mechanism in endometrial cancer would contribute to the development of more promising therapies. Relevant lncRNAs and mRNAs expression data in endometrial cancer cell line Ishikawa pretreated and post-treated with progesterone were derived from Gene Expression Omnibus (accession no. GSE29435), and then we analyzed long noncoding RNAs and mRNAs with differential expressions in two different conditions. The Cytoscape software, TargetScan, miRanda, and Human microRNA Disease Database (HMDD) websites were employed. Gene set enrichment analysis (GSEA) was used to determine related Kyoto Encyclopedia of Genes and Genomes pathways alteration in Ishikawa cells treated with progesterone. In addition to bioinformatics analysis, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot, and dual-luciferase reporter assays were performed. The impact of progesterone on cell propagation and cell cycle was testified by colony formation and flow cytometry analysis. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was the most significantly downregulated lncRNA in endometrial cancer cells treated with progesterone. Lymphoid enhancing factor 1 (LEF1) was positively associated with NEAT1, and eventually hsa_miR-146b-5p was validated to target both LEF1 and NEAT1. Wnt/ß-catenin signaling pathway was identified to involve in endometrial cancer. NEAT1 or LEF1 was overexpressed in endometrial cancer cells while downregulated following post-treatment with progesterone. Conversely, miR-146b-5p was notably decreased in Ishikawa cells while upregulated after treatment with progesterone. Downstream gene c-myc or MMP9 regulated by upstream gene LEF1 in Wnt/ß-catenin signaling pathway was remarkably increased in Ishikawa cells and positively related with NEAT1. Progesterone inhibited cell cycle and viability through regulating NEAT1/miR-146b-5p axis via Wnt/ß-catenin signaling pathway. Progesterone exerted suppressive influence on endometrial cancer progression via regulation of lncRNA NEAT1/miR-146b-5p-mediated Wnt/ß-catenin signaling pathway, which might reveal new strategies for developing more effective therapeutics. © 2018 IUBMB Life, 71(1):223-234, 2019.

Cervical human papillomavirus among women in Guangdong, China 2008-2017: Implication for screening and vaccination.

Our study aimed to analyze genotype-specific, age-specific prevalence, and year-on-year trend of cervical human papillomavirus (HPV) detection among women in Guangdong, China 2008 to 2017. A total of 199 963 women attending the gynecological department and 11 999 women attending the medical examination center at Guangdong Women and Children Hospital were included. Prevalent HPV detection significantly differed between these two groups of women (20.16% vs 17.25%; P < .001). HPV genotypes of these two populations have a large overlap, with HPV52, 16, 58, CP8304, and 53 being the dominant subtypes among gynecological outpatients and HPV52, CP8304, 58, 53, and 16 among women receiving physical examinations. The distribution of prevalent HPV detection showed a bimodal pattern across age groups among these two populations. However, prevalent HPV detection among these two populations exhibited different trends from 2008 to 2017. Our study demonstrated that prevalent HPV detection among women in Guangdong is associated with age and different from that among women from other regions of China. Our study may provide valuable data to inform cervical cancer screening and HPV vaccination programs for women in this province.

The convenient Michael addition of imidazoles to acrylates catalyzed by Lipozyme TL IM from Thermomyces lanuginosus in a continuous flow microreactor.

A fast and green protocol for the Michael addition of imidazoles to acrylates catalyzed by Lipozyme TL IM from Thermomyces lanuginosus in a continuous flow microreactor was developed. In contrast with existing methods, this method is simple (35 min), uses mild reaction conditions (45 °C) and is environmentally friendly. This enzymatic Michael addition performed in continuous flow microreactors is an innovation that may open up the use of enzymatic microreactors in imidazole analogue biotransformations.

Conservative Management of Retroperitoneal Ectopic Pregnancy by Computed Tomographic-guided Methotrexate Injection in the Gestational Sac: 2 Case Reports and Literature Review.

Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy. Currently, surgery is the most widely used treatment method although it involves a high likelihood of intraoperative hemorrhage. In this case report, we describe a safe and effective alternative method for managing epigastric REP. We conducted a retrospective analysis of the clinical data of 2 patients with REP in the epigastrium who were treated at our hospital using our nonsurgical method. The treatment involved conservative management by computed tomographic-guided methotrexate injection in the gestational sac. We also present a literature review of 26 case reports and discuss the clinical features and various methods for treating REP. Our experience with the successful treatment of 2 patients suggests that the novel approach of computed tomographic-guided methotrexate injection in the gestational sac may be a safe and effective approach to manage REP. Further studies are warranted to confirm our findings.

The clinical significance of FAM19A4 methylation in high-risk HPV-positive cervical samples for the detection of cervical (pre)cancer in Chinese women.

BACKGROUND: To explore the diagnostic value of FAM19A4 methylation in high-risk human papilloma virus (hrHPV)-positive cervical samples from Chinese women for estimating cervical cancer or its precancerous lesions. METHODS: Cervical samples from 215 women infected with high-risk HPV were collected by smear testing. We purposely chose 61 patients with cervical cancer, 57 with high-grade squamous intraepithelial lesions (HSIL), 31 with low-grade squamous intraepithelial lesions (LSIL), and 66 without cervical intraepithelial neoplasia (CIN) after histological confirmation. Taqman probe-based quantitative PCR (qPCR) was utilized to detect the methylation status of FAM19A4 in the cervical samples and further evaluate the use of this gene in the diagnosis of cervical cancer. RESULTS: (1) An increasing level of FAM19A4 methylation was detected with increasing progression of cervical lesions, with methylation rates of 10.61%(7/66), 35.48%(11/31), 56.14%(32/57) and 93.44%(57/61) in no CIN, LSIL, HSIL and cervical carcinoma samples respectively. (2) In all hrHPV-positive samples, the levels of FAM19A4 methylation in HPV16/18 groups were higher than that in 12 other hrHPV groups (P < 0.05), but there was no significant difference between two groups after grouping cervical lesions into cervical cancer, HSIL, LSIL and no CIN groups (P>0.05). (3)There were no significant differences of FAM19A4 methylation in different clinicopathological parameters of cervical cancer. (4) Though the sensitivity of FAM19A4 methylation test was inferior to that of cytology and FAM19A4 combining with HPV16/18 genotyping, but showed the best specificity with 81.44% both for detection HSIL alone and ≥ HSIL, with favorable youden index (YI) and area under curve (AUC). CONCLUSION: FAM19A4 is a specific biomarker of cancerous lesions of the cervix. FAM19A4 methylation analysis may serve as an auxiliary screening method for diagnosis of cervical (pre)cancer. However, in consideration of the limitations of this retrospective study, prospective population-based studies are necessary for further confirmation of the diagnostic value of FAM19A4 methylation for detection of cervical (pre)cancer in Chinese women.

Removal of methylene blue from aqueous solution by modified bamboo hydrochar.

Four hydrochars (labeled as HC, AHC, MHC, and MAHC, respectively) were prepared by hydrothermal carbonization of bamboo with and without chlorane or followed by NaOH modification. Various techniques were adopted to characterize the physicochemical properties of hydrochars and the removal of methylene blue (MB) by these hydrochars from aqueous solution was investigated. The MB adsorption isotherm and kinetic onto MAHC and MHC can be preferably interpreted by Langmuir adsorption mode and the pseudo-second-order model, respectively. Thermodynamic parameters implied that adsorption was a spontaneous and exothermic process. The adsorption capacity of MAHC was 655.76 mg g-1, which was 2-3 times compared to that of MHC (268.93 mg g-1) at 303 K. The high adsorption capacity of MAHC for MB suggests that hydrothermal carbonization in acidic medium followed by alkaline treatment has the potential application to produce efficient MB adsorbents used in wastewater treatment.

The association between fine particulate matter exposure during pregnancy and preterm birth: a meta-analysis.

BACKGROUND: Although several previous studies have assessed the association of fine particulate matter (PM2.5) exposure during pregnancy with preterm birth, the results have been inconsistent and remain controversial. This meta-analysis aims to quantitatively summarize the association between maternal PM2.5 exposure and preterm birth and to further explore the sources of heterogeneity in findings on this association. METHODS: We searched for all studies published before December 2014 on the association between PM2.5 exposure during pregnancy and preterm birth in the MEDLINE, PUBMED and Embase databases as well as the China Biological Medicine and Wanfang databases. A pooled OR for preterm birth in association with each 10 µg/m(3) increase in PM2.5 exposure was calculated by a random-effects model (for studies with significant heterogeneity) or a fixed-effects model (for studies without significant heterogeneity). RESULTS: A total of 18 studies were included in this analysis. The pooled OR for PM2.5 exposure (per 10 µg/m(3) increment) during the entire pregnancy on preterm birth was 1.13 (95% CI = 1.03-1.24) in 13 studies with a significant heterogeneity (Q = 80.51, p < 0.001). The pooled ORs of PM2.5 exposure in the first, second and third trimester were 1.08 (95% CI = 0.92-1.26), 1.09 (95% CI = 0.82-1.44) and 1.08 (95% CI = 0.99-1.17), respectively. The corresponding meta-estimates of PM2.5 effects in studies assessing PM2.5 exposure at individual, semi-individual and regional level were 1.11 (95% CI = 0.89-1.37), 1.14 (95% CI = 0.97-1.35) and 1.07 (95% CI = 0.94-1.23). In addition, significant meta-estimates of PM2.5 exposures were found in retrospective studies (OR = 1.10, 95% CI = 1.01-1.21), prospective studies (OR = 1.42, 95% CI = 1.08-1.85), and studies conducted in the USA (OR = 1.16, 95 % CI = 1.05-1.29). CONCLUSIONS: Maternal PM2.5 exposure during pregnancy may increase the risk of preterm birth,but significant heterogeneity was found between studies. Exposure assessment methods, study designs and study settings might be important sources of heterogeneity, and should be taken into account in future meta-analyses.

[Association of the H770H of PR gene polymorphism with susceptibility to endometriosis].

OBJECTIVE: To investigate the association of PR gene exon 5 region H770H (rs1042839) single nucleotide polymorphism (SNP) with the genetic susceptibility to endometriosis (EM) in southern Han Chinese women. METHODS: Totally 431 EM patients and 499 non-EM women were collected and separated into EM group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in EM and control groups to evaluate the association of these SNP with the susceptibility to EM by using a fluorescent quantitative PCR-based high resolution melting (HRM) method. RESULTS: The C and T of PR H770H allele frequencies among the EM and control groups were 97.9% (844/862), 2.1% (18/862) and 99.4% (992/998), 0.6% (6/998), respectively. The CC, CT and TT of PR H770H genotype frequencies among the EM and control groups were 95.8% (413/431), 4.2% (18/431), 0 and 98.8% (493/499), 1.2% (6/499), 0, respectively. There were statistical significances in the PR H770H alleles and genotypes distributions between the two groups (χ(2)=7.386, P=0.007; χ(2)=8.135, P=0.004). Carrying allele C reduced the risk of EM (OR=0.986, 95%CI: 0.976-0.996), while carrying allele T enhanced the risk of EM (OR=3.319, 95% CI: 1.323-8.325); carrying genotype CC reduced the risk of EM 0.970 time (OR=0.970, 95% CI: 0.949-0.991), whereas carrying genotype CT enhanced the risk of EM 3.473 times (OR=3.473, 95%CI: 1.391-8.671). CONCLUSION: There is significant association between the polymorphism of PR H770H and genetic susceptibility to EM in southern Han Chinese women.

A genetic variant in pre-miR-27a is associated with a reduced cervical cancer risk in southern Chinese women.

OBJECTIVE: MicroRNAs (miRNAs) play critical roles in cervical carcinogenesis. Common single nucleotide polymorphisms (SNPs) in pre/pri-miRNAs may change their property through altering miRNAs expression and/or maturation. Here we aimed to investigate the influence of three common SNPs in pre/pri-miRNAs (pri-miR-26a-1 rs7372209, pre-miR-27a rs895819 and pri-miR-100 rs1834306) on individual susceptibility to cervical cancer. METHODS: We genotyped these three polymorphisms in 103 cervical cancer cases and 417 cancer-free female subjects using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Unconditional logistic regression analysis was utilized to estimate the association between these polymorphisms and the risk of cervical cancer. RESULTS: In a logistic regression analysis, we found that the rs895819 polymorphism in pre-miR-27a exhibited a significant effect on cervical cancer risk; T allele (OR = 0.68, 95% CI = 0.49-0.95, P = 0.025), and CT (OR = 0.33, 95% CI = 0.15-0.74, P = 0.007) or TT (OR = 0.33, 95% C I= 0.15-0.72, P = 0.006) genotype were associated with the decreased risk, compared to C and CC respectively. As we used further genotype association models, we found a similar trend of the association in additive (OR = 0.70, P = 0.041) and recessive model (OR = 0.33, P = 0.004). We did not detect any association of the other two SNPs in pri-miR-26a-1 (rs7372209) and pri-miR-100 (rs1834306) with cervical cancer risk. CONCLUSION: Our study provides the first evidence that the miR-27a rs895819 polymorphism is associated with a decreased risk of cervical cancer in southern Chinese women.

RNA modifications in gynecological cancer: current status and future directions.

Currently, more than 170 modifications have been identified on RNA. RNA modification mainly regulates RNA splicing, intracellular transport, degradation, translation, and stability. Gynecologic cancer (GC) mainly includes cervical cancer (CCA), ovarian cancer (OC), Endometrial cancer (EMC), among others, is the leading cause of cancer-related death. At present, there is still a lack of effective means to eradicate such diseases, so it is important to conduct more in-depth research on gynecological cancers. Numerous studies have shown that a series of epigenetic changes occur during the development of gynecologic cancer. This article reviews the latest findings on the functional significance of RNA modification in gynecologic cancer and discusses the therapeutic potential of RNA modification-related inhibitors in the treatment of gynecologic cancer.

Acute Q fever pneumonia diagnosed by metagenomic next-generation sequencing.

INTRODUCTION: Q fever, a zoonotic disease caused by Coxiella burnetii (C. burnetii), presents diagnostic challenges due to its clinical and radiological nonspecificity, which often mimics community-acquired pneumonia, coupled with the limitations of traditional diagnostic methods. Metagenomic next-generation sequencing (mNGS) has become an indispensable tool in clinical diagnostics for its high-throughput pathogen identification capabilities. Herein, we detail a case of acute Q fever pneumonia diagnosed with mNGS. CASE PRESENTATION: The patient exhibited symptoms of fever, cough, expectoration, and diarrhea for three days, with the pathogen undetected in initial laboratory assessments. Bronchoscopy and bronchoalveolar lavage (BAL) were conducted, leading to the identification of C. burnetii in the lavage fluid via mNGS. Consequently, the patient was promptly initiated on a treatment regimen of 100 mg doxycycline, administered orally every 12 hours. RESULTS: Post-treatment, the patient's temperature normalized, and a full recovery was observed. The follow-up chest CT scan revealed complete resolution of the right lower lobe consolidation. CONCLUSIONS: The clinical presentation of Q fever pneumonia lacks specificity, making diagnosis based solely on symptoms and imaging challenging. mNGS offers a superior alternative for identifying elusive or rarely cultured pathogens.

Impact of high-performance human papillomavirus testing to improve cervical cancer screening in China: a prospective population-based multicentre cohort study.

OBJECTIVES: The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. METHODS: A total of 9829 eligible women aged 21-64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. RESULTS: At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34-99.31%] vs. 62/80, 77.50% [67.21-85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80-88.12%] vs. 8900/9749, 91.29% [90.72-91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91-96.39%] vs. 87/172, 50.58% [43.18-57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72-89.16%] vs. 6933/7660, 90.51% [89.83-91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old. DISCUSSION: The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.

Preparation of Aminated Sodium Lignosulfonate and Efficient Adsorption of Methyl Blue Dye.

The aminated sodium lignosulfonate (AELS) was prepared through a Mannich reaction and characterized via FT-IR, TG, SEM and XPS in this study. Subsequently, the adsorption capacity of AELS for methyl blue (MB) was evaluated under various conditions such as pH, adsorbent dosage, contact time, initial concentration and temperature. The adsorption kinetics, isotherms and thermodynamics of AELS for methyl blue were investigated and analyzed. The results were found to closely adhere to the pseudo-second-order kinetic model and Langmuir isotherm model, suggesting a single-molecular-layer adsorption process. Notably, the maximum adsorption capacity of AELS for methyl blue (153.42 mg g-1) was achieved under the specified conditions (T = 298 K, MAELS = 0.01 g, pH = 6, VMB = 25 mL, C0 = 300 mg L-1). The adsorption process was determined to be spontaneous and endothermic. Following five adsorption cycles, the adsorption capacity exhibited a minimal reduction from 118.99 mg g-1 to 114.33 mg g-1, indicating good stability. This study contributes to the advancement of utilizing natural resources effectively and sustainably.