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Abstract Objective This study aims to evaluate the feasibility and applicability of an online cervical cancer screening program using a website as the public platform and self-collected HPV testing as the primary screening method. Methods A website (mcareu.com) was developed to facilitate the online cervical cancer screening program by Peking University Shenzhen Hospital (PUSH). Women in Shenzhen could register for participation on the website by providing essential demographic data. Sampling kits and specimens were delivered through regular logistics. Eligible women collected vaginal samples by themselves using the provided kits and in referring of the graphic guidance. The specimens were tested for HPV at PUSH or a reference lab, and the results were accessible on the website through participants' personal accounts. Participants who tested positive for high-risk HPV were scheduled for colposcopy and biopsies. The demographic and social background data of the eligible participants were analyzed to evaluate the feasibility and applicability of the online screening approach. Results A total of 1712 applicants registered for participation, with 99.9% (1710/1712) completing registration with full data. The analysis included 1560 applicants aged 30–59, with an average age of 41.1 (± 7.6) years. Among them, 83.3% (1299/1560) provided self-collected samples for testing. Age-group analysis revealed an overall sample provision rate (SPR) exceeded 80% in all age groups. A significant difference in SPR was observed only between the 30–34 and 45–49 age groups (p

Abstract There is a deficiency in population-based studies investigating the impact of HPV infection on vaginal microenvironment, which influences the risk of persistent HPV infection. This prospective study aimed to unravel the dynamics of vaginal microbiota (VM) and vaginal metabolome in reaction to the changed state of HPV infection. Our results propose that the vaginal metabolome may be a superior indicator to VM when assessing the impact of altered HPV state on the vaginal microenvironment.

BackgroundFew articles have focused on the cytological misinterpretation of high-grade squamous intraepithelial lesion (HSIL). Due to estrogen deficiency, cervical epithelial cells in postmenopausal women tend to show atrophic change that looks like HSIL on Papanicolaou-stained cytology slides, resulting in a higher rate of cytological misinterpretation. P16INK4a immunocytochemical staining (P16 cytology) can effectively differentiate diseased cells from normal atrophic ones with less dependence on cell morphology.ObjectiveTo evaluate the role of P16 cytology in differentiating cytology HSIL from benign atrophy in women aged 50 years and above.MethodsIncluded in this analysis were women in a cervical cancer screening project conducted in central China who tested positive for high-risk human papillomavirus (hr-HPV) and returned back for triage with complete data of primary HPV testing, liquid-based cytology (LBC) analysis, P16 immuno-stained cytology interpretation, and pathology diagnosis. The included patients were grouped by age: ≥50 (1,127 cases) and

Abstract Objective To evaluate the feasibility of an internet-facilitated community model for cervical cancer screening using self-collected HPV testing as primary screening. Method A population-based cervical cancer screening program was conducted in the suburb of Shenzhen, China, from September 2014 to July 2017. Women with 25–60 years of age and no pregnancy were eligible for participation. Participants could register for screening by logging in a website by themselves or with the aids of local community workers. A unique barcode was issued to each applicant upon successful registration. After registration, women could get sampling kits from community screening site/study clinic, collect vaginal samples privately or in group, and provide their sample for Hr-HPV tests on Cobas4800 and SeqHPV assays. Testing reports were checkable through personal account for all participant and phone calls were given to all women positive of Hr-HPV. Participants positive of both or either the 2 assays were identified as the positives. The positives could return the study clinic for triage or search medical care in other clinics. Colposcopy directed or ramdom biopsies were performed on all positives who returned to the study clinics. Results A total of 10,792 community women registered for screening, among whom, 10,010 provided their vaginal samples for tests. 99.5% of the participants were confirmed to have correct personal identifiable information and samples, and 98.9% of them got HPV testing results from both or either assays. No adverse event was reported. Conclusion When self-collected HPV testing is used as the primary testing, the internet-based data platform facilitates the screening in registration, data collection, and data tracking, and increases the screening coverage. Internet-facilitated community model is promising to cervical cancer control and applicable in regions with variety of resources.

Abstract Background To compare the triage performance of HPV viral loads reflected by cycle threshold values (CtV) from two different HPV testing assays: the PCR based Cobas4800 and the isothermal amplification based AmpFire assay. Methods We used the data from a sub-study of The Chinese Multi-Center Screening Trial and analyzed the data of the cases positive in both Cobas4800 and AmpFire assays with recorded CtV. Spearman’s correlation was applied to analyze the association between CtV from AmpFire and Cobas4800 assays, as well as the correlation between CtV and the histological lesion grades. The 50th percentile of CtV was used as the cutoff to construct triage algorithms for HPV-positive cases. McNemar’s test was used to analyze the differences in sensitivity and specificity for detecting CIN2 + and CIN3 + in different triage algorithms. Results Four hundred forty-six HPV positive women who had consistent HPV results from Cobas4800 and AmpFire in terms of the HPV genotype and reported Ct values were included in the analysis. The mean CtV of hrHPV tested by Cobas4800 and AmpFire were linear correlated. Direct association were showed between the severity of cervical lesions and the HPV viral loads reflected by CtV of hrHPV, HPV16, non-16/18 hrHPV and A9 group from both assays. HPV16/18 genotyping combined with low-CtV for non-16/18 hrHPV, especially A9 group, were demonstrated to be satisfactory in the sensitivity and specificity for detecting CIN2 + or CIN3 + . Conclusion Ct value represented a good triage marker in both PCR-based and isothermal amplification HPV detection.

Since 1998, Preventive Oncology International, Inc. (POI) has been at the forefront of studying human papillomavirus (HPV) self-collection for cervical cancer screening, with a significant focus in China. Through multiple clinical trials over the past 25 years, POI has explored various aspects related to self-collection methodologies. In 2004–2006, POI established that self-collection could be equivalent to direct endocervical samples. Subsequently, a large randomized trial involving 10,000 patients in 2010 further confirmed that self-collected vaginal specimens, tested for high-risk HPV (hrHPV) using a PCR-based assay with high analytic sensitivity, could effectively replace endocervical specimens with minimal loss of sensitivity and a slight decrease in specificity. Throughout the years, POI's research has encompassed several crucial topics, including patient acceptance, the development of new cost-effective, simpler, and faster assays, exploring different collection devices, devising efficient methods of specimen transport, and implementing population-based screening systems. The findings strongly support the integration of self-collection methodologies into cervical cancer control programs worldwide, particularly in medically underserved regions. As HPV self-collection continues to evolve, ongoing research and innovations are expected to play a pivotal role in achieving the global mission of combating cervical cancer.

Krukenberg tumor refers to a malignancy in the ovary that metastasizes from a primary site, classically the gastrointestinal tract. Pregnancy complicated with a Krukenberg tumor is very rare. In this report, we present two unusual cases of pregnant women with Krukenberg tumors of gastric origin. One case was a full-term pregnant woman with preeclampsia (PE) who underwent a caesarean section when bilateral enlarged ovaries were incidentally identified. Histopathology of the wedge resection biopsy showed single-ring cell carcinoma; this was followed by gastroscopy, which indicated a gastric origin. The woman received chemotherapy but died 6 months later. Another case was a pregnant woman at 30 gestational weeks with abdominal pain complicated with early-onset PE. Ultrasonography and magnetic resonance imaging showed bilateral enlarged ovaries and elevated tumor markers. Gastroscopy indicated linitis plastica. After an emergency caesarean section, adnexectomy was performed, and postoperative histopathology confirmed a Krukenberg tumor. The woman died 2 months after delivery. Gastrointestinal symptoms during pregnancy may indicate a malignancy of rare gastrointestinal origin. PE complicated with Krukenberg tumors in pregnancy should be considered in future studies.

Abstract Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. Methods Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. Results Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. Conclusions Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

Given the shortage of cytologists, women in low-resource regions had inequitable access to cervical cytology which plays an pivotal role in cervical cancer screening. Emerging studies indicated the potential of AI-assisted system in promoting the implementation of cytology in resource-limited settings. However, there is a deficiency in evaluating the aid of AI in the improvement of cytologists’ work efficiency. This study aimed to evaluate the feasibility of AI in excluding cytology-negative slides and improve the efficiency of slide interpretation. Well-annotated slides were included to develop the classification model that was applied to classify slides in the validation group. Nearly 70% of validation slides were reported as negative by the AI system, and none of these slides were diagnosed as high-grade lesions by expert cytologists. With the aid of AI system, the average of interpretation time for each slide decreased from 3 minutes to 30 seconds. These findings suggested the potential of AI-assisted system in accelerating slide interpretation in the large-scale cervical cancer screening.

Psoriasis is a recurring inflammatory skin condition characterized by scaly, red patches on the skin. It affects approximately 3% of the US population and is associated with histological changes such as epidermal hyperplasia, increased blood vessel proliferation, and infiltration of leukocytes into the skin’s dermis. T cells, which are classified into various subtypes, have been found to play significant roles in immune-mediated diseases, particularly psoriasis. This paper provides a review of the different T lymphocyte subtypes and their functions in psoriasis, as well as an overview of targeted therapies for treating psoriasis.

IntroductionThin endometrium leads to an impaired implantation rate. The aim of the study is to compare the clinical outcomes of tamoxifen (TAM) and hormone replacement therapy (HRT) used in patients with thin endometrium (0.05). The early miscarriage rate was significantly lower in the TAM group compared with the HRT group (5.9% Vs 26.8%, adjusted OR 0.10, p

Discoid lupus erythematosus (DLE) and systemic LE (SLE) can present as cutaneous lesions. Here the authors characterise an scRNA dataset of cutaneous lesions from these patients and compare these to healthy controls showing differential immune cell recruitment, cell type and gene expression.

Abstract Background Autoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases. Methods Twenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated. Results 92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P

Psoriasis vulgaris (PV) is a common inflammatory skin disorder with immune imbalance contributing to its pathology. It has been reported that auranofin, a known anti-rheumatic drug, has the therapeutic effects on inflammatory diseases. However, the effects and underlying mechanisms of auranofin on PV have not been reported. Here, we showed that auranofin significantly attenuated the mixture of five proinflammatory cytokines (termed as M5) induced hyperproliferation and inflammation in HaCaT cells, a kind of human immortalized keratinocyte cell line. Topical administration of auranofin markedly alleviated the imiquimod (IMQ)-induced mouse psoriatic dermatitis both in appearance and in pathology. The psoriasis area and severity index (PASI) score, acanthosis, dermal infiltrated inflammatory cells and Ki-67 expression were improved obviously. The results of RNA-sequencing from both M5-induced HaCaT cells and IMQ-treated mouse dermatitis showed that auranofin could regulate inflammation-related signaling pathway. Meanwhile, we observed that fatty acid 2-hydroxylase (FA2H), a key molecule in lipid metabolism, was significantly increased after auraonfin treatment in both M5-induced HaCaT cells and IMQ-treated mouse skin. Knockdown of FA2H in HaCaT cells remarkably inhibited cell apoptosis, increased cell proliferation and the expression profiles of inflammatory-related genes, whereas FA2H overexpression had opposite effect. In conclusion, auranofin notably alleviated IMQ-induced psoriasis-like skin inflammation, which might be mediated by increasing FA2H expression, suggesting its potential to be a novel strategy for psoriasis treatment.

Abstract Objective To verify the association of high-risk human papillomavirus (hrHPV) viral load reflected by cycle threshold (Ct) values from HPV testing on Cobas4800 assay with the histologic grades of cervical lesions via analysis on the combined data from two cervical cancer screening trials and to explore the referability of Ct values in management of the abnormalities from cervical cancer primary screening. Methods We analyzed the data from Chinese Multi-Center Screening Trial (CHMUST) and BUJI Cervical Cancer Screening Study Project (BUJI Study). All data to be analyzed in this paper were related to provider-collected samples. One-way ANOVA was performed to compare the Ct values among different histological groups, and Kendall’s tau-b correlation was applied to examine the association between Ct values and cervical lesion grades. The stepwise incidence of CIN2+ and CIN3+ in every 100 HPV positive individuals were calculated according to the descending of the genotype specific Ct values. The highest Ct values related to CIN3+ incidence rate 4% (or 25%) were used as the cutoffs to distinguish low-Ct value cases from the high-Ct value ones. Results A total of 1376 women in CHUMUST and BUJI Study who were aged 30–59 and positive of hrHPV for provider-collected samples on Cobas4800 with complete data in terms of the relevant Ct values (CtV) and the histological diagnosis were included for analysis. Our data showed significant difference among different histological grades of cervical lesions in the CtV of hrHPV, HPV16-plus (positive of HPV16 only or HPV16 plus 18 and/or pooled 12-HPV), and pooled 12-HPV (P 0.05). The CIN2+ or CIN3+ incidence per 100 positives significantly increased corresponding to the descending of the CtV of hrHPV, HPV16-plus and pooled 12-HPV. Compared with high-CtV groups (CtV > 33.2 for hrHPV, CtV > 29.6 for pooled 12-HPV), the relevant risks (RRs) of CIN2+ for hrHPV and pooled 12-HPV positive groups with low-CtV (CtV ≤ 33.2 and ≤ 29.6, respectively) were 3.2 (95%CI 2.18–4.80) and 2.3 (95%CI 1.50–3.45). Similarly, the RRs of CIN3+ for hrHPV and pooled 12-HPV positive groups with low-CtV were 6.5 (95%CI 2.83–14.80) and 2.7 (95%CI 1.15–6.39), respectively. The RRs of CIN2+ for medium- (30.3 37.4) groups, and the CIN3+ incidence in low-CtV value group was nine-fold higher of that in medium-CtV ones [RRs, 9.0 (95%CI 2.89–28.10)]. In comparing with the algorithms of “HPV16-plus/18-plus + cytology ≥ ASCUS for pooled 12-HPV”, triage algorithm “HPV16-plus/18-plus + Ct value ≤ 33.2 for pooled 12-HPV” could achieve a comparable sensitivity of 93.2%. Conclusion HPV viral loads reflected by Ct values for hrHPV, HPV16-plus and pooled 12-HPV from Cobas4800 HPV testing were directly associated with the severity of cervical lesions. A lower HPV genotype-specific Ct value prompted a significantly high CIN3+ risk of 4% or higher in women positive of hrHPV, HPV16-plus or pooled 12-HPV, indicating that HPV viral load reflected by Ct values on Cobas4800 may be a promising risk indicator in management of abnormalities from primary cervical cancer screening.

Objective Lupus erythematosus (LE) is a complicated disease with highly heterogeneous clinical manifestations. Previous studies have rarely included all subgroups of patients with lupus and have overlooked the importance of the cutaneous manifestations thereof. We aimed to compare the demographic and clinical differences among patients with different subtypes of lupus.Methods This is the first real-world study with a relatively large sample size that simultaneously includes patients with isolated cutaneous lupus erythematosus (iCLE) and SLE. All samples were obtained from the Lupus Erythematosus Multicenter Case–control Study in Chinese populations (LEMCSC) (registration number: ChiCTR2100048939). Comparative analyses between different LE subgroups were performed.Results A total of 2097 patients with lupus were included, with 1865 patients with SLE, 1648 with cutaneous lupus erythematosus (CLE), and 232 with iCLE. Among the patients with CLE, 1330 had acute cutaneous lupus erythematosus (ACLE); 160 had subacute cutaneous lupus erythematosus (SCLE); and 546 had chronic cutaneous lupus erythematosus (CCLE). The study included a relatively large number of patients with CCLE subtypes, including 311 with discoid lupus erythematosus (DLE), 262 with chilblain lupus erythematosus (CHLE) and 45 with lupus erythematosus profundus (LEP). Demographic characteristics, systemic involvement, mucocutaneous manifestations and autoantibodies were significantly different among the groups.Conclusions CLE and iCLE are two distinct disease states, and the selection of broad or narrow CLE definitions should be emphasised in scientific reports. LE-non-specific cutaneous lesions imply more severity, while self-reported photosensitivity and LE-specific cutaneous manifestations imply milder severity. Generalised ACLE appears to be a more severe state than localised ACLE, and CHLE appears to be more severe than DLE. Anti-Sjögren’s syndrome-related antigen B (SSB) antibodies have higher specific directivity than anti-Sjögren’s syndrome-related antigen A (SSA) antibodies for SCLE lesions. Anti-double-stranded DNA antibodies have a higher co-occurrence with ACLE and a lower co-occurrence with SCLE and CCLE. Compared with DLE, CHLE has significantly higher positive rates of anti-SSA/Ro60 (71%) and anti-SSA/Ro52 (42.4%) antibodies, whereas LEP is associated with a higher positive rate of antinucleosome antibodies (31.1%).

Primary ovarian insufficiency (POI) is among the foremost causes of women infertility due to premature partial or total loss of ovarian function. Resistant ovary syndrome (ROS) is a subtype of POI manifested as normal ovarian reserve but insensitive to gonadotropin stimulation. Inactivating variants of follicle-stimulating hormone receptor (FSHR), a class A G-protein coupled receptor, have been associated with POI and are inherited via an autosomal recessive pattern. In this study, we investigated the genetic causes of a primary infertility patient manifested as POI with ROS, and elucidated the structural and functional impact of variants of uncertain significance. Next-generation sequencing (NGS) combined with Sanger sequencing revealed novel compound heterozygous FSHR variants: c.1384G>C/p.Ala462Pro and c.1862C>T/p.Ala621Val, inherited from her father and mother, respectively. The two altered amino acid sequences, localized in the third and seventh transmembrane helix of FSHR, were predicted as deleterious by in silico prediction. In vitro experiments revealed that the p.Ala462Pro variant resulted in barely detectable levels of intracellular signaling both in cAMP-dependent CRE-reporter activity and ERK activation and displayed a severely reduced plasma membrane receptor expression. In contrast, the p.Ala621Val variant resulted in partial loss of receptor activation without disruption of cell surface expression. In conclusion, two unreported inactivating FSHR variants potentially responsible for POI with ROS were first identified. This study expands the current phenotypic and genotypic spectrum of POI.

Background: Cryopreservation of ovarian tissue is a promising method for preserving fertility. Transmission electron microscopy (TEM) is an evaluation system for cryo-injury during the cooling and warming process which is very laborious and needs to be optimized. Objective: In this study, we evaluated that serum 17β-oestradiol (E2) may be used as an indicator of vitrified ovarian tissue. Methods: Immunodeficient nude mice were used as hosts for xenografting of vitrified-warmed human ovarian tissues. A total of 54 mice were divided into two group: vitrified ovarian xenotransplant (VOX) group (n ​= ​45) and non-transplant control group (n ​= ​9). The transplanted mice were grouped into vitrified/warmed grafted-4 weeks (VOX-4w, n ​= ​15), vitrified/warmed grafted-6weeks (VOX-6w n ​= ​15) and vitrified/warmed grafted-12 weeks (VOX-12w n ​= ​15) according to the time after transplantation.The viable and functional recovery of grafted ovarian tissue was assessed by light microscopy, transmission electron microscopy, and hormone (E2) assays. Results: Serum E2 concentration was significantly higher in VOX-6w (group (21.07 ​pg/ml) than that of VOX-12w group (15.59 ​pg/ml). VOX-12w group showed a lower value (12.61 ​pg/ml) for E2 concentration. The trend for E2 concentration was consistent with the morphological identification of the grafts. Conclusion: In vivo serum hormone E2 released by cortical biopsies can be used as a functional marker for xenotransplanted vitrified-warmed human ovarian tissue reserve.

Abstract Background The aim of the study was to investigate the risk of human papillomavirus (HPV) genotyping particularly vaccine genotypes and multiple infections for cervical precancer and cancer, which might contribute to developing genotype-specific screening strategy and assessing potential effects of HPV vaccine. Methods The HPV genotypes were identified using the Seq HPV assay on self-collected samples. Hierarchical ranking of each genotype was performed according to positive predictive value (PPV) for cervical intraepithelial neoplasia 2/3 or worse (CIN2+/CIN3+). Multivariate logistic regression model was used to estimate the odds ratios (ORs) with 95% confidence interval (CI) of CIN2+ according to multiplicity of types and vaccine types. Results A total of 2811 HPV-positive women were analyzed. The five dominant HPV genotypes in high-grade lesions were 16/58/52/33/18. The overall ranking orders were HPV16/33/35/58/31/68/18/ 56/52/66/51/59/45/39 for CIN2+ and HPV16/33/31/58/45/66/52/18/35/56/51/68/59/39 for CIN3+. The risks of single infection versus co-infections with other types lower in the hierarchy having CIN2+ were not statistically significant for HPV16 (multiple infection vs. single infection: OR = 0.8, 95%CI = 0.6-1.1, P = 0.144) or other genotypes (P > 0.0036) after conservative Bonferroni correction. Whether HPV16 was present or not, the risks of single infection versus multiple infection with any number (2, ≥2, or ≥ 3) of types for CIN2+ were not significantly different. In addition, HPV31/33/45/52/58 covered by nonavalent vaccine added 27.5% of CIN2, 23.0% of CIN3, and 12.5% of cancer to the HPV16/18 genotyping. These genotype-groups were at significantly higher risks than genotypes not covered by nonavalent vaccine. Moreover, genotypes covered by nonavalent vaccine contributed to 85.2% of CIN2 lesions, 97.9% of CIN3 and 93.8% of cancers. Conclusions Partial extended genotyping such as HPV33/31/58 but not multiplicity of HPV infections could serve as a promising triage for HPV-positive self-samples. Moreover, incidence rates of cervical cancer and precancer were substantial attributable to HPV genotypes covered by current nonavalent vaccination.

Endometrial cancer (EC) is a major gynecological malignancy with rising morbidity and mortality worldwide. The aim of this study was to explore a safe and readily available sample and a sensitive and effective detection method and its biomarkers for early diagnosis of EC, which is critical for patient prognosis. This study designed a panel targeting variants for EC-related genes, assessed its technical performance by comparing it with whole-exon sequencing, and explored the diagnostic potential of endometrial biopsies using the Pipelle aspirator, cervical samples using the Pap brush, and vaginal specimens using the swab from 38 EC patients and 208 women with risk factors for EC by applying targeted panel sequencing (TPS). TPS produced high-quality data (Q30 > 85% and mapping ratios > 99.35%) and was found to have strong consistency with whole-exome sequencing (WES) in detecting pathogenic mutations (92.11%), calculating homologous recombination deficiency (HRD) scores (r = 0.65), and assessing the microsatellite instability (MSI) status of EC (100%). The sensitivity of TPS in detection of EC is slightly better than that of WES (86.84% vs. 84.21%). Of the three types of samples detected using TPS, endometrial biopsy using the Pipelle aspirator had the highest sensitivity in detection of pathogenic mutations (81.87%) and the best consistency with surgical tumor specimens in MSI (85.16%). About 84% of EC patients contained pathogenic mutations in PIK3CA, PTEN, TP53, ARID1A, CTNNB1, KRAS, and MTOR, suggesting that this small gene set can achieve an excellent pathogenic mutation detection rate in Chinese EC patients. The custom panel combined with ultra-deep sequencing serves as a sensitive method for detecting genetic lesions from endometrial biopsy using the Pipelle aspirator.

Abstract Background Congenital anatomic abnormalities of fallopian tubes and ovaries are rarely reported. Herein, we describe four cases of undescended ovary during laparoscopic surgery with abnormal anatomy of fallopian tube, yet without abnormal uterine development and urinary system abnormalities, which are analyzed by their clinical features and effects on reproductive function. Case presentation For the patients with undescended ovary, the location of unilateral or bilateral upper poles of the ovaries were usually much higher than that of the bifurcation of the common iliac vessel, and the fallopian tubes at the same side opened in the para-colonic sulcus. Among these four patients, two patients had primary infertility, one patient had tubal pregnancy rupture and bleeding, and one patient had uterine leiomyoma. The development of uterus was normal in all cases, and there was no abnormal development of urinary system. During the infertility examination, the fact that fallopian tubes lifted up in hysterosalpingography (HSG) might be regarded as an indicator of possible undescended ovary. The pelvic ultrasonography examination was of limited use in diagnosing undescended ovary. Conclusion Laparoscopy is the gold standard for the diagnosis of undescended ovary. When there is periodic post-sacral spinal pain, MRI or HSG can be used for diagnosis of undescended ovary.

ObjectiveTo validate the HPV viral loads that are reflected by the cycle threshold values of Cobas4800 as the viral load indicators by verifying the consistency of the viral loads per unit (10,000 cells) from the BMRT assay.MethodsThe analysis is based on data from the Chinese Multi-Center Screening Trial (CHIMUST). The cases included in the analysis are all positive for physician-collected hrHPV on SeqHPV and/or Cobas4800 or negative for hrHPV but abnormal in cytology (≥LSIL), and some cases selected by nested case-control randomization from those negative for physician-collected hrHPV and cytology. With HPV testing results and relevant Ct values from Cobas4800 available, we tested the entire sample set with the BMRT HPV testing assay and analyzed their agreement with Cobas4800, followed by a comparison of the CtV from Cobas4800 and viral loads (lg) from BMRT by lesion grade.ResultsWe included 4,485 women (mean age: 45.4 years) in the study, and 4,290 had complete data. The consistency of genotypes from Cobas4800 and BMRT for hrHPV, HPV-16, HPV-18, and 12-HPV pools was 94.9% (4070/4290, Kappa = 0.827), 99.1% (4251/4290, Kappa = 0.842), 99.6% (4,273/4,290, Kappa = 0.777), and 95.3% (4,089/4,290, Kappa = 0.821), respectively. Further analysis shows that any inconsistency between the two assays is likely among samples with comparatively lower viral loads. When analyzing per lesions of CIN2+ and CIN3+, the CtV from Cobas4800 and VL (lg) from BMRT are highly correlated inversely and follow the linear regression for HPV16 and 12-HPV pool (Pearson's or Spearman's correlation coefficient (r): In CIN3+, r HPV16 = −0.641, P < 0.001; r 12−HPVpool = −0.343, P = 0.109; In CIN2+, r HPV16 = −0.754, P < 0.001; r 12−HPVpool = −0.429, P < 0.001).ConclusionThe CtV from Cobas4800 and the viral loads (lg) of per unit cells from the BMRT are well correlated for lesion grading when tested on physician-collected samples. Cobas-CtV is worthy of further study for clinical application.

ObjectivesWorldwide, around 18.2% of cervical cancer occurred in China, mainly because of lower screening coverage and screening quality in regional disparities. To assess self-sampling for human papillomavirus (HPV) testing, combined with the internet, as a primary cervical cancer screening (CCS) method in low-resource settings, and to establish an internet-based self-sampling CCS-management model.MethodsThe women who participated registered on a CCS website. We recruited 20,136 women, aged 30–59 years, from 13 provinces in China, to perform vaginal self-sampling for HPV testing as a primary CCS, based on the internet. A questionnaire was subsequently used to investigate the acceptability of self-sampling.ResultsOf the 20,103 women with qualified samples, 35.80% lived in remote areas, 37.69% had never undergone CCS, 59.96% were under-screened, and the overall prevalence of a high-risk of HPV was 13.86%. Of 8,136 respondents, 95.97% of women felt that self-sampling was easy to perform, 84.61% had no discomfort when using a self-sampling brush, 62.37% women were more likely to choose self-sampling for CCS in future, and 92.53% were willing to introduce the concept to others around them. The reliability and ease of self-sampling were independent factors influencing selection of self-sampling (p < 0.05).ConclusionsThe Internet-facilitated self-sampling for HPV testing and management model for cervical cancer prevention is feasible and effective. It can be used as a supplement to the conventional screening, particularly in outlying areas with few medical resources, to improve the coverage of CCS.Clinical trial registrationhttps://www.chictr.org.cn, identifier: ChiCTR2000032331.

Human papillomavirus (HPV) clearance is important in eliminating cervical cancer which contributes to high morbidity and mortality in women. Nevertheless, it remains largely unknown about key players in clearing pre-existing HPV infections. HPV antigens can be detected by the most important cervical antigen-presenting cells (Langerhans cells, LCs), of which the activities can be affected by cervicovaginal microbiota. In this review, we first introduce persistent HPV infections and then describe HPV-suppressed LCs activities, including but not limited to antigen uptake and presentation. Given specific transcriptional profiling of LCs in cervical epithelium, we also discuss the impact of cervicovaginal microbiota on LCs activation as well as the promise of exploring key microbial players in activating LCs and HPV-specific cellular immunity.

This study was to explore whether postponing frozen embryo transfers (FET) after oocyte pickup (OPU) improves clinical and neonatal outcomes. From May 2018 to Dec 2020, a total of 1109 patients underwent their first OPU cycles adopting a non-selective freeze-all policy were included in this retrospective cohort study. In the immediate group (n=219), patients underwent FET in the first menstrual cycle after OPU, and patients in the postponed group (n=890) waited for more than 1 menstrual cycle after OPU to perform FET. A propensity score matching (PSM) model was used to evaluate the clinical outcomes and neonatal outcomes between the two groups. There were 209 patients in the immediate group and 499 patients in the postponed one after PSM. Patients waited for a significantly shorter period for FET in the immediate group (30.74 ± 3.85 days) compared with the postponed group (80.39 ± 26.25 days, P 0.05). No statistical significance was found in the average birth weight (3088.82 ± 565.35 g vs 3038.64 ± 625.78 g, P > 0.05) and height (49.08 ± 1.87 cm vs 49.30 ± 2.52 cm) of neonates between the two groups. The gender ratio, the incidence of macrosomia and low birth weight did not differ significantly between the two groups. In conclusion, postponing FET does not improve clinical and neonatal outcomes. If patients have no contraindications, FETs should be carried out immediately after OPU.

Lower female genital tract is colonized by a variety of microbes (cervicovaginal microbiota, CVM) which associate with the risk of genital infection. This study characterized CVM for 149 Chinese women with different status of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL): no HPV infection (HPV-), HPV infection without significant SIL (HPV+NoSIL), HPV infection with low-grade SIL (HPV+LSIL) and HPV infection with high-grade SIL (HPV+HSIL). Analysis results showed CVM has dramatically changed in HPV+HSIL group when compared to HPV+LSIL group, but it exhibited no significant differences between HPV- and HPV+NoSIL groups as well as between HPV+NoSIL and HPV+LSIL groups. In consistence, random forest analysis found more notable differences in HPV+HSIL vs HPV+LSIL comparison than in other comparisons. In addition, depletion of Lactobacillus in CVM was more to be frequently identified in SIL-positive women as compared to SIL-negative individuals. Our findings suggested that significant CVM differences occurred when SIL developed to HSIL which was caused by persistent HPV infection.

Objective: To compare the degree of agreement and consistency of urodynamic studies (UDS) with low urinary tract symptoms (LUTS) questionnaires for evaluating LUTS in cervical cancer patients following radical hysterectomy (RH) and pelvic lymphadenectomy. Methods: From January 2012 to March 2015, 204 cervical cancer patients who underwent RH in 13 hospitals were evaluated using the Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and the Overactive Bladder Symptom Score (OABSS). Urodynamic tests were also performed on these patients during the same period. Results: Study participants’ age ranged from 23 to 75 years, with a mean (standard deviation) of 48.0 ​± ​9.3 years. Using questionnaires, the prevalence of patients with LUTS symptoms, including storage symptoms, voiding symptoms, stress urinary incontinence (SUI) and overactive bladder (OAB) was 86.3%, 77.0%, 62.7%, 52.9% and 14.7%, respectively. For UDS, the corresponding prevalence was 89.7%, 70.1%, 66.7%, 46.6% and 13.2%, respectively. The diagnostic concordance of questionnaires and UDS for storage symptoms, voiding symptoms, SUI and OAB was 79.9%, 66.7%, 66.7%, 57.4% and 79.9%, respectively. For voiding symptoms, the correlation coefficient was 0.272, which was higher than that of storage symptoms, SUI and OAB. Conclusions: In cervical cancer patients who have undergone RH, there was a moderate degree of agreement between UDS and symptom questionnaires in evaluating LUTS, but the consistency was poor. Medical personnel should be adequately trained in UDS to ensure LUTS are adequately diagnosed in patients.

Abstract Background Systemic sclerosis (SSc) is a multisystem rheumatic disease. Orofacial manifestations are commonly in SSc but maybe usually ignored and overshadowed by other systemic complications. Multiple comparative studies have been conducted to investigate the possible links between SSc and oral manifestations. The present study aimed to investigate the oral health status in patients with SSc. Methods Pubmed, Embase, Web of Science, and Scopus were searched up to July 2020. Following outcomes were evaluated: Probing depth (PD), Attachment loss (AL), Bleeding on probing (BOP), Number or percentage of Sites with PD ≥ 4 mm, Prevalence of periodontitis, Number of teeth, Decayed Teeth, Missing teeth, Filled teeth, DMFT index, and the interincisal distance. Newcastle-Ottawa Scale (NOS) were applied for quality assessment. The statistical analysis was processed using the software STATA. Results 11 eligible studies were included. The maximum interincisor distance was significantly restricted in SSc patients (SMD − 1.061; 95 %CI [− 1.546, − 0.576]; Z = 4.29, P = 0.000).The prevalence of Periodontitis (OR 7.007; 95 %CI [3.529, 13.915]; Z = 5.56, P = 0.000), PD (SMD 3.101; 95 %CI [1.374, 4.829]; Z = 3.52, P = 0.000), AL(SMD 2.584; 95 %CI [0.321, 4.846]; Z = 2.24, P = 0.025), sites with PD ≥ 4mm (SMD 2.071 ; 95 %CI [0.267, 3.875]; Z = 2.25, P = 0.024) and the number of decayed teeth (SMD, 0.186; 95 %CI [0.007, 0.365]; Z = 2.04, P = 0.041) were increased significantly in SSc population in comparison with the controls. Conclusions SSc patients have limited mouth opening, higher periodontitis prevalence, and worse periodontal status, as well as an increased number of decayed teeth. Routinely oral hygiene instruction and initial periodontal treatment is recommended for SSc patients.

Abstract Background Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women. Methods A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + . Results A total of 2731 HPCN women aged 30–64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; ‘HPV16+ or HPV33/58/31/35+&p16+’; ‘HPV16/33+ or HPV58/31/35+&p16+’; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the ‘HPV16/33+’ strategy: p16+; ‘HPV16+ or HPV33/58/31/35 + &p16+’; HPV16/18/31/33/45/52/58 + &p16 + . Conclusions Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.

BackgroundThe disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia.MethodsGenotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results.ResultsThe hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,−52,−18/-58,−31/-39, and−59 while in Mongols were−16,−31,−58,−18 and−52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40–44 (20.5%) and 55–59 (23.5%) years in Han women while three peaks were observed at age of 30–34 (22.1%), 45–49 (22.9%), and 55–59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively.ConclusionThe prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.

Background: For cervical cancer screening, routine cytology has a high specificity but a lower sensitivity. In older women, atrophy, which may mimic HSIL, presents a diagnostic challenge. p16 is a widely used biomarker for histological diagnosis of HSIL. Our objective was to evaluate PathCIN® p16INK4a immunocytology in identification of high grade dysplasia vs. benign atrophy. Methods: As part of a multi-center screening program, 3351 women were co-tested by p16 immunocytology. Among women referred for colposcopy on basis of cytology and high-risk HPV status, those with atrophy were older than the population screened (52 vs. 43 years). Cases from older women with atrophy (n ​= ​116) and controls without atrophy (n ​= ​47) were identified by re-examination of Pap smears. The detection of CIN2+ was compared for p16, cytology and HR-HPV results. Results: The sensitivity of routine cytology (≥LSIL) was much lower for cases with atrophy (17%) than non-atrophic cases (75%). The sensitivity of p16 immunocytology and of HR-HPV testing was high (88%–100%) both with and without atrophy. The specificity of routine cytology (≥LSIL) was higher for cases with atrophy (79%) than non-atrophic cases (38%). The specificity of p16 immunocytology was high (88–95%) and the specificity of HR-HPV testing was low (31%–33%) both with and without atrophy. Combining p16 with HPV testing and/or routine cytology had no benefit, as compared to p16 staining alone. Conclusions: p16 immunocytology compares favorably with routine cytology and HPV testing in the differential diagnosis of HSIL and benign atrophy. It is more sensitive than cytology for atrophic specimens, and is more specific than HPV testing. p16 immunocytology may decrease the need for colposcopy referrals and could be a useful tool for early detection of cervical cancer in peri- and post-menopausal women, who are more likely to have HSIL coexisting with atrophy.

Abstract Objective To assess the prevalence and distribution of HPV genotypes among Chinese Han women, and to explore the risk of high-grade cervical lesions associated with individual hr-HPV genotypes. Methods Genotyping and histopathology data from the Chinese Multi-Center Screening Trial (CHIMUST) and its pilot screening trial, from 6 regions across mainland China, were re-analyzed. The data from physician- and self-collected samples from 10,867 Chinese Han women (ages 30–69) were used to determine the prevalence and distribution of hr-HPV and to explore the risk association between hr-HPV genotypes and precancerous lesions. Results 9.2% of the study population tested hr-HPV positive in physician-collected sample. The prevalence varied regionally from the lowest in Guangdong (6.3%) to the highest in Inner Mongolia (13.0%). The most prevalent genotypes found were HPV-52 (21.7%), HPV-16 (19.2%), HPV-58 (15.0%), HPV-39 (8.9%), and HPV-51 (8.2%). The overall odds ratios for CIN2+ and CIN3+ for the presence of HPV-16 was 58.6 (95% CI 39.2–87.5) and, 91.6 (95%CI 54.3–154.6), respectively and remained the highest odds ratio for CIN3+ in all 6 regions. Conclusion Geographical variation exists in the prevalence and distribution of hr-HPV in mainland China. HPV-16/52/58 were the most prevalent genotypes, and HPV-16 had the highest risk for high-grade cervical lesions. Trial registration CHIMUST, Registration number: ChiCTR-EOC-16008456 . Registered 11 May 2016.

Purpose: This study aims to share the experience of minimally invasive ultrasound-guided methotrexate intervention in the treatment of heterotopic interstitial pregnancy (HIP) with good pregnancy outcomes, and to review the treatment, pregnancy outcomes, and impact on the future fertility of HIP patients. Methods: The paper describes the medical history, clinical manifestations, treatment history, and clinical prognosis of a 31-year-old woman with HIP, and reviews cases of HIP from 1992 to 2021 published in the PubMed database. Results: The patient was diagnosed with HIP by transvaginal ultrasound (TVUS) at 8 weeks after assisted reproductive technology. The interstitial gestational sac was inactivated by ultrasound-guided methotrexate injection. The intrauterine pregnancy was successfully delivered at 38 weeks of gestation. Twenty-five HIP cases in 24 studies published on PubMed from 1992 to 2021 were reviewed. Combined with our case, there were 26 cases in total. According to these studies, 84.6% (22/26) of these cases were conceived by in vitro fertilization embryo transfer, 57.7% (15/26) had tubal disorders, and 23.1% (6/26) had a history of ectopic pregnancy; 53.8% (14/26) of the patients presented with abdominal pain and 19.2% (5/26) had vaginal bleeding. All cases were confirmed by TVUS. In total, 76.9% (20/26) of intrauterine pregnancies had a good prognosis (surgery vs. ultrasound interventional therapy 1:1). All fetuses were born without abnormalities. Conclusions: The diagnosis and treatment of HIP remain challenging. Diagnosis mainly relies on TVUS. Interventional ultrasound therapy and surgery are equally safe and effective. Early treatment of concomitant heterotopic pregnancy is associated with high survival of the intrauterine pregnancy.

(1) Background: Ferroptosis is a newly coined form of programmed cell death marked by lethal accumulation of lipid peroxidation and ferrous iron overload. A few studies on the specific mechanism of ferroptosis in the genesis and development of psoriasis are available. (2) Methods: Levels of lipid reactive oxygen species (ROS) and ferrous iron were measured by flow cytometry. Ultrastructure analysis was performed by transmission electron microscopy. Imiquimod-induced psoriasis-like mice were treated with a ferroptosis inducer. The expressions of mRNA of genes were measured by qRT-PCR. HaCaT cells were used to explore the function of Cyb561d2. (3) Results: In this work, we observed that levels of lipid ROS and ferrous iron in the epidermis of psoriasis vulgaris (PV) patients were increased. The existence of ferroptosis activation in the epidermis of individuals with PV was confirmed by transmission electron microscope both in patients with PV and psoriasis-like mice models. Intradermal injection of the ferroptosis inducer RSL3 in psoriasis-like mice significantly promoted and aggravated the development of psoriasis-like dermatitis, and the level of serum transferrin was also increased in PV samples. Moreover, abnormal expression of some genes related to iron metabolism was also proved in the epidermis of PV cases, among which Cyb561d2 was shown to promote ferrous iron overload and lipid peroxidation accumulation in HaCaT cells. (4) Conclusions: In summary, our study suggested that ferroptosis activation owing to iron overload may be a novel mechanism underlying the formation of skin lesions in individuals with PV.

Abstract Background The solid transport media is a small size card that allows fast, easy DNA extraction from a variety of biological samples. In 2016 we developed a solid media transport card; for that pilot study to control the self-collection we used a pseudo-self-collection technique. The current study expands this prior work using true self-collections and only the POI card, and aims to evaluate the solid media transport card to detect HR-HPV in self-samples compared to liquid transport media. Methods Ten thousand eight hundred eighty-five women between the ages of 30–59 with no screening for 3 years were enrolled. The self-collected sample was first applied to a new solid media transport card (Labeled as SC) then the brush placed in 6 ml ThinPrep liquid (Labeled as SL). Then a physician collected a direct endocervical specimen into ThinPrep liquid (Labeled as DL). Samples were tested with Cobas 4800 and the SeqHPV NGS assay for HR-HPV. Patients positive on any test were recalled for colposcopy and biopsy. Results Ten thousand three hundred thirty-nine participants had complete data. The mean age was 43.9 years. CIN 2+ rates were 1.4% (142/10339). The agreement in HPV detection between the two different self-sample collection media was also good (Cobas HPV kappa = 0.86; SeqHPV kappa = 0.98). Tested with Cobas, the sensitivity of Cobas-SL and Cobas-SC for CIN 2+ was95.07 and 94.37%; and for CIN3+ was 96.30, 96.30% respectively. The specificity of Cobas-SC, and Cobas-SL for CIN2+ was 88.74 and 87.35%; for CIN3 was 88.04and 86.65% respectively. Tested with SeqHPV, the sensitivity for CIN2+ of Seq-SC and Seq-SL was 95.77 and 96.48%; for CIN3+, both the SC and SL specimens had a sensitivity of 100%. The specificity for CIN2+ of Seq-SC and Seq-SL was 89.54 and 89.53%; for CIN3+ was 88.84,88.82% respectively. For both HR-HPV assays, the sensitivities were similar for the two self-sample media (SC vs SL, p = 1.00). Conclusions The solid transport card for collecting vaginal self-samples as accurate as liquid transport media assayed by two different PCR based HR-HPV tests. The solid transport media is a suitable medium for collecting and storing vaginal self-samples.

Background: This study aimed to evaluate three different patterns of cervical cancer screening strategies for detection of cervical diseases. Methods: In total, 10,186 women aged 21–70 years attending cervical screening program were recruited and cotested by human papillomavirus (HPV) assays and cytology. Three-year histological follow-up data was recorded on women with abnormal screening results, and six clinically common screening algorithms were evaluated. Results: Significantly better protection against cervical intraepithelial neoplasia 2 or worse (CIN2+) at three-year follow-up was associated with a negative HPV result than by normal cytology at baseline. HPV screening was more sensitive and less specific than cytology screening. Moreover, HPV screening with HPV16/18 and reflex cytology (atypical squamous cells of undetermined significance [ASCUS] threshold) showed a similar sensitivity (94.6% vs. 98.2%, p = 0.125) and a superior specificity as compared to cotesting reflex HPV16/18 and cytology (ASCUS threshold) for CIN2+ (95.8% vs. 95.1%, p < 0.0001), achieving a colposcopy referral rate of 5.4%, and consuming 4.8 colposcopies and 4.4 cytology tests to find one CIN2+. Conclusions: HPV screening with triage of HPV-positive women by HPV16/18 genotyping and cytology provided a good equilibrium between screening effectiveness, the number of cytology tests required, and referral rates; HPV testing was similar in sensitivity to cotesting and safer than cytology, thus especially suitable for large population-based screening programs.

Abstract Objective The aim of this research was to evaluate independently the performance of a new isothermal amplification assay for cervical cancer screening compared to two previously validated PCR-based assays and histologic endpoints. Methods This is a sub-study from the Chinese multi-center screening trial (CHIMUST). The self-collected and clinician-collected specimens stored in PreservCyt at − 4 °C from 6042 women with complete data were tested with the AmpFire assay. These specimens had been previously tested with Cobas and SeqHPV assays. In the primary study all patients with an abnormal test were referred to colposcopy where all had directed and/or random biopsies plus ECC. No additional patients were called back based on the AmpFire results. Results 6042/6619 women had complete data (mean age 44.1). There were 57 cases of CIN 2, 35 cases of CIN 3 and 2 cancers. The sensitivity for CIN2+ and CIN3+ were similar among the three assays (both direct and self-collected). For the specificities in all categories (CIN2+/CIN3+ and self and direct collection), isothermal amplification assay was either equal to or more specific than Cobas but consistently less specific than SeqHPV. Conclusion The AmpFire HPV assay showed similar sensitivity to Cobas and SeqHPV for CIN2+ and CIN3+ on both self and clinician-collections (P>0.05), with good specificity. The speed, low cost, and simplicity of this assay will make it particularly suited for low and middle resource settings. Its accuracy with self-collection makes it applicable for mass screening programs.

Background. Interferon-inducible 44 like (IFI44L) is a newly discovered interferon-induced gene and has been reported to overexpress in systemic lupus erythematosus (SLE). However, little is known about the mechanism and function of IFI44L overexpression in SLE. In this study, we aimed to investigate the epigenetic mechanism of IFI44L overexpression in SLE monocyte and its potential functions contributing to the pathogenesis of SLE. Methods. We collected peripheral blood from 20 SLE patients and 20 healthy controls. Expression of IFI44L in monocytes and effects of different signal transducers and activators of transcription (STAT) pathway inhibitors on IFI44L expression were detected. Recruitment of ten-eleven translocation protein (TET) by STAT and methylation of IFI44L promoter were evaluated. Effects of IFI44L overexpression on the expression of surface markers on monocyte-derived dendritic cells (Mo-DCs) were analyzed. T cell differentiation mediated by Mo-DCs and related cytokines production were also analyzed. Results. Expression level of IFI44L was significantly increased in SLE monocyte. IFI44L expression was decreased most significantly in STAT3 inhibitor compared with other inhibitors. STAT3 regulated IFI44L expression and interacted with TET2 which induced DNA demethylation of IFI44L promoter. Overexpression of IFI44L in monocyte enhanced the maturation and functions of Mo-DC by upregulating costimulatory receptors and inducing Th1/Th17-related cytokines when cocultured with naïve CD4+ T cells. Conclusion. TET2 recruited by STAT3 induces DNA demethylation of IFI44L promoter which promotes IFI44L overexpression in monocyte contributing to the pathogenesis of SLE by enhancing the maturation and functions of Mo-DC. IFI44L is expected to become a new target for treatment of SLE.

Abstract Endometriosis (EMS) is a multifactorial disease that affects 10%–15% women of reproductive age and is associated with chronic pelvic pain and infertility. The pathogenesis of EMS has not been consistently explained until now. In this study, we involved 36 endometriosis patients and 14 control subjects who performed laparoscopic surgery due to gynecological benign tumor. The samples from lower third of vagina (CL), posterior vaginal fornix (CU), cervical mucus (CV), endometrium (ET) and peritoneal fluid (PF), were collected and sequenced by 16S rRNA amplicon. The continuous change of the microbiota distribution was identified along the reproductive tract. The flora in lower reproductive tract (CL, CU) were dominated by Lactobacillus. Significant difference of the community diversity began showing in the CV of EMS patients and gradually increased upward the reproductive tract. It indicates the microbiota in cervical samples is expected to be an indicator for the risk of EMS. This study also highlights the decreasing of Lactobacillus in vaginal flora and the increasing of signature Operational Taxonomic Units (OTUs) in transaction zone (CV) and upper reproductive tract (ET, PF) of EMS patients, which reflect the alteration of microbial community associated with EMS, participation of specific colonized bacteria in the EMS pathogenesis and relationship between microbiota and development of disease.

Persistent high-risk human papillomavirus (hrHPV) infection is the highest risk to cervical cancer which is the fourth most common cancer in women worldwide. A growing body of literatures demonstrate the role of cervicovaginal microbiome (CVM) in hrHPV susceptibility and clearance, suggesting the promise of CVM-targeted interventions in protecting against or eliminating HPV infection. Nevertheless, the CVM-HPV-host interactions are largely unknown. In this review, we summarize imbalanced CVM in HPV-positive women, with or without cervical diseases, and the progress of exploring CVM resources in HPV clearance. In addition, microbe- and host-microbe interactions in HPV infection and elimination are reviewed to understand the role of CVM in remission of HPV infection. Lastly, the feasibility of CVM-modulated and -derived products in promoting HPV clearance is discussed. Information in this article will provide valuable reference for researchers interested in cervical cancer prevention and therapy.

Egg-white protein has an abundance of hydrophobic amino acids and could be a potential emulsifier after modification. Here, egg-white protein was modified via ultrasonic and transglutaminase treatments to destroy the globular structure. The egg-white protein gel particles (EWP-GPs) were prepared and then a novel highly stable EWP-chitosan double-layer emulsion was constructed. When ultrasonic treatment was applied at 240 W and TGase (20 U/g EWP) treatment, the EWP-GPs had a low particle size and good emulsification performance. The particle size of EWP-GPs was a minimum of 287 nm, and the polymer dispersity index (PDI) was 0.41. The three-phase contact angle (θo/w) of EWP-GPs was 79.6° (lower than 90°), performing with good wettability. Based on these results, the EWP-chitosan double-layer emulsion was prepared through the EWP-GPs being treated with 240 W ultrasound, TGase, and chitosan in this study. When the double-layer emulsion had 0.6% (v/v) chitosan, the zeta potential of the double-layer emulsion was −1.1 mV and the double-layer emulsion had a small particle size (56.87 µm). The creaming index of double-layer emulsion at 0.6% (v/v) chitosan was 16.3% and the droplets were dispersed uniformly. According to the rheological results, the storage modulus (G′) was larger than the loss modulus (G″) in the whole frequency, indicating the formation of an elastic gel network structure in the emulsion. It is hoped to develop a novel food-grade stabilizer and a stable double-layer emulsion, providing new environment-friendly processing in hen egg products and delivery systems.

Abstract Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.

As a subgroup of CD4+ T helper cells, follicular helper T (Tfh) cells provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Dysregulation of Tfh cells is associated with several major autoimmune diseases. Although recent studies showed that Tfh cell differentiation is controlled by the transcription factor Bcl6, cytokines, and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTMs) of proteins in human Tfh cells. In the present study, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells using the tandem mass tag (TMT) labeling technique, antibody-based affinity enrichment, and high-resolution liquid chromatography-mass spectrometry (LC-MS)/mass spectrometry (MS) analysis. In total, we identified 802 upregulated proteins and 598 downregulated proteins at the threshold of 1.5-fold in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, the biological process, the cellular compartment, the molecular function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein–protein interaction of these differentially expressed proteins were revealed. Moreover, the acetylome data showed that 22 lysine (K) acetylated proteins are upregulated and 26 K acetylated proteins are downregulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated K residues in core histones were identified, indicating that protein acetylation and epigenetic mechanism are involved in regulating Tfh cell differentiation. The study provides some important clues for investigating T cell activation and Tfh cell differentiation.

Human urine is traditionally considered to be sterile, and whether the urine harbours distinct microbial communities has been a matter of debate. Potential links between female urine and reproductive tract microbial communities is currently not clear. Here, we collected urine samples from 147 Chinese women of reproductive age and explored the nature of colonization by 16S rRNA gene amplicon sequencing, quantitative real-time PCR, and live bacteria culture. To demonstrate the utility of this approach, the intra-individual Spearman’s correlation was used to explore the relationship between urine and multiple sites of the female reproductive tract. PERMANOVA was also performed to explore potential correlations between the lifestyle and various clinical factors and urinary bacterial communities. Our data demonstrated distinct bacterial communities in urine, indicative of a non-sterile environment. Streptococcus-dominated, Lactobacillus-dominated, and diverse type were the three most common urinary bacterial community types in the cohort. Detailed comparison of the urinary microbiota with multiple sites of the female reproductive tract microbiota demonstrated that the urinary microbiota were more similar to the microbiota in the cervix and uterine cavity than to those of the vagina in the same women. Our data demonstrate the potential connectivity among microbiota in the female urogenital system and provide insight and resources for exploring diseases of the urethra and genital tract.

Objective Psoriasis is an immune-mediated chronic inflammatory disease with skin and joint manifestations. Smoking is considered an unfavorable lifestyle factor for psoriasis. We aimed to explore the association between smoking, disease risk, and treatment efficacy in relation to psoriasis. Methods We searched the Cochrane Library, Embase, and PubMed databases for studies examining the relationship between smoking and psoriasis, up to 12 April 2020. We then conducted a meta-analysis using a fixed-effects model to obtain odds ratios (ORs) with 95% confidence intervals (CIs). Results Ever, current, and former smokers all had higher risks of developing psoriasis than non-smokers (pooled ORs (95% CIs): 1.60 (1.51–1.69), 1.63 (1.48–1.80), and 1.36 (1.13–1.64), respectively). Ever smokers were less likely to show disease improvement at 6 months following treatment with biologic agents than non-smokers (pooled OR (95% CI): 0.80 (0.67–0.95)). Conclusions Smoking increases psoriasis risk and negatively impacts the benefits of biologic agents. However, the number of reports is limited and more studies are needed to confirm the effects of smoking and smoking cessation on therapeutic response in patients with psoriasis. Education to encourage a healthy lifestyle remains a valuable approach in clinical practice.

Background: Lupus erythematosus (LE) is a broad-spectrum, heterogeneous disease. At one end of the spectrum is the cutaneous LE (CLE) without systemic involvement, and at the other end is the systemic LE (SLE) with multisystem involvement. Analyses of clinical and immunological indicators and pathological examinations are helpful for early diagnosis, differential diagnosis, and prognosis of LE. Aim and Objectives: We described the clinical and laboratory characteristics of patients with LE and assessed the diagnostic value of immunohistochemical detection of C3d, C4d, IgG, IgG4, and CD123 in skin lesions of LE. Materials and Methods: Clinical and laboratory data of 62 patients with LE were collected. The expression levels of C3d, C4d, IgG, IgG4, and CD123 in skin lesions of LE were detected by immunohistochemistry (IHC). Results: Clinical manifestations such as hematological involvement, C3, C4, ESR, hematuresis, proteinuria, anti-Sm, anti-ribosomal P-protein, anti-U1-RNP, anti-histone, and anti-nucleosome antibodies are helpful for classificatory diagnosis of LE. The positive rate of C3d and/or C4d along the basement membrane zone in LE skin lesions by IHC was 74.6%, which was higher than that by direct immunofluorescence (47.5%) (P = 0.002). The expression of CD123 protein and the number of CD123+ plasmacytoid dendritic cells (PDCs) in skin lesions of patients with LE were higher than those of dermatomyositis (DM), while the distributed form of CD123 + PDCs in the dermis was different between LE and DM. Conclusions: The diagnosis of CLE and SLE requires a combination of clinical manifestations, laboratory indicators, and pathological examination. Immunohistochemical detection of C3d, C4d, and CD123 in skin lesions is important for the classificatory diagnosis of LE.

OBJECTIVE:Evaluate the significance of BMRT HPV assay viral load and its performance for secondary screening. METHODS:BMRT-HPV reports type-specific viral loads/10,000 cells. We tested 1,495 physician collected, stored specimens from Chinese Multiple-center Screening Trial (CHIMUST), that were positive by Cobas, SeqHPV, and/or Cytology (≥LSIL); and 2,990 age matched, negatives in a nested case control study. We explored the relationship between BMRT HR-HPV viral load and cervical lesions, determined alternative CIN2+ cut-points by ROC curve, and evaluated BMRT HR-HPV for primary / secondary cervical cancer screening. RESULTS:The viral loads of HPV16/18, 12 other subtypes HR-HPV and 14 HR-HPV were statistically different in all grades of cervical lesions (P0.05), specificity was higher than Cobas (84.8% vs 83.3%, 83.5% vs 82.0%, P0.05). However, the BMRT HR-HPV viral load combined with subtypes did not require cytology. CONCLUSION:BMRT is as sensitive as Cobas4800 for primary cervical cancer screening. BMRT HR-HPV viral load combined with subtypes can be used as a secondary strategy for cervical cancer screening, especially for areas with insufficient cytological resources.

Background/objectiveHuman papillomavirus (HPV) genotyping and cytology have been recommended for colposcopy triage, but it is unclear which combinations of high-risk HPV (hrHPV) types and cytology with various thresholds provide clinically useful information for the triage after primary HPV screening on self-collected samples.MethodChinese Multi-site Screening Trial (CHIMUST) database focused on self-collected samples was reviewed using the results of Cobas4800 HPV assay. Absolute risks of each genotype for cervical intraepithelial neoplasia 2 or worse/ 3 or worse (CIN2+/CIN3+) were calculated. Triage of atypical squamous cells of undetermined significance (ASCUS) or worse cytology was used as the comparator, and diagnostic accuracy for paired comparisons between algorithms was obtained using McNemar's test.ResultsA total of 10, 498 women were included, the overall prevalence of hrHPV, HPV16, HPV18, and Other hrHPV genotypes were 13.7%, 2.4%, 0.8%, and 10.5%, respectively. HPV16-positive women had the highest absolute risk among various genotypes for CIN2+/CIN3+ whether in normal or abnormal cytology (ASCUS or worse) and among all age groups. When compared with the comparator, combining HPV16 positivity and/or high-grade squamous intraepithelial lesion (HSIL) or worse yielded higher specificity (97.7% vs. 97.0%, pConclusionsTriage of HPV-positive women on self-collected samples by combining HPV16 or HPV16/18 genotyping with different thresholds of cytology could provide tradeoffs in sensitivity for detecting cervical lesions and colposcopy referral rates, and tailor management in various circumstances of clinical practice.