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Abstract Background Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. Methods We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. Results We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. Conclusions The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.

Abstract Background To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). Methods Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan–Meier and Cox proportional hazard regression analyses. Results This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108–1.798, P = 0.005; DFS: 65.5% vs 55.3%, P 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103–1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110–1.633, P = 0.002) groups. Conclusions This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Objectives To assess the effect and safety of Zoladex (Goserelin acetate) 10.8 mg in patients with uterine fibroids.Methods Fifty-three patients received Goserelin acetate 10.8 mg once and surgery was conducted at 12 weeks ± 7 days after drug injection. All assessments form baseline to week12/before surgery were carried out: fibroids volume, uterine volume, serum hormone (E2, FSH, LH), hemoglobin concentration, uterine arterial resistance index (UA-RI), fibroid arterial RI (FA-RI) and improvements of symptoms (Uterine Fibroid Symptom and Quality of Life (UFS-QOL) and Health-Related Quality of Life (HRQL) scores). Adverse events (AEs) were recorded to evaluate the safety.Results After 12 weeks of treatment, the volume of uterine fibroids was significantly smaller than before (249.19 ± 297.04 vs. 195.77 ± 418.27 cm3, p

Objective: It is evident that periodontitis is linked to various adverse pregnancy outcomes. This prospective study explored the potential link of maternal periodontal diseases to neonatal adverse outcomes. Materials and Methods: A total of 193 generally healthy females in their third trimester (34–36 weeks) of pregnancy were enrolled. All subjects received full-mouth periodontal assessment, and the periodontal inflamed surface area (PISA) was calculated. Demographic data, lifestyles and anthropometric measurements of the neonates (e.g., body length and head circumference) were recorded. Herein, small-for-gestational age (SGA) referred to gender- and age-adjusted birth weight below the 10th percentile in line with the standard reference. Multivariable logistic regression analysis and restricted cubic spline were performed for examining the association of periodontal parameters with SGA. Results: There were 8.3% (16/193) of neonates with SGA. Significantly positive correlation existed between the percentage of tooth sites with increased probing depth and an elevated risk of SGA (OR: 1.052; P < 0.05). Yet, the PISA was positively associated with the risk of SGA (OR: 1.002; P < 0.05) as well. No significant link occurred between maternal periodontal status and other neonatal outcome measures. Conclusion: Within the limitations of this study, the findings suggest that there could be a link between maternal periodontal diseases and neonatal adverse outcomes like SGA. Further investigation is required to clarify the current findings and potential implications for promoting maternal oral/periodontal health and newborn health.

Abstract Background To compare the oncological outcomes of radical chemotherapy (R‐CT), abdominal radical hysterectomy (ARH), and neoadjuvant chemotherapy and radical surgery (NACT) for International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC cervical cancer, according to histological types: squamous cell carcinoma (SCC) and adenocarcinoma (AC)/adenosquamous cell carcinoma (ASC). Methods A comparison of 5‐year overall survival (OS) and disease‐free survival (DFS) was performed for the SCC and AC/ASC subgroups for the three initial treatments, assessed using Kaplan–Meier and Cox proportional hazards regression analysis and validated using propensity score matching (PSM). Results The study included 4086 patients: R‐CT, n = 1913; ARH, n = 1529; and NACT, n = 644. AC/ASC had a lower survival rate (63.7%) than SCC (73.6%) and a higher recurrence and mortality rate (36.3% and 26.4%, respectively). The 5‐year OS and DFS rates were different in the SCC group for R‐CT, ARH, and NACT (OS: 69.8% vs. 80.8% vs. 73.0%, p

Abstract Background Polycystic ovary syndrome (PCOS) and periodontitis significantly affect women’s oral and systemic health worldwide, and yet increase the risk of cardiovascular-metabolic diseases like diabetes and coronary heart disease. Regarding the PCOS-periodontitis connection, whether sex hormones, metabolic and inflammatory mediators could account for the underlying linking mechanism needs to be further investigated. This case–control study evaluated the hormonal, metabolic and inflammatory profiles in PCOS and non-PCOS subjects with various periodontal conditions, via assessing serum and saliva samples by Raman spectroscopy. Methods A total of 66 females with PCOS and 22 systemically healthy female volunteers were recruited in a single hospital. Full-mouth periodontal examination was undertaken for identifying the subjects with periodontal health, gingivitis or periodontitis. The datasets of sex hormones and metabolic indicators were retrieved from the hospital information system. Both serum and saliva samples were collected for detecting inflammatory mediators and Raman spectroscopic assessment. The subjects were categorized into four groups according to their conditions of PCOS and periodontitis for Raman spectroscopic analysis. Partial least squares discriminant analysis was performed to examine the inter-group differences in Raman spectra. Results PCOS patients exhibited greater mean probing depth (P

Abstract Background Aicardi–Goutières syndrome (AGS) is a rare, autosomal recessive, hereditary neurodegenerative disorder. It is characterized mainly by early onset progressive encephalopathy, concomitant with an increase in interferon-α levels in the cerebrospinal fluid. Preimplantation genetic testing (PGT) is a procedure that could be used to choose unaffected embryos for transfer after analysis of biopsied cells, which prevents at-risk couples from facing the risk of pregnancy termination. Methods Trio-based whole exome sequencing, karyotyping and chromosomal microarray analysis were used to determine the pathogenic mutations for the family. To block the inheritance of the disease, multiple annealing and looping-based amplification cycles was used for whole genome amplification of the biopsied trophectoderm cells. Sanger sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used to detect the state of the gene mutations. Copy number variation (CNV) analysis was also carried out to prevent embryonic chromosomal abnormalities. Prenatal diagnosis was preformed to verify the PGT outcomes. Results A novel compound heterozygous mutation in TREX1 gene was found in the proband causing AGS. A total of 3 blastocysts formed after intracytoplasmic sperm injection were biopsied. After genetic analyses, an embryo harbored a heterozygous mutation in TREX1 and without CNV was transferred. A healthy baby was born at 38th weeks and prenatal diagnosis results confirmed the accuracy of PGT. Conclusions In this study, we identified two novel pathogenic mutations in TREX1, which has not been previously reported. Our study extends the mutation spectrum of TREX1 gene and contributes to the molecular diagnosis as well as genetic counseling for AGS. Our results demonstrated that combining NGS-based SNP haplotyping for PGT-M with invasive prenatal diagnosis is an effective approach to block the transmission of AGS and could be applied to prevent other monogenic diseases.

Abstract Background To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). Methods Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan–Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. Results We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150–2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255–2.182, P

This nested case-control study aimed to investigate the determinants of low birth weight among newborn babies delivered in Shenzhen, Guangdong, China. We recorded socio-demographic data, health status before pregnancy, pregnancy outcomes and complications in a Shenzhen mother and infant cohort. Among 8951 cases, 401 (4.48%) had low birth weight and 1.65% were full-term with LBW. Maternal body mass index, family income, history of pregnancy, hypertension before pregnancy, vaginal bleeding in 1st trimester, pregnancy-related diabetes, hypertension, placenta previa, placental abruption, premature rupture of membrane, oligohydramnios, and placental types were significantly associated with low birth weight (P

Background: To compare the oncological outcomes of Chinese patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC cervical cancer (CC) receiving radical chemoradiotherapy (R-CT), abdominal radical hysterectomy (ARH), or neoadjuvant chemotherapy and radical surgery (NACT). Methods: Overall, 4086 patients in 47 hospitals from 2004 to 2018 were divided into groups according to stage (4029 with stage IIIC1 and 57 with stage IIIC2). Kaplan-Meier and Cox regression analyses were applied to compare the 5-year overall survival (OS) and disease-free survival (DFS) of the three initial treatments before and after propensity score matching (PSM). Results: The 5-year DFS was worse in patients with stage IIIC2 than in those with stage IIIC1 (post-PSM: 68.3% vs. 39.9%, p < 0.001). For stage IIIC1, the ARH group had better 5-year OS (post-PSM: 71.0% vs. 80.0%, p < 0.001) and DFS (post-PSM: 67.2% vs. 71.0%, p < 0.001) than the R-CT group, while the NACT group had worse 5-year DFS (post-PSM: 67.7% vs. 55.3%, p = 0.002). The 5-year OS (post-PSM: 80.9% vs. 70.5%, p < 0.001) and DFS (post-PSM: 70.7% vs. 54.1%, p < 0.001) were better in the ARH than in the NACT group. For stage IIIC2, the 5-year DFS was better in the ARH than in the NACT group (45.4% vs. 30.1%, p = 0.025). Conclusions: The oncological prognosis of patients with stage IIIC1 CC was generally better than that of patients with stage IIIC2, thereby supporting the rationale behind the classification of stage IIIC. In less developed areas, the ARH is a promising alternative treatment option for patients with stage IIIC; nonetheless, the use of NACT is not advisable. Clinical Trial Registration: The study was registered at http://apps.who.int/trialsearch/, registration number CHiCTR1800017778.

BackgroundFetal growth restriction (FGR) is attributed to various maternal, fetal, and placental factors. Trophoblasts participate in the establishment and maintenance of pregnancy from implantation and placentation to providing nutrition to fetus. Studies have reported that impaired trophoblast invasion and proliferation are among factors driving development of FGR. Circular RNAs (circRNAs) can regulate trophoblast function. We assessed the significance of circRNAs underlying FGR development.Materials and methodsNext generation sequencing (NGS) was carried out to quantify levels of circRNAs in placenta tissues with and without FGR. In vitro experiments including transfection, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) assays, flow cytometry analyses, Transwell assays, wound healing assays, western blotting, qRT-PCR, dual-luciferase assays, immunofluorescence staining, and RIP assay were performed.ResultsThere were 18 differentially expressed circRNAs between FGR placentas and uncomplicated pregnancies, while levels of hsa-circ-0005238 were markedly low in FGR placentas. Our in vitro experiments further revealed that hsa-circ-0005238 suppressed apoptosis and enhanced proliferation, migration, invasion of trophoblast cell lines. The hsa-miR-370-3p was identified as a direct target of hsa-circ-0005238. Mechanistically, hsa-miR-370-3p prevents invasion as well as migration of trophoblast cells by downregulating CDC25B.ConclusionThe hsa-circ-0005238 modulates FGR pathogenesis by inhibiting trophoblast cell invasion and migration through sponging hsa-miR-370-3p. Hence, targeting this circRNA may be an attractive strategy for FGR treatment.

Abstract Background Premature ovarian insufficiency (POI) is characterized by impairment of ovarian function on a continuum before the age of 40 years. POI is affected by multiple factors. Considering new insights from recent gut microbiome studies, this study aimed to investigate the relationship between gut microbial community structure and POI. Methods Subjects were recruited at the Shenzhen Maternity & Child Healthcare Hospital. Fecal microbial community profiles of healthy women (n = 18), women with POI (n = 35) were analyzed using 16S rRNA gene sequencing based on Illumina NovaSeq platform. Results Compared to the controls, the serum levels of FSH, LH, T and FSH/LH ratio significantly increased in women with POI, whereas E2 and AMH decreased significantly. Higher weighted UniFrac value was observed in POI women compared with healthy women. Phylum Firmicutes, genera Bulleidia and Faecalibacterium were more abundant in healthy women, while phylum Bacteroidetes, genera Butyricimonas, Dorea, Lachnobacterium and Sutterella enriched significantly in women with POI. Moreover, these alterations of the gut microbiome in women with POI were closely related to FSH, LH, E2, AMH level and FSH/LH ratio. Conclusions Women with POI had altered microbial profiles in their gut microbiome, which were associated with serum hormones levels. These results will shed a new light on the pathogenesis and treatment for POI.

Abstract Background The age-specific definition of low anti-müllerian hormone (AMH) is lacking. This study aims to define an age-specific reference for low AMH and to evaluate the associated outcome in women undergoing IVF treatment. Methods A retrospective study was performed in women receiving IVF treatment at the Shenzhen maternity and child healthcare hospital between September 2016 and September 2018. We excluded cases without AMH concentration. Polynomial least-squares regression was used to estimate the age-specific reference ranges for AMH after log-transformed. The age-specific 10th centile was defined as the threshold of low AMH concentration. Results A total of 909 patients were analyzed in this study. The age-specific reference ranges for AMH were established using linear regression model and resulted in an age-specific equation for mean: mean of LnAMH = (− 0.085 × age) + 3.722 (ng/ml, in unit). Women with AMH level higher than 10th centile had favorable outcomes in ovarian stimulation compared to those with low AMH level. In patients younger than 35 years, the rates of clinical pregnancy per transfer and ongoing pregnancy per transfer in the subgroup with AMH level higher than 10th centile were significantly higher than that in the subgroup of low AMH level, 57% versus 31.3% p = 0.003 and 51.9% versus 21.9% p = 0.001, respectively. Conclusion Women with AMH lower than age-specific 10th centile had significantly unfavorable outcomes after IVF treatment. The age-specific 10th centile of AMH concentration may be useful to predict the outcome of IVF treatment.

Perinatal exposure to heat and air pollution has been shown to affect the risk of preterm birth (PTB). However, limited evidence exists regarding their joint effects, particularly in heavily polluted regions like China. This study utilized data from the ongoing China Birth Cohort Study, including 103 040 birth records up to December 2020, and hourly measurements of air pollution (PM _2.5 , NO _2 , and O _3 ) and temperature. We assessed the nonlinear associations between air pollution and temperature extereme exposures and PTB by employing generalized additive models with restricted cubic slines. Air pollution and temperature thresholds (corresponding to minimum PTB risks) were determined by the lowest Akaike Information Criterion. We found that maternal exposures to PM _2.5 , NO _2 , O _3 , and both low and high temperature during the third trimester of pregnancy were independently associated with increased risk of PTB. The adjusted risk ratios for PTB of PM _2.5 , O _3 , NO _2 , and temperature at the 95th percentile against thresholds were 1.32 (95% CI: 1.23, 1.42), 1.33 (95% CI: 1.18, 1.50), 1.44 (95% CI: 1.33, 1.56) and 1.70 (95% CI: 1.56, 1.85), respectively. Positive additive interactions [relative excess risk due to interaction (RERI) > 0] of PM _2.5 –high temperature (HT), O _3 –HT, O _3 –low temperature (LT) are identified, but the interactive effects of PM _2.5 and LT were negative (RERI < 0). These observed independent effects of air pollution and temperature, along with their potential joint effects, have important implications for future studies and the development of public health policies aimed at improving perinatal health outcomes.

Purpose: To examine the association between surgical volume and surgical and oncological outcomes of women with stage IB1 cervical cancer who underwent laparoscopic radical hysterectomy (LRH).Methods: We retrospectively analyzed the oncological outcomes of 1,137 patients with stage IB1 cervical cancer receiving LRH from 2004 to 2016. The surgical volume for each surgeon was defined as low [fewer than 50 surgeries, n = 392(34.5%)], mid [51-100 surgeries, n = 315(27.7%)], and high [100 surgeries or more, n = 430(37.8%)]. Surgical volume-specific survival was examined with Kaplan–Meier analysis, multivariable analysis, and propensity score matching.Results: The operative times of the high-volume group (227.35 ± 7.796 min) were significantly shorter than that of the low- (272.77 ± 4.887 min, p < 0.001) and mid-volume (255.86 ± 4.981 min, p < 0.001) groups. Blood loss in the high-volume group (169.42 ± 8.714 ml) was significantly less than that in the low-volume group (219.24 ± 11.299 ml, p = 0.003). The 5-year disease-free survival (DFS) and overall survival (OS) in the low-volume, mid-volume, and high-volume groups were similar (DFS: 91.9, 86.7, and 89.2%, p = 0.102; OS: 96.4, 93.5, and 94.2%, p = 0.192). Multivariable analysis revealed surgical volume was not an independent risk factor for OS or DFS. The rate of intraoperative and postoperative complications was similar among the three groups (p = 0.210).Conclusions: Surgical volume of LRH may not be a prognostic factor for patients with stage IB1 cervical cancer. Surgery at high-volume surgeon is associated with decreased operative time and blood loss.

Abstract Background For definitive diagnosis of cryptococcal meningitis, Cryptococcus neoformans and/or C. gattii must be identified within cerebral spinal fluid from the patients. The traditional methods for detecting Cryptococcus spp. such as India ink staining and culture are not ideal. Although sensitive and specific enough, detection of cryptococcal antigen polysaccharide has a high dose hook effect. Therefore, the aim of this study was to introduce a new rapid and simple detection method of Cryptococcus neoformans and C. gattii in cerebral spinal fluid. Methods The lateral flow strips combined with recombinase polymerase amplification (LF-RPA) assay was constructed to detect the specific DNA sequences of C. neoformans and C. gattii. The detection limit was evaluated using serial dilutions of C. neoformans and C. gattii genomic DNA. The specificity was assessed by excessive amount of other pathogens genomic DNA. The optimal detection time and amplification temperature were also analyzed. The diagnostic parameters were first calculated using 114 clinical specimens and then compared with that of other diagnostic method. A brief analysis and comparison of different DNA extraction methods was discussed, too. Results The LF-RPA assay could detect 0.64 pg of genomic DNA of C. neoformans per reaction within 10 min and was highly specific for Cryptococcus spp.. The system could work well at a wide range of temperature from 25 to 45 °C. The overall sensitivity and specificity were 95.2 and 95.8% respectively. As amplification template for LF-RPA assay, both cell lysates and genomic DNA produce similar experimental results. Conclusions The LF-RPA system described here is shown to be a sensitive and specific method for the visible, rapid, and accurate detection of Cryptococcus spp. in cerebral spinal fluid and might be useful for clinical preliminary screening of cryptococcal meningitis.

The aim of this study was to investigate the role of the anti-Mullerian hormone (AMH) signalling pathway in the pathophysiology of idiopathic primary ovarian insufficiency (POI) and age at natural menopause (ANM) using a genetic approach. DNA sequencing was used to detect the genotype distribution and allele frequency of the genes AMH and AMH receptor II (AMHR2) in 120 cases of idiopathic POI and 120 normal-ANM women. Fourteen sequence variants of AMHR2, including 10 novel variants, were identified. Two novel exonic missense variants were p.I209N and p.L354F. The missense variant p.I209N, which is conserved in different species, was predicted to have functional and structural impacts on the AMHR2 protein. The clinical significance of one additional variant (p.L354F) remains arguable pending functional studies. The genotype frequencies of AMH and AMHR2 were similar in distribution for POI patients and normal-ANM women. These findings suggest that POI patients and normal-ANM women in China share AMH and AMHR2 genetic variants. The AMH signalling pathway associated with ANM also may contribute to POI. [ABSTRACT FROM AUTHOR]