Oleic acid availability impacts thymocyte preprogramming and subsequent peripheral Treg cell differentiation.

The nature of activation signals is essential in determining T cell subset differentiation; however, the features that determine T cell subset preference acquired during intrathymic development remain elusive. Here we show that naive CD4+ T cells generated in the mouse thymic microenvironment lacking Scd1, encoding the enzyme catalyzing oleic acid (OA) production, exhibit enhanced regulatory T (Treg) cell differentiation and attenuated development of experimental autoimmune encephalomyelitis. Scd1 deletion in K14+ thymic epithelia recapitulated the enhanced Treg cell differentiation phenotype of Scd1-deficient mice. The dearth of OA permitted DOT1L to increase H3K79me2 levels at the Atp2a2 locus of thymocytes at the DN2-DN3 transition stage. Such epigenetic modification persisted in naive CD4+ T cells and facilitated Atp2a2 expression. Upon T cell receptor activation, ATP2A2 enhanced the activity of the calcium-NFAT1-Foxp3 axis to promote naive CD4+ T cells to differentiate into Treg cells. Therefore, OA availability is critical for preprogramming thymocytes with Treg cell differentiation propensities in the periphery.

Genome-wide association study on coordination and agility in 461 Chinese Han males.

There is growing evidence that genetic factors can influence human athletic performance. In many sports performances, excellent coordination and agility are the keys to mastery. However, few studies have been devoted to identifying genetic influences on athletic performance. Methods: We generated a derived measure of coordination and agility from the data of hexagonal jumps and T-runs and conducted genome-wide association and meta-analysis studies focused on coordination and agility. Results: The phenotypic correlation and genetic covariance analysis indicated that hexagonal jumps and T-runs were possibly influenced by the same set of genetic factors (R = 0.27, genetic covariance = 0.59). Meta-analysis identified rs117047321 genome-wide significant association (N = 143, P < 10E-5) with coordination and agility, and this association was replicated in the replication group (N = 318, P < 0.05). The CG genotype samples of this single nucleotide polymorphism (SNP) required a longer average movement time than the CC genotype samples, and the CG genotype only exists in Asia, which may belong to the East Asia-specific variation. This SNP is located on MYO5B, which is highly expressed in tissues such as the brain, heart, and muscle, suggesting that this locus might be a genetic factor related to human energy metabolism. Conclusion: Our study indicated that genetic factors can affect the athletic performance of coordination and agility. These findings may provide valuable insights for using genetic factors to evaluate sports characteristics.

Two cases of spontaneous rupture of the uterine artery in the perinatal period: A case report.

RATIONALE: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication during pregnancy and puerperium. The lack of typical symptoms makes it difficult to diagnose, which can result in serious consequences for both the mother and fetus. PATIENT CONCERNS: Case 1 presented with fainting and lower abdominal discomfort, while Case 2 developed hypotension after delivery and remained in poor condition even after rehydration. DIAGNOSES: Both cases were diagnosed with uterine artery spontaneous rupture, with intraoperative findings revealing ruptures in different branches of the uterine artery. INTERVENTIONS: Both cases underwent surgical interventions, with laparoscopic surgery performed in Case 1 and repair of the ruptured artery in Case 2. OUTCOMES: Both cases had successful outcomes, with the ruptured arteries repaired and the patients discharged from the hospital within a week after surgery. LESSONS: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication that may present with atypical symptoms. Early diagnosis and prompt surgical intervention are crucial in preventing serious complications for both the mother and fetus. Clinicians should maintain a high level of suspicion for this condition when evaluating patients presenting with unexplained symptoms or signs of peritoneal irritation during pregnancy and puerperium.

The prenatal weekly temperature exposure and neonatal congenital heart disease: a large population-based observational study in China.

We aim to explore the link between maternal weekly temperature exposure and CHD in offspring and identify the relative contributions from heat and cold and from moderate and extreme atmospheric temperature. From January 2019 to December 2020, newborns who were diagnosed with CHD by echocardiography in the Network Platform for Congenital Heart Disease (NPCHD) from 11 cities in eastern China were enrolled in the present study. We appraised the exposure lag response relationship between temperature and CHDs in the distributed lag nonlinear model and further probed the pooled estimates by multivariate meta-analysis. We further performed the exposure-response curves in extreme temperature (5th percentile for cold and 95th for hot events). We also delve into the cumulative risk ratios (CRRs) of temperature on CHDs in general and subgroups. In this study, 5904 of 983, 523 infants were diagnosed with CHDs. The temperature-CHD combination performed positive significance in two exposure windows, gestational weeks 10-16 and 26-31, and reached the maximum effect in the 28th week. Compared with extreme cold (5th, 6.14℃), these effects were higher in extreme heat (95th, 29.26℃). The cumulative exposure-response curve showed a steep nonlinear rise in the hot tail but showed non-significance at low temperatures. In this range, the CRRs of temperature showed an increment to a ceiling of 3.781 (95% CI: 1.460-10.723). The temperature- CHD curves for both sex groups showed a general growth trend. No statistical significance was observed between these two groups (P = 0.106). The cumulative effect of the temperature related CHD was significant in regions with lower education levels (maximum CRR was 9.282 (3.019-28.535)). A degree centigrade increase in temperature exposure was associated with the increment of CHD risk in the first and second trimesters, especially in extreme heat. Neonates born in lower education regions were more vulnerable to temperature-related CHDs.

Noninvasive prenatal diagnosis based on cell-free DNA for tuberous sclerosis: A pilot study.

BACKGROUND: Noninvasive prenatal diagnosis (NIPD) based on cell-free DNA (cfDNA) has been introduced into the clinical application for some monogenic disorders but not for tuberous sclerosis (TSC) yet, which is an autosomal dominant disease caused by various variations in TSC1 or TSC2 gene. We aimed to explore the feasibility of NIPD on TSC. METHODS: We recruited singleton pregnancies at risk of TSC from 14 families with a proband child. Definitive NIPD for TSC was performed using targeted next-generation sequencing of cfDNA in parallel with maternal white blood cell DNA (wbcDNA). The NIPD results were validated by amniocentesis or postnatal gene testing and follow-up of the born children. RESULTS: Missense mutations, nonsense mutations, frameshift mutations, and splice-site variants which were obtained through de-novo, maternal, or paternal inheritance were included. The mean and minimum gestational weeks of NIPD were 17.18 ± 5.83 and 8 weeks, respectively. The NIPD results were 100% consistent with the amniocentesis or postnatal gene testing and follow-up of the born children. CONCLUSION: This study demonstrates that NIPD based on cfDNA is feasible for TSC, but required to be confirmed with more samples. Studies on TSC can contribute to the application and promotion of NIPD for monogenic disorders.

Association of Immune and Inflammatory Gene Polymorphism With the Risk of IgA Nephropathy: A Systematic Review and Meta-Analysis of 45 Studies.

IgA nephropathy is the most prevalent primary glomerulonephritis worldwide, with identical immunopathological characteristics caused by multiple etiologies as well as influenced by geographical and ethnical factors. To elucidate the role of immunologic and inflammatory mechanisms in the susceptibility to IgA nephropathy, we explored single nucleotide polymorphisms of related molecules in the immune pathways. We searched the PubMed database for studies that involved all gene variants of molecules in the 20 immunologic and inflammatory pathways selected from the Kyoto Encyclopedia of Genes and Genomes database. The odds ratios with their corresponding 95% confidence intervals in six genetic models (allele model, dominant model, homozygote model, heterozygote model, overdominant model, and recessive model) were summarized using fixed or random effect models. Subgroup analysis was conducted based on different ethnicities with generalized odds ratios. Heterogeneity was evaluated using the Q and I2 tests. Begg's funnel plot and Egger's linear regression test were used to evaluating possible publication bias among the included studies, and sensitivity analysis was used to test the stability of the overall results. A total of 45 studies met our selection criteria and eight related genetic association studies were retrieved, including 320 single-nucleotide polymorphisms from 20 candidate pathways, ranging from 2000 to 2021. A total of 28,994 healthy people versus 20,600 IgA nephropathy patients were enrolled. Upon meta-analyzed results that TGFB1 (rs1800469, rs1982073, rs1800471), IL-1B (rs1143627), IL-18 (rs1946518), and TLR1 (rs5743557) showed effect with or without ethnicity difference. And 10 variants presented stable and robust related to IgA nephropathy. This research showed that genetic variants are related to the immunologic and inflammatory effects of IgA nephropathy pathogenesis. The meta-analysis results supported the previous researches, and may help deepen the understanding of pathogenesis and explore new targets for IgA nephropathy-specific immunotherapy.

The Relationship between Prenatal Diagnosis Indications and Abnormal Chromosomal Karyotypes: A Retrospective Cohort of 4646 Cases in Beijing from 2012-2019.

BACKGROUND AND OBJECTIVE: Chromosomal abnormalities are one of the genetic disorders caused by abnormal chromosome number or structure and can endanger multiple organs, morphology and function of the systems in the human body. This study aims to investigate the relationship between prenatal diagnosis indications and abnormal karyotypes to improve prenatal screening. METHODS: The karyotype analyses were carried out on 4646 pregnant women with prenatal diagnosis indications referred to the first medical center of Chinese PLA General Hospital from 2012 to 2019. The incidence, distribution, and statistical features of chromosomal abnormality of different prenatal diagnosis indications were analyzed, and the relationships with the prenatal diagnosis indications were assessed. RESULTS: A total of 351 fetal chromosomal abnormalities were detected in 4646 karyotypes, with an incidence of 7.6%. The chromosomal abnormality incidence in the single indication group, two indications group, and three indications group was 5.8%, 16.1%, and 70.0%, respectively, indicating a statistically significant difference (p < 0.05). Advanced maternal age (AMA), high-risk maternal serum screening (MSS), and non-invasive prenatal DNA testing (NIPT) were the important indications for predicting abnormal karyotype. The number of prenatal diagnosis indications was highly correlated with fetal chromosomal abnormalities. The overall incidence of chromosomal abnormalities showed a tendency to increase with age. The incidence of Trisomy 21 was 3.2%, accounting for 42.5% of all chromosomal abnormalities, and the incidence tended to increase with maternal age. CONCLUSION: Prenatal karyotype analysis of pregnant women with prenatal diagnosis indications can effectively prevent the birth of defective children. AMA, MSS and NIPT were the important indications for predicting abnormal karyotype. In addition, the number of prenatal diagnosis indications is highly correlated with chromosomal abnormalities.

Combined exome sequencing and deep phenotyping in highly selected fetuses with skeletal dysplasia during the first and second trimesters improves diagnostic yield.

OBJECTIVE: To investigate the genetic etiology of skeletal dysplasia in highly selected fetuses during the first and second trimesters using deep phenotyping and exome sequencing (ES). METHOD: Fetuses with short femurs were identified using the established prenatal diagnostic approach. A multidisciplinary team reviewed fetal phenotypic information (prenatal ultrasound findings, fetal postmortem, and radiographs) in a cohort of highly selected fetuses with skeletal dysplasia during the first and second trimesters. The affected families underwent multiplatform genetic tests. RESULTS: Of the 27 affected fetuses, 21 (77.8%) had pathogenic or potential pathogenic variations in the following genes: COL1A1, FGFR3, COL2A1, COL1A2, FLNB, DYNC2LI1, and TRIP11. Two fetuses had compound heterozygous mutations in DYNC2LI1 and TRIP11, respectively, and the other 19 carried de novo autosomal dominant variants. Novel variants were identified in COL1A1, COL2A1, COL1A2, DYNC2LI1, and TRIP11 in 11 fetuses. We also included the first description of the phenotype of odontochondrodysplasia in a prenatal setting. CONCLUSIONS: ES or panel sequencing offers a high diagnostic yield for fetal skeletal dysplasia during the first and second trimesters. Comprehensive and complete phenotypic information is indispensable for genetic analysis and the expansion of genotype-phenotype correlations in fetal skeletal abnormalities.

Risk factors to discriminate neoplastic polypoid lesions of gallbladder: A large-scale case-series study.

BACKGROUND: Polypoid lesion of gallbladder (PLG) size larger than 10 mm is considered to be one of the surgical indications, but the final pathological results are mostly non-neoplastic polyps. The aim of the study was to define the risk factors to discriminate neoplastic PLG and create more precise criteria for surgical indications. METHODS: A large scale, case-series study based on 2704 patients who underwent cholecystectomy for PLG was designed. Logistic regression analysis and receiver operating characteristic curve (ROC) was adopted to identify risk factors and the optimal size criteria for predicting neoplastic PLG. RESULTS: Patients in the neoplastic group were significantly older than those in the non-neoplastic group and the average PLG size is much larger in the neoplastic group (18.5 ± 4.7 mm vs 12.6 ± 3.6 mm). Neoplastic PLGs are prone to be single and non-neoplastic polyps are usually multiple. On Multivariate logistic regression analysis, PLG size larger than 15 mm and age older than 43 years were found to be the independent risk factors to discriminate neoplastic PLG （Odds ratio 3.546 and 2.77 respectively）. The ROC curve showed that 12 mm might be the more reasonable PLG size threshold for the surgical suggestion. CONCLUSIONS: Considering its moderate diagnostic accuracy, the size of gallbladder polyp larger than 10 mm is insufficient to indicate surgical therapy for PLG and 12 mm should be the more optimal polyp's size threshold. Patients older than 43 years have a higher risk of having neoplastic polyps.

Whole-exome sequencing identified two novel mutations of DYNC2LI1 in fetal skeletal ciliopathy.

BACKGROUND: Skeletal ciliopathies are a group of clinically and genetically heterogeneous disorders with the spectrum of severity spanning from relatively mild to prenatally lethal. The aim of our study was to identify pathogenic mutations in a Chinese family with two siblings presenting a Short-rib polydactyly syndrome (SRPS)-like phenotype. METHOD: Karyotyping and NGS-based CNVseq were performed. Obtaining the negative results in karyotyping and CNVseq, whole-exome sequencing (WES) using genomic DNA (gDNA) extracted from the umbilical cord blood of the first fetus was carried out, followed by bioinformation analysis. The candidate pathogenic variants were confirmed by Sanger sequencing in the family. RESULTS: No chromosomal abnormalities and pathogenic copy number variations (CNVs) were detected in the affected fetus with SRPS-like phenotype. WES analysis identified two novel compound heterozygous variants in DYNC2LI1, c.358G>T (p.Pro120Ser; NM_001193464), and c.928A>T (p.Lys310Ter; NM_ 001193464). Bioinformatics analysis suggested that c.358G>T (p.Pro120Ser) was likely pathogenic and c.928A>T (p.Lys310Ter) was pathogenic. Sanger sequencing of the two variants in family reveal that c.358G>T was from paternal origin and c.928A>T was from maternal origin, and the second affected fetus had the same compound heterozygous variants in DYNC2LI1. Definitive diagnosis of short-rib thoracic dysplasia 15 with polydactyly (SRTD15) was made in the family. CONCLUSION: Our results expand the mutational spectrum of DYNC2LI1 in severe skeletal ciliopathies. WES facilitates the accurate prenatal diagnosis of fetal skeletal ciliopathy, and provides helpful information for genetic counseling.

Requirement for etoposide in the treatment of pregnancy related hemophagocytic lymphohistiocytosis: a multicenter retrospective study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare severe clinical syndrome. HLH manifesting during pregnancy has been paid much attention in recent years. Despite the specificity of pregnancy-related HLH, there has not been any consensus regarding its treatment. According to a previous study, corticosteroid/IVIG is the mainstream therapy; however, the efficacy is controversial. Etoposide is an important agent in the HLH-94 regimen; nevertheless, its use is limited because of possible toxicity to the fetus. METHODS: In this study, we summarized 13 cases from 4 medical institutions from April 2011 to April 2018. Treatment regimens and outcomes were observed. RESULTS: The median age was 26 (20-36) years old. The median gestational age was 28 (10-35) weeks. In these 13 patients, 10 were treated with methylprednisolone/IVIG and was effective in only two patients. In 6 patients who used etoposide during their treatment, all achieved remission. The median time from onset of disease to use of etoposide was 36 (17-131) days. Five of these 6 patients were treated with corticosteroids with/without IVIG before etoposide. One patient with pulmonary tuberculosis and one with lymphoma were treated according to etiology and achieved long survival. CONCLUSION: For treatment of pregnancy-related HLH, particularly for patients who do not respond to corticosteroids/IVIG therapy, etoposide should be used bravely. Nevertheless, suitable dosages and toxic and side-effects require further clinical observation.

Noninvasive prenatal test for FGFR3-related skeletal dysplasia based on next-generation sequencing and plasma cell-free DNA: Test performance analysis and feasibility exploration.

OBJECTIVE: To explore the feasibility and accuracy of a noninvasive prenatal test for fibroblast growth factor receptor 3 (FGFR3)-related skeletal dysplasia based on next-generation sequencing (NGS) of plasma cell-free DNA. METHOD: Fragmented genome DNA (gDNA) of fetuses with achondroplasia (ACH) and thanatophoric dysplasia type I (TD I) was mixed with postdelivery maternal plasma cell-free DNA to generate spiked samples of different modeled fetal fractions. Multiplex polymerase chain reaction was used to amplify the 19 FGFR3 loci, and the amplification products were then sequenced by NGS to detect the fetal mutant alleles. Then, maternal plasma samples of pregnant women carrying ACH (n = 4) and TD I fetuses (n = 2), as well as healthy controls (n = 15), were tested by NGS, and the test performance was evaluated. RESULTS: Fetal FGFR3 mutations were detected in all artificial mixtures with fetal gDNA concentrations above 3%. In clinical validation, our method identified all fetal FGFR3 mutant alleles from maternal plasma, with no false positive results. The sensitivity and specificity of our method were 100% (95% CI, 54.1%-100%) and 100% (78.2%-100%), respectively. CONCLUSION: Our method had a favorable performance for noninvasively detecting fetal FGFR3 mutations in maternal plasma, highlighting its promising value in developing a noninvasive prenatal test for de novo and paternally inherited disorders.

Arctigenin promotes apoptosis in ovarian cancer cells via the iNOS/NO/STAT3/survivin signalling.

Arctigenin is a biologically active lignan extracted from the seeds of Arctium lappa and shows anticancer activity against a variety of human cancers. The aim of this study was to determine the effects of arctigenin on ovarian cancer cell proliferation and survival and associated molecular mechanisms. Human ovarian cancer OVCAR3 and SKOV3 cells were treated with arctigenin, and cell proliferation and apoptosis were assessed. Western blot analysis was used to examine signal transducer and activator of transcription-3 (STAT3) phosphorylation and survivin and inducible nitric oxide synthase (iNOS) expression. The involvement of STAT3/survivin/iNOS/NO signalling in arctigenin action was checked. Arctigenin treatment resulted in a significant and dose-dependent inhibition of cell proliferation. Arctigenin-treated cells showed a 4-6 times increase in the percentage of apoptosis, compared with control cells. Pre-treatment with Ac-DEVD-CHO, a specific inhibitor of caspase-3, counteracted the induction of apoptosis by arctigenin. Arctigenin treatment significantly inhibited STAT3 phosphorylation and survivin and iNOS expression. Arctigenin-induced apoptosis was impaired by pre-transfection with survivin-expressing plasmid or addition of chemical nitric oxide (NO) donors. Additionally, exogenous NO prevented the suppression of STAT3 phosphorylation and survivin expression by arctigenin. Arctigenin treatment inhibits the proliferation and induces caspase-3-dependent apoptosis of ovarian cancer cells. Suppression of iNOS/NO/STAT3/survivin signalling is causally linked to the anticancer activity of arctigenin. Therefore, arctigenin may be applicable to anticancer therapy for ovarian cancer.

Hypoxia-induced miR-210 in epithelial ovarian cancer enhances cancer cell viability via promoting proliferation and inhibiting apoptosis.

miR-210 is upregulated in a HIF-1α-dependent way in several types of cancers. In addition, upregulated miR-210 promotes cancer proliferation, via its anti-apoptotic effects. It is blind to the regulation of miR-210 under hypoxia conditions for ovarian cancer cells and to the effect of miR-210 on ovarian cancer growth. In the present study, we determined the expression of miR-210 in epithelial ovarian cancer specimens, and in ovarian cancer cell lines under hypoxia conditions, and determined in detail the effect of miR-210 overexpression on tumor cell proliferation, and the possible mechanisms of tumor growth by miR-210 regulation. It was shown that miR-210 expression is upregulated, in response to hypoxia conditions in epithelial ovarian cancer specimens as well as epithelial ovarian cancer cell lines, with an association to HIF-1α overexpression. Furthermore, upregulated miR-210 promoted tumor growth in vitro via targeting PTPN1 and inhibiting apoptosis. Therefore, our findings shed light on the mechanism of ovarian cancer adaptation to hypoxia.

Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease.

PURPOSE: This article demonstrates a prominent noninvasive prenatal approach to assist the clinical diagnosis of a single-gene disorder disease, maple syrup urine disease, using targeted sequencing knowledge from the affected family. METHODS: The method reported here combines novel mutant discovery in known genes by targeted massively parallel sequencing with noninvasive prenatal testing. RESULTS: By applying this new strategy, we successfully revealed novel mutations in the gene BCKDHA (Ex2_4dup and c.392A>G) in this Chinese family and developed a prenatal haplotype-assisted approach to noninvasively detect the genotype of the fetus (transmitted from both parents). CONCLUSION: This is the first report of integration of targeted sequencing and noninvasive prenatal testing into clinical practice. Our study has demonstrated that this massively parallel sequencing-based strategy can potentially be used for single-gene disorder diagnosis in the future.

ARHI overexpression induces epithelial ovarian cancer cell apoptosis and excessive autophagy.

OBJECTIVE: ARHI is a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence of ARHI on epithelial ovarian cancer cell death and the underlying mechanisms behind how ARHI regulates cancer cells still require further studies. METHODS: Epithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected with ARHI vectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy. RESULTS: ARHI expression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). Overexpressed ARHI inhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response to ARHI overexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2-Beclin 1 complex were observed in ARHI overexpressing cells. Moreover, modulation of ARHI to Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation. CONCLUSIONS: The silence of ARHI expression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressed ARHI in TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.

High expression of astrocyte elevated gene-1 (AEG-1) is associated with progression of cervical intraepithelial neoplasia and unfavorable prognosis in cervical cancer.

BACKGROUND: Astrocyte elevated gene-1(AEG-1) plays an important role in the development and progression of certain types of human cancers. However, the expression dynamics of AEG-1 in cervical cancer and its clinical/prognostic significance are unclear. METHOD: In present study, the methods of tissue microarrays (TMA) and immunohistochemistry (IHC) were utilized to investigate AEG-1 expression in cervical intraepithelial neoplasia (CIN) and cervical cancer. Receiver operating characteristic (ROC) curve analysis, χ2 test, Kaplan-Meier plots, and multivariate Cox regression analysis were used to analyze the data. RESULTS: The expression level of AEG-1 was increased from CIN I to CIN III. High expression of AEG-1 could be observed in 61.1% (55/90) of cervical cancer. Moreover, high expression of AEG-1 correlated with tumor size and lymph node metastasis (all P <0.05). More importantly, high expression of AEG-1 was closely associated with cervical cancer patient shortened survival time as evidenced by univariate and multivariate analysis (P <0.05). CONCLUSIONS: Our data suggest for the first time that high expression of AEG-1 is associated significantly with progression of cervical cancer. AEG-1 overexpression, as examined by IHC, has the potential to be used as an immunomarker to predict prognosis of cervical cancer patients.

[Prognosis and reproductive outcome of laparoscopic intracapsular myomectomy].

OBJECTIVE: To assess the prognosis and reproductive outcomes of laparoscopic intracapsular myomectomy. METHODS: A total of 673 women received subserosal and intramural intracapsular laparoscopic myomectomy between March, 2007 and March, 2012, and their post-operative complications, the need for subsequent surgery, symptomatic relief and reproductive outcomes were analyzed. RESULTS: Of these patients, 42.4% had subserosal myomas and 57.6% had intramural myomas. The mean total operative time was 96∓41 min with a mean blood loss of 128∓46.2 ml, and 82.3% of the patients were discharged 48 h after the operation without early complications. A small fraction (2.3%) of the patients had a second laparoscopic myomectomy for recurrent fibroids. Of the fertility-demanding women who underwent myomectomy, 71% achieved pregnancy, 49.8% underwent caesarean section, 8% had operative vaginal deliveries, and 42.2% had spontaneous deliveries; uterine rupture occurred in none of the cases. CONCLUSION: Laparoscopic intracapsular myomectomy, by preserving the fibroid pseudocapsule and myometrial integrity, has no early postoperative complications and ensures good fertility rates and reproductive outcomes.

STAT3 acetylation-induced promoter methylation is associated with downregulation of the ARHI tumor-suppressor gene in ovarian cancer.

ARHI is a Ras-related imprinted tumor-suppressor gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of ovarian cancer cells, and promoter methylation is considered to be associated with its loss of expression. however, the underlying mechanisms are not well understood. Thus, the present study aimed to investigate the specific functions of ARHI and its methylation in ovarian cancer cell proliferation. Furthermore, we examined the possible role of acetylated STAT3 in modulating the expression of ARHI and its methylation. In accordance with the majority of previous studies, reduced ARHI expression was found in epithelial ovarian cancer tissues and cancer cell lines as indicated by immunohistochemistry and RT-PCR. In addition, CpG islands I and II within ARHI promoter regions were partially methylated or hypermethylated in cancer cell lines (SKOV-3 and HO-8910) as analyzed by pyrosequencing assays, resulting in enhanced proliferation of the cancer cells. This proliferation was reversed by the administration of 5-aza-2'-deoxycytidine. Subsequently, we demonstrated that STAT3 acetylation was increased in HO-8910 cells, and the methylation status of CpG I was altered in response to the acetylation of STAT3 using western blotting. Finally, chromatin immunoprecipitation (ChIP) and IP analysis indicated that acetylated STAT3 bound to the ARHI promoter and recruited DNA methyltransferase 1 for genetic modification. In conclusion, acetylated STAT3-induced promoter gene methylation accounts for the loss of ARHI expression and cancer cell proliferation.

[Application of acellular allograft dermal tissue patch in the repair of transvaginal rectovaginal fistula].

OBJECTIVE: To investigate the clinical effect of acellular allograft dermal tissue patch used in transvaginal rectovaginal fistula repair. METHODS: From Jan. 2008 to Dec. 2011, 22 patients with rectovaginal fistula undergoing treatment in Chinese People's Liberation Army General Hospital were studied retrospectively. Twelve patients treated by tissue patch were classified into study group matched with 10 patients with general surgery as controls. RESULTS: In study group, 11 patients were successfully repaired by their first surgery;one patient was successfully fixed by the second surgery. The successful rate of first operation was 11/12 in study group and 4/5 in recurrent transvaginal rectovaginal fistula. In control group, 7 patients were fixed successfully in their first surgeries, the successful rate of first surgery was 7/10. Two primary patients and 1 recurrent patient were successfully fixed by their second surgeries. All of the patients were followed up for (9.0 ± 2.0) months, and no recurrence diseases were observed. CONCLUSION: The transvaginal rectovaginal fistula fixed using acellular allograft dermal tissue patch could get less trauma and higher cure rate.