Immune-related LncRNAs scores predicts chemotherapeutic responses and prognosis in cervical cancer patients.

BACKGROUND: Long non-coding RNAs (LncRNAs) regulating the immune microenvironment of cancer is a hot spot. But little is known about the influence of the immune-related lncRNA (IRlncRs) on the chemotherapeutic responses and prognosis of cervical cancer (CC) patients. The purpose of the study was to identify an immune-related lncRNAs (IRlncRs)-based model for the prospective prediction of clinical outcomes in CC patients. METHODS: CC patients' relevant data was acquired from The Cancer Genome Atlas (TCGA). Correlation analysis and Cox regression analyses were applied. A risk score formula was formulated. Prognostic factors were combined into a nomogram, while sensitivity for chemotherapy drugs was analyzed using the OncoPredict algorithm. RESULTS: Eight optimal IRlncRs(ATP2A1-AS1, LINC01943, AL158166.1, LINC00963, AC009065.8, LIPE-AS1, AC105277.1, AC098613.1.) were incorporated in the IRlncRs model. The overall survival (OS) of the high-risk group of the model was inferior to those in the low-risk group. Further analysis demonstrated this eight-IRlncRs model as a useful prognostic marker. The Nomogram had a concordance index of survival prediction of 0.763(95% CI 0.746-0.780) and more robust predictive accuracy. Furthermore, patients in the low-risk group were found to be more sensitive to chemotherapy, including Paclitaxel, Rapamycin, Epirubicin, Vincristine, Docetaxel and Vinorelbine. CONCLUSIONS: An eight-IRlncRs-based prediction model was identified that has the potential to be an important tool to predict chemotherapeutic responses and prognosis for CC patients.

Efficacy and safety of transvaginal mesh repair in a cohort with a minimum of 10-year follow-up.

Although transvaginal mesh (TVM) repair is no longer used in some countries, long-term outcomes after TVM surgery are of great importance globally. However, reports with follow-up >10 years are limited. Thus, this study aimed to report outcomes in a prospective cohort with at least 10 years of follow-up. Women with stage III-IV symptomatic prolapse were approached consecutively from 2008 to 2013 at one tertiary hospital. The main outcome measure was symptomatic failure. Secondary outcomes included anatomic failure, recurrence, patient satisfaction, complications, and reoperation. The Kaplan-Meier curve was used to estimate the cumulative failure rate. Of the 121 patients enrolled in the study, 103 (85.1%) completed a median follow-up of 11 years. The estimated probability rates of symptomatic and anatomic failure were 17.6% and 8.8% in 11 years, respectively. The estimated incidence of symptomatic failure increased by 8.2% between 5 and 11 years; however, the corresponding rate for anatomic failure was 3.7%. The most common complication was vaginal mesh exposure, and its estimated probability increased from 19.3% to 28.4% from 5 to 11 years, respectively. Office trimming resolved 80.0% of vaginal exposures. These patients did not report decreased overall satisfaction. Patients with vaginal mesh exposure requiring>3 office procedures or mesh removal in the operating room (5.8% by 11 years) had lower satisfaction rates (P<0.01) and were defined as having severe mesh exposure. The rates of postoperative pain, reoperation, and Patient Global Impression of Improvement ⩾2 were 2.5%, 3.3%, and 94.2%, respectively. The results of this study implied that TVM treatment gradually increased the symptomatic failure rate but provided durable anatomical support of the vaginal wall. Vaginal mesh exposure was common in women who were largely not sexually active; however, 80% of the cases could be managed in the outpatient clinic, which did not affect patient satisfaction.

A comprehensive evaluation of spontaneous pelvic organ prolapse in rhesus macaques as an ideal model for the study of human pelvic organ prolapse.

Pelvic organ prolapse (POP) seriously affects a woman's quality of life, and the treatment complications are severe. Although new surgical treatments are being developed, the host tissue responses and safety need to be evaluated in preclinical trials. However, there is a lack of suitable animal models, as most quadrupeds exhibit different structural and pathological changes. In this study, 72 elderly rhesus macaques (Macaca mulatta) were physically examined, and the incidence of spontaneous POP was similar to that in humans. The vaginal wall from five control monkeys and four monkeys with POP were selected for further analysis. Verhoeff-van Gieson staining showed that elastin content decreased significantly in monkeys with POP compared with control samples. Immunohistological staining revealed that the smooth muscle bundles in monkey POP appeared disorganized, and the number of large muscle bundles decreased significantly. The collagen I/III ratio in monkey POP also significantly decreased, as revealed by Sirius Red staining. These histological and biochemical changes in monkeys with POP were similar to those in humans with POP. Moreover, we generated a single-cell transcriptomic atlas of the prolapsed monkey vagina. Cross-species analysis between humans and monkeys revealed a comparable cellular composition. Notably, a differential gene expression analysis determined that dysregulation of the extracellular matrix and an immune disorder were the conserved molecular mechanisms. The interplay between fibroblasts and macrophages contributed to human and monkey POP. Overall, this study represents a comprehensive evaluation of spontaneous POP in rhesus macaques and demonstrates that monkeys are a suitable animal model for POP research.

Results of sacrospinous ligament fixation using conventional instruments for symptomatic stage 2 and 3 apical prolapse over 3 years.

OBJECTIVE: To evaluate the long-term efficacy and quality of life concerning sacrospinous ligament fixation (SSLF) using conventional instruments for Chinese women with symptomatic stage 2 and 3 apical prolapse. METHODS: This single-arm prospective cohort study was conducted at our hospital between October 2011 and December 2018. Eligible participants were followed up over 3 years after surgery. The primary surgical outcome was composite surgical failure. Secondary outcomes included rate of satisfaction, quality of life (QoL) scores, and long-term complications. RESULTS: Fifty-nine patients were enrolled (mean age 57.1 years), of whom 55 (93.22%) completed the 3-year follow up. At year 3, the composite failure rate was 21.34% (95% confidence interval [CI] 9.30%-31.79%), and satisfaction rate was 81.40% (95% CI 66.09%-91.08%). Right thigh pain and de novo dyspareunia occurred in 1.8% and 14.6% patients after year 1, respectively, but at year 3 there were no complications. Lower urinary tract symptoms were present in 5.5% of patients. Improvement was found in urinary symptoms and prolapse symptoms, but sexual function showed no significant change. CONCLUSIONS: Compared with results at year 1, complication rates of SSLF decreased at year 3. The composite failure rate was relatively low and satisfaction rate was relatively high at year 3. Prolapse and urinary symptoms improved significantly after surgery.

Aerobic Exercise Regulates Apoptosis through the PI3K/Akt/GSK-3ß Signaling Pathway to Improve Cognitive Impairment in Alzheimer's Disease Mice.

Neuronal apoptosis is an important factor in the etiology of Alzheimer's disease (AD). Aerobic exercise (AE) enhances learning and memory, improves cognitive impairment, increases telomere binding protein expression, and decreases apoptosis regulators, but it remains unclear whether it can improve cognitive impairment caused by neuronal apoptosis in AD. Therefore, this study investigated whether an 8-week running table exercise intervention could reduce apoptosis and improve cognitive function in the hippocampal neurons of AD model mice. After the exercise intervention, we evaluated the learning memory ability (positioning, navigation, and spatial search) of mice using a Morris water labyrinth, Nissl staining, immunohistochemistry, and protein application to detect hippocampal PI3K/Akt/GSK-3ß signaling pathway protein and hippocampal neuronal cell apoptosis protein B cell lymphoma 2 (Bcl-2) and apoptosis-promoting protein bcl-2-related X (Bax) protein expression. The results showed that aerobic exercise improved the location and spatial exploration ability of mice, increased the number of PI3K- and p-Akt-positive cells, increased the expression of PI3K, p-Akt, and bcl-2 proteins, decreased the expression of GSK-3ß and Bax proteins, and increased the bcl-2/Bax ratio of mice. The results suggest that aerobic exercise can reduce apoptosis and improve cognitive function in AD mice. The molecular mechanism may involve activation of the PI3K/Akt/GSK-3ß signaling pathway.

Functional characteristics of a broad spectrum of TBX6 variants in Mayer-Rokitansky-Küster-Hauser syndrome.

PURPOSE: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in females. Whole-gene deletion and loss-of-function variants in TBX6 have been identified in association with MRKHS. We aimed to expand the spectrum of TBX6 variants in MRKHS and explore the biological effect of the variant alleles. METHODS: Rare variants in TBX6 were called from a combined multiethnic cohort of 622 probands with MRKHS who underwent exome sequencing or genome sequencing. Multiple in vitro functional experiments were performed, including messenger RNA analysis, western blotting, transcriptional activity assay, and immunofluorescence staining. RESULTS: We identified 16 rare variants in TBX6 from the combined cohort, including 1 protein-truncating variant reported in our previous study and 15 variants with unknown effects. By comparing the prevalence of TBX6 variants in the Chinese MRKHS cohort vs 1038 female controls, we observed a significant mutational burden of TBX6 in affected individuals (P = .0004, odds ratio = 5.25), suggesting a causal role of TBX6 variants in MRKHS. Of the 15 variants with uncertain effects, 7 were shown to induce a loss-of-function effect through various mechanisms. The c.423G>A (p.Leu141=) and c.839+5G>A variants impaired the normal splicing of TBX6 messenger RNA, c.422T>C (p.Leu141Pro) and c.745G>A (p.Val249Met) led to decreased protein expression, c.10C>T (p.Pro4Ser) and c.400G>A (p.Glu134Lys) resulted in perturbed transcriptional activity, and c.356G>A (p.Arg119His) caused protein mislocalization. We observed incomplete penetrance and variable expressivity in families carrying deleterious variants, which indicates a more complex genetic mechanism than classical Mendelian inheritance. CONCLUSION: Our study expands the mutational spectrum of TBX6 in MRKHS and delineates the molecular pathogenesis of TBX6 variants, supporting the association between deleterious variants in TBX6 and MRKHS.

A Two-Stage Enzymolysis Method and Its Application in Exerting Antioxidant Activity of Walnut Protein.

Traditional enzymolysis method for producing bioactive peptides does not consider the utilization of digestive enzymes in the human gastrointestinal tract, leading to the possibility of excessive hydrolysis and higher production cost. Therefore, a two-stage enzymolysis method was established in this study based on in vitro limited enzymolysis and gastrointestinal digestion, and applied it to the research of walnut protein (WP) in exerting antioxidant activity. Results showed that WP could be well-digested by pepsin and pancreatin. WP with limited enzymolysis degree of 0% could achieve high antioxidant activity after the simulated gastrointestinal digestion, and the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and reducing power were 66.53% and 8.55 µmoL TE/mL, respectively. In vivo experimental results also exhibited that both WP and WP hydrolysate (WPH) could alleviate the oxidative damage induced by D-galactose in SD rats to some extent. Considering the digestive function of human body, in vitro limited enzymolysis, in vitro simulated gastrointestinal digestion and in vivo validation are necessary processes for the production of bioactive peptides.

Burch colposuspension for stress urinary incontinence: a 14-year prospective follow-up.

We aimed to evaluate the long-term effectiveness and safety of Burch colposuspension (BC) for stress urinary incontinence (SUI). In this prospective cohort study, 84 patients with SUI undergoing BC were enrolled from February 2004 to January 2010. Data on long-term subjective success and postoperative complications were collected at clinic visits and by telephone follow-up. During a mean follow-up period of 14.2 years, 68% (57/84) patients completed the follow-up. A total of 68.4% of patients (39/57) reported absence of SUI symptoms, 73.6% (42/57) were subjectively satisfied according to the Patient Global Impression of Improvement, and 68.4% (39/57) reported subjective success regarding urinary symptoms via the Urinary Distress Inventory Short Form. However, 28.1% (16/57) suffered at least one long-term postoperative complication and incident. Specifically, 1 in 25 (4.0%) sexually active patients reported dyspareunia, 3 patients (5.3%) had de novo overactive bladder, and 6 patients (10.5%) reported voiding dysfunction. Four patients (7.0%) reported new onset prolapse symptoms, and 3 patients (5.3%) underwent secondary urinary incontinence surgery. Our study indicated that Burch colposuspension is an effective procedure for SUI, and the cure effect was largely maintained for the 14-year follow-up period, with relatively low complication rates. BC should be considered a surgical option for SUI.

A genotype-first analysis in a cohort of Mullerian anomaly.

Müllerian anomaly (M.A.) is a group of congenital anatomic abnormalities caused by aberrations of the development process of the Müllerian duct. M.A. can either be isolated or be involved in Mendelian syndromes, such as Dandy-Walker syndrome, Holt-Oram syndrome and Bardet-Biedl syndrome, which are often associated with both uterus and kidney malformations. In this study, we applied a genotype-first approach to analyze the whole-exome sequencing data of 492 patients with M.A. Six potential pathogenic variants were found in five genes previously related to female urogenital deformities (PKD1, SON, SALL1, BMPR1B, ITGA8), which are partially overlapping with our patients' phenotypes. We further identified eight incidental findings in seven genes related to Mendelian syndromes without known association with reproductive anomalies (TEK, COL11A1, ANKRD11, LEMD3, DLG5, SPTB, BMP2), which represent potential phenotype expansions of these genes.

Clinical Features and Management of Endometriosis among Patients with MRKH and Functional Uterine Remnants.

OBJECTIVE: This study aimed to determine the clinical features of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients with functional uterine remnants and endometriosis in a large cohort of Chinese patients. DESIGN: This was a retrospective study. PARTICIPANTS: This study had a cohort of 511 MRKH patients. A total of 34 MRKH patients with functional remnant were finally included. SETTING: This study included a tertiary referring hospital in China. METHODS: Patients with MRKH diagnosed and treated at Peking Union Medical College Hospital from January 2009 to January 2020 were recruited. A cohort of 511 MRKH patients were retrospectively screened, and a total of 34 MRKH patients with functional remnant were finally included. Relevant clinical data were reviewed retrospectively from medical charts. RESULTS: Of 34 patients with MRKH and functional uterine remnants, 23 (68%) had endometriosis. These patients had a greater mean age at MRKH diagnosis than patients without endometriosis (15.9 ± 3.3 years vs. 13.2 ± 3.5 years; p = 0.03). Similarly, these patients experienced a longer time between age at onset of symptoms and age at operation than patients without endometriosis (45.5 ± 39.6 years vs. 19.8 ± 13.2 years; p = 0.04). In addition, the CA125 level was significantly higher in patients with endometriosis than in those without it (64.9 ± 85.9 U/mL vs. 25.5 ± 19.1 U/mL; p = 0.03). LIMITATIONS: The number of patients with MRKH analyzed in this study was low as we restricted inclusion to patients with at least 1 functional uterine remnant or endometriosis. CONCLUSIONS: It is reasonable to monitor the uterine remnant of patients with MRKH closely, regardless of age, to achieve early intervention. The level of CA125 might be helpful to differentiate active uterine remnants with endometriosis and schedule individualized treatments.

Mesenchymal stem cell-based bioengineered constructs enhance vaginal repair in ovariectomized rhesus monkeys.

Transvaginal meshes repair for treating pelvic organ prolapse (POP) was halted by the U. S. Food and Drug Administration (FDA) because they can lead to severe complications. Therefore, investigations of new therapeutic strategies are urgently needed. Cell-based regenerative therapy holds great promise for the repair and restoration of damaged tissue. Here, we generated a bioengineered graft by seeding human umbilical cord mesenchymal stem cells (HUMSCs) on bioscaffolds to reconstruct the damaged vagina. In the in vitro study, HUMSCs proliferated well and the density was appropriate after 5 days of culture. Besides, we demonstrated that the differentiation potential of HUMSCs was maintained with external growth factor stimulation. The complete transcriptomic profile of HUMSCs revealed that HUMSCs cultured on grafts produced significantly higher levels of proangiogenic cytokines than cells cultured in tissue culture plates (TCPs). Three months after implantation of the bioengineered grafts into ovariectomized (OVX) rhesus monkeys via sacrocolpopexy, extracellular matrix reorganization, large muscle bundle formation, angiogenesis and, mechanical properties of the vagina were enhanced. To our knowledge, this is the first demonstration of the utility of stem cell-based bioengineered grafts for repairing damaged vaginal tissue in rhesus monkeys. These results elucidate a new approach for vagina repair and provide new ideas for treating POP.

CCR7 Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change.

The tumor microenvironment (TME) has an essential role in the development of cervical squamous cell carcinoma (CSCC); however, the dynamic role of the stromal and immune cells is still unclear in TME. We downloaded data from The Cancer Genome Atlas (TCGA) database and applied ESTIMATE and CIBERSORT algorithms to measure the quantity of stromal and immune cells and the composition of tumor-infiltrating immune cell (TIC) in 253 CSCC cases. The protein-protein interaction (PPI) network and Cox regression analysis presented the differentially expressed genes (DEGs). Then, C-C chemokine receptor type 7 (CCR7) was screened out as a prognostic marker by the univariate Cox and intersection analysis of PPI. Further analysis showed a positive correlation between the expression of CCR7 and the survival of CSCC patients. The result of the Gene Set Enrichment Analysis (GSEA) of genes in the high CCR7 expression group displayed a predominant enrichment in immune-related pathways. An enrichment in metabolic activities was observed in the low CCR7 expression group. CIBERSORT analysis showed a positive correlation between Plasma cells, CD8+ T cells, and regulatory T cells and the CCR7 expression, suggesting that CCR7 might play a crucial role in maintaining the immunological dominance status for TME. Therefore, the expression level of CCR7 might help predict the survival of CSCC cases and be an index that the status of TME transitioned from immunological dominance to metabolic activation, which presented a new insight into the treatment of CSCC.

The necessity of enzymatically hydrolyzing walnut protein to exert antihypertensive activity based on in vitro simulated digestion and in vivo verification.

Since not all proteins are suitable for preparing bioactive peptides by enzymatic degradation, the purpose of this study is to evaluate the necessity of walnut protein (WP) enzymolysis to exert its potential antihypertensive activity. Five proteases were used to hydrolyze WP to produce WP hydrolysate (WPH) enzymatically. The angiotensin-I-converting enzyme (ACE) inhibitory activity of WP and WPH before and after simulated digestion in vitro was measured, and the antihypertensive effect was evaluated in vivo. The results showed that after simulated digestion in vitro, the ACE inhibitory activity of WP digests (44.85%) was not significantly different from that of WPH digests (p > 0.05). In vivo experimental results showed that both WP and WPH had significant blood pressure lowering effects in the acute and long-term administrative experiments. The mechanism of its antihypertensive activities was regulating the balance of the renin-angiotensin-aldosterone system and the kallikrein-kinin system by inhibiting ACE activities in tissues and regulating the level of endothelium-derived vasoconstrictor factors and relaxing factors in serum. It seems unnecessary to carry out enzymatic hydrolysis to produce walnut peptides with antihypertensive activity.

Vaginal pessary treatment in women with symptomatic pelvic organ prolapse: a long-term prospective study.

OBJECTIVE: To evaluate the 5-year pessary continuation rate and identify clinical risk factors associated with discontinuation in patients with symptomatic pelvic organ prolapse (POP). METHODS: In this prospective observational study, 312 women with symptomatic POP received pessary treatment between November 2013 and July 2015 in Peking Union Medical College Hospital, China, a tertiary referral center. Patients were initially fitted with a ring pessary with support. Those who failed were fitted with a Gellhorn pessary. A successful pessary fitting was defined as a patient who was fitted and continued to use the pessary 2 weeks later. Patients with successful pessary fitting were followed for 5 years. Data analysis was performed with t tests, nonparametric tests, chi-square tests, and logistic regression. RESULTS: In total, 265 patients (84.9%) had successful pessary fitting. After 5 years, 180 of 239 patients continued pessary use (75.3% continuation rate), with 26 lost to follow-up. The discontinuation rates decreased over time, from 8.7% at 1 year to 2.7% at 5 years. Total vaginal length < 7.5 cm (TVL, OR = 2.7, 95% CI 1.3-5.7, P = 0.007), improvement in Urinary Impact Questionnaire-7 scores < 50% at 3 months (OR = 2.1, 95% CI 1.1-4.2, P = 0.025), and incapability of self-care (OR = 2.6, 95% CI 1.3-5.1, P = 0.008) were potential discontinuation risk factors. CONCLUSION: Three-quarters of patients with symptomatic POP had successful pessary treatment at 5-year follow-up. TVL < 7.5 cm, poor urinary symptom relief at 3 months, and incapability of self-care were potential discontinuation risk factors.

Clinical outcomes and uroflowmetry assessment in patients with apical prolapse after laparoscopic uterosacral ligament suspension.

OBJECTIVE: The aim was to evaluate the voiding function and voiding dysfunction 3 months after laparoscopic uterosacral ligament suspension (LUSLS). We identified risk factors for postoperative voiding dysfunction. STUDY DESIGN: This retrospective study included 57 women with apical prolapse who underwent LUSLS with stage II or greater apical prolapse and without advanced anterior vaginal prolapse (stage III or IV). Data were collected from electronic medical records. Voiding function was assessed by uroflowmetry, PVR examination, and self-report questionnaires (the Pelvic Floor Distress Inventory-20 and the Urinary Impact Questionnaire) at baseline and 3 months after surgery. Voiding dysfunction was defined as an average flow rate (Qave)＜10 ml/s, a maximum flow rate (Qmax)＜15 ml/s, or a postvoid residual volume (PVR)＞50 ml. Statistical analyses were performed using paired-sample t tests, χ2 tests, and multivariate logistic regression. RESULTS: Thirty-five percent of women suffered from voiding dysfunction preoperatively. Uroflowmetry parameters and PVR, objective symptoms including voiding difficulties, incomplete empty, frequency and urinary incontinence didn't show significant improvement postoperatively (all p＞0.05). Low Qave was identified as an independent risk factor of post voiding dysfunction (odds ratio, 0.558; 95 % CI, 0.324-0.963). CONCLUSIONS: Approximately one-third of women suffering from apical prolapse without advanced anterior vaginal wall had evidence of voiding dysfunction preoperatively. LUSLS has no obvious effect on uroflowmetry parameters and clinical symptoms.

Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.

Laparoscopically Assisted Uterovaginal Canalization and Vaginoplasty for Patients with Congenital Cervical and Vaginal Atresia: A Step-by-step Guide and Long-term Outcomes.

STUDY OBJECTIVE: To study the long-term outcomes of laparoscopically assisted uterovaginal canalization and vaginoplasty in patients with congenital cervical and vaginal atresia and to introduce the surgery step by step. DESIGN: A prospective observational study from January 2016 to September 2019. SETTING: A tertiary teaching hospital. PATIENTS: Ten women diagnosed with congenital cervical and vaginal atresia. INTERVENTIONS: All women underwent laparoscopically assisted uterovaginal canalization and vaginoplasty. MEASUREMENTS AND MAIN RESULTS: All procedures went smoothly, with no case requiring conversion to laparotomy, and no intraoperative complications occurred. Postoperative febrile morbidity occurred in 1 patient (1/10, 10%). The median (interquartile range) follow-up time was 26.0 (21.3, 48.3) months. All patients resumed menstruation, including 9 patients (9/10, 90%) with regular monthly menstruation. Eight patients (8/10, 80%) experienced mild to moderate dysmenorrhea; the remaining 2 patients (2/10, 20%) had no dysmenorrhea. Cervical restenosis occurred in 1 patient (1/10, 10%) 12 months postoperatively, and cervical dilation was performed. So far, 8 months after the second surgery, no restenosis has been found. The mean postoperative vaginal length was 7.9 ± 1.3-cm at the time of the last follow-up. Only 1 patient attempted to conceive for 2 years, but she had not conceived yet. CONCLUSION: Laparoscopically assisted uterovaginal canalization and vaginoplasty is an easy, safe, and promising management option for correcting congenital cervical and vaginal atresia.

The effects of progesterones on blood lipids in hormone replacement therapy.

The safety of progestogens as a class has drawn much attention after the publication of data from the Women's Health Initiative (WHI) trial, particularly with respect to cardiovascular disease. Depending on the chemical structure, pharmacokinetics, receptor affinity and potency of action, progestogens have a divergent range of properties that may translate to very different clinical effects. The purpose of this review is to describe the role of varied progestogens in hormone replacement therapy (HRT), especially focusing on blood lipids, which are the most important parameters for assessing cardiovascular disease risk.

Association Between HIF-1 Alpha Gene Polymorphisms and Response in Patients Undergoing Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer.

BACKGROUND The aim of the study was to assess whether HIF-1α polymorphisms have an effect on the response to chemotherapy of locally advanced cervical cancer (LACC) patients treated with platinum-based neoadjuvant chemotherapy (NACT) and radical surgery. MATERIAL AND METHODS We conducted a retrospective study in 162 LACC patients. Hypoxia-inducible factor 1α C1772T and G1790A genetic polymorphisms were ascertained using direct sequencing methods. RESULTS The C1772T polymorphism was significantly related to response to chemotherapy (P=0.002), and there was an increased chance of treatment response in patients with the C/C genotype (OR=4.7; 95% CI: 1.67-13.49; P=0.004). The C1772T polymorphism was also associated with poor tumor grade (adjusted OR, 2.98; 95% CI: 1.08-8.13; P=0.037). However, The G1790A polymorphism was not associated with response (P>0.05). CONCLUSIONS The C1772T polymorphism was significantly related to response to chemotherapy and poor tumor grade. Our results may help to better manage individual patients and to improve clinical decision making regarding use of NACT.

Prognostic Impact of Epidermal Growth Factor Receptor Overexpression in Patients with Cervical Cancer: A Meta-Analysis.

Clinical trials have provided conflicting results regarding whether epidermal growth factor receptor (EGFR) overexpression predicts poor survival in cervical cancer patients. In this study, we perform a meta-analysis of the association between EGFR expression and survival in cervical cancer patients. We searched clinical studies in the Medline, PubMed, Embase, and Web of Science databases. A total of 22 studies with 2,505 patients were included, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each study. Heterogeneity was assessed using Higgins I2 to select a Mantel-Haenszel fixed effects model (I2 ≤50%) or a DerSimonian-Laird random effects model (I2 ≥50%). High EGFR levels predicted poor overall survival (OS) (HR: 1.40, 95% CI: 1.10-1.78) and disease-free survival (DFS) (HR: 1.84, 95% CI: 1.51-2.24). Stratified analyses showed that EGFR overexpression was significantly related to poor DFS in patients treated with chemoradiation or surgery. Moreover, the pooled odds ratios (ORs) revealed associations between EGFR expression and clinicopathological features, such as lymph node metastasis (OR: 1.72, 95% CI: 1.23-2.40) and tumor size ≥4 cm (OR: 1.64, 95% CI: 1.20-2.23). This meta-analysis demonstrates that EGFR overexpression is closely associated with reduced survival in patients with cervical cancer. These results may facilitate the individualized management of clinical decisions for anti-EGFR therapies in cervical cancer patients.