Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Background::Extracellular matrix (ECM) remodeling is the most important pathomechanism of pelvic organ prolapse (POP). Fibroblasts are the key to ECM regulation. The passaging capacity of human vaginal wall fibroblasts (hVWFs) is limited in vitro. Here, we aimed to immortalize hVWFs through the introduction of human telomerase reverse transcriptase (hTERT). Methods::Primary cells were derived from the vaginal wall tissue of patients with POP. Cellular senescence was detected via senescence-associated β-galactosidase staining. We employed a lentiviral transfection vector to stably express hTERT in hVWFs at passage 3, generating immortalized hVWFs (i-hVWFs). We then assessed cellular proliferation via the CCK-8 and EdU assays as well as cellular migration via wound healing assays. G-banded chromosome karyotypic analysis was performed to evaluate chromosomal karyotype stability. Finally, cellular tumorigenesis capacity was assessed in nude mice. A two-tailed Student’s t test was used to compare differences between the two groups. Results::Our results showed that senescence of primary hVWFs significantly increased from passage seven. From passage 11, hVWFs showed a significantly higher senescence percentage than i-hVWFs. During the continuous passage, i-hVWFs presented stability in proliferation, migration capacity, expression of ECM regulation-related genes, and chromosome karyotype. In vivo tumorigenesis was absent in i-hVWFs. Conclusions::The senescence of hVWFs significantly increased from the seventh passage, and we successfully used hTERT to immortalize hVWFs derived from patients with POP. Studies on POP that require a long-lived hVWF line will benefit from our technique.

Adenocarcinoma, Clear Cell/pathology* ; Carcinoma in Situ ; Cell Transformation, Neoplastic ; China ; Endometriosis/pathology* ; Female ; Humans

OBJECTIVE: To explore the genetic basis for a case of Lamb-Shaffer syndrome. METHODS: Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing. RESULTS: The patients was found to harbor a heterozygous c.1495delA(p.Thr499Glnfs*5) frameshift variant of the SOX5 gene by WES. Sanger sequencing confirmed that the same variant was a de novo variant. Based on the American College of Medical Genetics and Genomics guidelines, c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.
Animals ; Genomics ; Heterozygote ; Humans ; Mutation ; SOXD Transcription Factors/genetics* ; Sheep ; Whole Exome Sequencing

Objective:To study the clinical characteristics of cornual pregnancy and compare the effects of various surgical methods on the outcomes.Methods:This was a single-center retrospective study. The clinical records of patients with cornual pregnancy who underwent surgery in Peking Union Medical College Hospital from June 2012 to December 2020 were collected. Surgical interventions included curettage (guided by ultrasound or monitored by laparoscope), and cornuostomy/cornectomy (the surgical approach by laparoscopy or laparotomy). The baseline data, perioperative treatment and whether persistent ectopic pregnancy (PEP) occurred after surgery were collected and analyzed statistically.Results:A total of 109 patients with cornual pregnancy diagnosed by surgical treatment were included in this study, whose average age was (32.9±4.8) years. Among them, the incidence of postoperative PEP was 16.5% (18/109). The risk of PEP in multipara was significantly higher than that in nulliparous women ( OR=7.639, 95% CI: 2.063-28.279, P=0.001). The risk of PEP in patients with the maximum diameter of lesion<1.5 cm was significantly higher than that in patients with the maximum diameter of lesion≥1.5 cm ( OR=8.600, 95% CI: 2.271-32.571, P=0.002). Among all surgical approaches for cornual pregnancy, the proportion of PEP in curettage under ultrasound monitoring was the highest (56.0%, 14/25), which was higher than that in curettage under laparoscope monitoring (1/10; χ2=6.172， P=0.013); the proportion of PEP in curettage group (42.9%, 15/35) was higher than that in cornuostomy/cornectomy group (4.1%, 3/74; χ2=25.950， P<0.01). Neither salpingectomy in the operation nor the routine use of methotrexate (MTX) in perioperative period could significantly reduce the incidence of PEP (all P>0.05). Conclusions:Among the patients with cornual pregnancy, multipara, the maximum diameter of lesion<1.5 cm and ultrasound-guided curettage are the risk factors of PEP after operation. Cornuostomy or cornectomy is recommended for patients with cornual pregnancy. If the patients would perform the curettage operation, laparoscopic monitoring is recommended. For patients with possible satisfactory operation outcome, it is not recommended to use MTX as a routine preventing measure.

Objective:To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI +）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods:Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results:(1) A total of 4 891 patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.367, 95% CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS ( HR=1.420, 95% CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS ( P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups ( P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.705, 95% CI: 1.088-2.674, P=0.020). Conclusions:For patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Objective:To investigate the clinical features, etiology, and prognosis of sepsis during pregnancy and the postpartum period.Methods:Sixty-eight pregnant women with maternal sepsis treated in Peking Union Medical College Hospital from January 1997 to December 2019 were collected, and divided into obstetric infection group (30 cases) and non-obstetric infection group (38 cases) according to different infection sources. Clinical manifestations, types of infection sources, microbiological characteristics, treatment and outcomes were studied and analyzed.Results:(1) General conditions and clinical features: sepsis occurrence rate was 57% (39/68) and 43% (29/68) in prenatal and postpartum period, repectively. Statistical analysis showed that incidence of respiratory, renal, liver and coagulation dysfunction in non-obstetric infection group were significantly higher than those in obstetric infection group, and multiple organ dysfunction, cardiac arrest and blood lactate≥4 mmol/L were more common (all P<0.05). Sequential organ failure score in non-obstetric infection group was also significantly higher than that in obstetric infection group ( P<0.05). (2) Types of infection sources and microbiological characteristics: the most common maternal sepsis was genital tract sepsis (37%, 25/68). Chorioamnionitis was the most common cause in obstetric sepsis (40%, 12/30), while intra-abdominal infection was the most common cause in non-obstetric sepsis (34%, 13/38). Thirty-seven patients (54%, 37/68) were diagnosed as bloodstream infection (BSI). Gram-negative bacteremia accounted for 70% (26/37), the most common pathogen of which was Escherichia coli. BSI was most commonly secondary to a genital tract infection (65%, 17/26). (3) Treatment: the ICU hospitalization rates and the utilization rate of mechanical ventilation and vasoactive agents in non-obstetric group were higher than those in obstetric group with significant differences (all P<0.05). Thirty-two patients (47%, 32/68) underwent surgery to remove the infection sources, including 5 cases of hysterectomy. (4) Prognosis: the case fatality rate of maternal sepsis was 19% (13/68), which was significantly higher in the non-obstetric infection group (29%,11/38) compared with the obstetric infection group (7%,2/30; P=0.020). The time from diagnosis of sepsis to termination of pregnancy was (5.5±8.6) days in prenatal women, and time in obstetric infection group [(1.9±2.2) days] was significantly less than that of non-obstetric infection group [(7.7±10.3) days, P=0.029]. Adverse pregnancy outcomes were higher in the first and second trimester (72%, 18/25) than in the third trimester (21%, 3/14), and the difference was statistically significant ( P=0.002). Conclusions:Sepsis during pregnancy and the postpartum period is a potentially life-threatening disease. Pregnant women with non-obstetric sepsis have more complications, more serious condition and worse prognosis than those with obstetric infection. Timely detection of risk factors, early identification and active treatment are helpful to improve maternal and fetal prognosis.

Objective: To evaluate the actual efficacy of cervical cancer and precancerous lesions screening approaches in real-world regions with different economic levels in China. Methods: The demonstrative application and effect evaluation of cervical cancer screening program were conducted in 21 hospitals nationwide from 2015 to 2018. Multi-stage sampling method was adopted to divide the country into 7 large areas according to geographical location. Two to four screening sites of two types of cancer (cervical cancer and breast cancer) were selected in each area, and the grassroots screening sites were implemented under the guidance of superior hospitals. In rural areas, women were initially screened using cytology, human papillomavirus (HPV) testing and visual inspection. The women with positive cytology or visual inspection were referred for colposcopy, and the women with positive HPV infection were randomly referred for reflex cytology or visual inspection, or direct colposcopy examination. In urban areas, women were primarily randomized into cytology or HPV testing groups. The women with abnormal cytology or positive HPV 16/18 infection were directly referred for colposcopy examination, whereas the women with positive infection of the other 12 high-risk subtypes of HPV were referred for reflex cytology or colposcopy. All of recruited women would be follow-up and screened by the baseline screening techniques in the third year while the positive women underwent colposcopy examination. The positive rates, referral rates, the detection rates of grade 2 and above of cervical intraepithelial neoplasia (CIN 2+ ) were compared. Results: A total of 63 931 women were recruited at the baseline. Among them, 11 rural sites included 33 823 women: 15 577, 11 157 and 7 089 women were screened by HPV testing, visual inspection via acetic acid or Lugol′s iodine (VIA/VILI) and cytology, respectively. Additionally, 30 108 women were from 10 urban sites: 9 907 and 20 201 women were screened by cytology and HPV subtyping, respectively. The HPV positive rate for urban women was 9.34%, whereas that for rural women was 12.53%. The abnormal rate of cytology for urban women was 5.63%, and that for rural women was 4.24%. The positive rate of VIA/VILI in the rural women was 12.25% Furthermore, the detection rate of CIN2+ at the baseline was 0.56%, and that was statistically higher in HPV-positive group than cytology-positive group (P<0.05). Conclusions All of screening sites completed the baseline screening tasks as expected. The prevalence of HPV infection is higher in rural women than urban women. The performance of HPV testing is better than cytology for detecting CIN2+ cases. This real-world demonstration study provides evidences for cervical cancer prevention and control in different regions.

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

Objective To evaluate the impact of gonadotropin-releasing hormone agonist(GnRH-a) used before surgery on natural pregnancy rates in patients with ovarian endometriomas. Methods In this retrospective study, 57 patients with ovarian endometriomas who had a consecutive laparoscopic surgery between June, 2010 to September, 2015 in Peking Union Medical College Hospital were included. Those patients were divided into preoperative GnRH-a treatment group(n=31)and non-GnRH-a treatment group (n=26). There were no differences in patients'characteristics between the two groups. All of them had a desire for natural pregnancy postoperatively. GnRH-a was no longer used after surgery. After the surgical procedure, the patients were observed over a period of 12 months, during which the frequency of natural pregnancy was assessed. The two groups were compared in terms of natural pregnancy rates. Results Totally 33 patients had natural pregnancy after surgery. The univariate analysis showed that the pregnancy rates of age, r-AFS stage, infertility, preoperative use of GnRH-a, tumor size, tumor side, deep infiltrating endometriosis and adenomyosis did not have statistically significant differences (all P>0.05). The two classified logistic regression showed that OR for preoperative use of GnRH-a was 0.250(95％CI: 0.064-0.978)with a statistical difference(P=0.046). Conclusion The use of GnRH-a preoperatively may have a negative effect on natural pregnancy rates of patients after surgery with ovarian endometriomas.