Risk factors analysis of recurrent disease after treatment with a loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the risk factors of recurrent high-grade cervical intraepithelial neoplasia grade 2 or worse (CIN2+) after loop electrosurgical excision procedure (LEEP). METHODS: This retrospective study included patients with histopathologically confirmed CIN2/3 who underwent LEEP in 2015-2020. Cox regression analysis was used to evaluate the risk factors of recurrence. RESULTS: Recurrent CIN2+ was found in 268 patients after LEEP (268/4369, recurrence rate, 6.1%). High-risk (hr-) HPV infection (hazard ratio [HR] 12.09, 95% confidence interval [CI] 7.78-18.79), margin status (HR 6.48, 95% CI 4.75-8.84), baseline diagnosis (HR 1.45, 95% CI 1.08-1.95), smoking (HR 3.17, 95% CI 2.27-4.43), and immunosuppression (HR 1.96, 95% CI 1.33-2.91) were significant independent risk factors of recurrence. HPV16 (HR 3.61, 95% CI 2.43-5.37), HPV33 (HR 2.62, 95% CI 1.12-6.12), and HPV52 (HR 1.61, 95% CI 1.02-2.55) infection showed a higher risk of recurrence. High-risk HPV had the highest accuracy (sensitivity 88.5%; negative predictive values 98.7%) in predicting recurrence compared with liquid-based cytology test and margins. CONCLUSION: Given that positive margins present a higher risk, wide excision may be required to avoid residual lesions. More attention should be paid to the correlation between recurrence and hr-HPV genotypes. After treatment for high-grade CIN, HPV-based testing is recommended at 6 months. Timely identification of high-risk factors enables risk stratification, and enables individual management or individual follow-up and recall strategies.

A recurrent inflammatory myofibroblastic tumor patient with two novel ALK fusions: a case report.

Background: Inflammatory myofibroblastic tumor (IMT) is a rare disease that mainly involves the lung and the abdomen. The gold standard of the IMT treatment is radical surgery, while chemotherapy and radiotherapy are represented usually for unresectable lesions. Anaplastic lymphoma kinase (ALK) rearrangements are present in approximately 50% of IMT patients, and several clinical trials of ALK tyrosine kinase inhibitors (TKIs) in the treatment of ALK-positive IMT patients are underway. Case Description: We reported a case of IMT in the right pelvic cavity. Initially, the patient underwent resection of multiple lesions. Unfortunately, the patient's tumor recurred half a year later, and enhanced computerized tomography (CT) of the whole abdomen revealed multiple low-density masses. Then the patient underwent resection of the recurrent tumors. Immunohistochemical staining exhibited the expression of ALK in the tumor cells, and next-generation sequencing (NGS) technology revealed two novel ALK fusions, ALK-ribosome binding protein 1 (RRBP1) and hydroxyacid oxidase 1 (HAO1)-ALK fusions. These fusions were able to be transcribed and captured by RNA level. And the two fusions have not been reported in the IMTs. Conclusions: This case expanded the range of ALK fusion types and provided a promising molecular-targeted treatment strategy. In addition, the two novel ALK fusions may be the recurrent oncogenic mechanism in clinically aggressive IMT.

Research progress in teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis: The gynecological perspective.

AIM: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the autoimmune encephalitis, which often occurs in children and young adults, especially in young women. In addition to viral infection, teratoma is an important causative factor. Anti-NMDAR encephalitis is well known to neurologist. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Therefore, from the perspective of gynecologists, we provide an overview of the relationship between the encephalitis and ovarian teratoma, the clinical features and treatment of this disease, and prognosis of pregnant women with this encephalitis. METHODS: We searched the PubMed database using the search terms in various combinations "teratoma," "dermoid cyst," "ovary," "ovarian," "anti-NMDAR encephalitis," and "N-methyl-D-aspartate receptor." RESULTS: According to the current literature, the mechanism of anti-NMDAR encephalitis is probably due to the ectopic expression of the NMDAR in the teratomas tissue. The disease has a high mortality rate if not treated promptly and effectively. An important way to improve patients' outcome is to remove the ovarian tumor in time. Pregnant women are also at risk of developing anti-NMDAR encephalitis during pregnancy. The fetal outcome is usually better in patients with mid- to late-pregnancy onset than in early pregnancy, and patients are often able to maintain their pregnancies into late pregnancy. CONCLUSION: Young women with sudden onset of abnormal psychiatric behavior should be actively screened for ovarian tumors and, if confirmed to be teratoma-associated anti-NMDAR encephalitis, should undergo gynecologic surgery as early as possible, which can help improve their prognosis.

N-cadherin inhibitor creates a microenvironment that protect TILs from immune checkpoints and Treg cells.

BACKGROUND: Few patients with prostate cancer benefit from current immunotherapies. Therefore, we aimed to explore new strategies to change this paradigm. METHODS: Human tissues, cell lines and in vivo experiments were used to determine whether and how N-cadherin impacts the production of programmed death ligand-1 (PD-L1) and indole amine 2,3-dioxygenase (IDO-1) and whether N-cadherin can increase the production of effector (e)Treg cells. Then, we used PC3-bearing humanized non-obese diabetic/severe combined immunodeficiency IL2Rγnull (hNSG) mice with an intravenous injection of human CD34+ hematopoietic stem cells into the tail vein to evaluate whether the N-cadherin antagonist N-Ac-CHAVC-NH2 (designated ADH-1) could improve the therapeutic effect of tumor-infiltrating lymphocyte (TIL)-related treatment. RESULTS: N-cadherin dramatically upregulated the expression of PD-L1 and IDO-1 through IFN-γ (interferongamma) signaling and increasing the production of free fatty acids that could promote the generation of eTreg cells. In preclinical experiments, immune reconstitution mediated by TILs slowed tumor growth and extended the survival time; however, this effect disappeared after immune system suppression by PD-L1, IDO-1 and eTreg cells. Furthermore, ADH-1 effectively reduced immunosuppression and enhanced TIL-related therapy. CONCLUSIONS: These data show that the N-cadherin antagonist ADH-1 promotes TIL antitumor responses. This important hurdle must be overcome for tumors to respond to immunotherapy.

Perinatal outcome in women with bacterial sepsis: A cross-sectional study from West China.

Maternal bacterial sepsis during pregnancy and the postpartum period is a common cause of maternal mortality and fetal morbidity and mortality. This study was performed to analyze perinatal prognosis and related factors of maternal bacterial sepsis in west China.We conducted a cross-sectional study of pregnant women with bacterial sepsis who were admitted into a tertiary care center in western China between 2011and 2015. Data from these cases were collected and analyzed.Eighty six women were identified with bacterial sepsis in our hospital, and the incidence of maternal bacterial sepsis was 1.7 per 1000 maternities, the incidence of septic shock was 1.8 per 10,000 maternities, and 1 maternal death occurred. Among the 86 pregnant women with bacterial sepsis, genital tract infection was the most common source of infection (41/86, 47.7%). The most common bacteria in the Gram-positive bacteria group was Listeria monocytogenes and in the Gram-negative bacteria group was Escherichia coli. The premature delivery rate (65.7%) was substantially higher in the Gram-negative bacteria group (P = .011), and the miscarriage rate (31.3%) was higher in the Gram-positive bacteria group (P = .042). The fetal/neonatal mortality rate was 20% (21/105) and higher in the Gram-positive bacteria group (P = .008), and the infant mortality rate in 1 year was 7.1% (6/84).Bacterial sepsis remains an alarming cause of both maternal and fetal morbidity and mortality, and infant mortality. Key treatment involves a multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women with sepsis and early initiation of appropriate antibiotics according to the type of bacterial infection. The effect of maternal sepsis on long-term fetal outcome should be investigated.

Pregnancy outcome in women with Eisenmenger's syndrome: a case series from west China.

BACKGROUND: Eisenmenger's syndrome (ES) consists of pulmonary hypertension with a reversed or bidirectional shunt at the atrioventricular, or aortopulmonary level. The cardiovascular changes that occur during the pregnancy contribute to the high maternal morbidity and mortality in patients with ES. This study is to assess maternal and fetal outcomes in patients with ES. METHODS: This study is a retrospective analysis of 11 pregnancies in women with ES who delivered at a tertiary care center in west China between 2010 and 2014. Cases were divided into group I (maternal survival) and group II (maternal death). Clinical data were noted and analyzed. RESULTS: All ES patients presented with severe pulmonary arterial hypertension (PAH). Four maternal deaths were recorded (maternal mortality of 36%). Only one pregnancy continued to term. Ventricular septal defect diameter in group II was larger than that in group I (2.93 ± 0.76 cm vs. 1.90 ± 0.54 cm, p < 0.05). Arterial oxygen saturation and pre-delivery arterial oxygen tension during oxygen inhalation were significantly lower in group II (p < 0.05). Pulmonary arterial blood pressure (PABP) in both groups were high while ejection fractions (EF) were significantly lower in group II (p < 0.05). The incidence of pre-delivery heart failure in group II was substantially higher than in survivors (100 vs.14.3%, p < 0.05). Fetal complications were exceptionally high: preterm delivery (88%), small for gestational age (83%), fetal mortality (27%) and neonatal mortality (25%). CONCLUSIONS: In west China,the perinatal outcome of pregnant women with ES is poor, especially when complicated with high pulmonary arterial hypertension (PAH). Pregnancy remains strongly contraindicated in ES. Effective contraception is essential, and the option of terminating pregnancy in the first trimester should be presented to pregnant women with ES.

Short-stem prostheses in primary total hip arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: Short-stem (SS) prostheses require less resection of the femoral neck, produce a more physiological load pattern in the proximal femur, reduce stress shielding, and aid bone conservation and are, therefore, beneficial for young patients. Conventional cementless implants in total hip arthroplasty (THA) have shown excellent clinical results; however, it is unclear whether SS prostheses can obtain the same clinical and radiological outcomes. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate whether SS prostheses are superior to conventional implants after primary THA. METHODS: We reviewed the literature published up to June 2016 from PubMed, Web of Science, and the Cochrane Library to find relevant RCTs comparing SSs and conventional stems in primary THA. Quality assessment was performed by 2 independent reviewers. The RevMan 5.3 software program of the Cochrane Collaboration was used to analyze the data. Random- or fixed-effect models were used to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) for each comparison. RESULTS: Six RCTs involving 552 patients with 572 hips were identified. Strong evidence indicated that SS prostheses were more effective for reducing thigh pain than conventional implants (I = 46%, P = 0.002; risk ratio [RR], 95% CI 0.15, 0.04-0.49). However, there were no significant differences between the 2 groups in Harris Hip Scores (I = 0%, P = 0.84; SMD, 95% CI 0.02, -0.15-0.18), Western Ontario and McMaster Universities Osteoarthritis Index Scores (I = 0%, P = 0.35; SMD, 95% CI 0.09, -0.10-0.27), femoral offset of stem (I = 0%, P = 0.57; SMD, 95% CI 0.06, -0.16-0.29), and leg-length discrepancy (I = 79%, P = 0.88; SMD, 95% CI 0.04, -0.44-0.51). CONCLUSION: SS prostheses achieve the same clinical and radiological outcomes as conventional implants, and were superior in terms of reducing thigh pain. But whether the postoperative thigh pain applied in 2nd-generation cementless prosthesis still needs further large-scale multicenter studies with longer follow-up to confirm.

Insertion/deletion polymorphism in IL1A 3'-UTR is associated with susceptibility to endometrial cancer in Chinese Han women.

AIM: The aim of this study was to investigate whether a functional insertion/deletion polymorphism (rs3783553) located in the 3'-untranslated regions of interleukin-1 A is associated with susceptibility to endometrial cancer (EC) in Chinese Han women. METHODS: A total of 272 patients and 294 age-matched healthy controls were included in the study. The genotype of the rs3783553 polymorphism was determined by polymerase chain reaction polyacrylamide gel electrophoresis. RESULTS: Our results showed that a significantly reduced risk of EC was found to be associated with the II (insertion/insertion) genotype compared with DD (deletion/deletion) only (P = 0.037, odds ratio = 0.56, 95% confidence interval = 0.32-0.97) as well as compared with the DD + DI (deletion/insertion) genotype (P = 0.032, odds ratio = 0.57, 95% confidence interval = 0.34-0.96) in the recessive model. No significant association was detected between certain clinical features of EC patients and genotype of rs3783553. CONCLUSIONS: This study demonstrates that the rs3783553 polymorphism may be involved in susceptibility to EC. The II genotype seems to be a protective factor for EC in Chinese Han women.

Significant association between IL-32 gene polymorphisms and susceptibility to endometrial cancer in Chinese Han women.

Interleukin-32 (IL-32), a pro-inflammatory chemokine, has been reported to be involved in inflammatory, infectious diseases and even cancers. This study aimed to investigate whether two genetic variants (rs28372698 and rs12934561) of IL-32 were associated with susceptibility to endometrial cancer (EC) in Chinese Han women by a hospital-based study with 272 EC patients and 337 healthy controls. Our results showed that the frequencies of TT genotype (P = 0.012, OR = 2.37, 95 % CI = 1.32-4.28) and T allele (P = 0.026, OR = 1.320, 95 % CI = 1.036-1.681) of rs28372698 in EC patients were significantly higher than controls. Clinical analyses indicated the TT genotype frequency was relevant to high clinical stage and cervical invasion. Furthermore, the frequencies of CC genotype (P = 0.0077, OR = 1.62, 95 % CI = 1.05-2.50) and C allele (P = 0.043, OR = 1.269, 95 % CI = 1.011-1.592) of rs12934561 were also significantly higher in EC patients than controls. Stratification analyses revealed that CC genotype was more frequent in endometrioid adenocarcinoma or EC without parametrial invasion. This study demonstrates that IL-32 gene polymorphisms are significantly associated with increased EC susceptibility in Chinese Han women.

[Expression and clinical signification of IL-10 and IL-17 in endometrial cancer].

OBJECTIVE: To explore the expression of IL-10 and IL-17 in endometrial cancer and their relationships with tumor progression. METHODS: The sera levels of IL-10 and IL-17 were detected by enzyme-linked immune-sorbent assay in 15 benign hysterectomies and 15 endometrial cancers, the expressions of IL-10 and IL-17 in the tissue were measured by immunohistochemistry assay (SABC) with the evaluation of IOD value, clinic-pathological characteristics were retrieved and analyzed. RESULTS: Both sera expression and tissue IOD value of IL-10 were significantly higher in endometrial cancer than those in benign uterine, while no difference was found in IL-17 between the two groups. Sera IL-10 of I B-II stage, G2-G3, with myoinvasion, with vas tumor emboli was higher than that of I A stage, G1, without myoinvasion, and without vas tumor emboli, while no difference was found among tissue types. Sera IL-17 of I B-II stage, with myoinvasion, with vas tumor emboli was lower than that of IA stage, without myoinvasion, and without vas tumor emboli, while no difference was found among tumor grades nor tissue types. CONCLUSION: High expression of IL-10 may participate in the genesis and development of uterine endometrial cancer, while low expression of IL-17 may participate in its development.

A reusable localized surface plasmon resonance biosensor for quantitative detection of serum squamous cell carcinoma antigen in cervical cancer patients based on silver nanoparticles array.

Squamous cell carcinoma antigen (SCCa), as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR) technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA) to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.1-1,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0), the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients.

Association between IL17 polymorphisms and risk of cervical cancer in Chinese women.

Interleukin-17 (IL-17) is a proinflammatory cytokine that is associated with inflammation, autoimmune disorders, and even tumors. Previous studies revealed that a large group of human malignant tumors have abnormally high IL-17 expression. In the present study, we analyzed two single-nucleotide polymorphisms (SNPs) in the IL17A (rs2275913) and IL17F (rs763780) in 311 cervical cancer patients and 463 controls using TaqMan assays. Our results indicated that the frequencies of AA genotype and A allele of rs2275913 were significantly different between the cervical cancer patients and controls (P = 0.008, OR = 1.32, 95% CI, 1.07-1.62). Stratified analyses revealed that the polymorphism of rs2275913 was also associated with positive peritumor intravascular cancer emboli and high clinical stage. The genotype and allele frequencies of rs763780 did not show any difference between patients and controls or relate to patient clinical characteristics. Collectively, these findings suggested that IL17 gene polymorphism rs2275913 was associated with the susceptibility as well as positive peritumor intravascular cancer emboli and high clinical stage of cervical cancer in Chinese women.

Detection of serum human epididymis secretory protein 4 in patients with ovarian cancer using a label-free biosensor based on localized surface plasmon resonance.

BACKGROUND: Detection of the human epididymis secretory protein 4 (HE4) biomarker plays an important role in the early diagnosis of ovarian cancer. This study aimed to develop a novel localized surface plasmon resonance (LSPR) biosensor for detecting HE4 in blood samples from patients with ovarian cancer. METHODS: Silver nanoparticles were fabricated using a nanosphere lithography method. The anti-HE4 antibody as a probe, which can distinctly recognize HE4, was assembled onto the nanochip surface using an amine coupling method. Detection was based on the shift in the extinction maximum of the LSPR spectrum before and after the HE4-anti-HE4 antibody reaction. These nanobiosensors were applied to detect HE4 in human serum samples and compare them using an enzyme-linked immunosorbent assay. RESULTS: Tests relating to the detection of HE4 demonstrated that the LSPR-based biosensor featured a fast detection speed, good specificity, effective reproducibility, and long-term stability. The linear range for LSPR was between 10 pM and 10,000 pM, with a detection limit of 4 pM. An excellent correlation between LSPR and enzyme-linked immunosorbent assay results was observed in human serum. CONCLUSION: This study is the first clinical diagnostic application of the LSPR biosensor in ovarian cancer. The LSPR biosensor, a rapid, low-cost, label-free and portable screening tool, can serve as a very effective alternative for the clinical serological diagnosis of ovarian cancer.