Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Severe ovarian hyperstimulation syndrome induced by clomiphene: a case report.

This article reported a rare case of severe ovarian hyperstimulation syndrome (OHSS) following oral clomiphene. The patient was instructed to take clomiphene on the 5th day of menstruation, 50 mg daily for 5 days, without any medical examination or laboratory tests before administration of clomiphene. The treatment outcome was ideal by conservative treatment. This reminded that full assessment and risk prediction should be performed before the prescription of clomiphene. And clomiphene should be used only when indicated. What's more, high risk factors of the particular patient should be taken into full consideration.

The prevalence and influencing factors of the oropharyngeal carriage of Haemophilus influenzae in healthy children in a high-altitude area of China: A cross-sectional study.

Haemophilus influenzae is a common commensal organism of the human upper respiratory tract and an important cause of human disease. No data on H influenzae carriage rate has been carried out on the Qinghai-Tibet Plateau of China. This study aims to present the H influenzae carriage rate and influencing factors of H influenzae in healthy children <15 years of age in Qinghai Province, an area located on the Qinghai-Tibet Plateau in China. Oropharyngeal swabs for the detection of H influenzae DNA were collected between September and October 2019. Taqman real-time polymerase chain reaction was used to detect the nucleic acids from the oropharyngeal swabs. Self-designed questionnaires were used to investigate the related information among this group of children. A number of 284 children were enrolled in this study. The carriage rate of H influenzae was 44.7%. The carriage rate in cities was 47.5%, in rural areas was 21.9%, and in pastoral areas was 52.8%. The carriage rate was found to be higher among children of minority ethnic groups than those of Han ethnicity (55.6% vs 38.1%). H influenzae carriage rate was influenced by tobacco smoke exposure (adjusted odds ratio [aOR] = 2.31, 95% CI [confidence interval]: 1.14-4.70), having siblings <5 years of age (aOR = 2.36, 95% CI: 1.21-4.59), respiratory infections during the last 30 days (aOR = 2.37, 95% CI: 1.11-5.06), and parent/guardian education level (aOR = 0.08, 95% CI: 0.02-0.27). H influenzae was highly prevalent in healthy children in Qinghai Province, especially among children of minority ethnicities and those living in pastoral areas. Tobacco smoke exposure, having siblings <5 years of age, and respiratory infections during the last 30 days were risk factors for H influenzae carriage. Parents or guardians having education levels of college or higher was a protective factor for H influenzae carriage. It is of critical importance that the government take effective measures to reduce the carriage rate and the occurrence of H influenzae related diseases in susceptible populations.

Perimenopausal giant hydatidiform mole complicated with preeclampsia and hyperthyroidism: A case report and literature review.

Gestational trophoblastic disease (GTD) commonly occurs in reproductive females, but is extremely rare in perimenopausal females. In this study, we reported a case of hydatidiform mole in a 48-year-old perimenopausal female admitted due to a giant uterine mass of 28 weeks' gestational size. The serum human chorionic gonadotropin (HCG) level ranged from 944 to 1,286 mIU/mL before treatments. The signs of preeclampsia and hyperthyroidism were relatively prominent. Hysterectomy was performed and chemotherapy was scheduled when the serum HCG level remained at a plateau, about 528 mIU/mL. The symptoms of preeclampsia and hyperthyroidism were relieved after treatment. Accordingly, we concluded that GTD could occur in perimenopausal woman and hysterectomy usually is the optimal treatment.

An Immune-Gene-Based Classifier Predicts Prognosis in Patients With Cervical Squamous Cell Carcinoma.

Objective: Immunity plays a vital role in the human papilloma virus (HPV) persistent infection, and closely associates with occurrence and development of cervical squamous cell carcinoma (CSCC). Herein, we performed an integrated bioinformatics analysis to establish an immune-gene signature and immune-associated nomogram for predicting prognosis of CSCC patients. Methods: The list of immunity-associated genes was retrieved from ImmPort database. The gene and clinical information of CSCC patients were obtained from The Cancer Genome Atlas (TCGA) website. The immune gene signature for predicting overall survival (OS) of CSCC patients was constructed using the univariate Cox-regression analysis, random survival forests, and multivariate Cox-regression analysis. This signature was externally validated in GSE44001 cohort from Gene Expression Omnibus (GEO). Then, based on the established signature and the TCGA cohort with the corresponding clinical information, a nomogram was constructed and evaluated via Cox regression analysis, concordance index (C-index), receiver operating characteristic (ROC) curves, calibration plots and decision curve analyses (DCAs). Results: A 5-immune-gene prognostic signature for CSCC was established. Low expression of ICOS, ISG20 and high expression of ANGPTL4, SBDS, LTBR were risk factors for CSCC prognosis indicating poor OS. Based on this signature, the OS was significantly worse in high-risk group than in low-risk group (p-value < 0.001), the area under curves (AUCs) for 1-, 3-, 5-years OS were, respectively, 0.784, 0.727, and 0.715. A nomogram incorporating the risk score of signature and the clinical stage was constructed. The C-index of this nomogram was 0.76. AUC values were 0.811, 0.717, and 0.712 for 1-, 3-, 5-years OS. The nomogram showed good calibration and gained more net benefits than the 5-immune-gene signature and the clinical stage. Conclusion: The 5-immune-gene signature may serve as a novel, independent predictor for prognosis in patients with CSCC. The nomogram incorporating the signature risk score and clinical stage improved the predictive performance than the signature and clinical stage alone for predicting 1-year OS.

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.

The diagnostic accuracy of a real-time optoelectronic device in cervical cancer screening: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: This study aimed to assess the diagnostic accuracy of a real-time optoelectronic device (TruScreen) for uterine cervical cancer screening. METHODS: On the basis of Preferred Reporting Items for Systematic Reviews and Meta-analyses (the PRISMA statement) we performed this systematic review and meta-analysis. We searched PubMed, EMBASE, the Cochrane Library, CNKI, CBM, and WanFang Data using medical subject headings (MeSH) and text words. Title/abstract screening, full text check, data extraction, and methodological quality assessment (with the QUADAS-2 tool) were performed by 2 reviewers independently. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the summary receiver operator characteristic curve, and the area under the curve (AUC) were analyzed with Meta-DiSc software. Statistical heterogeneity was evaluated by Cochran's Q test and I, meta-regression was conducted based on patient type, and the possibility of publication bias was evaluated using Deeks funnel plot in Stata software. RESULTS: Of 293 publications, nine met our inclusion criteria. These studies included a total of 2730 patients and 567 cervical intraepithelial neoplasias. The pooled test characteristics for the TruScreen were as follows: sensitivity 76% (95% CI, 73-80%), specificity 69% (95% CI, 67%-71%), PLR 2.30 (95% CI, 1.59-3.33), and NLR 0.34 (95% CI, 0.23-0.51). The corresponding pooled DOR was 7.03 (95% CI, 3.40-14.55). The AUC was 0.7859 (Q = 0.7236). CONCLUSION: The diagnostic accuracy of the TruScreen device is moderately good. The study findings are based on Chinese studies only and could not be generalized to other populations.

Directed Evolution of a Highly Specific FN3 Monobody to the SH3 Domain of Human Lyn Tyrosine Kinase.

Affinity reagents of high affinity and specificity are very useful for studying the subcellular locations and quantities of individual proteins. To generate high-quality affinity reagents for human Lyn tyrosine kinase, a phage display library of fibronectin type III (FN3) monobodies was affinity selected with a recombinant form of the Lyn SH3 domain. While a highly specific monobody, TA8, was initially isolated, we chose to improve its affinity through directed evolution. A secondary library of 1.2 × 109 variants was constructed and screened by affinity selection, yielding three variants, two of which have affinities of ~ 40 nM, a 130-fold increase over the original TA8 monobody. One of the variants, 2H7, displayed high specificity to the Lyn SH3 domain, as shown by ELISA and probing arrays of 150 SH3 domains. Furthermore, the 2H7 monobody was able to pull down endogenous Lyn from a lysate of Burkitt's lymphoma cells, thereby demonstrating its utility as an affinity reagent for detecting Lyn in a complex biological mixture.

Generation of recombinant antibodies to rat GABAA receptor subunits by affinity selection on synthetic peptides.

The abundance and physiological importance of GABAA receptors in the central nervous system make this neurotransmitter receptor an attractive target for localizing diagnostic and therapeutic biomolecules. GABAA receptors are expressed within the retina and mediate synaptic signaling at multiple stages of the visual process. To generate monoclonal affinity reagents that can specifically recognize GABAA receptor subunits, we screened two bacteriophage M13 libraries, which displayed human scFvs, by affinity selection with synthetic peptides predicted to correspond to extracellular regions of the rat α1 and ß2 GABAA subunits. We isolated three anti-ß2 and one anti-α1 subunit specific scFvs. Fluorescence polarization measurements revealed all four scFvs to have low micromolar affinities with their cognate peptide targets. The scFvs were capable of detecting fully folded GABAA receptors heterologously expressed by Xenopus laevis oocytes, while preserving ligand-gated channel activity. Moreover, A10, the anti-α1 subunit-specific scFv, was capable of detecting native GABAA receptors in the mouse retina, as observed by immunofluorescence staining. In order to improve their apparent affinity via avidity, we dimerized the A10 scFv by fusing it to the Fc portion of the IgG. The resulting scFv-Fc construct had a Kd of ∼26 nM, which corresponds to an approximately 135-fold improvement in binding, and a lower detection limit in dot blots, compared to the monomeric scFv. These results strongly support the use of peptides as targets for generating affinity reagents to membrane proteins and encourage investigation of molecular conjugates that use scFvs as anchoring components to localize reagents of interest at GABAA receptors of retina and other neural tissues, for studies of receptor activation and subunit structure.

Polymorphisms of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) in ovarian cancer risk.

Glutathione S-transferases (GSTs) are ubiquitous, multifunctional phase II metabolic enzymes responsible for the detoxification of estrogen involved in the development of ovarian cancer. Data from epidemiological studies show conflicting results that remain to be further clarified. We estimated in this study the genetic effects of GSTM1 and GSTT1 polymorphisms on ovarian cancer risk. Eligible studies of the two polymorphisms and ovarian cancer risk were identified from China National Knowledge Infrastructure (CNKI), PubMed, Embase, and Web of Science. We summarized all data and performed a meta-analysis. Odds ratio (OR) and 95 % CI was calculated by using the fixed effects model to estimate the associations. Eight eligible studies were finally identified providing 2,397 cases and 2,910 controls for GSTM1 polymorphism and 2,049 cases and 2,668 controls for GSTT1 polymorphism. The overall data showed that carries of the GSTM1 null genotype did not have significantly increased ovarian cancer risk compared with those who carried the GSTM1 present genotype (null vs. present-OR, 1.01; 95 % CI, 0.91-1.11; heterogeneity, P=0.672). Similarly, for GSTT1 polymorphism, we observed no association under the investigated model in the overall analysis (null vs. present-OR, 1.02; 95 % CI, 0.89-1.17; heterogeneity, P=0.372), and in the subgroup of Caucasian subjects (null vs. present-OR, 0.99; 95 % CI, 0.86-1.14; heterogeneity, P=0.959). The meta-analysis does not provide a strong evidence for causal associations between GSTM1 and GSTT1 polymorphisms and risk of ovarian cancer in Caucasians.

Controlling the recurrence of pelvic endometriosis after a conservative operation: comparison between Chinese herbal medicine and western medicine.

OBJECTIVE: To compare the clinical effect of Chinese medicine (CM) and Western medicine (WM) for controlling the recurrence of pelvic endometriosis after a conservative operation. METHODS: The study was a multi-center, randomized, parallel controlled and prospective clinical trial. Patients were randomly divided into two groups: CM group (106 cases) and WM group (102 cases). Drugs were given to patients during 1-5 days of the first menstruation after a conservative operation in both groups. Patients with stages I and II (revised American Fertility Society) were treated for 3 months, while the patients with stages III and IV were treated for 6 months. The patients in the CM group were treated using three types of Chinese herbal medicine based on syndrome differentiation. Patients in the WM group were treated using gonadotropin releasing hormone agonist (GnRH-a) or gestrinone. Patients treated with GnRH-a received add-back therapy of Tibolone Tablets once a day after 4 months of treatment. Any cases of dysmenorrheal chronic pelvic pain, menstruation and any adverse reactions of patients were recorded once a month during the preoperative and postoperative periods and once every 3 months during the follow-up period. During the preoperative, postoperative and the follow-up periods, patients underwent type B ultrasonography of the pelvis and measurements of serum CA125 levels, gynecologic examination, routine evaluations of blood, urine, hepatic function (glutamate pyruvate transaminase), renal function (blood urea nitrogen) and electrocardiograms. During the follow-up period they underwent type B pelvic ultrasonography, measurement of serum CA125 levels and further gynecologic examinations. The two treatments were compared for clinical recurrence rates, pregnancy rates and the incidence of adverse reactions. RESULTS: The incidence and timing of recurrence of endometriosis were not significantly different between the two groups. The first pregnancy achieved by the patient in the CM group was significantly earlier than that in the WM group (P <0.05). Moreover, the incidence of adverse reactions in the WM group was significantly higher than in the CM group (P <0.01). CONCLUSIONS: Treatment with Chinese herbal medicines prevented the recurrence of endometriosis after a conservative operation, improved the conception rate and showed fewer and lighter adverse reactions than did treatment with WM therapy. Treatment with Chinese herbal medicine meets the need of patients wishing to have a child following endometriosis and is an appropriate form of clinical treatment.

Chinese medicine improves postoperative quality of life in endometriosis patients: a randomized controlled trial.

OBJECTIVE: To investigate the effect of Chinese medicine (CM) and Western medicine (WM) on quality of life (QOL) after conservative surgery for endometriosis. METHODS: A total of 320 patients with endometriosis were randomized into two groups by using random block design, CM group (160 cases, activating blood circulation and removing blood stasis treatment based on syndrome differentiation) and WM group (160 cases, gonadotropin-releasing hormone agonist or gestrinone treatment) after conservative surgery. Treatment was given for 3-6 months (according to the revised American Fertility Society scoring system stage), and the World Health Organization QOL-BREF (WHOQOL-BREF) was applied to patients before and after treatment to assess QOL. RESULTS: There were 136 cases in the CM group and 141 cases in the WM group completing therapy. In the CM group, the use of the WHOQOL-BREF showed that the physical, psychological and environmental scores posttreatment were significantly higher than those at pre-treatment (P < 0.05), and for 12 items (pain and discomfort, energy and fatigue, sleep and rest, mobility, activities of daily living, work capacity, negative feelings, health and social care: accessibility and quality, participation in and opportunities for recreation/leisure activities, appetite, QOL score, overall health status and QOL), the difference in scores was significant (P < 0.05). In the WM group, 4 items (pain and discomfort, opportunities for acquiring new information and skills, QOL score, overall health status and QOL) had significantly different scores post-treatment compared with those at pre-treatment (P < 0.05). Before treatment, the QOL in the two groups of patients showed no significant difference (P > 0.05). After treatment, the scores for physical health in the CM group were significantly higher than those of the WM group (P < 0.05) and the scores of 4 items (mobility, activities of daily living, sexual activity, QOL score) in the CM group were significantly higher than those in the WM group (P < 0.05). CONCLUSIONS: CM and WM treatment could improve the QOL of patients with endometriosis after conservative surgery. CM treatment is more effective than WM.

Combination of 4-HPR and oral contraceptive in monkey model of chemoprevention of ovarian cancer.

4-(N-hydroxyphenyl) retinamide (4-HPR) and the oral contraceptives (OCP) are currently being used alone, and in combination, for the prevention of ovarian cancer. However, the mechanism of their effects has not been studied. Non-human primate models are ideal for studying the role of these and other drugs for cancer chemoprevention because of the genetic similarity between primates and humans in respect to hormone regulation and menstrual cycle. 4-HPR and OCP were administered to sixteen female adult Macacca mulatta (Rhesus macaques) for three months alone and in combination. Laparotomy was performed before and after treatment, and ovarian biopsies were obtained to evaluate the expression of retinoid and hormone receptors, and apoptosis. ER alpha was undetectable, but ER beta, PR, RXR alpha, and RXR gamma were constitutively expressed in the ovaries. 4-HPR induced RXR alpha and RXR gamma expression at a low level and, OCP induced expression of ER beta. However, the combination of 4-HPR with OCP had a larger effect on expression of retinoid receptors. Apoptosis was detected in the 4-HPR group (equivalent dose: 200 mg/day).

Vascular endothelial cells express isoforms of protein kinase A inhibitor.

The expression and function of the endogenous inhibitor of cAMP-dependent protein kinase (PKI) in endothelial cells are unknown. In this study, overexpression of rabbit muscle PKI gene into endothelial cells inhibited the cAMP-mediated increase and exacerbated thrombin-induced decrease in endothelial barrier function. We investigated PKI expression in human pulmonary artery (HPAECs), foreskin microvessel (HMECs), and brain microvessel endothelial cells (HBMECs). RT-PCR using specific primers for human PKI alpha, human PKI gamma, and mouse PKI beta sequences detected PKI alpha and PKI gamma mRNA in all three cell types. Sequencing and BLAST analysis indicated that forward and reverse DNA strands for PKI alpha and PKI gamma were of >96% identity with database sequences. RNase protection assays showed protection of the 542 nucleotides in HBMEC and HPAEC PKI alpha mRNA and 240 nucleotides in HBMEC, HPAEC, and HMEC PKI gamma mRNA. Western blot analysis indicated that PKI gamma protein was detected in all three cell types, whereas PKI alpha was found in HBMECs. In summary, endothelial cells from three different vascular beds express PKI alpha and PKI gamma, which may be physiologically important in endothelial barrier function.