San Jie Tong Mai Fang Protects Against Atherosclerosis Progression by Regulating Macroautophagy through the PI3K/AKT/mTOR Signaling Pathway.

ABSTRACT: Many studies have confirmed that macrophage autophagy injury negatively impacts the pathogenesis of atherosclerosis (AS). Meanwhile, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway affects AS progression by regulating macrophage autophagy. We previously reported that the herbal formula San Jie Tong Mai Fang (SJTMF) elicits lipid regulatory and anti-inflammatory properties. Hence, the current study used an ApoE -/- high-fat diet-fed mouse model to determine whether SJTMF elicits protective effects against AS progression by means of the regulation of macrophage autophagy through the PI3K/AKT/mTOR signaling pathway. Our results show that SJTMF reduced the number of atherosclerotic plaques, foam cell formation, and intimal thickness in mouse aorta. In addition, SJTMF improved blood lipid metabolism and inflammatory levels in mice. We also observed that SJTMF caused macrophages to be polarized toward the M2 phenotype through the inhibition of the PI3K/AKT/mTOR signaling pathway. In addition, the abundances of LC3-II/I and beclin1 proteins-key autophagy molecules-were increased, whereas that of p62 was decreased, resulting in the promotion of macrophage autophagy. Taken together, these findings indicate that SJTMF may regulate the polarization of macrophages by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby reducing atherosclerotic plaque damage in ApoE -/- mice, thereby promoting macrophage autophagy and eliciting a significant antiarteriosclerosis effect. Hence, SJTMF may represent a promising new candidate drug for the treatment of AS.

Elevated mid-trimester 4-h postprandial triglycerides for predicting late-onset preeclampsia: a prospective screening study.

BACKGROUND: Abnormal maternal lipid concentrations are associated with increased risk of preeclampsia. However, previous studies mainly focused on fasting lipid concentrations, scarce data have been published on the relationship between postprandial triglyceride (TG) concentrations in the second trimester and the risk of preeclampsia. Our aim is to evaluate the potential of triglyceride (TG) concentrations at the time of oral lipid tolerance test (OLTT) measurement in the second trimester to predict preeclampsia and to elucidate the lipid metabolic changes related to these diseases. METHODS: This is a prospective cohort study of Pregnant women at 12-24 weeks of gestation undergone an OLTT in a university affiliated hospital between May 2019 and January 2020. Data were stratified into binaries according to the OLTT results. The receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off points of TG, HDL-C, LDL-C, sd-LDL, FFA, and BG for predicting preeclampsia. RESULTS: 438 pregnant women were recruited to undergo an OLTT at 12-24 weeks of gestation. Among these, 24 women developed preeclampsia and 414 women remained normotensive. Women who subsequently developed preeclampsia had higher concentrations of 4-h postprandial TG than those who remained normotensive. In the linear logistic regression analyses of potential confounding factors, mid-trimester 4-h postprandial TG concentrations at the time of OLTT measurement were significantly higher in preeclamptic cases than in controls. CONCLUSIONS: Dyslipidemia in the second trimester of pregnancy, particularly postprandial hypertriglyceridemia, appears to be associated with an increased risk of preeclampsia. Mid-trimester 4-h postprandial TG concentration at the time of OLTT measurement may be a potential predictive marker of preeclampsia. Trial registration Data of registration: 2018/10/15. Date of initial participant enrollment: 2019/05/01. Clinical trial identification number: chiCTR1800018884. URL of the registration site: http://www.chictr.org.cn/showproj.aspx?proj=25526 . Data sharing information: The data including individual participant data, detailed study protocols, statistical analysis plans will be shared upon request to the corresponding author.

Abnormally increased DNA methylation in chorionic tissue might play an important role in development of ectopic pregnancy.

BACKGROUND: Human Ectopic Pregnancy (hEP) is the second most common cause of pregnancy-related deaths in the first trimester. Without timely detection, EPs can lead to an increased rate of infertility and an elevated risk for future tubal EPs. In addition, most studies in the field focus on the effect of the fallopian tube (maternal factors) and ignore epigenetic changes in genes and proteins of the embryo, which may also cause EPs. Therefore, the present study hypothesized that embryos also play an important role in the development of EP. The study also speculated that DNA methylation is associated with ectopic pregnancy. Consequently, the effects of DNA methylation on the occurrence and development of ectopic pregnancy were investigated. Moreover, genome-wide DNA methylation of chorionic tissue from ectopic and intrauterine pregnancies was detected using Illumina HumanMethylation450 arrays. RESULTS: Forty-three hypermethylated genes involved in the regulation of adhesion as well as gene transcription and translation were identified. Furthermore, the PPI network showed that AMOTL1, SDR42E1, CAMTA1, PIP5K1C, KIAA1614, TSTD1 and DNER may play important roles in the occurrence and development of ectopic pregnancy. In addition, SDR42E1, CAMTA1 and TSTD1 displayed higher levels of methylation in ectopic pregnancy while PIP5K1C and DNER showed low degrees of methylation. CONCLUSIONS: The study reveals that abnormal increase in methylation may be an early indicator or an inducer of ectopic pregnancy. In addition, AMOTL1, SDR42E1, CAMTA1, PIP5K1C, KIAA1614, TSTD1 and DNER might play important roles in the occurrence and development of ectopic pregnancy. However, the specific molecular mechanisms are still unclear and require further studies.

An HMGA2-p62-ERα axis regulates uterine leiomyomas proliferation.

Uterine leiomyomas (ULM) are a major public health issue contributing to high morbidity and poor pregnancy outcomes. However, its molecular pathogenesis is poorly understood. HMGA2-ULM is the second major subtype of human ULM and associates with large sizes, fast-growth, and high percentages of estrogen receptor α (ERα). As altered ERα expression plays a distinct role in ULM growth, here, we investigate a regulatory mechanism driving ULM growth via HMGA2 and ERα. We reveal a positive correlation of HMGA2 with ERα protein and demonstrate that HMGA2 promotes ULM cells proliferation via ERα. In addition, autophagy pathway and p62/SQSTM1 (a selective autophagy receptor) are found to participate in the regulation of HMGA2 and ERα. Moreover, HMGA2 suppresses the transcription of p62 by binding to its promoter, meanwhile, p62 interacts with ERα, and inhibition of p62 increases ERα expression and enhances cell viability in ULM, suggesting a novel mechanism of the HMGA2-p62-ERα axis in ULM proliferation. Notably, rapamycin, a familiar autophagy agonist, reduces ERα levels and the proliferation ability of ULM cells. This study demonstrates a causal role of the HMGA2-p62-ERα axis in preventing autophagy and increasing ERα expression in HMGA2-ULM. Therefore, blocking HMGA2-p62-ERα axis and targeting autophagy pathway establish a roadmap toward HMGA2-ULM medical treatment.

Systematic retrospective analysis of 13 cases of uterine arteriovenous fistula: Pathogeny, diagnosis, treatment and follow-up.

AIM: To analyze the causes, clinical manifestations, diagnosis and treatment of uterine arteriovenous fistula (UAVF). METHODS: We retrospectively analyzed 13 patients with UAVF admitted to our hospital from October 2016 to April 2019. RESULTS: All patients had a history of intrauterine surgery (curettage for abortion, artificial removal of placenta, hysteroscopy, diagnostic curettage and intrauterine device removal). The main clinical manifestation of UAVF is paroxysmal massive vaginal bleeding; this involved a massive gush of vaginal blood that stopped suddenly. Sonographic images with typical features of UAVF were observed for 12 patients. Pelvic contrast-enhanced magnetic resonance imaging was performed as a noninvasive adjuvant examination method for diagnosis. Twelve patients underwent uterine arteriography and a diagnosis of UAVF was confirmed. Then, bilateral uterine artery embolization (UAE) was performed. One patient underwent laparoscopic hysterectomy directly instead of uterine arteriography because of unstable vital signs and one patient underwent laparoscopic hysterectomy 25 weeks after the second UAE. The median time until menstrual recovery was 33 days (range, 20-70 days) after UAE. The median time until normal ultrasound examination results was 10 weeks (range, 2-35 weeks). CONCLUSION: Acquired UAVF was associated with a history of previous intrauterine surgery. The ultrasound examination and pelvic contrast-enhanced MRI were noninvasive adjuvant examination method to effectively assist in diagnosis. Uterine arteriography is considered the gold standard for the diagnosis of UAVF, and UAE is considered an effective intervention for treating UAVF and maintaining reproductive function with less damage. Hysterectomy is an appropriate option when conservative measures have failed to prevent a life-threatening hemorrhage.

A Prospective Study of Sentinel Lymph Node Mapping for Endometrial Cancer: Is It Effective in High-Risk Subtypes?

BACKGROUND: The efficacy of sentinel lymph node (SLN) mapping for high-risk endometrial cancer remains unclear. This prompted us to evaluate the sensitivity, negative predictive value (NPV), and false-negative (FN) rate of cervical injection of indocyanine green (ICG) SLN mapping in patients with endometrial cancer. MATERIALS AND METHODS: This prospective interventional study was performed at a single university teaching hospital. Consecutive patients with early-stage endometrial cancer who underwent laparoscopic surgical staging were included. Cervical injection of ICG and near-infrared SLN identification and biopsy were performed for all study patients followed by systematic pelvic lymphadenectomy, whereas para-aortic lymphadenectomy was performed in all patients with high-risk histologies. SLN detection rates, sensitivity, NPV, and FN rates were calculated. RESULTS: Between July 2016 and July 2018, 131 patients were enrolled. The overall SLN detection rate was 93.1%, with a bilateral detection rate of 61.8%. Four positive SLNs were identified in four patients. Lymph node metastasis was observed in four additional patients without positive SLNs. These four patients belonged to a group of patients with a high-risk subtype. Three of the four patients had isolated para-aortic node metastases. In low-risk endometrial cancers, the sensitivity of the SLN technique to identify nodal metastatic disease was 100% (95% confidence interval [CI] 31.0-100), with an NPV and FN rate of 100% (95% CI 95.1-100) and 0%, respectively. In high-risk endometrial cancers, the sensitivity, NPV, and FN rate were 20% (95% CI 1.0-70.1), 83.3% (95% CI 61.8-94.5), and 80%, respectively. CONCLUSION: Cervical injection of ICG and SLN mapping yielded a low sensitivity and a high FN rate for the identification of node metastasis in endometrial cancer with high-risk histologies. IMPLICATIONS FOR PRACTICE: The efficacy of sentinel lymph node (SLN) mapping for high-risk endometrial cancer remains unclear. This study enrolled 131 patients with early-stage endometrial cancer who underwent cervical injection of indocyanine green SLN mapping followed by systematic pelvic lymphadenectomy and para-aortic lymphadenectomy. The key result was that SLN mapping yielded a low sensitivity and a high false-negative rate for the identification of node metastasis in endometrial cancer with high-risk histologies. The SLN strategy in these patients may increase the risk of missed diagnosis of isolated para-aortic node metastases and seems to be unacceptable in clinical practice.

Cai's Neiyi Prescription promotes apoptosis and inhibits inflammation in endometrial stromal cells with endometriosis through inhibiting USP10.

To observe the effect of Cai's Neiyi Prescription (CNYP) on the apoptosis and inflammation in endometrial stromal cells with endometriosis (EM) both in vivo and in vitro, EM model rats and endometrial stromal cells were treated with CNYP and the level of USP10, p-ERK1/2, ERK1/2, and apoptosis-related protein as well as the levels of proinflammatory factors were measured by Western blotting and ELISA, respectively. Rats with surgically induced EM showed increased USP10 expression and ERK/2 activation. Intragastric administration of CNYP granule significantly inhibited EM-induced ERK1/2 activation and expression of USP10 and Bcl-2, but increased the expression of Bax and Caspase-7 in EM-induced rats. CNYP granule administration also inhibited EM-induced inflammation in rats. Moreover, the ectopic endometrial stromal cells isolated from EM patients demonstrated decreased ERK1/2 activation and expression of USP10 and Bcl-2 and increased expression of Bax and Caspase-7 after cultured in DMEM containing CNYP-medicated rat serum, which were reversed by USP10 overexpression and were enhanced by USP10 siRNA. USP10 overexpression also inhibited while USP10 siRNA enhanced the CNYP-induced inhibition of inflammation in ectopic endometrial stromal cells. Taken together, our results suggest that CNYP granule promotes apoptosis and inhibits inflammation in endometrial stromal cells with EM through inhibiting USP10.

Follicle-stimulating hormone promoted pyruvate kinase isozyme type M2-induced glycolysis and proliferation of ovarian cancer cells.

PURPOSE: Reprogramming of cell metabolism is essential for tumor progression and the best-studied metabolic phenomenon of cancer cells is aerobic glycolysis, in which pyruvate kinase isozyme type M2 (PKM2) plays a critical role. Follicle-stimulating hormone (FSH) contributes to epithelial ovarian cancer progression and has been shown to regulate cell metabolism in ovaries. The aim of this study was to investigate the interaction between FSH and PKM2 and their effect on aerobic glycolysis and cell proliferation in ovarian cancer. METHODS: SKOV3 and OVCAR3 ovarian cancer cells were treated with FSH at various doses to investigate its effect on cell proliferation and PKM2 expression. siRNA-PKM2-transfected SKOV3 and OVCAR3 cells were treated with FSH to examine whether the changes induced by FSH could be altered by siRNA-PKM2. Glucose and lactate levels were evaluated to observe the change in glycolysis in these cells. RESULTS: In the current study, FSH upregulated the expression of PKM2 and glycolysis in SKOV3 and OVCAR3 cells. PKM2 knockdown reduced FSH-induced cell growth and glycolysis. Moreover, FSH attenuated apoptosis that was induced by the inhibition of PKM2. CONCLUSIONS: Collectively, the findings of this study indicated that FSH promoted glycolysis in epithelial ovarian cancer cells. Knockdown of PKM2 inhibited aerobic glycolysis and cell proliferation induced by FSH.

USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

Endometriosis has been initially described as endometrial-like tissue outside of the uterine cavity. The mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway playing an important role in the regulation of cell proliferation, apoptosis, and migration has been found to be activated in endometriosis. However, regulation of the MEK/ERK signaling pathway in endometriosis has not been fully understood. In this study, primary-cultured endometrial stromal cells were collected from patients with endometriosis and healthy controls, and the proliferation, apoptosis, and migration of ectopic endometrial stromal cells transfected with ubiquitin-specific protease 10 (USP10)-small-interfering RNA (siRNA) or pLVX-Puro-USP10 with or without MEK inhibitor PD-98059 or exogenous signaling stimulation such as epidermal growth factor (EGF) were measured by CCK-8, flow cytometry, and Transwell, respectively. The gene and protein expressions were measured by real-time PCR or Western blot. USP10 overexpression promoted ectopic endometrial stromal cell migration and proliferation, suppressed cell apoptosis, and activated MEK/ERK signaling that is a critical downstream target of the serine/threonine protein kinase Raf-1, which was significantly blocked by PD-98059. USP10 silencing demonstrated the inverse effects, and these effects induced by USP10 silencing were significantly blocked by EGF. USP10 overexpression promoted Raf-1 protein expression, but not mRNA expression, through deubiquitination. In conclusion, these results suggest that USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway.

L-selectin ligands expression in human fallopian tube epithelia of tubal pregnancies.

The objective of the study was to evaluate the expression of L-selectin ligands in tubal epithelia during tubal ectopic pregnancy. Sixteen fallopian tube samples from ectopic pregnancies and four normal control fallopian tubes from women undergoing sterilization were obtained for the study. Oviduct tissues from ectopic pregnancies were separated into implantation sites and matched nonimplantation sites. Expression of L-selectin ligands was evaluated by immunohistochemistry with antibodies against HECA-452 and MECA-79 and by real-time PCR. Immunoreactivity levels against HECA-452 and MECA-79 were significantly higher at the implantation site than at the paired nonimplantation site or at the normal oviducts. Moreover, compared with MECA-79 staining, stronger HECA-452 staining was observed in the implantation and nonimplantation groups. HECA-452 histologic scores at implantation sites correlated with serum human chorionic gonadotropin levels. Increased expression of L-selectin ligands may be involved in the implantation process in tubal pregnancy.

Exploration and prognostic analysis of two types of high-risk ovarian cancers: clear cell vs. serous carcinoma: a population-based study.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers. METHODS: Patients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3). RESULTS: In the Cox analysis for advanced OCCC, age (45-65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes. CONCLUSION: Advanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy.

Day 4 and day 0 neutrophil-to-lymphocyte ratios as predictors of treatment failure with single-dose methotrexate for ectopic pregnancies.

OBJECTIVE: To evaluate changes in the neutrophil-to-lymphocyte ratio (NLR) between day 4 and day 0 in ectopic pregnancy (EP) patients treated with single-dose methotrexate (MTX) and investigate its predictive value for treatment outcome. METHODS: A total of 406 EP patients receiving single-dose MTX therapy at Shanghai First Maternity and Infant Hospital from January 10, 2013 to September 30, 2019 were studied. A multivariate model was constructed to predict treatment outcome. RESULTS: Among the 406 patients, 281 were treated successfully. Treatment success declined significantly when NLR decreased by less than 23% (74.8% vs 58.5%, P = 0.004). Multivariate regression analysis identified NLR reduction of less than 23% on day 4 (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.27-3.44), a human chorionic gonadotropin (hCG) decrease of 15% or less (OR 3.17, 95% CI 1.62-6.34), and an hCG increase of more than 15% on day 4 (OR 5.47, 95% CI 3.05-10.22) as independent risk factors for single-dose MTX treatment failure. The final predictive model had a sensitivity of 0.768 and a specificity of 0.569, using a cut-off value of 3. The area under the receiver operating characteristic curve was 0.712. Patients with a predictive score of ≥3 were more likely to fail single-dose MTX therapy. CONCLUSION: The present study concluded that an NLR decrease of less than 23% on day 4, a plateau or increase in serum hCG on day 4, and an hCG value greater than 1000 mIU/mL on day 0 were predictors of single-dose MTX treatment failure in EP patients.

Epigenetic inactivation of BRCA1 through promoter hypermethylation in ovarian cancer progression.

AIM: The BRCA1 promoter is hypermethylated in ovarian cancer patients. We postulated that this hypermethylation might be involved in ovarian cancer progression. METHODS: To confirm our hypothesis, tissue and serum samples were collected from ovarian carcinoma patients and categorized according to tumor stage. Healthy or benign ovarian disease tissue samples and corresponding serum samples were used as controls. Breast and ovarian cancer susceptibility gene 1 (BRCA1) promoter methylation levels were detected by real-time polymerase chain reaction (PCR). Real-time PCR was also used to evaluate BRCA1 gene expression, and Western blot was performed to assay the expression of BRCA1 protein. RESULTS: BRCA1 showed hypomethylation in 30 normal ovarian and 30 benign ovarian tumors, but showed hypermethylation or methylation in ovarian cancer patients. There was also a significant difference in the BRCA1 promoter methylation levels between different ovarian cancer stages. Compared to stage I and the control groups, there were higher BRCA1 promoter methylation frequencies in stage II and III ovarian cancers. BRCA1 methylation correlated with the loss of BRCA1 expression. BRCA1 promoter in stage I tumors showed hypomethylated. CONCLUSION: Promoter hypermethylation may act as a biomarker for sporadic ovarian cancer progression, but is unlikely to be helpful in the early diagnosis of ovarian cancer.

Evaluation of pretreatment and early treatment changes in serum ß-hCG with methotrexate.

BACKGROUND: Serum beta-human chorionic gonadotropin (ß-hCG) is an important biomarker for the detection of ectopic pregnancies (EPs). The ß-hCG levels between days 1 and 4 after methotrexate (MTX) treatment as an indicator of the success of the MTX in EP have been the focus of research. OBJECTIVES: To determine whether the change in the ß-hCG levels at day 1 and 4 and pretreatment at 48-hour increments can predict early treatment failure of single-dose MTX in EP. MATERIAL AND METHODS: This was a retrospective study of 1120 EPs treated with a single dose of MTX. Treatment failure was defined as an obligation to proceed to surgery or the need for additional doses of MTX. RESULTS: A total 722 out of 1120 EPs had an increase in ß-hCG on day 4 after MTX treatment. The logistic regression analysis indicated that 3 dependents were significantly associated with treatment failure: 1) a pretreatment 48-hour increase in ß-hCG (odds ratio (OR): 1.249, 95% confidence interval (95% CI): 1.008-2.049, p < 0.001); 2) a change in ß-hCG between day 1 and 4 (OR: 1.384, 95% CI: 1.097-2.198, p < 0.001); and 3) a history of EP (OR: 1.208, 95% CI: 1.041- 2.011, p < 0.001). The optimal cutoff point for the prediction of treatment failure was an increase of more than 19% in the 48 h before the treatment, and an increase of more than 36% between day 1 and day 4 in ß-hCG concentrations. Patients with an increase in ß-hCG levels of less than 36% on day 4 experienced MTX treatment failure in 4.2% (n = 25), compared to 74.5% (n = 88) of the patients with an increase above 36%. CONCLUSIONS: A serum ß-hCG increase of more than 36% on day 4 after the administration of MTX alongside a more than 19% increase in ß-hCG concentration 48 h before the MTX treatment may predict the early failure of medical treatment for an EP.

Efficacy and safety of Qiangli Dingxuan tablet combined with amlodipine besylate for essential hypertension: a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial.

Background: Hypertension, a major cardiovascular risk factor, severely impacts patients' quality of life. Qiangli Dingxuan tablet (QDT) is a formally approved Chinese patent medicine, which has been widely used as an adjunctive treatment for hypertension. This study aimed to investigate the antihypertensive efficacy and safety of QDT combined with amlodipine besylate in patients with essential hypertension. Methods: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial conducted in China, patients diagnosed with grade 1 to 2 essential hypertension were randomly assigned in a 1:1 to the treatment of QDT or placebo for 12 weeks, alongside their ongoing treatment with amlodipine besylate. The primary outcome was the change in office blood pressure (BP) from baseline to 12 weeks. In addition, safety analysis included the assessment of vital signs and laboratory values. Results: At baseline, 269 patients were randomly assigned to the QDT group (n = 133) or the placebo group (n = 136), and there were no significant differences in baseline characteristics between the two groups. The primary outcome based on the full analysis set from baseline to 12 weeks showed that the mean difference in the change of office systolic BP reduction between the two groups was 6.86 mmHg (95%CI, 4.84 to 8.88, p < 0.0001), for office diastolic BP, the mean difference in the change of office diastolic BP reduction between the two groups was 4.64 mmHg (95%CI, 3.10 to 6.18, p < 0.0001). In addition, traditional Chinese medicine symptom scores were significantly decreased in the QDT group compared with the placebo group. No severe adverse events attributable to QDT were reported. Conclusion: The combination of QDT and amlodipine besylate demonstrates superior efficacy compared to amlodipine besylate monotherapy in the management of essential hypertension. QDT shows potential as an adjunctive treatment for essential hypertension. However, further rigorous clinical trials are warranted to validate these findings. Clinical Trial Registration: [https://clinicaltrials.gov/study/NCT05521282?cond=NCT05521282&rank=1]; Identifier: [NCT05521282].

Abdominal heterotopic pregnancy after in vitro fertilization and embryo transfer following bilateral salpingectomy: A case report and literature review.

Background: Risk of heterotopic pregnancy following bilateral salpingectomy has increased considerably due to the widespread use of assisted reproductive technology. Poor understanding of this condition often causes delayed or missed diagnosis. Objective: In this report, we describe the case of a 30-year-old pregnant woman with lower abdominal pain lasting for half a day and a history of bilateral salpingectomy. Two embryos had been transferred 21 days preceding her presentation. Methods: Case report. Results: Laparoscopic surgery revealed intraperitoneal hemorrhage and proper ovarian ligament pregnancy confirmed by histopathology. Viable intrauterine pregnancy was verified 3 days later by ultrasound examination. Conclusion: Heterotopic pregnancy is a serious condition that may be life-threatening. Clinicians should be aware of the potential for heterotopic pregnancy in patients receiving in vitro fertilization and embryo transfer after bilateral salpingectomy.

Comprehensive analyses identify RIPOR2 as a genomic instability-associated immune prognostic biomarker in cervical cancer.

Cervical cancer (CC) is a malignancy that tends to have a poor prognosis when detected at an advanced stage; however, there are few studies on the early detection of CC at the genetic level. The tumor microenvironment (TME) and genomic instability (GI) greatly affect the survival of tumor patients via effects on carcinogenesis, tumor growth, and resistance. It is necessary to identify biomarkers simultaneously correlated with components of the TME and with GI, as these could predict the survival of patients and the efficacy of immunotherapy. In this study, we extracted somatic mutational data and transcriptome information of CC cases from The Cancer Genome Atlas, and the GSE44001 dataset from the Gene Expression Omnibus database was downloaded for external verification. Stromal components differed most between genomic unstable and genomic stable groups. Differentially expressed genes were screened out on the basis of GI and StromalScore, using somatic mutation information and ESTIMATE methods. We obtained the intersection of GI- and StromalScore-related genes and used them to establish a four-gene signature comprising RIPOR2, CCL22, PAMR1, and FBN1 for prognostic prediction. We described immunogenomic characteristics using this risk model, with methods including CIBERSORT, gene set enrichment analysis (GSEA), and single-sample GSEA. We further explored the protective factor RIPOR2, which has a close relationship with ImmuneScore. A series of in vitro experiments, including immunohistochemistry, immunofluorescence, quantitative reverse transcription PCR, transwell assay, CCK8 assay, EdU assay, cell cycle detection, colony formation assay, and Western blotting were performed to validate RIPOR2 as an anti-tumor signature. Combined with integrative bioinformatic analyses, these experiments showed a strong relationship between RIPOR2 with tumor mutation burden, expression of genes related to DNA damage response (especially PARP1), TME-related scores, activation of immune checkpoint activation, and efficacy of immunotherapy. To summarize, RIPOR2 was successfully identified through comprehensive analyses of the TME and GI as a potential biomarker for forecasting the prognosis and immunotherapy response, which could guide clinical strategies for the treatment of CC patients.

A Model to Identify Candidates for Lymph Node Dissection Among Patients With High-Risk Endometrial Endometrioid Carcinoma According to Mayo Criteria.

Background: The Mayo criteria are the most widely accepted algorithm for predicting the risk of lymph node metastasis in endometrial endometrioid carcinoma (EEC). However, the clinical value of these criteria in high-risk patients is limited and inconclusive. Methods: A total of 240 patients with EEC meeting the Mayo high-risk criteria between January 1, 2015, and December 31, 2018 were included in our study. We retrospectively collected the laboratory reports, basic clinical information, clinicopathological and immunohistochemistry (IHC) findings, and the sequences of molecular pathological markers of these patients. A nomogram for predicting the likelihood of positive lymph node status was established based on these parameters. Results: Among the 240 patients, 17 were diagnosed with lymph node metastasis. The univariable analyses identified myometrial invasion >50%, aberrant p53 expression, microsatellite instable (MSI), and cancer antigen 125 (CA125) ≥35 U/ml as potential risk factors for lymph node metastasis. The multivariable analyses showed that aberrant p53 expression, MSI, and CA125 ≥35 U/ml were independent predictors of lymph node metastasis. The area under the curve (AUC) for the nomogram was 0.870, as compared to 0.665 for the Mayo criteria. Conclusions: Our novel prediction model effectively identifies patients at high risk for lymphatic metastasis. This model is a promising strategy for personalized surgery in patients with high risk according to the Mayo criteria.

Serum calponin 2 is a novel biomarker of tubal ectopic pregnancy.

OBJECTIVE: To evaluate serum protein calponin 2 (CNN2) as a candidate biomarker for tubal ectopic pregnancy (EP). DESIGN: Retrospective study. SETTING: Single University affiliated tertiary hospital. PATIENT(S): Serum samples were obtained from 84 patients with EP, 39 with viable intrauterine pregnancy (vIUP), and 42 with miscarriage. Moreover, 10 fallopian tube and corresponding villous tissue samples from patients with EP, 6 villous tissue samples from patients with vIUP, and 10 villous tissue samples from patients with miscarriage were collected. INTERVENTION(S): Serum CNN2 concentrations were measured using enzyme-linked immunosorbent assay; CNN2 expression in tissues was evaluated via immunohistochemistry and quantitative real-time polymerase chain reaction analysis. MAIN OUTCOME MEASURE(S): The diagnostic performance of serum CNN2 to discriminate an EP from vIUP and miscarriage. RESULT(S): CNN2 was highly expressed in villous stromal cells isolated from patients with EP, and CNN2 messenger ribonucleic acid expression was upregulated in villous tissues from women with EP compared with that in women with vIUPs and miscarriages. Serum CNN2 concentration was higher in women with EP than that in women with vIUP and miscarriage. The serum CNN2 predicted EP from vIUP and miscarriage with areas under the curve (AUCs) of 0.931 (95% confidence interval: 0.889-0.975). For discriminating EP from miscarriage only, the AUC was 0.906 (95% confidence interval: 0.835-0.977). In contrast, the AUCs for serum human chorionic gonadotropin were 0.809 and 0.637, respectively. CONCLUSION(S): Our data highlight the possibility of serum CNN2 as a single biomarker for the diagnosis of EP. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR 1900020483.

Evaluation of the effectiveness and safety of acupuncture in the treatment of premature ventricular contractions: A protocol for systematic review and meta-analysis.

BACKGROUND: Premature ventricular contractions are the most common type of arrhythmia. The clinical symptoms are mainly palpitations. In severe cases, syncope, angina pectoris and heart failure may occur, which seriously affect people's lives and ability to work. Antiarrhythmic drugs have many side effects and should not be taken for long periods. Acupuncture has a significant effect on the treatment of premature ventricular contractions. Therefore, to evaluate the effectiveness and safety of acupuncture in the treatment of premature ventricular contractions, we conducted this study, with the goal of providing a scientific methodology for this alternative treatment. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Science Journal Database, and China Biomedical Literature Database. We selected all randomized clinical trials related to the use of acupuncture in the treatment of premature ventricular contractions published on or before October 10, 2021, and we will conduct literature screening and data extraction based on specific inclusion and exclusion criteria. We will use the bias risk assessment tool from the Cochrane Systematic Review Manual to evaluate the quality of the research selected for inclusion in our study. RevMan5.3 software will be used to perform statistical analysis on the data. RESULTS: The results of this study will provide evidence for the effectiveness and safety of acupuncture in the treatment of premature ventricular contractions. CONCLUSION: The purpose of this study is to explore the efficacy of acupuncture in the treatment of patients with premature ventricular contractions and to provide an effective reference for clinicians and patients on its use. INPLASY REGISTRATION NUMBER: INPLASY2021100040.