Mechanism of HCG regulating epithelial-mesenchymal transition progression in endometrial cells through the FoxO1/miR223-5p/Wnt5α pathway.

RESEARCH QUESTION: Does human chorionic gonadotrophin (HCG) influence endometrial receptivity and epithelial-mesenchymal transition (EMT) via the FoxO1/miR223-5p/Wnt5α pathway? DESIGN: This study aimed to establish the co-culture system of human embryonic trophoblast cell line (HTR-8-Svneo) cells and human endometrial epithelial cell line (HEEC) cells. The expression of Wnt5α protein and EMT-related proteins in HTR-8-Svneo and HEEC cells treated in a gradient-dependent manner using HCG and exosome inhibitor GW4869 were detected in the co-culture system. RESULTS: In the HTR-8-Svneo/HEEC co-culture system, miR223-5p in HEEC cells increased significantly with induction of HTR-8-Svneo cells by 100 IU/ml HCG for 48 h (P = 0.046), and Wnt5α protein decreased significantly in HEEC cells (P = 0.021). Pretreatment of HTR-8-Svneo cells with GW4869, and knockdown of FoxO1 in HTR-8-Svneo cells, significantly inhibited the above effects of HCG on miR223-5p and Wnt5α expression in HEEC cells in the HTR-8-Svneo/HEEC co-culture system. HTR-8-Svneo cells induced with 100 IU/ml HCG for 48 h significantly enhanced the logarithmic phase proliferation activity of HEEC cells in the co-culture system (P < 0.001), while knockdown of FoxO1 in HTR-8-Svneo cells and inhibition of miR223-5p in HEEC cells suppressed proliferation of HEEC cells in the HTR-8-Svneo/HEEC co-culture system (P < 0.001). CONCLUSIONS: HCG exposure induces HTR-8-Svneo cells to up-regulate miR223-5p expression, which enters HEEC cells in the co-culture system through the exosomal pathway, and inhibits Wnt5α expression and the progress of EMT.

Delayed euDKA Associated With Dapagliflozin After Pancreatitis.

Euglycemic diabetic ketoacidosis (euDKA) is a rare but life-threatening adverse effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We present a case of delayed euDKA seven days after cure of acute pancreatitis and discharge from the hospital of a 51-year-old man with type 2 diabetes mellitus (T2DM) managed with a combination of antidiabetic medications, including the SGLT2 inhibitor dapagliflozin. Prior acute pancreatitis was postulated to be a contributing factor to the development of SGLT2 inhibitor-associated euDKA in this patient discharged from the hospital. The patient was managed accordingly and improved clinically while his oral hypoglycemic agents were stopped. The risk of euDKA from SGLT2 inhibitor therapy may be increased by some stress factors (eg, infection, surgery, acute illness, low-carbohydrate diet, excessive alcohol intake). As these SGLT2 inhibitors become a popular therapeutic strategy for the management of hyperglycemia in T2DM, clinicians should be aware that acute illnesses such as pancreatitis in patients with T2DM can be potential predisposing factors for the development of SGLT2 inhibitor-associated euDKA.

Nomogram to predict FSH starting dose in poor ovarian response women in progestin primed ovarian stimulation protocol.

Prediction of individual ovarian response to exogenous gonadotropin is a cornerstone for success and safety in all controlled ovarian stimulation (COS) protocols. Providing the best FSH starting dose according to each woman's own characteristics is the key to the success of individualized treatment. The objective of this investigation was to evaluate the potential application of a novel nomogram based on antral follicle counting (AFC), anti-Müllerian hormone (AMH) and body mass index (BMI) as a tool to optimize the follicle-stimulating hormone (FSH) starting dose in women with poor ovarian response in in-vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) cycles in progestin-primed ovarian stimulation (PPOS). We performed a retrospective analysis involving 130 poor ovarian responders undergoing IVF/ICSI cycles in a PPOS protocol from June 2017 to February 2019 in our reproductive center. The individual FSH starting dose was selected according to patients' clinical history and characteristics. The influence of variables including age, BMI, AMH and AFC on the FSH starting dose was assessed through multiple regression analysis. We used the variables reaching the statistical significance for calculation for the final predictive model. In the univariate analysis, BMI, AMH and AFC were significant (P < 0.05) predictors of FSH starting dose, age was canceled. In the multivariate analysis, BMI, AMH and AFC remained significant (P < 0.05). According to the nomogram, 118 patients (90.77% of 130) would have received a higher FSH starting dose and 12 patients (9.23% of 130) a lower FSH starting dose than practice dose. The application of the nomogram based on three variables easily determined in clinical practice: BMI, AMH and AFC would lead to a more tailored FSH starting dose in women with poor ovarian response.

A Comparison of Coagulation Function in Patients Receiving Aspirin and Cefoperazone-Sulbactam With and Without Vitamin K1: A Retrospective, Observational Study.

PURPOSE: The study objective was to explore whether prophylaxis with vitamin K1 improves abnormal coagulation function-associated cefoperazone-sulbactam in patients treated in the long term with low-dose aspirin. METHODS: This retrospective, observational study assessed patients treated with long-term low-dose aspirin in a naval military hospital in China from 2004 to 2018, including all patients treated concurrently with cefoperazone-sulbactam with or without vitamin K1. Differences in the coagulation index were analyzed statistically before and after receipt of cefoperazone-sulbactam. FINDINGS: The cohort included 227 patients. After cefoperazone-sulbactam treatment, the mean (SD) prothrombin time (PT) was 14.07 (3.07) seconds, activated partial thromboplastin time (aPTT) was 35.15 (4.78) seconds, and international normalized ratio (INR) was 1.49 (0.49) in the cefoperazone-sulbactam group, which was significantly higher than the PT of 11.55 (1.29), aPTT of 31.37 (2.20), and INR of 1.12 (0.35) before cefoperazone-sulbactam treatment. No significant difference was in the cefoperazone-sulbactam plus vitamin K1 group. In addition, no significant difference was found in the thrombin time or fibrinogen level between before and after cefoperazone-sulbactam treatment in both groups. The mean (SD) platelet counts of the 2 groups were 197.34 (71.82) × 109/L and 187.75 (72.66) × 1 09/L after cefoperazone-sulbactam treatment, respectively, which was significantly lower than 231.77 (77.05) × 109/L and 232.08 (84.48) × 109/L before cefoperazone-sulbactam treatment. There were greater proportions of coagulation disorders (prolongation of PT, aPTT, INR, and bleeding) after cefoperazone-sulbactam treatment in the cefoperazone-sulbactam group compared with that in the cefoperazone-sulbactam plus vitamin K1 group. IMPLICATIONS: Results indicate that, after adding cefoperazone-sulbactam to the regimens of patients receiving long-term low-dose aspirin, therapy contributed to remarkable increase in abnormal coagulation function and coagulation disorders. Prophylaxis with vitamin K1 decreased the risk of these abnormalities in blood coagulation parameters associated with cefoperazone-sulbactam in patients taking long-term aspirin.

Effect comparison of salpingectomy versus proximal tubal occlusion on ovarian reserve: A meta-analysis.

INTRODUCTION: The women with hydrosalpinx have lower pregnancy rates in assisted reproductive technology, and only laparoscopic salpingectomy and tubal occlusion has proven to be effective to improve the outcome of in vitro fertilization. The main objective of the present meta-analysis was to assess and compare the ovarian reserve after salpingectomy or proximal tubal occlusion (PTO) in the published literature. MATERIAL AND METHODS: We considered all published cohort (retrospective and prospective) and cross-sectional studies as well as randomized controlled trials that investigated changes in serum anti-Müllerian hormone (AMH), follicle-stimulating hormone levels or antral follicle count (AFC) following salpingectomy or PTO. Two investigators (SW, QZ) independently screened the full text of all identified articles to assess relevance to our meta-analysis. RESULTS: In total, 648 patients were included in 5 studies. In the analysis of comparative studies. In the analysis of comparative studies, the follicle-stimulating hormone of salpingectomy had no significant difference with that of PTO (WMD 0.46IU/L, 95% CI[-0.14,1.05]). The AMH and AFC of salpingectomy were significantly higher than that of PTO (AFC: WMD -0.80IU/L, 95% CI [-1.46, -0.14]; AMH: WMD -1.01IU/L, 95% CI [-1.28, -0.74]). CONCLUSIONS: Salpingectomy did more harm to ovarian reserve than PTO in the short-term. However, the long-term effects on ovarian reserve remains uncertain.

Hemolytic jaundice induced by pharmacological dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency: A case report.

RATIONALE: Hemolysis induced by high dose ascorbic acid (AA) in patients with G6PD deficiency has been reported, but is rare. To our knowledge, this is the first reported case of a male with G6PD deficiency, coexpressed with cholecystolithiasis and cholecystitis, who developed extreme hemolysis and hyperbilirubinemia after receiving pharmacological doses ascorbic acid infusion. PATIENT CONCERNS: A 27-year-old man history with glucose-6-phosphate dehydrogenase deficiency was admitted to our hospital because of cholecystolithiasis and cholecystitis. He appeared with scleral jaundice and very deep colored urine after receiving pharmacological doses ascorbic acid infusion. DIAGNOSES: Clinical findings when combined with his medical history and various laboratory results confirmed the diagnosis as hemolysis and hyperbilirubinemia induced by ascorbic acid. INTERVENTIONS: The patient was treated with steroids, hepatoprotective drugs, and folic acid in addition avoidance of agents with known hemolysis risk (such as vitamin C). OUTCOMES: As a result, the patient's symptoms from hemolytic jaundice improved, hemoglobin remained stable, and the patient was discharged 11 days later. LESSONS: Clinicians should bear in mind the possibility that vitamin C exposure may result in hemolysis in patients with G6PD deficiency, especially in those with known severe disease.

Comparison of Procalcitonin Guidance-Administered Antibiotics with Standard Guidelines on Antibiotic Therapy in Children with Lower Respiratory Tract Infections: A Retrospective Study in China.

OBJECTIVE: To establish the efficacy of an algorithm based on the biomarker procalcitonin (PCT) to reduce antibiotic exposure in pediatric patients with lower respiratory tract infection (LRTI). MATERIALS AND METHODS: The clinical data of 357 patients (<14 years of age) who were discharged home with LRTI from January 1, 2010 to July 31, 2016 were analyzed. Antibiotic exposure, antibiotic prescription rate, length of hospital stay, and antibiotic-associated adverse effects were compared between the PCT group (n = 183) and the standard group (n = 174) using SAS 9.1.3 software. RESULTS: The overall adverse effect rates were similar in both the PCT and standard groups: 42 (22.95%) and 51 (29.31%), respectively. The length of hospital stay was not significantly different between the PCT (9.96 ± 5.81 days) and standard groups (10.58 ± 4.24 days) (difference: -0.62%; 95% CI: -1.68 to 0.43). Antibiotic prescribing rates were significantly different in the PCT group compared to the standard group: 54.64% versus 83.91% (difference: -29.26%; 95% CI: -38.31, -20.22; p = 0.23). Mean duration of antibiotic exposure in the PCT group (3.98 ± 2.17 days) was lower than the standard groups (6.66 ± 5.59 days) (difference: -2.68%; 95% CI: -3.21 to -2.16). CONCLUSION: This study showed that PCT guidance of antibiotic treatment in children and adolescents with LRTI reduced the duration of antibiotic exposure and antibiotic prescribing rates, but did not affect the adverse effect rate and length of hospital stay.

hsa-miR-631 resensitizes bortezomib-resistant multiple myeloma cell lines by inhibiting UbcH10.

Although bortezomib (BTZ) remains a first-line agent for multiple myeloma (MM) therapy, the development of BTZ resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to BTZ. This study demonstrated, for the first time, that UbcH10 is highly expressed in BTZ-resistant myeloma cell lines U-266/BTZ, NCI-H929/BTZ and RPMI-8226/BTZ, which is attributed to the inactivation of post-transcriptional control. The in-depth study revealed that during the development of BTZ resistance in these cells, the hsa-miR-631 levels were decreased, which resulted in the increased expression of the target gene UbcH10. We also found that the multiple drug-resistant protein MDR1 exhibited a positive correlation with UbcH10 due to the reduced ubiquitination of MDR1, which was caused by high UbcH10 expression. Following overexpression of miR-631, both BTZ sensitivity and BTZ-induced apoptosis were enhanced in the resistant cells. Meanwhile, resensitization by miR-631 overexpression was blocked by exogenous expression of UbcH10, which was not regulated by intracellular miR-631. In conclusion, the miR-631/UbcH10/MDR1 pathway is closely associated with the development of BTZ resistance in myeloma cells, and the overexpression of miR-631 can significantly improve BTZ sensitivity in resistant myeloma cells.