Downregulation of NUP93 aggravates hypoxia-induced death of cardiomyocytes in vitro through abnormal regulation of gene transcription.

Nuclear pore complex in the nuclear envelope plays an important role in controlling the transportation of RNAs, proteins and other macromolecules between the nucleus and cytoplasm. The relationship between abnormal expression of nucleoporins and cardiovascular diseases is unclear. In this study we investigated how myocardial infarction affected the expression and function of nucleoporins in cardiomyocytes. We separately knocked down 27 nucleoporins in rat primary myocardial cells. Among 27 nucleoporins, knockdown of Nup93, Nup210 and Nup214 markedly increased the expression of ANP and BNP, two molecular markers of cardiomyocyte function. We showed that Nup93 was significantly downregulated in hypoxic cardiomyocytes. Knockdown of Nup93 aggravated hypoxia-induced injury and cell death of cardiomyocytes, whereas overexpression of Nup93 led to the opposite effects. RNA-seq and bioinformatics analysis revealed that knockdown of Nup93 did not affect the overall transportation of mRNAs from the nucleus to the cytoplasm, but regulated the transcription of a large number of mRNAs in cardiomyocytes, which are mainly involved in oxidative phosphorylation and ribosome subunits. Most of the down-regulated genes by Nup93 knockdown overlapped with the genes whose promoters could be directly bound by Nup93. Among these genes, we demonstrated that Nup93 knockdown significantly down-regulated the expression of YAP1. Overexpression of YAP1 partially rescued the function of Nup93 knockdown and attenuated the effects of hypoxia on cell injury and cardiomyocyte death. We conclude that down-regulation of Nup93, at least partially, contributes to hypoxia-induced injury and cardiomyocyte death through abnormal interaction with the genome to dynamically regulate the transcription of YAP1 and other genes. These results reveal a new mechanism of Nup93 and might provide new therapeutic targets for the treatment of ischemia-induced heart failure.

Effect of different antibiotic therapies on the reproductive outcomes of fresh embryo transfer for chronic endometritis: A retrospective cohort study.

OBJECTIVE: To investigate the reproductive outcomes by comparing two kinds of antibiotic schemes for chronic endometritis (CE) in infertile women's fresh embryo transfer (FET) cycles and identify subgroups of patients with CE who need long-term antibiotics treatment. DESIGN: A retrospective cohort study. SETTING: University-based reproductive medical center. PATIENT(S): A total of 492 women with CD138-positive plasmacytes per 10 high-power fields (CD138+/10HPF). INTERVENTION(S): Hysteroscopy was performed and endometrial biopsy samples were collected in the proliferative phase. Long-term or short-term antibiotics were administrated. After antibiotics treatment, patients underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) and received ET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate, clinical pregnancy rate, clinical miscarriage rate. RESULT (S): There were no significant differences in pregnancy outcomes between patients with CD138+/10HPF 1-4 (low-grade CE) who received long-term antibiotic therapy and short-term antibiotics groups. Among women with CD138+/10HPF ≥5 (high-grade CE), live birth rate (48.4% vs. 14.7%, p = .001), clinical pregnancy rate (66.7% vs. 35.3%, p = .002) and ongoing pregnancy rate (59.1% vs. 20.6%, p < .001) in the long-term arm were significantly higher than that in the short-term arm. The clinical miscarriage rate (21.0% vs. 58.3%, p = .013) was statistically lower in the long-term antibiotics group, but no statistical differences were found between the two groups in preterm delivery rate. CONCLUSION: Long-term antibiotics treatment was a sensible choice to improve pregnancy outcomes in women with CD138+/10HPF ≥5 (high-grade CE). The pregnancy outcomes of women with low-grade CE only defined by histological diagnosis were not greatly improved after antibiotic therapy. Therefore, we recommended the proper diagnosis criteria were CD138+/10HPF ≥5 pathologically.

Sarcopenia increases the risk of early biliary infection after percutaneous transhepatic biliary stent placement.

Purpose: To assess the association between sarcopenia and the risk of early biliary infection (EBI) after percutaneous transhepatic biliary stent (PTBS) placement in patients with inoperable biliary tract cancer (BTC). Patients and methods: In this single center, retrospective observational study, patients diagnosed with inoperable BTC undergoing PTBS placement between January 2013 and July 2021 were enrolled. Preoperative sarcopenia was defined based on skeletal muscle mass measured by computed tomography images on the level of third lumbar vertebra within one month before PTBS placement. Patients were divided into two groups in accordance with the status of sarcopenia. Univariate and further multivariate logistic analyses were performed to determine predictors for EBI. Stratified and interactive analyses were conducted to investigate the stability of results. Further receiver operating characteristic curve was performed to determine the predictive value of sarcopenia on EBI after PTBS placement. Results: Totally, 134 patients were included in this retrospective study, with 45 (33.6%) patients characterized as sarcopenia. The incidence rate of EBI was 26.9% (36/134). Multivariate analyses demonstrated that sarcopenia [Odds ratio (OR), 2.75; 95%CI: 1.11-6.77; P=0.028], obstruction length (OR, 1.04; 95%CI: 1.00-1.08; P=0.030) and diabetes (OR, 2.46; 95%CI: 1.01-5.96; P=0.047) were significant predictors of EBI. There were no significant interactions in different subgroups (P for interaction > 0.05). Moreover, the areas under the curves (AUC) revealed that the combined index containing sarcopenia, obstruction length, and diabetes showed the better predictive value (AUC= 0.723) than either one alone. Conclusion: Sarcopenia increased the risk of EBI in patients with inoperable BTC after PTBS placement. Preoperative assessment of sarcopenia may aid in risk stratification. Patients with sarcopenia should be given intensive monitoring.

Learning curve of laparoscopic and robotic pancreas resections: a systematic review.

BACKGROUND: Minimally invasive pancreatic resection has been shown recently in some randomized trials to be superior in selected perioperative outcomes compared with open resection when performed by experienced surgeons. However, minimally invasive pancreatic resection is associated with a long learning curve. This study aims to summarize the current evidence on the learning curve of minimally invasive pancreatic resection and define the number of cases required to surmount the learning curve. METHODS: A systematic search was performed on PubMed, Embase, Scopus, and the Cochrane database using a detailed search strategy. Studies that did not describe the learning curve were excluded from the study. Data on the method of learning curve analysis, single surgeon versus institutional learning curve, and outcome measures were extracted and analyzed. RESULTS: A total of 32 studies were included in the pooled analysis: 12 on laparoscopic pancreatoduodenectomy, 9 on robotic pancreatoduodenectomy, 12 on laparoscopic distal pancreatectomy, and 3 on robotic distal pancreatectomy. Sample population was comparable between laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy (median 63 vs 65). Six of 12 studies and 7 of 9 studies used nonarbitrary methods of analysis in laparoscopic pancreatoduodenectomy and robotic pancreatoduodenectomy, respectively. Operating time was used as the single outcome measure in 4 of 12 studies in laparoscopic pancreatoduodenectomy and 5 of 9 studies in robotic pancreatoduodenectomy. Overall, there was no significant difference between the number of cases required to surmount the learning curve for laparoscopic pancreatoduodenectomy versus robotic pancreatoduodenectomy (laparoscopic pancreatoduodenectomy 34.1 [95% confidence interval 30.7-37.7] versus robotic pancreatoduodenectomy 36.7 [95% confidence interval 32.9-41.0]; P = .8241) and laparoscopic distal pancreatectomy versus robotic distal pancreatectomy (laparoscopic distal pancreatectomy 25.3 [95% confidence interval 22.5-28.3] versus robotic distal pancreatectomy 20.7 [95% confidence interval 15.8-26.5]; P = .5997.) CONCLUSION: This study provides a detailed summary of existing evidence around the learning curve in minimally invasive pancreatic resection. There was no significant difference between the learning curve for robotic pancreatoduodenectomy versus laparoscopic pancreatoduodenectomy and robotic distal pancreatectomy versus laparoscopic distal pancreatectomy. These findings were limited by the retrospective nature and heterogeneity of the studies published to date.

Obestatin ameliorates water retention in chronic heart failure by downregulating renal aquaporin 2 through GPR39, V2R and PPARG signaling.

AIMS: Obestatin regulates water metabolism by inhibiting arginine vasopressin (AVP) release and upregulated obestatin has been detected in patients with chronic heart failure (CHF). However, the significance of obestatin in CHF, particularly with regard to water retention and aquaporin 2 (AQP2) expression, remains unknown. MAIN METHODS: Using a CHF rat model, the effects of 2-week exogenous obestatin administration were evaluated. Expression of AQP2 was evaluated by immunoblotting, immunohistochemical staining, and quantitative real-time PCR (qPCR) in CHF rat model and mouse inner medullary collecting duct (mIMCD) 3 cell line. Moreover, the influence of obestatin on the genetic transcription profile in mIMCD3 cells was evaluated by microarray, and the potential regulatory mechanisms of obestatin on AQP2 were evaluated by RNA silencing of vasopressin receptor 2 (V2R), peroxisome proliferator-activated receptor gamma (PPARG), and G protein-coupled receptor 39 (GPR39). KEY FINDINGS: Obestatin increased urinary output and improved expression of CHF biomarker without significantly altering cardiac function, plasma electrolyte concentrations, or the plasma AVP concentration. AQP2 expression was significantly reduced. The results of microarray analyses and qPCR indicated that mRNA levels of Aqp2, Pparg, and V2r were significantly decreased. Inhibition of V2r and Pparg mRNA further reduced the expression of AQP2, while the inhibitory efficacy of obestatin on AQP2 was significantly offset after Gpr39 knockdown. SIGNIFICANCE: Long-term treatment with obestatin improves water retention in CHF by increasing urinary output through downregulation of AQP2 expression in renal IMCD cells. These effects may be at least partially mediated by regulation of GPR39, V2R and PPARG signaling.

The reproductive performance of female Forest musk deer (Moschus berezovskii) in captivity.

Reproductive performance of 750 adult female Forest musk deer (FMD, Moschus berezovskii) was monitored (from 2005 to 2009) on two Forest musk deer farms in Sichuan province, China. The mean (± SEM) lengths of the estrous cycle, pregnancy, and consecutive fawning intervals were 17.5 ± 0.8 d (n = 64), 182.9 ± 0.8 d (n =190), and 363.2 ± 2.4 d (n = 120), respectively. Copulation occurred from the end of October to early March, with the majority (84.1 ± 1.9%) during November and December (P < 0.05). The fawning rate was 68.7 ± 2.2% in yearling hinds and 73.3 ± 1.3% in adult hinds. Fawning occurred from the end of April to early September, with the majority (88. 9 ± 2.2%) during May and June (P < 0.005), including a peak in May (52.0 ± 1.0%). Yearling hinds fawned later (7.3 ± 1.8 d) than adult hinds. Rates of premature delivery and dystocia were 2.7 ± 0.4 and 2.0 ± 0.3%, respectively. There was a 1.07:1 female-to-male ratio at birth (P > 0.05), with 67.7% twins, but only two cases of triplets and one set of quadruplets among 537 fawns. Birth weight averaged 518.7 ± 10.3 g, ranging from 304 to 775 g (n = 240), with male fawns slightly heavier than females (521.1 ± 14.8 vs 516.9 ± 14.3 g). Postnatal and pre-weaning mortality rates were 25.0 ± 1.2 and 17.9 ± 3.1%, respectively. Postnatal mortality and urinary calculus were much more common in male fawns (P < 0.01). The mortality rate due to suppuration and dyspepsia were different (P < 0.001) between postnatal and pre-weaning periods. Due to higher mortality of male fawns, the adult sex ratio was significantly female-biased. In conclusion, captive FMD had similar seasonal patterns of copulation and fawning as wild FMD and other musk deer species.