Nicotinamide protects against diabetic kidney disease through regulation of Sirt1.

PURPOSE: To investigate the effect of nicotinamide (Nam) on diabetic kidney disease (DKD) in mice and explore its mechanism. METHODS: Thirty DBA/2 J mice were randomly assigned to three groups. After 8 weeks of hyperglycemia induced by streptozocin (STZ), Nam and saline were administrated to STZ + Nam and STZ + NS mice, respectively, for 8 weeks. Non-diabetic mice (NDM) were used as control group. Twenty In2-/- Akita mice were randomly divided into two groups. After 8 weeks of hyperglycemia, Nam and saline were administered to Akita + Nam and Akita + NS mice, respectively, for 6 weeks. Wild-type littermates were used as control group. Markers of renal injury were analyzed, and the molecular mechanisms were explored in human proximal tubular HK2 cells. RESULTS: Urinary albumin-to-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1) decreased in the STZ + Nam and Akita + Nam groups. Pathological analysis showed that Nam improved the structure of glomerular basement membrane, ameliorated glomerular sclerosis, and decreased the accumulation of extracellular matrix and collagen. Compared to the diabetic control group, renal fibrosis, inflammation, and oxidative stress were reduced in the Nam-treated mice. The expression of sirtuin 1 (Sirt1) in human proximal tubular HK2 cells was inhibited by high glucose and Nam treatment enhanced its expression. However, in HK2 cells with Sirt1 knockdown, the protective effect of Nam was abolished, indicating that the beneficial effect of Nam was partially dependent on Sirt1. CONCLUSIONS: Nam has a renoprotective effect against renal injury caused by hyperglycemia and may be a potential target for the treatment of DKD.

Laparoscopic adenomyomectomy combined with levonorgestrel-releasing intrauterine system is effective for long-term management of adenomyosis.

BACKGROUD: Laparoscopic adenomyomectomy combined with intraoperative placement of levonorgestrel-releasing intrauterine device (LNG-IUS) is a novel conservative surgical procedure for adenomyosis. Our study aimed to compare the efficacy of surgery with or without intraoperative placement of LNG-IUS treatment in adenomyosis. METHODS: We retrospectively reviewed the medical records of adenomyosis patients who received laparoscopic adenomyomectomy from January 2014 to April 2020, finally including 70 patients undergoing surgery-LNG-IUS as group A and 69 patients undegoing surgery only as group B. Risk factors for three-year relapse were analyzed using Cox's multivariate proportional hazard analysis. RESULTS: Visual analog scale and Mansfield-Voda-Jorgensen Menstrual Bleeding Scale scores of group A at 3, 6, 12, 24, and 36 months were significantly lower than those of group B at the corresponding points (P < .001 for both scales). Individuals in both groups showed statistically significant symptom relief. The recurrence rate in group A was significantly lower than that in group B at 36 months after the surgery (2.94% vs. 32.84%, P < .001). A cox proportional hazard model showed that relapse was significantly associated with coexisting ovarian endometriosis (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 1.33-7.02, P = .015). Patients who received surgery-LNG-IUS had a lower risk of recurrence than those with surgery-alone (aHR, 0.07; 95% CI, 0.016-0.31, P < .001). CONCLUSIONS: Conservative surgery with intraoperative placement of LNG-IUS is effective and well-accepted for long-term therapy with a lower recurrence rate for adenomyosis. Coexistent ovarian endometriosis is a major factor for adenomyosis relapse.

ACMSD mediated de novo NAD+ biosynthetic impairment in cardiac endothelial cells as a potential therapeutic target for diabetic cardiomyopathy.

OBJECT: The highly conserved α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) is the key enzyme that regulates the de novo NAD+ synthesis from tryptophan. NAD+ metabolism in diabetic cardiomyopathy (DCM) was not elucidated yet. METHODS: Mice were assigned to non-diabetic (NDM) group, streptozocin (STZ)-induced diabetic (DM) group, and nicotinamide (NAM) treated (DM + NAM) group. ACMSD mediated NAD+ metabolism were studied both in mice and patients with diabetes. RESULTS: NAD+ level was significantly lower in the heart of DM mice than that of the NDM group. Supplementation with NAM could partially increased myocardial capillary density and ameliorated myocardial fibrosis by increasing NAD+ level through salvage pathway. Compared with NDM mice, the expression of ACMSD in myocardial endothelial cells of DM mice was significantly increased. It was further confirmed that in endothelial cells, high glucose promoted the expression of ACMSD. Inhibition of ACMSD could increase de novo NAD+ synthesis and improve endothelial cell function by increasing Sirt1 activity. Targeted mass spectrometry analysis indicated increased ACMSD enzyme activity in diabetic patients, higher ACMSD activity increased risk of heart diastolic dysfunction. CONCLUSION: In summary, increased expression of ACMSD lead to impaired de novo NAD+ synthesis in diabetic heart. Inhibition of ACMSD could potentially improve DCM.

Risk Factors for Symptomatic Recurrence after Laparoscopic Adenomyomectomy: A 3-Year Follow-up.

STUDY OBJECTIVE: To identify the clinical risk factors for symptomatic recurrence of adenomyosis after laparoscopic adenomyomectomy with a three-year follow-up. DESIGN: Retrospective study. SETTING: University-affiliated hospital. PATIENTS: A total of 149 patients were included in this study, including 52 patients with symptomatic recurrence and 97 without recurrence. INTERVENTION: Laparoscopic adenomyomectomy was performed first. MEASUREMENTS AND MAIN RESULTS: General clinical data, including preoperative, intraoperative, and postoperative indices, symptomatic recurrence, and follow-up information, were collected. Comparison of women with and without symptomatic recurrence revealed significant differences for age at surgery (p = .026), presence of concomitant ovarian endometrioma (p <.001), and prescription of postoperative hormonal suppression (yes/no) (p <.0001). A Cox proportional hazard model indicated that concomitant ovarian endometrioma was a significant risk factor for recurrence (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.10-3.85, p = .001). Patients who received postoperative hormonal suppression had a lower risk of recurrence than those without hormonal suppression (HR, 0.30; 95% CI, 0.16-0.55, p <.0001). Those aged ≥40 years also had a lower risk of symptomatic recurrence than those <40 years (HR, 0.46; 95% CI, 0.24-0.88, p = .03). CONCLUSIONS: Concomitant ovarian endometrioma is a risk factor for symptomatic recurrence of adenomyosis after laparoscopic adenomyomectomy. Postoperative hormonal suppression and older age at surgery (≥40 years) are protective factors.

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

Objective: To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. Methods: This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. Results: The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine ß2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Conclusion: Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

Extracellular vesicle-derived long non-coding RNA as circulating biomarkers for endometriosis.

RESEARCH QUESTION: Could extracellular vesicle-derived long non-coding RNA (lncRNA) serve as promising circulating biomarkers for endometriosis? DESIGN: To obtain novel diagnostic markers, 85 patients with endometriosis were enrolled as the endometriosis group and 86 unaffected participants as the control group. RNA sequencing was performed to identify extracellular vesicle-derived lncRNA that were differentially expressed between women with endometriosis (n = 5) and unaffected participants (n = 6). Messenger RNA and lncRNA sequences of the plasma extracellular vesicles were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. lncRNA expression levels were further validated using quantitative reverse transcriptase polymerase chain reaction. Moreover, receiver operating characteristic curve analysis was performed to determine the diagnostic value of candidate lncRNA. Clinical features were correlated to the expression levels of candidate lncRNA. RESULTS: It was found that 210 lncRNA were significantly dysregulated; among these, expression of LINC01569, RP3-399L15.2, FAM138B and CH507-513H4.6 was significantly decreased, whereas expression of RP11-326N17.2, KLHL7-AS1 and MIR548XHG was increased, in the plasma of patients with endometriosis. Combined expression level of RP3-399L15.2 and CH507-513H4.6 was used to distinguish patients with endometriosis from control participants; the results revealed a sensitivity of 80.00% and specificity of 85.45% at the cut-off point, and an area under the ROC curve of 0.9045. The findings demonstrated the potential of these two lncRNA as diagnostic biomarkers for endometriosis. Moreover, CH507-513H4.6 alone may be useful in detecting early-stage endometriosis lesions. CONCLUSIONS: The combination of RP3-399L15.2 and CH507-513H4.6 may be a potential candidate for endometriosis biomarkers.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Observation of pregnancy outcomes in patients with hysteroscopic resection on submucous myomas.

OBJECTIVE: The aim of this study was to assess postoperative pregnancy outcomes in patients with different types of submucous myomas after hysteroscopic resection. MATERIALS AND METHODS: This retrospective unicentric study used data from the electronic medical records system of the hospital. All patients (n = 77) who underwent hysteroscopy for submucous myomas between November 2010 and December 2018 were included. Patients were divided into three groups according to the myoma classification (G0, G1, and G2). Medical files were reviewed and phone questionnaires were conducted to evaluate demographic characteristics, clinical features, surgical treatment, and pregnancy outcomes. RESULTS: The median age of the patients was 32 (30.0, 34.0) years. The myoma diameter was 2.9 (2.0, 3.8) cm. The operation duration was 50.0 (30.0, 75.0) min. There were 15 patients in Group G0, 20 patients in Group G1, and 37 patients in Group G2. Follow-up data were available for 65 of the 77 patients. The total pregnancy rate was 58 (89.2%) of 65. The live birth rate was 41 (70.7%) of 58. There was no significant difference in pregnancy rate (G0 100% vs. G1 76.5% vs. G2 91.2%; p = 0.097) or in live birth rates among the three groups (G0 78.6% vs. G1 53.8% vs. G2 74.2%; p = 0.325). CONCLUSION: There was no difference in pregnancy outcome among the three types of submucosal myomas. Our results support the idea that hysteroscopic myomectomy is an effective option for submucous myomas with good long-term pregnancy outcomes.

Sleeve gastrectomy ameliorated high-fat diet (HFD)-induced non-alcoholic fatty liver disease and upregulated the nicotinamide adenine dinucleotide +/ Sirtuin-1 pathway in mice.

BACKGROUND: /Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and effective treatments are lacking. Bariatric surgery, including sleeve gastrectomy (SG), is a potential therapeutic strategy for NAFLD, but the molecular mechanisms underlying its effects are not fully understood. In this study, the effects of SG and the underlying mechanisms were evaluated in a mouse model of high-fat diet (HFD)-induced NAFLD. METHODS: C57BL/6 mice were randomly divided into three groups: normal diet with sham operation (NC-Sham group), HFD with sham operation (HFD-Sham group), and HFD with sleeve gastrectomy (HFD-SG group). Glucose metabolism and fat accumulation in the body and liver were analyzed before and after SG. Lipid metabolism and inflammation in the liver were evaluated. Nicotinamide adenine dinucleotide (NAD+) levels as well as nicotinamide riboside kinase (NRK1) and Sirtuin-1 (SIRT1) expression levels were evaluated. RESULTS: SG attenuated the HFD-induced increases in glucose and insulin levels, fat accumulation, and lipid droplet accumulation. Fatty acid biosynthesis, the expression of the metabolism-related genes ACC1, FASN, SCD1, and DGAT1, and the levels of inflammatory factors were higher in HFD mice than in NC mice and decreased after SG. NAD + concentrations were 54.9 ± 13.4 µmol/mg in NC-Sham mice, 37.6 ± 8.1 µmol/mg in HFD-Sham mice, and 79.9 ± 13.0 µmol/mg in HFD-SG mice (p < 0.05). NRK1 and SIRT1 expression increased dramatically after SG at both the RNA and protein levels. CONCLUSION: SG significantly alleviated NAFLD in HFD-induced obese mice with increasing the hepatic NAD + levels and upregulating the NRK1/NAD+/SIRT1 pathway.

Laparoscopic adenomyomectomy combined with levonorgestrel-releasing intrauterine system in the treatment of adenomyosis: Feasibility and effectiveness.

AIM: To evaluate the clinical efficacy and safety of laparoscopic adenomyomectomy combined with intraoperative replacement of levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of symptomatic adenomyosis. METHODS: This is a case-series study in a university medical center. A total of 52 patients with symptomatic adenomyosis were treated by laparoscopic adenomyomectomy combined with intraoperative replacement of LNG-IUS from January 2015 to July 2018. Visual analog scale, menstrual flow and uterine volume were compared before and after the surgery (3, 12 and 24 months). Meanwhile, LNG-IUS-induced adverse reactions (e.g. irregular vaginal bleeding, amenorrhea, expulsion, and perforation) were also recorded. RESULTS: All operations were successfully completed via laparoscopy without conversion to laparotomy. No severe complications were noted during the surgical procedure or follow-up period. The mean postoperative visual analog scale and menstrual flow scores and the volume of the uterus were significantly decreased (all P < 0.001) at 3, 12, and 24 months postoperatively, compared with preoperative scores. The clinical effective rates among the patients with dysmenorrhea were 98%, 96% and 96% at 3, 12 and 24 months after the operation, respectively. And the clinical effectiveness rate of menorrhagia was 97.6%, 95.2% and 95.2% at 3, 12 and 24 months after treatment, respectively. Among all related adverse reactions, amenorrhea was the most common (n = 12, 23.1%). There was one case of LNG-IUS perforation (1.9%) and two cases of expulsion (3.8%). CONCLUSION: Laparoscopic adenomyomectomy combined with intraoperative replacement of LNG-IUS is a novel and effective conservative surgical procedure for symptomatic adenomyosis treatment.

Efficacy and predictors of short-term first-generation somatostatin analog presurgical treatment in acromegaly: A hospital-based study of 237 cases.

OBJECTIVE: To investigate the effectiveness and predictors of short-term somatostatin analog (SSA) presurgical therapy in a large cohort and to assess the correlation between clinical and pathological variables. DESIGN: 237 newly diagnosed patients with acromegaly received presurgical SSA treatment for three months were recruited. Clinical characteristics were collected, and response to SSA in hormone and tumor size was evaluated. The correlation between clinical information and pathological variables were analyzed. RESULTS: After 3 months presurgical SSA therapy, 51 (21.5%) patients were biochemically responsive with ≥50% decrease in IGF-1 while 126 (53.2%) patients showed at least 20% tumor size decrease. Biochemical responders were associated with a smaller maximum tumor diameter (MTD) and an older age (OR, 0.448; P = 0.003; OR, 1.050; P = 0.001). Tumor size responders were associated with a smaller MTD (OR, 0.435; P < 0.001). A combination of MTD < 2 cm and age ≥49 years predicted biochemical responders (PPV, 54.5%; NPV, 86.0%; P < 0.001), while MTD ≤2.2 cm (PPV, 67.1%; NPV, 67.0%; P < 0.001) predicted tumor size responders. Compared to patients with MTD < 2 cm, patients with MTD ≥ 2 cm showed higher percentage of sparsely granulated (SG) adenoma (62.1% vs. 31.3%, P = 0.005). In addition, the percentage of SG adenoma tended to be higher in patients < 49 years than ≥49 years (48.1% and 31.0% P = 0.089). CONCLUSIONS: The baseline MTD and age correlate with granulation patterns and may be used as easily acquired predictors of presurgical SSA treatment in acromegaly. Patients over their 50s with a tumor less than 2 cm in diameter are more likely to have a response to the short-term presurgical SSA therapy.

The association of erythrocyte sedimentation rate, high-sensitivity C-reactive protein and diabetic kidney disease in patients with type 2 diabetes.

BACKGROUND: To evaluate the association between high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR), and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted in 1210 patients with T2DM, among whom 265 had DKD. The severity of DKD was assessed by estimated-glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (ACR). The relationship between ESR, hsCRP and DKD was analyzed by multivariate logistic analysis. The relationship between ESR and eGFR, ESR or ACR was analyzed by multivariate linear regression. RESULTS: ESR (23.0 [12.0 ~ 41.5] mm/h versus 12.0 [7.0 ~ 22.0] mm/h, P <  0.001) and hsCRP (3.60 [2.20 ~ 7.65] versus 2.90 [1.80 ~ 5.60] mg/L mg/L, P <  0.01) values were significantly higher in patients with DKD than those without. Patients with higher ESR or hsCRP had lower eGFR and higher ACR. After adjusted for gender, age, hemoglobin, plasma proteins, HbA1c, lipid profiles, and the usage of renin-angiotensin system inhibitors, ESR but not hsCRP was independently associated with the rate and severity of DKD in patients with T2DM. CONCLUSION: ESR was independently associated with the rate and severity of DKD in patients with T2DM.

Laparoscopic Management of 42 Cases of Tubal Stump Pregnancy and Postoperative Reproductive Outcomes.

STUDY OBJECTIVE: Tubal stump pregnancy is a rare variant of ectopic pregnancy. The aim of this study was to evaluate laparoscopic surgery for tubal stump pregnancy and to investigate postoperative pregnancy outcomes. DESIGN: Retrospective study. SETTING: University-affiliated hospital. PATIENTS: Patients (n = 42) diagnosed with tubal stump pregnancy. INTERVENTIONS: Data were extracted from the electronic medical records system of the hospital. MEASUREMENTS AND MAIN RESULTS: Patients diagnosed with tubal stump pregnancy between June 2010 and July 2018 were included. Data included demographic characteristics, gravidity and parity, history of pelvic surgery, clinical features, and treatment. All procedures were laparoscopic. Postoperative pregnancy outcomes were identified from electronic medical records or by telephone. Patients' mean age was 30 (range, 21-39) years. Twelve of 42 tubal stump pregnancies (28.6%) had ruptured ectopic pregnancy at the time of operation. The remaining 30 cases had intact stump pregnancy during surgery. Patients were followed for a mean of 31 (range, 10-60) months. Follow-up data were available for 33 of 39 patients (3 with heterotopic tubal stump pregnancy were not included in follow-up data because all resulted in a live births and had no desire for future pregnancy). Eighteen of 28 patients (64.3%) who attempted conception had intrauterine pregnancies (IUPs) during the follow-up period; of these 18 IUPs, 14 (77.8%) resulted in live births. There was 1 case of uterine rupture in a singleton pregnancy at 20+5 weeks that resulted in fetal death. Three of 18 IUPs (16.7%) ended in the first trimester with spontaneous abortions. CONCLUSION: Laparoscopic surgery is a feasible option for tubal stump pregnancy and is associated with favorable pregnancy outcomes.

Transcriptome sequencing of adenomyosis eutopic endometrium: A new insight into its pathophysiology.

The eutopic endometrium has been suggested to play a crucial role in the pathogenesis of adenomyosis. However, the specific genes in eutopic endometrium responsible for the pathogenesis of adenomyosis still remain to be elucidated. We aim to identify differentially expressed genes (DEGs) and molecular pathways/networks in eutopic endometrium from adenomyosis patients and provide a new insight into disease mechanisms at transcriptome level. RNA sequencing (RNA-Seq) was performed with 12 eutopic endometrium from adenomyosis and control groups. Differentially expressed genes in adenomyosis were validated by quantitative real-time PCR (qPCR) and immunochemistry. Functional annotations of the DEGs were analysed with Ingenuity Pathway Analysis (IPA). Quantitative DNA methylation analysis of CEBPB was performed with MassArray system. A total of 373 differentially expressed genes were identified in the adenomyosis eutopic endometrium compared to matched controls. Bioinformatic analysis predicted that IL-6 signalling and ERK/MAPK signalling were activated in adenomyosis endometrium. We also found that the increased expression and DNA hypomethylation of CEBPB were associated with adenomyosis. Our results revealed key pathways and networks in eutopic endometrium of adenomyosis. The study is the first to propose the association between C/EBPß and adenomyosis and can improve the understanding of the pathogenesis of adenomyosis.

Erratum to "Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study".

[This corrects the article DOI: 10.1155/2018/3015854.].

HIGHER GROWTH HORMONE LEVELS ARE ASSOCIATED WITH ERECTILE DYSFUNCTION IN MALE PATIENTS WITH ACROMEGALY.

Objective: To investigate in vivo correlates of erectile dysfunction (ED) in male patients with acromegaly. Methods: Fifty-one male patients with acromegaly were assessed by the International Index of Erectile Function-5 and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched nonacromegalic controls. Results: Among 51 patients analyzed, 32 (62.7%) had ED. Patients with ED showed lower Acro-QoL scores regarding global (69.8 ± 17.7 versus 79.4 ± 11.2; P = .035) and personal relationship dimensions (59.6 ± 22.1 versus 76.8 ± 17.6; P = .012) than non-ED patients. ED patients were older (44.5 ± 11.2 years versus 33.2 ± 8.5 years; P = .04) and showed higher growth hormone (GH) levels (15.5 µg/L [interquartile range of 9.5 to 34.5 µg/L] versus 5.9 µg/L [interquartile range of 3.4 to 13.9 µg/L]; P = .001) compared to non-ED patients. The cutoff values for identifying ED were 7.9 µg/L for random GH and 5.3 µg/L for GH nadir after oral administration of 75 g of glucose. There was no significant difference in total testosterone levels between the two groups (6.36 ± 4.24 nmol/L versus 9.54 ± 5.50 nmol/L; P = .299). The NO levels in patients with acromegaly were significantly lower than those in nonacromegalic controls (8.77 ± 1.78 µmol/L versus 19.19 ± 5.02 µmol/L, respectively; P = .049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14 ± 0.98 µmol/L versus 12.09 ± 3.44 µmol/L; P = .027). Conclusion: Our study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required. Abbreviations: Acro-QoL = Acromegaly Quality of Life; ED = erectile dysfunction; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; IIEF-5 = international index of erection function-5; LH = luteinizing hormone; MRI = magnetic resonance imaging; NO = nitric oxide; OGTT = oral glucose tolerance test; QoL = quality of life; ROC = receiver operating characteristic.

High glucose-induced ubiquitination of G6PD leads to the injury of podocytes.

Oxidative stress contributes substantially to podocyte injury, which plays an important role in the development of diabetic kidney disease. The mechanism of hyperglycemia-induced oxidative stress in podocytes is not fully understood. Glucose-6-phosphate dehydrogenase (G6PD) is critical in maintaining NADPH, which is an important cofactor for the antioxidant system. Here, we hypothesized that high glucose induced ubiquitination and degradation of G6PD, which injured podocytes by reactive oxygen species (ROS) accumulation. We found that G6PD protein expression was decreased in kidneys of both diabetic patients and diabetic rodents. G6PD activity was also reduced in diabetic mice. Overexpressing G6PD reversed redox imbalance and podocyte apoptosis induced by high glucose and palmitate. Inhibition of G6PD with small interfering RNA induced podocyte apoptosis. In kidneys of G6PD-deficient mice, podocyte apoptosis was significantly increased. Interestingly, high glucose had no effect on G6PD mRNA expression. Decreased G6PD protein expression was mediated by the ubiquitin proteasome pathway. We found that the von Hippel-Lindau (VHL) protein, an E3 ubiquitin ligase subunit, directly bound to G6PD and degraded G6PD through ubiquitylating G6PD on K366 and K403. In summary, our data suggest that high glucose induces ubiquitination of G6PD by VHL E3 ubiquitin ligase, which leads to ROS accumulation and podocyte injury.-Wang, M., Hu, J., Yan, L., Yang, Y., He, M., Wu, M., Li, Q., Gong, W., Yang, Y., Wang, Y., Handy, D. E., Lu, B., Hao, C., Wang, Q., Li, Y., Hu, R., Stanton, R. C., Zhang, Z. High glucose-induced ubiquitination of G6PD leads to the injury of podocytes.

Cesarean scar endometriosis: presentation of 198 cases and literature review.

BACKGROUND: Cesarean scar endometriosis (CSE) is the most common type of abdominal wall endometriosis (AWE). The aim of this study was to systematically identify the clinical features of CSE and recommend precautionary measures. METHODS: A large, retrospective study was undertaken with CSE patients treated surgically at our hospital between January 2005 and December 2017. RESULTS: A total of 198 CSE patients were enrolled, with a mean age of 32.0 ± 4.0 years. The main complaint of the patients was abdominal mass (98.5%), followed by cyclic pain (86.9%). The latency period of CSE was 31.6 ± 23.9 months, and the duration between the onset of symptoms and this surgery was 28.3 ± 25.0 months. A majority (80.8%, n = 160) of the patients had undergone a Pfannenstiel incision, and a minority (19.2%, n = 38) a vertical midline incision. The latency period of CSE in the case of a Pfannenstiel incision was significantly shorter than that in the case of a vertical midline incision (24.0 vs 33.0 months, P = 0.006). A total of 187 (94.4%) patients had a single endometrioma, 11 (5.6%) patients had multiple endometriomas, and the 11 multiple-endometrioma patients had all undergone a Pfannenstiel incision. Lesions of endometrioma were common in corner sites, after either incision: 142/171 (83.0%) in Pfannenstiel incision scars and 32/38 (84.2%) in vertical incision scars. CONCLUSIONS: The findings of this study indicate that the Pfannenstiel incision carries a higher risk of CSE than the vertical midline incision. Thorough cleaning at the conclusion of CS, particularly of both corner sites of the adipose layer and the fascia layer, is strongly recommended for CSE prevention. Further studies might provide additional recommendations.

Spironolactone Protects against Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetic Rats.

Spironolactone (SPR) has been shown to protect diabetic cardiomyopathy (DCM), but the specific mechanisms are not fully understood. Here, we determined the cardioprotective role of SPR in diabetic mice and further explored the potential mechanisms in both in vivo and in vitro models. Streptozotocin- (STZ-) induced diabetic rats were used as the in vivo model. After the onset of diabetes, rats were treated with either SPR (STZ + SPR) or saline (STZ + NS) for 12 weeks; nondiabetic rats were used as controls (NDCs). In vitro, H9C2 cells were exposed to aldosterone, with or without SPR. Cardiac structure was investigated with transmission electron microscopy and pathological examination; immunohistochemistry was performed to detect nitrotyrosine, collagen-1, TGF-ß1, TNF-α, and F4/80 expression; and gene expression of markers for oxidative stress, inflammation, fibrosis, and energy metabolism was detected. Our results suggested that SPR attenuated mitochondrial morphological abnormalities and sarcoplasmic reticulum enlargement in diabetic rats. Compared to the STZ + NS group, cardiac oxidative stress, fibrosis, inflammation, and mitochondrial dysfunction were improved by SPR treatment. Our study showed that SPR had cardioprotective effects in diabetic rats by ameliorating mitochondrial dysfunction and reducing fibrosis, oxidative stress, and inflammation. This study, for the first time, indicates that SPR might be a potential treatment for DCM.

Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes.

Aims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms. Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 weeks. Non-diabetic rats were used as controls. PKK administration attenuated the mitochondria swelling, Z line misalignments, myofibrosis and interstitial collagen accumulation in diabetic myocardial tissue. The oxidative stress imbalance including increased nitrotyrosine, decreased anti-oxidative components such as nuclear receptor nuclear factor like 2 (Nrf2), glutathione peroxidase 1(GPx-1), catalase (CAT) and superoxide dismutase (SOD), were recovered in the heart of PKK-treated diabetic rats. In diabetic rats, protein expression of TGF-ß1 and accumulation of collagen I in the heart tissues was decreased after PKK administration. Markers for inflammation were decreased in diabetic rats by PKK treatment. Compared to diabetic rats, PKK reversed the degradation of IκB-α, an inhibitive element of heterotrimer nuclear factor kappa B (NF-κB). The endothelial nitric oxide synthase (eNOS) protein and myocardial nitrate/nitrite were impaired in the heart of diabetic rats, which, however, were restored after PKK treatment. The sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLN) were mishandled in diabetic rats, while were rectified in PKK-treated diabetic rats. The plasma NT-proBNP level was increased in diabetic rats while was reduced with PKK treatment. Conclusion: PKK protects against DCM via reducing fibrosis, inflammation, and oxidative stress, promoting nitric oxide production, as well as restoring the function of the calcium channel.