Neutrophil-Mediated Nanozyme Delivery System for Acute Kidney Injury Therapy.

Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil-mediated delivery system able to hijack neutrophil to transport nanozyme-loaded cRGD-liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvß1 is reported. The neutrophil-mediated nanozyme delivery system demonstrated great antioxidant and anti-apoptosis ability in HK-2 and NRK-52E cell lines. Moreover, in ischemia-reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD-LPs 12 h post-ischemia significantly reduces renal function indicators, alleviates renal pathological changes, and inhibits apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD-LPs markedly inhibits the process of Nrf2 to the nucleus and reduces the expression of the downstream HO-1, achieves a 99.51% increase in renal tissue Nrf2 levels, and an 86.31% decrease in HO-1 levels after LM@cRGD-LPs treatment. In short, the strategy of neutrophil-mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases.

A PSMA PET/CT-based risk model for prediction of concordance between targeted biopsy and combined biopsy in detecting prostate cancer.

PURPOSE: This study is to investigate the diagnostic value of 68Ga-PSMA-11 in improving the concordance between mpMRI-TB and combined biopsy (CB) in detecting PCa. METHODS: 115 consecutive men with 68Ga-PSMA-11 PET/CT prior to prostate biopsy were included for analysis. PSMA intensity, quantified as maximum standard uptake value (SUVmax), minimum apparent diffusion coefficient (ADCmin) and other clinical characteristics were evaluated relative to biopsy concordance using univariate and multivariate logistic regression analyses. A prediction model was developed based on the identified parameters, and a dynamic online diagnostic nomogram was constructed, with its discrimination evaluated through the area under the ROC curve (AUC) and consistency assessed using calibration plots. To assess its clinical applicability, a decision curve analysis (DCA) was performed, while internal validation was conducted using bootstrapping methods. RESULTS: Concordance between mpMRI-TB and CB occurred in 76.5% (88/115) of the patients. Multivariate logistic regression analyses performed that SUVmax (OR= 0.952; 95% CI 0.917-0.988; P= 0.010) and ADCmin (OR= 1.006; 95% CI 1.003-1.010; P= 0.001) were independent risk factors for biopsy concordance. The developed model showed a sensitivity, specificity, accuracy and AUC of 0.67, 0.78, 0.81 and 0.78 in the full sample. The calibration curve demonstrated that the nomogram's predicted outcomes closely resembled the ideal curve, indicating consistency between predicted and actual outcomes. Furthermore, the decision curve analysis (DCA) highlighted the clinical net benefit achievable across various risk thresholds. These findings were reinforced by internal validation. CONCLUSIONS: The developed prediction model based on SUVmax and ADCmin showed practical value in guiding the optimization of prostate biopsy pattern. Lower SUVmax and Higher ADCmin values are associated with greater confidence in implementing mono-TB and safely avoiding SB, effectively balancing benefits and risks.

Total weight loss rather than preoperative body mass index correlates with remission of irregular menstruation after sleeve gastrectomy in patients with polycystic ovary syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. Some retrospective studies with small sample sizes have reported that bariatric metabolic surgery is effective in remission of irregular menstruation in patients with PCOS and obesity. However, the correlation between preoperative body mass index (BMI), postoperative weight loss, and remission of irregular menstruation in patients with obesity and PCOS after sleeve gastrectomy (SG) is lack of consensus. Methods: We enrolled 229 participants with obesity and PCOS who underwent SG. All patients were followed up for one year after surgery. Remission of irregular menstruation was defined as a spontaneous consecutive six-month menstrual cycle in one year. Subgroup analysis was conducted using tertiles of preoperative BMI and postoperative total weight loss (TWL)% to determine their correlation with the remission of irregular menstruation after SG. Results: 79.03% (181/229) patients achieved remission of irregular menstruation one year after SG with a TWL% of 33.25 ± 0.46%. No significant difference was detected in the remission rate among the subgroups with different BMI (P=0.908). TWL% was correlated with the remission of irregular menstruation (OR 1.78, 95% CI 1.18-2.69, P<0.05). Conclusions: SG had a significant effect on the remission of irregular menstruation in patients with obesity and PCOS. Preoperative BMI did not emerge as a decisive factor correlated with remission; instead, TWL% showed potential as a key factor.

ß-Cell Function and Insulin Dynamics in Obese Patients With and Without Diabetes After Sleeve Gastrectomy.

Improved ß-cell function seems to be essential for better glucose homeostasis after Roux-en-Y gastric bypass but is less studied after sleeve gastrectomy (SG). We evaluated the effects of SG on ß-cell function in obese patients with diabetes (DM group) and without (control group) in response to both oral and intravenous glucose stimulation. The DM group demonstrated impaired insulin sensitivity and insulin response to glucose before surgery. The insulin sensitivity index of both groups significantly improved after SG. In addition, the insulin response to glucose (early insulinogenic index in oral glucose tolerance test and acute insulin response to glucose in an intravenous glucose tolerance test) increased in the DM group but decreased in the control group. As a result, ß-cell function improved significantly in both groups after SG since the disposition index (DI) increased in both. However, the DI of the DM group was not restored to the level of control group up to 1 year after SG. Our results support that obese patients, with and without diabetes, could benefit from SG in ß-cell function. For obese patients at risk for or who have been diagnosed with diabetes, interventions should be recommended early to preserve or restore ß-cell function, and SG could be an effective choice. Further studies are needed for long-term effects.

MIOX inhibits autophagy to regulate the ROS -driven inhibition of STAT3/c-Myc-mediated epithelial-mesenchymal transition in clear cell renal cell carcinoma.

The specific mechanism of clear cell renal cell carcinoma (ccRCC) progression, a pathological type that accounts for the highest proportion of RCC, remains unclear. In this study, bioinformatics analysis of scRNA-seq dataset in ccRCC revealed that MIOX was a gene specifically down-regulated in tumor epithelial cells of ccRCC. Analysis of the TCGA database further validated the association between decreased MIOX mRNA levels and ccRCC malignant phenotype and poor prognosis. Immunohistochemistry indicated the down-regulation of MIOX in ccRCC tissues compared to paired adjacent renal tissues, with further down-regulation of MIOX in the primary tumors of patients with primary metastasis compared to those without metastasis. Also, patients with low expression of MIOX showed shorter metastasis-free survival (MFS) compared to those with high MIOX expression. In vitro results showed that overexpression of MIOX in ccRCC cells inhibited the proliferation, migration and invasion and promoted apoptosis. Mechanistically, up-regulation of MIOX inhibited autophagy to elevate the levels of ROS, and thus suppressed STAT3/c-Myc-mediated epithelial-mesenchymal transition in ccRCC cells. In vivo data further confirmed that increased MIOX expression suppressed the growth and proliferation of RCC cells and reduced the ability of RCC cells to form metastases in the lung. This study demonstrates that MIOX is an important regulatory molecule of ccRCC, which is conducive to understanding the potential molecular mechanism of ccRCC progression.

Sex dimorphism in the effect and predictors of weight loss after sleeve gastrectomy.

Background: No sex-specific guidelines for surgical anti-obesity strategies have been proposed, partially due to the controversy regarding sex-related differences in weight loss after bariatric metabolic surgery. Objectives: To explore sex dimorphism in the effect and predictors of weight loss after sleeve gastrectomy (SG), thereby providing clinical evidence for the sex-specific surgical treatment strategy. Methods: In a prospective cohort design, participants scheduled for SG at an affiliated hospital between November 2020 and January 2022 were assessed for eligibility and allocated to the Male or Female group with a 1-year follow-up after surgery. The primary outcome was the sex difference in the weight-loss effect after SG indicated by both percentage of total weight loss (TWL%) and excess weight loss (EWL%). The secondary outcome was the analysis of sex-specific preoperative predictors of weight loss after SG based on univariate and multivariate analyses. Independent predictors were obtained to construct a nomogram model. The discrimination, calibration, and clinical utility of the nomogram were based on receiver operating characteristic curve, concordance index, calibration curve, and decision curve analysis, respectively. Results: Ninety-five male and 226 female patients were initially included. After propensity score matching by baseline body mass index (BMI), 85 male and 143 female patients achieved comparable TWL% and EWL% for 1 year after SG. For male patients, baseline BMI, area under the curve for insulin during oral glucose tolerance test, and progesterone were independent predictors of weight loss after SG. Baseline BMI, age, thyroid stimulating hormone, and Self-Rating Anxiety Scale score were independent predictors for female patients. Conclusion: No obvious sex difference is detected in the weight-loss effect after SG. Sex dimorphism exists in the predictors of weight loss after SG. Further research with long-term and a multicenter design is needed to confirm the predictive model.

Metabolic Surgery on Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease that is closely related to obesity. Metabolic surgery ameliorates a series of clinical manifestations and related comorbidities of PCOS. However, the overall efficacy of metabolic surgery on PCOS remains uncertain. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of metabolic surgery on obese patients with PCOS. A systematic literature search for relevant studies was conducted on PubMed, Embase, Web of Science, and the Cochrane Library from inception to June 2021. Data extraction and quality evaluation were performed by three researchers, and RevMan 5.4 software was used to conduct the meta-analysis. A total of 14 studies involving 501 obese patients with PCOS were included. Incidence of PCOS in obese women ranged from 5.5% to 63.5% among the included studies. The results showed the incidence of abnormal menstruation decreased from 81% to 15% (OR=0.03, 95% confidence interval (CI): 0.01-0.08), while the incidence of hirsutism dropped from 71% to 38% (OR=0.21, 95% CI: 0.06-0.74). Serum total testosterone and free testosterone levels decreased by 25.92 ng/dL (MD = -25.92, 95% CI: -28.90- -22.93) and 2.28 ng/dL (SMD = -2.28, 95% CI: -3.67- -0.89), respectively. Sex hormone-binding globulin (SHBG) levels increased by 26.46 nmol/L (MD = 26.46, 95% CI: 12.97-39.95). Serum anti-Mullerian hormone (AMH) levels decreased by 1.29 ng/mL (MD = -1.29, 95% CI: -1.92- -0.66). Small sample size studies revealed that pregnancy rates ranged from 95.2% to 100% postoperatively. Metabolic surgery contributed to marked improvement of abnormal menstruation, hirsutism, and levels of free testosterone, total testosterone, SHBG, and AMH in patients with PCOS. Our findings indicate that patients with PCOS are expected to benefit from metabolic surgery, and could help potentially improve their reproductive outcomes. Metabolic surgery could thus be a new viable option for the clinical treatment of PCOS. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021251524.