The impact of type 2 diabetes on polycystic ovary syndrome in patients undergoing sleeve gastrectomy.

STUDY QUESTION: Does the concurrent type 2 diabetes mellitus (T2DM) aggravate the features and prognosis of PCOS in patients undergoing sleeve gastrectomy (SG)? SUMMARY ANSWER: For patients undergoing SG with obesity, concurrent T2DM is associated with aggravated metabolic but milder reproductive features of PCOS and did not attenuate the resumption of regular menstruation for up to 1 year after surgery. WHAT IS KNOWN ALREADY: Women with T2DM have an increased risk of PCOS. However, whether concurrent T2DM further increases the disease burden and treatment difficulty of PCOS in patients with obesity requires further investigation. STUDY DESIGN, SIZE, DURATION: This was a single-center, two-arm, prospective, cohort study enrolling a total of 329 women with PCOS and scheduled for SG because of obesity at an university-affiliated hospital between January 2020 and August 2023, with a 1-year follow-up after surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Comparisons were made between patients with T2DM (PCOS+T2DM) and without (PCOS) to examine the impact of T2DM on the metabolic, reproductive, and psychological features of PCOS. The follow-up data of weight loss and menstruation were analyzed to determine the impact of T2DM on PCOS prognosis for up to 1 year after SG. MAIN RESULTS AND THE ROLE OF CHANCE: After controlling for confounders, patients in the PCOS+T2DM group (n = 98) showed more severe insulin resistance, glucose intolerance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD) (NAFLD activity score 4.31 ± 1.15 versus 3.52 ± 1.42, P < 0.001) than those in the PCOS group (n = 149). In addition, the PCOS+T2DM group had a lower level of total testosterone (1.63 ± 0.69 versus 1.82 ± 0.76, P = 0.045), a lower ratio between luteinizing hormone and follicle-stimulating hormone (median 1.48 versus 1.68, P = 0.030), and a lower proportion of patients with polycystic ovarian morphology (88% versus 96%, P = 0.022) than the PCOS group. As a result, the two groups differed significantly in terms of the Rotterdam classification of PCOS (P = 0.009). No significant difference was detected by group in the psychological features of PCOS except a lower degree of emotional eating in the PCOS+T2DM group (P = 0.001). Although the PCOS+T2DM group took longer to resume regular menstruation after SG (P = 0.037), the two groups had similar proportions of patients with regular menstruation (85% versus 87%, P = 0.758) 1 year after SG, which was further confirmed by subgroup analyses by body mass index. LIMITATIONS, REASONS FOR CAUTION: The prognosis of PCOS after SG mainly focused on the results of menstruation rather than a complete evaluation of the remission of the disease. WIDER IMPLICATIONS OF THE FINDINGS: Our study showed that, for patients with obesity, concurrent T2DM is associated with aggravated metabolic but milder reproductive features of PCOS and did not attenuate the resumption of regular menstruation for up to 1 year after surgery. Our study also highlights the need for high-quality studies with a more comprehensive evaluation of the impact of T2DM on the prognosis of patients with PCOS after SG. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Natural Science Foundation of China Grants (82100853), the Natural Science Foundation of Shandong Province of China (ZR2021QH028), and the Clinical Research Project of Shandong University (2020SDUCRCC024). The authors have no conflicts of interest. TRIAL REGISTRATION: Chinese Clinical Trial Registry with No. ChiCTR1900026845.

SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice.

BACKGROUND: Depression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS). METHODS: Depression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood-brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice. RESULTS: Intracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1ß, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1ß, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein. CONCLUSIONS: Our study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.

Sparstolonin B exerts beneficial effects on prostate cancer by acting on the reactive oxygen species-mediated PI3K/AKT pathway.

Prostate cancer is a major health concern in males worldwide, owing to its high incidence. Sparstolonin B (SsnB), a component of the Chinese herbal medicine Sparganium stoloniferum, is used to treat many diseases. However, the effects and mechanisms of action of SsnB in prostate cancer have not yet been reported. In this study, we evaluated the effects of SsnB on cellular processes and tumour growth. In particular, we verified that SsnB could inhibit the proliferation, migration and invasion of prostate cancer cells and induce apoptosis by activating G2/M phase arrest in vitro based on a series of cytological experiments. In vivo, we found that SsnB could inhibit tumour growth in nude mouse xenograft models. We further confirmed that SsnB could repress the PI3K/AKT pathway by increasing reactive oxygen species (ROS) accumulation and oxidative stress. Collectively, SsnB inhibits tumour growth and induces apoptosis in prostate cancer via the suppression of the ROS-mediated PI3K/AKT pathway and may be a new alternative to adjuvant therapy for prostate cancer.

Central GLP-1 contributes to improved cognitive function and brain glucose uptake after duodenum-jejunum bypass on obese and diabetic rats.

The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB), and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including glucose transporter 1 (GLUT-1), GLUT-4, phospho-Akt substrate of 160kDa (pAS160), AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups whereas the Exe-9 and Glp-1r KD were opposite. Known to activate insulin-signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB.NEW & NOTEWORTHY The improvement of cognitive function following bariatric surgery has been highlighted while its mechanisms remain elusive. The brain glucose uptake of patients was improved after RYGB, and the DJB and sham surgery performed on obese and diabetic Wistar rats revealed that the elevated central GLP-1 contributes to the dramatic improvement of cognitive function, brain glucose uptake, transport, glucose sensing, and neuronal activation.

Overexpression of Karyopherin Subunit alpha 2 (KPNA2) Predicts Unfavorable Prognosis and Promotes Bladder Cancer Tumorigenicity via the P53 Pathway.

BACKGROUND We sought to investigate the expression of KPNA2 in bladder cancer (BC) and its relationship with prognosis, and to analyze the potential mechanism of KPNA2 in promoting BC progression. MATERIAL AND METHODS The RNA-seq data on BC from The Cancer Genome Atlas (TCGA) database were imported into R statistical software for differential analysis. The clinical data for patients with BC were screened and analyzed with R software. The survival curve was drawn with the Kaplan-Meier Plotter. The expression of KPNA2 in 4 human BC cell lines and a human bladder epithelial cell line was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The proliferation of BC cells was detected with Cell Counting Kit-8 (CCK8), detection of apoptosis, and flow cytometry, and the migration and invasion of BC cells were detected through Transwell assays. WB was used to detect proteins involved in the P53 pathway. RESULTS The expression of KPNA2 was higher in BC. The difference in KPNA2 expression was associated with many clinicopathological factors, and high expression of KPNA2 was associated with shorter survival time. After KPNA2 knockout, the proliferation, migration, and invasion ability decreased significantly, the cell cycle was clearly arrested in the G0/G1 phase, and the number of apoptotic cells increased. Moreover, CyclinD1, BCL2, and pro-caspase3 decreased significantly, whereas P53, P21, BAX, and cleaved-caspase3 increased significantly. The results in the overexpression group were the opposite of results in the knockdown group. CONCLUSIONS KPNA2 is an oncogenic factor that facilitates BC tumorigenicity through the P53 pathway.

Comparative study of laparoscopic radical gastrectomy and open radical gastrectomy.

INTRODUCTION: At present, the main treatment of gastric cancer is surgical resection combined with radiotherapy and chemotherapy, the most important part of which is radical gastrectomy. Laparoscopic radical gastrectomy for advanced gastric cancer is difficult to operate, and whether it can achieve the same curative effect with the laparotomy is still controversial. MATERIALS AND METHODS: This study retrospectively analysed the clinical data of 269 gastric cancer patients surgically treated by our medical team from May 2011 to December 2015 for comparative analysis of the clinical efficacy of laparoscopic-assisted radical gastrectomy and traditional open radical gastrectomy. RESULTS: The laparoscopic surgery group had longer duration of surgery, less intra-operative blood loss, shorter post-operative exhaust time, shorter post-operative hospital stay and shorter timing of drain removal. The average number of harvested lymph nodes in the laparoscopic surgery group was 22.9 ± 9.5 per case. And in the laparotomy group the average number was 23.3 ± 9.9 per case. The difference had no statistical significance. With the increase of the number of laparoscopic surgical procedures, the amount of intra-operative blood loss gradually decreases, and the duration of surgery is gradually reduced. CONCLUSION: Laparoscopic radical gastrectomy is superior to open surgery in the aspects of intra-operative blood loss, post-operative exhaust time, post-operative hospital stay and timing of drain removal. With the number of laparoscopic radical gastrectomy cases increased, the duration of surgery is shortened and the amount of intra-operative blood loss will decrease.

Laparoscopic gastrectomy for early gastric cancer and the risk factors of lymph node metastasis.

Objective: Lymph node metastasis (LNM) is one of the important prognostic factors of early gastric cancer (EGC). Moreover, LNM is also important when choosing therapeutic intervention for EGC patients. The purpose of this study is to explore the risk factors of LNM in EGC and to discuss the corresponding treatment. Design: We retrospectively reviewed the medical records of 253 patients with EGC who underwent surgical therapy in our department between 2012 and 2015. Univariate analysis and Multivariate Cox regression were used to evaluate the independent risk factors of LNM. Results: LNM was present in 38 cases among 253 patients (15%). Univariate analysis showed an obvious correlation between LNM and tumour location, tumour size, depth of invasion, morphological classification, gross type of the lesion and venous invasion. Multivariate analysis indicated that poorly differentiated carcinoma, submucosal cancer, tumour size ≥2 cm and venous invasion were the independent risk factors for LNM. Conclusion: Tumour size, depth of invasion, morphological classification and blood vessel invasion were predictive risk factors for LNM in EGC. We propose that EGC patients with those risk factors should be accepted gastrectomy with LN dissection.

Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries.

Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.

Facilitated Ca2+ homeostasis and attenuated myocardial autophagy contribute to alleviation of diabetic cardiomyopathy after bariatric surgery.

Bariatric surgery has been reported to relieve diabetic cardiomyopathy (DCM) effectively. However, the mechanisms remain largely unknown. To determine the effects of bariatric surgery on DCM via modulation of myocardial Ca2+ homeostasis and autophagy, sleeve gastrectomy (SG), duodenal-jejunal bypass (DJB), and sham surgeries were performed in diabetic rats induced by high-fat diet and a low dose of streptozotocin. Cardiac remodeling was assessed by a series of morphometric and histological analyses. Transthoracic echocardiography and hemodynamic measurements were performed to determine cardiac function. Ca2+ homeostasis was evaluated by measuring Ca2+ transients with fura-2 AM in isolated ventricular myocytes along with detection of the abundance of Ca2+ regulatory proteins in the myocardium. Myocardial autophagic flux was determined by expression of autophagy-related proteins in the absence and presence of chloroquine. Both SG and DJB surgery alleviated DCM morphologically and functionally. Ca2+ transients exhibited a significantly higher amplitude and faster decay after SG and DJB, which could be partially explained by increased expression of ryanodine receptor 2, sarco(endo)plasmic reticulum Ca2+-2ATPase, 12.6-kDa FK506-binding protein, and hyperphosphorylation of phospholamban. In addition, a lower level of light chain 3B and higher level of p62 were detected after both SG and DJB, which was not reversed by chloroquine treatment and associated with activated mammalian target of rapamycin and attenuated AMP-activated protein kinase signaling pathway. Collectively, these results provided evidence that bariatric surgery could alleviate DCM effectively, which may result, at least in part, from facilitated Ca2+ homeostasis and attenuated autophagy, suggesting a potential choice for treatment of DCM when properly implemented. NEW & NOTEWORTHY The present study is the first to investigate the modulation of myocardial Ca2+ homeostasis and autophagy after bariatric surgery and to examine its effects on diabetic cardiomyopathy. Bariatric surgery could facilitate myocardial Ca2+ homeostasis and attenuate myocardial autophagy, contributing to the alleviation of cardiomyopathy morphologically and functionally in a diabetic rat model.

Sub-sleeve gastrectomy achieves good diabetes control without weight loss in a non-obese diabetic rat model.

BACKGROUND: Although weight loss has been implicated in anti-diabetic effects, sleeve gastrectomy (SG)-mediated anti-diabetic effects are induced through mechanisms beyond weight loss. Our aim was to investigate whether anti-diabetic effects can be achieved by surgically removing a smaller portion of the stomach instead of SG. METHODS: Male 11-week-old Goto-Kakizaki rats (N = 50) were randomized into five groups: sub-sleeve gastrectomy (SSG, only the gastric fundus is removed), SG, sham-operated SSG, sham-operated SG, and control. Body weight, food intake, hormone secretion, and glucose metabolism were measured up to 24 weeks after surgery. RESULTS: The data showed that (i) both SSG and SG surgeries significantly improved glucose homeostasis, with lower ghrelin levels and higher post-prandial glucagon-like peptide 1, peptide YY, and insulin levels; (ii) SG, but not SSG, produced sustained weight loss and significant reduction of food intake; and (iii) SG induced better long-term diabetic improvement than SSG. CONCLUSIONS: The SSG that only removed the gastric fundus exhibited significant diabetic improvement without weight loss, but did not induce long-term diabetic improvement comparable to that of SG. Our study helps to understand the role of hormones and weight loss in maintaining long-term diabetes improvement after SG.

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.

The current status and challenges of perioperative management of patients with a BMI of greater than or equal to 50 kg/m 2 undergoing bariatric surgery in China: a multicenter cross-sectional study.

BACKGROUND: Performing bariatric surgery on patients with a BMI of over 50 kg/m 2 is challenging. This study aimed to explore the status and challenges related to the perioperative management of such patients in China. MATERIALS AND METHODS: A prospective survey was designed to investigate the perioperative management of patients with a BMI of greater than or equal to 50 kg/m 2 undergoing bariatric surgery in China. The questionnaire of our survey included general information, preoperative management measures, surgical procedures performed, technical details regarding anaesthesia, and postoperative management measures. A response from only one attending physician per bariatric centre was accepted. RESULTS: Physicians from a total of 101 hospitals responded to the questionnaire, and the questionnaire data from 98 hospitals were complete. These centres had completed a total of 44 702 bariatric surgeries since the launch of such surgery to December 2021. A total of 3280 patients had a BMI exceeding 50 kg/m 2 . The preferred surgical procedures for patients with super obesity were sleeve gastrectomy by 62 centres, Roux-en-Y gastric bypass by 11 centres, sleeve gastrectomy plus jejunojejunal bypass by 19 centres, one anastomosis gastric bypass by 1 centre, and duodenal switch by 1 centre. The most worrying issues were cardiopulmonary failure and difficulty in extubation. 91 centres believed that preoperative weight loss was beneficial. A low-calorie diet was the specific measure mainly implemented, only three centres considered using intragastric balloon placement. Postoperative management measures varied greatly. CONCLUSION: Bariatric surgery has seen rapid development. Chinese physicians show significant differences regarding the perioperative management for patients with a BMI of over 50 kg/m 2 . The perioperative risks of these patients remain relatively high, making further development of clinical pathways is necessary.

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.

Impact of sleeve gastrectomy on the periodontal status of patients with and without type 2 diabetes: a 1-year prospective real-world study.

Background: Periodontitis is a chronic inflammatory disease potentially associated with obesity and type 2 diabetes (T2D). Sleeve gastrectomy (SG) has shown substantial effect on weight loss and treatment of T2D. However, there is no direct evidence comparing the impact of SG on the periodontal status of patients with and without T2D. Objectives: To determine the impact of SG on the periodontal status of patients with and without T2D in a real-world setting. Methods: In a prospective and two-armed cohort design, participants who were scheduled for SG at an affiliated hospital between April 2022 and December 2022 were approached for eligibility. After a clinical evaluation and oral examination, those with periodontitis were included and further divided into the DM group (diabetic) and the Control group (non-diabetic) with a 1-year follow-up after surgery. The primary outcome was the periodontal status of patients at 12 months after SG. The secondary outcomes included weight loss, diabetes remission, and alterations in inflammatory markers for up to 1 year after SG. Results: Fifty-seven and 49 patients were included in the DM and the Control group, respectively. Before surgery, patients in the DM group had further worsened periodontal condition compared with those in the Control group. Accompanied by weight loss and glucose reduction, patients in both groups demonstrated significant decreases in plaque index (PLI) and bleeding index (BI) with no alterations in probing depth or clinical attachment loss for up to 1 year after SG. Even patients in the DM group achieved less TWL% (32.79 ± 6.20% vs. 37.95 ± 8.34, P<0.01), their periodontal condition had more substantial improvement with no significant difference in PLI and BI between groups at 1 year after SG. We also observed a significant reduction in the levels of high sensitive C-reactive protein and interleukin-6 in both groups at 1 year after SG. Conclusion: Both patients with and without T2D demonstrated improved periodontal status for up to 1 year after SG. Patients with T2D achieved less weight loss but a more substantial improvement in periodontal condition. The significant reduction in inflammatory biomarkers contributed to the improvement of periodontal status after SG.

Association between the systemic immune-inflammation index and kidney stone: A cross-sectional study of NHANES 2007-2018.

Background: The incidence rate of kidney stones increased over the past decades globally, which brought medical expenditure and social burden. The systemic immune-inflammatory index (SII) was initially identified as a prognosis of multiple diseases. We performed an updated analysis on the impact of SII on kidney stones. Methods: This compensatory cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey 2007-2018. Univariate and multivariate logistic regression analyses were performed to investigate the association between SII and kidney stones. Results: Of the 22220 participants, the mean (SD) age was 49.45 ± 17.36 years old, with a 9.87% incidence rate of kidney stones. A fully adjusted model showed that SII higher than 330 x 109/L was parallel associated with kidney stones (Odds ratio [OR] = 1.282, 95% Confidence interval [CI] = 1.023 to 1.608, P = 0.034) in adults aged 20-50. However, no difference was found in the elderly subgroup. Multiple imputation analyses confirmed the robustness of our results. Conclusions: Our findings suggested SII was positively associated with a high risk of kidney stones in US adults aged less than 50. The outcome compensated for previous studies that still needed more large-scale prospective cohorts for validation.

Pulmonary Function Test and Obstructive Sleep Apnea Hypopnea Syndrome in Obese Adults: A Retrospective Study.

Objective: We explore risk factors related to severe obstructive sleep apnea (OSA) in obese patients, including pulmonary ventilation function, diffusion function, and impulse oscillometry (IOS) data. Methods: The medical records of 207 obese patients who were prepared to undergo bariatric surgery in a hospital from May 2020 to September 2021 were retrospectively reviewed. Polysomnography (PSG), pulmonary ventilation function, diffusion function, and IOS parameters were collected according to the ethical standards of the institutional research committee (registration number: KYLL-202008-144). Logistic regression analysis was used to analyze the related independent risk factors. Results: There were significantly statistical difference in a number of pulmonary ventilation and diffusion function parameters among the non-OSAHS group, the mild-to-moderate OSA group, and the severe OSA group. However, only airway resistance parameters R5%, R10%, R15%, R20%, R25%, and R35% increased with increasing OSA severity and were positively correlated with apnea hypopnea index (AHI). Age (P = 0.012, 1.104 (1.022, 1.192)), body mass index (P< 0.0001, 1.12 (1.057, 1.187)), gender (P = 0.003, 4.129 (1.625, 10.49)), and R25% (P = 0.007, 1.018 (1.005, 1.031)) were independent risk factors for severe OSA. In patients aged 35 to 60, RV/TLC (P = 0.029, 1.272 (1.025, 1.577)) is an independent risk factor for severe OSA. Conclusion: R25% was an independent risk factor for severe OSA in obese individuals, while RV/TLC was also an independent risk factor in those aged 35 to 60. Pulmonary function tests (PFTs), particularly IOS levels, are recommended to assess severe OSA in obese patients.

Hypermethylation of RNF125 promotes autophagy-induced oxidative stress in asthma by increasing HMGB1 stability.

Asthma is a global chronic airway disease. The expression and role of RNF125, an E3 ubiquitin ligase, in asthma remain uncertain. In this study, we revealed that RNF125 was downregulated in the bronchial epithelium of mice and patients with asthma. Rnf125 hypermethylation was responsible for the low expression of RNF125 in primary airway epithelial cells of mice treated with OVA. Moreover, we demonstrated that RNF125 could attenuate autophagy, oxidative stress, and protect epithelial barrier in vivo and in vitro. Additionally, we identified HMGB1 as a substrate of RNF125, which interacted with the HMG B-box domain of HMGB1 and induced degradation via the ubiquitin proteasome system, reducing autophagy and oxidative stress. Overall, our findings elucidated that hypermethylation of Rnf125 reduced its expression, which promoted autophagy-induced oxidative stress in asthma by increasing HMGB1 stability. These findings offer a theoretical and experimental basis for the pathogenesis of asthma.

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.

Endothelial Sp1/Sp3 are essential to the effect of captopril on blood pressure in male mice.

Endothelial dysfunction represents a major cardiovascular risk factor for hypertension. Sp1 and Sp3 belong to the specificity protein and Krüppel-like transcription factor families. They are ubiquitously expressed and closely associated with cardiovascular development. We investigate the role of Sp1 and Sp3 in endothelial cells in vivo and evaluate whether captopril, an angiotensin-converting enzyme inhibitor (ACEI), targets Sp1/Sp3 to exert its effects. Inducible endothelial-specific Sp1/Sp3 knockout mice are generated to elucidate their role in endothelial cells. Tamoxifen-induced deletion of endothelial Sp1 and Sp3 in male mice decreases the serum nitrite/nitrate level, impairs endothelium-dependent vasodilation, and causes hypertension and cardiac remodeling. The beneficial actions of captopril are abolished by endothelial-specific deletion of Sp1/Sp3, indicating that they may be targets for ACEIs. Captopril increases Sp1/Sp3 protein levels by recruiting histone deacetylase 1, which elevates deacetylation and suppressed degradation of Sp1/Sp3. Sp1/Sp3 represents innovative therapeutic target for captopril to prevent cardiovascular diseases.

Angiotensin-converting enzyme inhibitor promotes angiogenesis through Sp1/Sp3-mediated inhibition of notch signaling in male mice.

Angiogenesis is a critical pathophysiological process involved in organ growth and various diseases. Transcription factors Sp1/Sp3 are necessary for fetal development and tumor growth. Sp1/Sp3 proteins were downregulated in the capillaries of the gastrocnemius in patients with critical limb ischemia samples. Endothelial-specific Sp1/Sp3 knockout reduces angiogenesis in retinal, pathological, and tumor models and induced activation of the Notch1 pathway. Further, the inactivation of VEGFR2 signaling by Notch1 contributes to the delayed angiogenesis phenotype. Mechanistically, endothelial Sp1 binds to the promoter of Notch1 and inhibits its transcription, which is enhanced by Sp3. The proangiogenic effect of ACEI is abolished in Sp1/Sp3-deletion male mice. We identify USP7 as an ACEI-activated deubiquitinating enzyme that translocated into the nucleus binding to Sp1/Sp3, which are deacetylated by HDAC1. Our findings demonstrate a central role for endothelial USP7-Sp1/Sp3-Notch1 signaling in pathophysiological angiogenesis in response to ACEI treatment.