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Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats

Purpose To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism. Methods Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats. Results A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation. Conclusion Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.

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Risk of adverse pregnancy outcomes in pregnant women with gestational diabetes mellitus by age: a multicentric cohort study in Hebei, China

Gestational diabetes mellitus (GDM) is an unique metabolic disorder that occurs during pregnancy. Both GDM and advanced age increase the risk of adverse pregnancy outcomes. This study used a GDM cohort study to investigate the role of age in the adverse pregnancy outcomes for pregnant women with GDM. From 2015 to 2021, 308,175 pregnant women were selected, and the data received from 22 hospitals by the Hebei Province Maternal Near Miss Surveillance System. There were 24,551 pregnant women with GDM that were divided into five groups by age (20–24, 25–29, 30–34, 35–39, 40–44 years old). Because the prevalence of adverse pregnancy outcomes was lower in pregnant women with GDM aged 25–29, they were used as a reference group (P < 0.05). Compared with GDM women aged 25–29 years, GDM women aged 35–44 years had a significant higher risk of cesarean delivery (aOR: 2.86, 95% CI 2.52–3.25) (P < 0.001), abnormal fetal position (aOR: 1.78, 95% CI 1.31–2.37) (P < 0.001), pre-eclampsia (aOR: 1.28, 95% CI 1.01–1.61) (P < 0.05), macrosomia (aOR: 1.25, 95% CI 1.08–1.45) (P < 0.05), and large for gestational age (LGA) (aOR: 1.16, 95% CI 1.02–1.31) (P < 0.05), GDM women aged 40–44 years had a higher risk of placenta previa (aOR: 2.53, 95% CI 1.01–6.35) (P < 0.05), anemia (aOR: 3.45, 95% CI 1.23–9.68) (P < 0.05) and small for gestational age (aOR: 1.32, 95% CI 1.01–1.60) (P < 0.05). Advanced maternal age was an independent risk factor for abnormal fetal position, pre-eclampsia, anemia, macrosomia, and LGA in pregnant women with GDM.

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Effects of Acupuncture-Point Stimulation on Perioperative Sleep Disorders: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

Perioperative sleep disorders exert a severe adverse impact on postoperative recovery. Recently, some observational studies reported that acupuncture-point stimulation (APS) provided benefits for promoting perioperative sleep quality. However, the effects of APS on perioperative sleep disorders following general anesthesia have not been thoroughly assessed by any systematic study and meta-analysis. Therefore, we conducted this systematic review and meta-analysis to reveal the effects of APS on perioperative sleep disorders. Eight databases (Chinese: CNKI, VIP, CBM, and Wanfang; English: PubMed, Embase, Web of Science, and Cochrane Library) were thoroughly searched to find randomized controlled trials (RCTs) that indicated a link between APS and the occurrence of perioperative sleep disorders. We applied RevMan 5.4 (Cochrane Collaboration) and Stata 16.0 (Stata Corp) to conduct our meta-analysis. In addition, the trial sequential analysis (TSA) tool was utilized to estimate the validity and reliability of the data. In this study, nine RCTs with 719 patients were conducted. Compared to the control group, APS significantly improved perioperative subjective sleep quality (SMD: -1.36; 95% CI: -1.71 to -1.01; P < 0.00001). Besides, it increased perioperative TST (preoperative period MD = 24.29, 95% CI: 6.4 to 42.18, P = 0.0008; postoperative period MD = 45.86, 95% CI: 30.00 to 61.71, P < 0.00001) and SE (preoperative MD = 3.62, 95% CI: 2.84 to 4.39, P < 0.00001; postoperative MD = 6.43, 95% CI: 0.95 to 11.73, P < 0.00001). The consequence of trial sequential analysis further confirmed the reliability of our meta-analysis results. According to the currently available evidence, APS could effectively improve perioperative sleep quality and play an essential role in decreasing the incidence of perioperative sleep disorders.

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Subtotal hysterectomy causes fewer long-term detrimental effects on ovary tissues than total hysterectomy.

Hysterectomy is the basic surgical procedure of gynecological surgery. Traditionally, it is divided into total hysterectomy (TH) and subtotal hysterectomy (STH) according to the scope of surgery. The ovary is a dynamic organ appended with the uterus, and the uterus provides vascular supply to the developing ovary. However, the long-term impacts of TH and STH on ovary tissues need to be evaluated. In this study, rabbit models of different ranges of hysterectomy were successfully created. The estrous cycle of animals was determined by vaginal exfoliated cell smear 4 months after the operation. The apoptosis rate of ovarian cells in each group was determined by flow cytometry, and the morphology of ovarian tissue and granulosa cells in the control group, triangular hysterectomy group and total hysterectomy group were observed under microscope and electron microscope, respectively. After total hysterectomy, the apoptotic events in ovarian tissues were significantly increased when compared to the sham and triangle hysterectomy group. Increased apoptosis was accompanied with the morphological changes and disrupted organelle structures in ovarian granulosa cells. The follicles in the ovarian tissue were dysfunctional and immature, with more atretic follicles being observed. In contrast, ovary tissues in triangular hysterectomy groups showed no obvious defects on the morphology of ovarian tissue and granulosa cells. Our data suggest that subtotal hysterectomy may serve as an alternative to total hysterectomy, with fewer long-term detrimental effects on ovary tissues.

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Atorvastatin Calcium Ameliorates Cognitive Deficits Through the AMPK/Mtor Pathway in Rats with Vascular Dementia.

In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular dementia (VD) rat models. VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear. The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD. The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Student's t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05. AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway. This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.

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Thrombolysis Versus Nonthrombolyzed in Patients With Mild Strokes and Large Vessel Occlusions: Results of a Multicenter Stroke Registration.

The safety and efficacy of intravenous thrombolysis (IVT) in acute ischemic stroke patients with large vessel occlusions and mild neurological deficits are controversial. Data of stroke patients presenting with mild initial stroke, which was defined as the National Institutes of Health Stroke Scale score (NIHSS) ≤5 and large vessel occlusion, were extracted from a large provincewide stroke registry. A total of 619 IVT and 2170 non-IVT patients were identified in this study. IVT patients had higher rates of favorable functional outcome Modified Rankin Scale(mRS) ≤1 (74.6% vs. 70.6%; P =0.047), lower mRS scores (1 vs. 1, P =0.001), and higher NIHSS score decreased (1 vs. 0, P <0.001) at discharge compared with the non-IVT patients. The rates were similar in symptomatic intracranial hemorrhage (2.1% vs. 2.0%, P =0.853), severe systemic bleeding (0.8% vs. 0.6%, P =0.474), and mortality at discharge (0.2% vs. 0.2%, P =0.906) between the 2 groups. A multiple Logistic regression model found that age above 80 years [adjusted OR (aOR) 2.056 (95% CI, 1.125 to 3.756)], history of stroke [aOR 1.577 (95% CI, 1.303 to 1.910)], hyperlipidemia [aOR 2.156 (95% CI, 1.059 to 4.388)], high admission NIHSS score [aOR 1.564 (95% CI, 1.473 to 1.611)], and non-IVT [aOR 1.667 (95% CI, 1.337 to 2.077)] were independent risk factors for mRS >1. IVT administration is safe and effective in eligible acute ischemic stroke patients. Age above 80 years, with a history of stroke and hyperlipidemia, high admission NIHSS score, and non-IVT were independent risk factors for mRS >1 at discharge in these patients.

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Thoracic delirium index for predicting postoperative delirium in elderly patients following thoracic surgery: A retrospective case-control study.

Postoperative delirium (POD) is an acute neurological complication in the elderly undergoing thoracic surgery and can result in serious adverse consequences. This study aimed to identify the related risk factors for POD following thoracic surgery, primarily focusing on preoperative serum biomarkers, and further to establish a novel delirium index to better predict POD. A total of 279 patients aged ≥60 years who underwent elective thoracic surgery from August 2021 to August 2022 were enrolled in this observational study. The platelet-to-white blood cell ratio (PWR) was calculated as number the of platelets divided by the number of white blood cells. POD was defined by the confusion assessment method twice daily during the postoperative first 3 days. Multivariate regression analysis was performed to identify all potential variables for POD. Moreover, a novel thoracic delirium index (TDI) was developed based on the related risk factors. The accuracy of TDI and its component factors in predicting POD was determined by the curve of receiver operating characteristic (ROC). In total, 25 of 279 patients developed POD (8.96%). Age, PWR, and average pain scores within the first 3 days after surgery were regarded as the independent risk factors for POD. Moreover, the ROC analysis showed the TDI, including age, PWR, and average pain scores within the first 3 days after surgery, can more accurately predict POD with the largest area under the curve of 0.790 and the optimal cutoff value of 9.072, respectively. The TDI can scientifically and effectively predict POD to provide optimal clinical guidance for older patients after thoracic surgery.

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Evaluating the impact of ultrasound-guided subsheath versus extrasheath sciatic nerve block on postoperative wound pain in tibial and foot surgeries: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluate the impact of ultrasound-guided subsheath versus extrasheath sciatic nerve blocks on postoperative wound pain in tibial and foot surgeries, crucial for effective pain management and patient recovery. Adhering to PRISMA guidelines, this study used a PICO framework, focusing on patients undergoing tibial and foot surgeries and comparing the efficacy and safety of subsheath and extrasheath sciatic nerve blocks. The literature search spanned four databases without time restrictions, assessing various outcomes like success rate, onset time, duration of analgesia and complication rates. Quality assessment employed the Cochrane Collaboration's risk of bias tool, and statistical analyses included heterogeneity assessment, fixed-effect and random-effects models, sensitivity analysis and publication bias evaluation using funnel plots and Egger's linear regression test. From an initial pool of 1213 articles, six met the inclusion criteria. The subsheath group showed a significantly higher success rate of complete sensory blockade within 30 min compared with the extrasheath group (OR = 5.39; 95% CI: 2.82-10.28; p < 0.01). No significant differences were found in procedure duration or incidence of nerve-related complications between the two techniques. The subsheath approach also demonstrated a quicker onset time of sensory blockade (MD = -8.57; 95% CI: -11.27 to -5.88; p < 0.01). Sensitivity analysis confirmed the stability of the results, and no significant publication bias was detected. Ultrasound-guided subsheath sciatic nerve blocks are more effective than extrasheath blocks in achieving rapid and complete sensory blockade for tibial and foot surgeries, with a quicker onset time and comparable safety profile. Subsheath injections are thus recommended as a preferred method for anaesthesia and postoperative pain management in these surgical procedures, enhancing overall patient outcomes.

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