Protective effect of short-chain fructo-oligosaccharides from chicory on alcohol-induced injury in GES-1 cells via Keap1/Nrf2 and NLRP3 inflammasome signaling pathways.

Numerous studies have demonstrated that polysaccharides derived from chicory possess the ability to regulate host signaling and modify mucosal damage. Yet, the effect and mechanism of short-chain fructo-oligosaccharides (scFOS) on gastric mucosa remain unclear. Hence, the protective effect of three scFOS (1-Kestose, Nystose, and 1F-Fructofuranosylnystose) against ethanol-induced injury in gastric epithelial (GES-1) cells, and the underlying molecular mechanism involved was investigated in this study. Treatment with 7% ethanol decreased the cell viability of GES-1 cells, resulting in oxidative stress and inflammation. However, pretreatment with scFOS exhibited significant improvements in cell viability, and mitigated oxidative stress and inflammation. scFOS markedly elevated the protein expression of Nrf2, HO-1, SOD1 and SOD2, while suppressing the expression of Keap1. scFOS pretreatment could also maintain mitochondrial membrane potential balance and reduce apoptosis. In addition, scFOS was observed to reduce the protein level of NLRP3, Caspase-1 and ASC. In conclusion, scFOS served a preventive function in mitigating oxidative stress and inflammation in ethanol-exposed GES-1 cells through modulation of the Keap1/Nrf2 and NLRP3 inflammasome signaling pathways. Collectively, the results indicated that scFOS could significantly mitigate ethanol-induced gastric cell damage, suggesting its potential for safeguarding gastrointestinal health.

Sotagliflozin versus dapagliflozin to improve outcome of patients with diabetes and worsening heart failure: a cost per outcome analysis.

Background and aim: Dapagliflozin inhibits the sodium-glucose cotransporter protein 2 (SGLT-2), while sotagliflozin, belonging to a new class of dual-acting SGLT-1/SGLT-2 inhibitors, has garnered considerable attention due to its efficacy and safety. Both Dapagliflozin and sotagliflozin play a significant role in treating worsening heart failure in diabetes/nondiabetes patients with heart failure. Therefore, this article was to analyze and compare the cost per outcome of both drugs in preventing one event in patients diagnosed with diabetes-related heart failure. Method: The Cost Needed to Treat (CNT) was employed to calculate the cost of preventing one event, and the Number Needed to Treat (NNT) represents the anticipated number of patients requiring the intervention treatment to prevent a single adverse event, or the anticipated number of patients needing multiple treatments to achieve a beneficial outcome. The efficacy and safety data were obtained from the results of two published clinical trials, DAPA-HF and SOLOIST-WHF. Due to the temporal difference in the drugs' releases, we temporarily analyzed the price of dapagliflozin to calculate the price of sotagliflozin within the same timeframe. The secondary analyses aimed to assess the stability of the CNT study and minimize differences between the results of the RCT control and trial groups, employing one-way sensitivity analyses. Result: The final results revealed an annualized Number Needed to Treat (aNNT) of 4 (95% CI 3-7) for preventing one event with sotagliflozin, as opposed to 23 (95% CI 16-55) for dapagliflozin. We calculated dapagliflozin's cost per prevented event (CNT) to be $109,043 (95% CI $75,856-$260,755). The price of sotagliflozin was set below $27,260, providing a favorable advantage. Sensitivity analysis suggests that sotagliflozin may hold a cost advantage. Conclusion: In this study, sotagliflozin was observed to exhibit a price advantage over dapagliflozin in preventing one events, cardiovascular mortality, or all-cause mortality in patients with diabetes.

3D printed VEGF-CPO biomaterial scaffold to promote subcutaneous vascularization and survival of transplanted islets for the treatment of diabetes.

Diabetes is a complex metabolic disease and islet transplantation is a promising approach for the treatment of diabetes. Unfortunately, the transplanted islets at the subcutaneous site are also affected by various adverse factors such as poor vascularization and hypoxia. In this study, we utilize biocompatible copolymers l-lactide and D,l-lactide to manufacture a biomaterial scaffold with a mesh-like structure via 3D printing technology, providing a material foundation for encapsulating pancreatic islet cells. The scaffold maintains the sustained release of vascular endothelial growth factor (VEGF) and a slow release of oxygen from calcium peroxide (CPO), thereby regulating the microenvironment for islet survival. This helps to improve insufficient subcutaneous vascularization and reduce islet death due to hypoxia post-transplantation. By pre-implanting VEGF-CPO scaffolds subcutaneously into diabetic rats, a sufficiently vascularized site is formed, thereby ensuring early survival of transplanted islets. In a word, the VEGF-CPO scaffold shows good biocompatibility both in vitro and in vivo, avoids the adverse effects on the implanted islets, and displays promising clinical transformation prospects.

Evidence of promoting effects of 6:2 Cl-PFESA on hepatocellular carcinoma proliferation in humans: An ideal alternative for PFOS in terms of environmental health?

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic chemicals, encompassing compounds like perfluorooctane sulfonate (PFOS), which have widespread applications across various industries, including food packaging and firefighting. In recent years, China has increasingly employed 6:2 Cl-PFESA as an alternative to PFOS. Although the association between PFAS exposure and hepatocellular carcinoma (HCC) has been demonstrated, the underlying mechanisms that promote HCC proliferation are uncleared. Therefore, we aimed to investigate the effects and differences of PFOS and 6:2 Cl-PFESA on HCC proliferation through in vivo and in vitro tumor models. Our results reveal that both PFOS and 6:2 Cl-PFESA significantly contribute to HCC proliferation in vitro and in vivo. Exposure led to reduced population doubling times, enlarged cell colony sizes, enhanced DNA synthesis efficiency, and a higher proportion of cells undergoing mitosis. Furthermore, both PFOS and 6:2 Cl-PFES) have been shown to activate the PI3K/AKT/mTOR signaling pathway and inhibit necroptosis. This action consequently enhances the proliferation of HCC cells. Our phenotypic assay findings suggest that the tumorigenic potential of 6:2 Cl-PFESA surpasses that of PFOS; in a subcutaneous tumor model using nude mice, the mean tumor weight for the 6:2 Cl-PFESA-treated cohort was 2.33 times that observed in the PFOS cohort (p < 0.01). Despite 6:2 Cl-PFESA being considered a safer substitute for PFOS, the pronounced effects of this chemical on HCC cell growth warrant a thorough assessment of hepatotoxicity risks linked to its usage.

Deep learning nomogram for preoperative distinction between Xanthogranulomatous cholecystitis and gallbladder carcinoma: A novel approach for surgical decision.

The distinction between Xanthogranulomatous Cholecystitis (XGC) and Gallbladder Carcinoma (GBC) is challenging due to their similar imaging features. This study aimed to differentiate between XGC and GBC using a deep learning nomogram model built from contrast enhanced computed tomography (CT) scans. 297 patients were included with confirmed XGC (94) and GBC (203) as the training and internal validation cohort from 2017 to 2021. The deep learning model Resnet-18 with Fourier transformation named FCovResnet18, shows most impressive potential in distinguishing XGC from GBC using 3-phase merged images. The accuracy, precision and area under the curve (AUC) of the model were then calculated. An additional cohort of 74 patients consisting of 22 XGC and 52 GBC patients was enrolled from two subsidiary hospitals as the external validation cohort. The accuracy, precision and AUC achieve 0.98, 0.99, 1.00 in the internal validation cohort and 0.89, 0.92, 0.92 in external validation cohort. A nomogram model combining clinical characteristics and deep learning prediction score showed improved predicting value. Altogether, FCovResnet18 nomogram has demonstrated its ability to effectively differentiate XGC from GBC preoperatively, which significantly aid surgeons in making informed and accurate surgical decisions for XGC and GBC patients.

High DC-Bias Stability and Reliability in BaTiO3-Based Multilayer Ceramic Capacitors: The Role of the Core-Shell Structure and the Electrode.

With the miniaturization of multilayer ceramic capacitors (MLCCs) and the increase of the electric field on a single dielectric layer, dielectric constant DC-bias stability and reliability have gradually aroused attention in the advanced electronics industry. In this study, MLCCs with outstanding DC-bias stability and reliability were prepared by using dielectric ceramic optimization and electrode optimization strategies. The effect of the Dy-Y doping concentration on the microstructure, dielectric properties, and reliability of BaTiO3-based ceramics was investigated. The shell ratio and effective shell doping concentration of the core-shell structure in ceramic grains play important roles in defects and electrical performances. The ceramic with appropriate doping contents shows a dielectric constant of 1800 and a dielectric constant change rate of -17% under a DC field of 4 kV/mm, which was fabricated into prototype MLCCs with different Ni electrodes. MLCCs exhibit outstanding DC-bias stability with a -28% degradation in the dielectric constant under a DC field of 4 kV/mm while possessing a dielectric constant of 2300 and satisfying the EIA X7S specification. Additionally, it was discovered that MLCCs prepared by using fine-size Ni particle electrodes have low electrode roughness and high interfacial Schottky barriers, resulting in better reliability. This study provides promising candidate materials and theoretical references for high-end and high DC-bias stability MLCCs.

Phosphorus balance calculator: an individualized tool for treatment of hyperphosphatemia in hemodialysis patients.

BACKGROUND AND HYPOTHESIS: Lack of evaluations of the dietary phosphorus and dialysis phosphorus removal in daily clinical practice are the common obstacle to assess phosphorus balance and control phosphorus in hemodialysis patients. We aimed to investigate whether the individualized therapy using phosphorus balance calculator improves phosphorus control. METHODS: A randomized, open-label, multicenter, 4-week clinical trial was conducted. 119 maintenance hemodialysis patients aged 18 to 85 years old and with serum phosphorus level higher than 1.45mmol/l from 3 university teaching hospitals in Shanghai were enrolled. Patients were randomized in a 1:1 ratio to individualized therapy (n=60), or conventional therapy (n=59). The primary outcome was the serum phosphorus concentration after 4-week treatment. Secondary outcomes included the serum calcium and parathyroid hormone (PTH) concentrations, changes in serum phosphorus, calcium and PTH concentrations, and the proportion of patients achieving target ranges of serum phosphorus, calcium and PTH after 4-week treatment. RESULTS: Among 119 randomized participants (mean age, 62 years; 68 male[57%]), 116 completed the trial. By using the phosphorus balance calculator, the individualized group achieved a better phosphorus balance state, significantly reduced the serum phosphorus (1.62±0.45mmol/l versus 1.85±0.45 mmol/l, P=0.006), increased the proportions of patients achieving target serum phosphorus range (41% versus 18%, P=0.006), and had greater adjusted mean difference in change in serum phosphorus over the 4 weeks (-0.47 versus -0.23mmol/l, P=0.010) when compared to conventional therapy. No significant changes were observed in serum calcium and PTH levels, the proportion of patients achieving target serum calcium or PTH levels, and adjusted mean difference of serum calcium and PTH levels over the treatment period. CONCLUSION: Phosphorus balance calculator was proved to improve serum phosphorus control in patients undergoing maintenance hemodialysis, offering a new tool for managing hyperphosphatemia.

The counterbalance of endothelial glycocalyx and high wall shear stress to low-density lipoprotein concentration polarization in mouse ear skin arterioles.

BACKGROUND AND AIMS: Atherosclerosis preferentially occurs at regions in arterial branching, curvature, and stenosis, which may be explained by the geometric predilection of low-density lipoprotein (LDL) concentration polarization that has been investigated in major arteries in previous studies. Whether this also happens in arterioles remains unknown. METHODS: Herein, a radially non-uniform distribution of LDL particles and a heterogeneous endothelial glycocalyx layer in the mouse ear arterioles, as shown by fluorescein isothiocyanate labeled wheat germ agglutinin (WGA-FITC), were successfully observed by a non-invasive two-photon laser-scanning microscopy (TPLSM) technique. The stagnant film theory was applied as the fitting function to evaluate LDL concentration polarization in arterioles. RESULTS: The concentration polarization rate (CPR, the ratio of the number of polarized cases to that of total cases) in the inner walls of curved and branched arterioles was 22% and 31% higher than the outer counterparts, respectively. Results from the binary logistic regression and multiple linear regression analysis showed that endothelial glycocalyx thickness increases CPR and the thickness of the concentration polarization layer (CPL). Flow field computation indicates no obvious disturbances or vortex in modeled arterioles with different geometries and the mean wall shear stress is about 7.7-9.0 Pa. CONCLUSIONS: These findings suggest a geometric predilection of LDL concentration polarization in arterioles for the first time, and the existence of an endothelial glycocalyx, acting together with a relatively high wall shear stress in arterioles, may explain to some extent why atherosclerosis rarely occurs in these regions.

MVI-TR: A Transformer-Based Deep Learning Model with Contrast-Enhanced CT for Preoperative Prediction of Microvascular Invasion in Hepatocellular Carcinoma.

In this study, we considered preoperative prediction of microvascular invasion (MVI) status with deep learning (DL) models for patients with early-stage hepatocellular carcinoma (HCC) (tumor size ≤ 5 cm). Two types of DL models based only on venous phase (VP) of contrast-enhanced computed tomography (CECT) were constructed and validated. From our hospital (First Affiliated Hospital of Zhejiang University, Zhejiang, P.R. China), 559 patients, who had histopathological confirmed MVI status, participated in this study. All preoperative CECT were collected, and the patients were randomly divided into training and validation cohorts at a ratio of 4:1. We proposed a novel transformer-based end-to-end DL model, named MVI-TR, which is a supervised learning method. MVI-TR can capture features automatically from radiomics and perform MVI preoperative assessments. In addition, a popular self-supervised learning method, the contrastive learning model, and the widely used residual networks (ResNets family) were constructed for fair comparisons. With an accuracy of 99.1%, a precision of 99.3%, an area under the curve (AUC) of 0.98, a recalling rate of 98.8%, and an F1-score of 99.1% in the training cohort, MVI-TR achieved superior outcomes. Additionally, the validation cohort's MVI status prediction had the best accuracy (97.2%), precision (97.3%), AUC (0.935), recalling rate (93.1%), and F1-score (95.2%). MVI-TR outperformed other models for predicting MVI status, and showed great preoperative predictive value for early-stage HCC patients.

Risk Factors Affecting Muscle Mass Decline in Maintenance Hemodialysis Patients.

Objective: There is a high prevalence of sarcopenia in maintenance hemodialysis (MHD) patients, which is known to be associated with increased mortality. This study is aimed at analyzing the risk factors affecting muscle mass decline in MHD patients. Methods: This retrospective study included MHD patients who underwent two body composition assessments in October 2013 and November 2017. Depending on whether there was muscle loss or not, the patients were divided into a normal muscle mass (NMM) group and a muscle mass decline (MMD) group. According to the muscle mass decline rate, patients in the MMD group were further classified into a low-rate group and a high-rate group. Biochemical variables, serum vitamin concentrations, anthropometric data, SGA, muscle mass, handgrip, and daily steps were assessed. Risk factors for muscle mass decline were screened by multivariate logistic analysis and linear regression analysis. Results: Of the 72 MHD patients included in this study, 33 were male and 39 were female with a mean age of 56.80 ± 10.86 years and a mean dialysis duration of 7.50 ± 5.20 years. Age (P = .014) and serum 25(OH)D (P = .040) were found to be associated with a higher risk of muscle mass decline after adjusting for gender, dialysis vintage, albumin, and hs-CRP (P = .040). Further analysis found that dialysis vintage (ß = 0.285, P = .030), 25(OH)D (ß = -0.351, P = .007), and log NT-proBNP (ß = 0.312, P = .020) were risk factors associated with the muscle mass decline rate in MHD patients. Conclusion: Age and serum 25(OH)D were associated with a higher risk of muscle mass decline, while 25(OH)D, dialysis vintage, and NT-proBNP were associated with the muscle mass decline rate in MHD patients.

Study on Subjective Evaluation of Acoustic Environment in Urban Open Space Based on "Effective Characteristics".

With the continuous expansion of urban scale with dense population and traffic and the gradual improvement of residents' requirements for environmental quality, the traditional evaluation method relying on acoustic energy is not enough to reflect the feelings of urban crowds about acoustic environment quality. The acoustic environment quality evaluation method based on human subjective perception has gradually become one of the research focuses in the field of environmental noise control. In recent years, various subjective and objective acoustic characteristic parameters have been introduced into the study of acoustic environment assessment in the global literature. However, the extraction of "effective characteristics" from a large number of physical and psychoacoustic characteristics contained in acoustic signals and the creation of a scientific and efficient subjective evaluation model have always been key technical problems in the field of acoustic environment evaluation. Based on subjective human perceptions, the overall acoustic environment quality evaluation of urban open spaces is studied in this paper. Based on the "effective characteristic" parameters and the subjective characteristic proposed in the previous research, including equivalent continuous A-weighted sound pressure level (LA), the difference between median noise and ambient background noise (L50 - L90), Sharpness (Sh), as well as satisfaction (Sat), the multivariable linear regression algorithm is used to further study the intrinsic correlation between the proposed "effective characteristics" and subjective perception. Then, a satisfaction evaluation model of the acoustic environment based on "effective characteristics" is built in this paper. Furthermore, the soundwalk evaluation experiment and the MATLAB numerical simulation experiment are carried out, which verify that the prediction accuracy of the proposed model is more than 92%, the consistency of satisfaction level is more than 88%, as well as the changes in the values of Sh and L50 - L90 have a significant impact on the satisfaction prediction of the proposed model. It shows that the proposed "effective characteristics" more comprehensively describe the quality level of the regional acoustic environment in urban open space compared with a single LA index, and the proposed acoustic environment satisfaction evaluation model based on "effective characteristics" has significant accuracy superiority and regional applicability.

Impaired endothelial cell proliferative, migratory, and adhesive abilities are associated with the slow endothelialization of polycaprolactone vascular grafts implanted into a hypercholesterolemia rat model.

Most small diameter vascular grafts (inner diameter<6 mm) evaluation studies are performed in healthy animals that cannot represent the clinical situation. Herein, an hypercholesterolemia (HC) rat model with thickened intima and elevated expression of pro-inflammatory intercellular adhesion molecular-1 (ICAM-1) in the carotid branch is established. Electrospun polycaprolactone (PCL) vascular grafts (length: 1 cm; inner diameter: 2 mm) are implanted into the HC rat abdominal aortas in an end to end fashion and followed up to 43 days, showing a relative lower patency accompanied by significant neointima hyperplasia, abundant collagen deposition, and slower endothelialization than those implanted into healthy ones. Moreover, the proliferation, migration, and adhesion behavior of endothelial cells (ECs) isolated from the HC aortas are impaired as evaluated under both static and pulsatile flow conditions. DNA microarray studies of the HC aortic endothelium suggest genes involved in EC proliferation (Egr2), apoptosis (Zbtb16 and Mt1), and metabolism (Slc7a11 and Hamp) are down regulated. These results suggest the impaired proliferative, migratory, and adhesive abilities of ECs are associated with the bad performances of grafts in HC rat. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications. STATEMENT OF SIGNIFICANCE: During the development of small diameter vascular grafts (D<6 mm), young and healthy animal models from pigs, sheep, dogs, to rabbits and rats are preferred. However, it cannot represent the clinic situation, where most cardiovascular grafting procedures are performed in the elderly and age is the primary risk factor for disease development or death. Herein, the performance of electrospun polycaprolactone (PCL) vascular grafts implanted into hypercholesterolemia (HC) or healthy rats were evaluated. Results suggest the proliferative, migratory, and adhesive abilities of endothelial cells (ECs) are already impaired in HC rats, which contributes to the observed slower endothelialization of implanted PCL grafts. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications.

Northward migration of the East Asian summer monsoon northern boundary during the twenty-first century.

The northern fringe area of the East Asian summer monsoon (EASM) between arid and semiarid regions is a fragile eco-environment zone and ecological transition zone, and it is highly sensitive to climate change. Predicting the future migration of the northern boundary of the EASM is important for understanding future East Asian climate change and formulating of decisions on ecological protection and economic development in arid and semiarid regions. The reanalysis dataset and simulations of 23 models from the Coupled Models Intercomparison Project Phase 6 (CMIP6) were used to investigate the response of the boundary of the ESAM to the global warming. The multi-model ensemble showed a northwestward migration of the EASM northern boundary during the near-term (2020-2060) and late-term (2061-2099) of the twenty-first century under various Shared Socioeconomic Pathways (SSPs). The northern boundary migrated northwestward by 23-28 and 74-76 km in the near-term and late-term respectively, under SSP1-2.6, 2-4.5 and 3-7.0 and by ~ 44 km and ~ 107 km respectively during the near-term and late-term under SSP5-8.5. During the twenty-first century, under various SSPs, the surface of the East Asian subcontinent warmed more than the ocean, thereby increasing the contrast of near-surface temperature and sea level pressure in summer between the East Asian subcontinent and the surrounding oceans. In turn, the intensified land-sea thermal contrast reinforced the EASM meridional circulation and thus transported more moisture from the Indian Ocean into northern China. Additionally, a poleward migration and weakening of the East Asian subtropical westerly jet would also favor an increase in precipitation, eventually caused a northwestward migration of the EASM northern boundary. The results suggest that the arid and semiarid ecotone will become wetter, which could dramatically improve the eco-environment in the future.

Early Renal-Replacement Therapy May Reduce the All-Cause Mortality of Severe COVID-19: An Observational Cohort Study.

INTRODUCTION: The efficacy of renal-replacement treatment (RRT) remains to be validated in COVID-19. In this retrospective cohort study, we aimed to assess the efficacy of early initiation of RRT in intensive care unit (ICU) adults with severe COVID-19. METHODS: Fifty-eight adult patients in ICU with critically ill or severe COVID-19 with a tendency of critical illness were recruited from February 9, 2020, to March 30, 2020. Early RRT were determined by the ICU medical team based on boom in cytokines levels, increased organs injury/failure, and rapid aggravation of condition. All participants were followed up from the first day of ICU admission to March 30, 2020. The primary outcome was all-cause mortality in ICU. RESULTS: The mean age of the cohort was 68.4 ± 14.6 years, with 81.0% having at least one comorbidity before hospitalization. Twenty patients (34.5%) initiated early RRT after 24.1 ± 10.4 days from the onset and 6.4 ± 3.6 days from ICU admission. Thirty-four of 58 participants (58.6%) died during ICU follow-up. Univariate and multivariate Cox proportional-hazards model showed that early RRT was associated with a lower risk of all-cause mortality in ICU with an adjusted HR of 0.280 (95% CI: 0.106-0.738, p = 0.010). Sudden unexpected death (SUD) was remarkably reduced in the early RRT group, compared with the control group (0.2 vs. 2.9 per 100 person-day, p = 0.02). CONCLUSION: Early RRT can reduce the all-cause in-hospital mortality, especially SUD in patients with severe COVID-19, but not improve multi-organ impairment or increase the risk of AKI. Early initiation of RRT merits an optional strategy in critically ill patients with COVID-19 (ChiCTR2000030773).

The interaction analysis between advanced age and longer dialysis vintage on the survival of patients receiving maintenance hemodialysis.

OBJECTIVE: To compare the all-cause mortality of aged and younger patients undergoing maintenance hemodialysis (MHD) over the long or short term, and to identify independent risk factors. METHODS: We performed a retrospective cohort study using the medical records of 181 patients undergoing MHD. We compared the clinical characteristics and laboratory data of survivors and participants who died, according to their age and the duration of MHD. Binary stepwise logistic regression was used to identify independent risk factors for all-cause mortality. RESULTS: Cardiovascular and cerebrovascular diseases were the principal causes of mortality. The number of aged participants with hypertensive nephropathy as their primary kidney disease was significantly higher than the number of younger participants. The proportion with chronic glomerulonephritis was significantly higher for participants undergoing long-term MHD. Logistic regression analysis revealed that low body mass index, single-pool Kt/V, serum albumin, platelet count, and total iron-binding capacity; and high intact parathyroid hormone and N terminal pro B type natriuretic peptide were independent risk factors for all-cause mortality. CONCLUSIONS: Aged patients are more susceptible to hypertensive nephropathy than younger patients. In addition, the survival of patients with chronic glomerulonephritis undergoing MHD is superior to that of those with hypertensive or diabetic nephropathy.

Effects of Cinacalcet and Parathyroidectomy on Blood Pressure in Maintenance Hemodialysis Patients with Secondary Hyperparathyroidism.

INTRODUCTION: Secondary hyperparathyroidism may cause an increase in blood pressure among maintenance hemodialysis (MHD) patients. The objective of this study were to observe the effects of different treatment modalities of hyperparathyroidism on blood pressure among MHD patients with secondary hyperparathyroidism. METHODS: This retrospective cohort study was conducted on 69 patients divided into three groups, based on the therapeutic strategies (parathyroidectomy, n = 22; cinacalcet, n = 14; calcitriol, n = 33). Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from pre- to post-treatment visits at 1st, 3rd, 6th, and 12th month were analyzed by mixed-effects repeated-measures model. Serum levels of the renin-angiotensin system (RAS) mediators (renin and aldosterone), endothelin, and echocardiography were compared before and after one year of treatment within the three groups. RESULTS: Changes in blood pressure were significantly different among the three groups (SBP: P for group < 0.05; DBP: P for group < .05; both P for group × time interaction < .05). SBP and DBP showed a significant downward trend in the surgery group (P for change in SBP < .05, P for change in DBP < .001, adjusted mean change of SBP = -12.16 (-19.70 to -4.62) mmHg and of DBP = -6.82 (-10.58 to -3.06) mmHg in the surgery group on the 12th month). Diastolic BP showed a significant upward trend in the cinacalcet group (P for change in DBP < .05, adjusted mean change of DBP = 6.03 (2.08 to 9.98) mmHg in cinacalcet group in the 12th month). No significant change in BP was observed in the calcitriol group. The levels of serum RAS mediators, endothelin, or cardiac ultrasonography didn't change and almost remained consistent during the treatment course. CONCLUSION: Blood pressure decreased significantly over a year in patients with parathyroidectomy, while DBP increased significantly over time by cinacalcet treatment.  DOI: 10.52547/ijkd.6686.

Calpain Inhibitor Calpeptin Alleviates Ischemia/Reperfusion-Induced Acute Kidney Injury via Suppressing AIM2 Inflammasome and Upregulating Klotho Protein.

Renal ischemia/reperfusion injury is a major contributor of acute kidney injury (AKI), leading to renal cell necrosis, apoptosis, and inflammation. Calpains, a family of Ca2+-dependent cysteine proteases, play a pivotal role in the pathogenesis of renal diseases. Several studies have reported calpain inhibitors showing remarkable reno-protective effects against proteinuria and α-klotho deficiency-induced renal aging symptoms, particularly against glomerulus injury. However, little is known about the role of the calpain inhibitor calpeptin in acute kidney injury. The present study aims to investigate the potential mechanism of downregulation of Calpain 1 and 2 activity by calpeptin in the ischemia/reperfusion (IR)-induced AKI model. Firstly, we observed that the contents of Calpain 1 and 2 were significantly increased in the renal biopsy of clinical AKI patients, especially in the diseased tubules space. To investigate the impacts of calpain activity inhibition, we further pretreated with calpeptin in both the IR mouse model and in the HK-2 cells hypoxia model. We found that the calpain inhibitor calpeptin improved renal functional deterioration, attenuated pathological structure damage, and decreased tubular cell apoptosis in the IR injury-induced AKI mice model. Mechanistically, calpeptin significantly suppressed the AIM2 (absent in melanoma 2) and NLRP3 (NOD-like receptor protein 3) inflammasome signaling pathways and increased Klotho protein levels. Furthermore, immunofluorescence assays demonstrated that the application of calpeptin effectively inhibited Calpain 1 activation and gasdermin D (GSDMD) cleavage in the renal tubules of IR mice. Taken together, our both in vivo and in vitro experiments suggest that calpeptin conveyed reno-protection in AKI might be mediated by the inhibition of AIM2 inflammasome activation and upregulation of Klotho protein. As such, we provide new evidence that Calpain 1 and 2 activation may be closely associated with the pathogenesis of clinical AKI. The calpain-mediated AIM2 inflammasome signaling pathway and distinct interaction between calpain and Klotho may provide a potential novel preventative and therapeutic target for acute kidney injury.

Morphological Lesion Types Are Associated with Primary and Secondary Patency Rates after High-Pressure Balloon Angioplasty for Dysfunctional Arteriovenous Fistulas.

BACKGROUND: Neointimal hyperplasia (NIH) is believed to be the main reason for arteriovenous fistula (AVF) dysfunction, but other mechanisms are also recognized to be involved in the pathophysiological process. This study investigated whether different morphological types of AVF lesions are associated with the patency rate after percutaneous transluminal angioplasty (PTA). METHODS: This retrospective study included 120 patients who underwent PTA for autogenous AVF dysfunction. All the cases were evaluated under Doppler ultrasound (DU) before intervention and divided into 3 types: Type I (NIH type), Type II (non-NIH type), and Type III (mixed type). Prognostic and clinical data were analyzed by Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: There was no statistical difference in baseline variables among groups, except for lumen diameter. The primary patency rates in Type I, Type II, and Type III groups were 78.4, 93.2, and 83.2% at 6 months and 59.5, 84.7, and 75.5% at 1 year, respectively. The secondary patency rates in Type I, Type II, and Type III groups were 94.4, 97.1, and 100% at 6 months and 90.5, 97.1, and 94.7% at 1 year, respectively. The Kaplan-Meier curve showed that the primary and secondary patency rates of Type I group were lower than those of Type II group. Multivariable Cox regression analysis demonstrated that postoperative primary patency was correlated with end-to-end anastomosis (hazard ratio [HR] = 2.997, p = 0.008, 95% confidence interval [CI]: 1.328-6.764) and Type I lesion (HR = 5.395, p = 0.004, 95% CI: 1.730-16.824). CONCLUSIONS: NIH-dominant lesions of AVF evaluated by DU preoperatively were a risk factor for poor primary and secondary patency rate after PTA in hemodialysis patients.

A Nomogram Estimation for the Risk of Microvascular Invasion in Hepatocellular Carcinoma Patients Meeting the Milan Criteria.

OBJECTIVE: We aimed to develop and validate a nomogram for preoperatively estimating the risk of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) within the Milan criteria. METHODS: The clinical data of 312 HCC patients who underwent liver surgery at the xxx from Jan 2017 to Dec 2019 were retrospectively collected. Then, the study population was categorized into the training and validation group based on the date of surgery. To identify risk factors related to MVI, we conducted a series of logistic regression analyses. By combining these risk factors, a nomogram was then established. We further clarified the usability of our model through the area under the ROC curve (AUC), decision curve analysis (DCA), and calibration curve. RESULTS: Pathological examination revealed MVI in 108 patients with HCC (34.6%). Three independent predictors were identified: level of alpha-fetoprotein (AFP) exceeds 194 ng/mL (OR = 2.20, 95% CI: 1.13-4.31, p = 0.021), size of tumor (OR = 1.59; 95% CI: 1.18-2.12; P < 0.001) and number of tumors (OR = 3.37, 95% CI: 1.64-7.28, p < 0.001). A nomogram was subsequently built with an AUC of 0.73 and 0.74 respectively in the training cohort and validation cohort. The calibration curve showed a relatively high consistency between predicted probability and observed outcomes. Besides, the DCA revealed that the model was clinically beneficial for preoperatively predicting MVI in HCC. CONCLUSIONS: A model for evaluating the risk of MVI HCC patients was developed and validated. The model could provide clinicians with a relatively reliable basis for optimizing treatment decisions.