Association between serum uric acid levels and clinical outcomes in patients with acute kidney injury.

BACKGROUND: The effects of serum uric acid (SUA) on clinical outcomes in patients with acute kidney injury (AKI) are unclear. The aim of this study was to investigate the association of SUA levels with clinical outcomes of AKI patients. METHODS: The data of AKI patients hospitalized in the Affiliated Hospital of Qingdao University were retrospectively reviewed. Multivariable logistic regression was utilized to assess the association between SUA levels and the clinical outcomes of AKI patients. Receiver operating characteristic (ROC) analysis was applied to assess the predictive ability of SUA levels for in-hospital mortality in patients with AKI. RESULTS: A total of 4,646 AKI patients were eligible for study inclusion. In multivariable analysis, after adjustment for various confounding factors in the fully adjusted model, a higher SUA level was found to be associated with increased in-hospital mortality of AKI patients with an odds ratio (OR) of 1.72 (95% CI, 1.21-2.33, p = 0.005) for the SUA level >5.1-6.9 mg/dl group and 2.75 (95% CI, 1.78-4.26, p < 0.001) for the SUA level >6.9 mg/dl group compared with the reference group (SUA ≤3.6 mg/dl). In the ROC analysis, the area under the curve (AUC) of SUA was 0.65 with a sensitivity of 51% and a specificity of 73%. CONCLUSIONS: An elevated SUA level is associated with an increased risk of in-hospital mortality in patients with AKI, and it appears to be an independent prognostic marker for these patients.

Mesenchymal stem cells protect against sepsis-associated acute kidney injury by inducing Gal-9/Tim-3 to remodel immune homeostasis.

OBJECTIVE: The present study investigated the specific mechanism by which mesenchymal stem cells (MSCs) protect against sepsis-associated acute kidney injury (SA-AKI). METHODS: Male C57BL/6 mice underwent cecal ligation and puncture surgery to induce sepsis and then received either normal IgG or MSCs (1 × 106 cells, intravenously) plus Gal-9 or soluble Tim-3 3 h after surgery. RESULTS: After cecal ligation and puncture surgery, the mice injected with Gal-9 or MSCs plus Gal-9 had a higher survival rate than the mice in the IgG treatment group. Treatment with MSCs plus Gal-9 decreased serum creatinine and blood urea nitrogen levels, improved tubular function recovery, reduced IL-17 and RORγt levels and induced IL-10 and FOXP3 expression. Additionally, the Th17/Treg cell balance was altered. However, when soluble Tim-3 was used to block the Gal-9/Tim-3 pathway, the septic mice developed kidney injury and exhibited increased mortality. Treatment with MSCs plus soluble Tim-3 blunted the therapeutic effect of MSCs, inhibited the induction of Tregs, and suppressed the inhibition of differentiation into Th17 cells. CONCLUSION: Treatment with MSCs significantly reversed the Th1/Th2 balance. Thus, the Gal-9/Tim-3 pathway may be an important mechanism of MSC-mediated protection against SA-AKI.

Associations between early thiamine administration and clinical outcomes in critically ill patients with acute kidney injury.

The effects of early thiamine use on clinical outcomes in critically ill patients with acute kidney injury (AKI) are unclear. The purpose of this study was to investigate the associations between early thiamine administration and clinical outcomes in critically ill patients with AKI. The data of critically ill patients with AKI within 48 h after ICU admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. PSM was used to match patients early receiving thiamine treatment to those not early receiving thiamine treatment. The association between early thiamine use and in-hospital mortality due to AKI was determined using a logistic regression model. A total of 15 066 AKI patients were eligible for study inclusion. After propensity score matching (PSM), 734 pairs of patients who did and did not receive thiamine treatment in the early stage were established. Early thiamine use was associated with lower in-hospital mortality (OR 0·65; 95 % CI 0·49, 0·87; P < 0·001) and 90-d mortality (OR 0·58; 95 % CI 0·45, 0·74; P < 0·001), and it was also associated with the recovery of renal function (OR 1·26; 95 % CI 1·17, 1·36; P < 0·001). In the subgroup analysis, early thiamine administration was associated with lower in-hospital mortality in patients with stages 1 to 2 AKI. Early thiamine use was associated with improved short-term survival in critically ill patients with AKI. It was possible beneficial role in patients with stages 1 to 2 AKI according to the Kidney Disease: Improving Global Outcomes criteria.

Acute exposure to air pollutants increase the risk of acute glaucoma.

BACKGROUND: Ambient air pollution is related to the onset and progression of ocular disease. However, the effect of air pollutants on the acute glaucoma remains unclear. OBJECTIVE: To investigate the effect of air pollutants on the incidence of acute glaucoma (acute angle closure glaucoma and glaucomatocyclitic crisis) among adults. METHODS: We conducted a time-stratified case-crossover study based on the data of glaucoma outpatients from January, 2015 to Dec, 2021 in Shanghai, China. A conditional logistic regression model combined with a polynomial distributed lag model was applied for the statistical analysis. Each case serves as its own referent by comparing exposures on the day of the outpatient visit to the exposures on the other 3-4 control days on the same week, month and year. To fully capture the delayed effect of air pollution, we used a maximum lag of 7 days in main model. RESULTS: A total of 14,385 acute glaucoma outpatients were included in this study. We found exposure to PM2.5, PM10, nitrogen dioxide (NO2) and carbon monoxide (CO) significantly increased the odds of outpatient visit for acute glaucoma. Wherein the odds of acute glaucoma related to PM2.5 and NO2 were higher and more sustained, with OR of 1.07 (95%CI: 1.03-1.11) and 1.12 (95% CI: 1.08-1.17) for an IQR increase over lag 0-3 days, than PM10 and CO over lag 0-1 days (OR:1.03; 95% CI: 1.01-1.05; OR: 1.04; 95% CI: 1.01-1.07). CONCLUSIONS: This case-crossover study provided first-hand evidence that air pollutants, especially PM2.5 and NO2, significantly increased risk of acute glaucoma.

Red Phosphorus Decorated TiO2 Nanorod Mediated Photodynamic and Photothermal Therapy for Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a serious and tenacious disease. Photodynamic therapy (PDT) and photothermal therapy (PTT) are effective means of cancer treatment. However, PDT combined with PTT has been rarely reported in ccRCC treatment. In the present study, by developing the core-shell structured TiO2 @red phosphorus nanorods (TiO2 @RP NRs) as a photosensitizer, the feasibility and effectiveness of synchronous PDT and PTT treatments for ccRCC are demonstrated. The core-shell structured TiO2 @RP NRs are synthesized to drive the PDT and PTT for ccRCC, in which the RP shell is the sensitizer even in the near-infrared (NIR) region. The optimized TiO2 @RP NRs can respond to NIR and produce local heat under irradiation. The NRs are estimated in ccRCC treatments via cell counting kit-8 assay, propidium iodide staining, qRT-PCR, and reactive oxygen species (ROS) probes in vitro, while terminal deoxynucleotidyl transferase dUTP nick-end labeling is conducted in vivo. After NIR irradiation, TiO2 @RP NRs can efficiently kill ccRCC cells by producing local heat and ROS and cause low injury to normal kidney cells. Furthermore, treatment with TiO2 @RP NRs and NIR can kill significant numbers of deep-tissue ccRCC cells in vivo. This work highlights a promising photo-driven therapy for kidney cancer.

Insulin receptor substrate-1 inhibits high-fat diet-induced obesity by browning of white adipose tissue through miR-503.

Genetic variation of insulin receptor substrate 1 (IRS-1) was found to modulate the insulin resistance of adipose tissues, but the underlying mechanism was not clear. To investigate how the IRS-1 was involved in the browning of white adipose tissue through miRNA, we identified a mutated Irs-1 (Irs-1-/- ) mice model and found that this mice had a reduced subcutaneous WAT (sWAT) and increased brown adipose tissue (BAT) in the interscapular region. So we isolated the bone marrow stromal cells and analyzed differentially expressed miRNAs and adipogenesis-related genes with miRNA arrays and PCR arrays. Irs-1-/- mice showed decreased miR-503 expression, but increased expression of its target, bone morphogenetic protein receptor type 1a (BMPR1a). Overexpression of miR-503 in preadipocytes downregulated BMPR1a and impaired adipogenic activity through the phosphotidylinositol 3-kinase (PI3K/Akt) pathway, while the inhibitor had the opposite effect. In both Irs-1-/- and cold-induced models, sWAT exhibited BAT features, and showed tissue-specific increased BMPR1a expression, PI3K expression, and Akt phosphorylation. Thus, our results showed that IRS-1 regulated brown preadipocyte differentiation and induced browning in sWAT through the miR-503-BMPR1a pathway, which played important roles in high-fat diet-induced obesity.

Nicotiflorin attenuates cell apoptosis in renal ischemia-reperfusion injury through activating transcription factor 3.

INTRODUCTION: Nicotiflorin is the main characteristic component of Nymphaea candida, which is a natural product that reportedly ameliorates acute injury of the liver and cerebral cortex, but the effect of nicotiflorin on acute kidney injury (AKI) remains unknown. This study aimed to investigate the effects of nicotiflorin on ischaemia/reperfusion (I/R) AKI and the associated mechanisms. METHODS: We performed both (a) in vivo experiments with C57BL/6 mice with bilateral renal pedicles clamped for 45 minutes and (b) in vitro experiments with human kidney epithelial cells (HK-2) exposed to hypoxia/reoxygenation to mimic I/R injury to study the role of nicotiflorin in AKI. RESULTS: In vivo, nicotiflorin administration exerted protective effects on renal injury, as demonstrated by reductions in the levels of caspase3 and Bad (P < .05), the upregulation of Bcl-2 expression (P < .05) and improved renal histologic changes, which suggested that nicotiflorin can alleviate I/R injury and cell apoptosis. In vitro, nicotiflorin at a concentration of 75 µg/mL protected cells from hypoxia, which further confirmed that nicotiflorin exerts beneficial effects on hypoxia/reoxygenation. Through computational molecular docking, we found that activating transcription factor 3 (ATF3) exhibits a robust interaction with nicotiflorin with a simulated binding energy of -9.2°. We verified the interaction of nicotiflorin with ATF3 in HK-2 cells, and found that nicotiflorin reduced the apoptosis of HK-2 through ATF3. CONCLUSION: Based on the above-described results, nicotiflorin appears to have a beneficial impact on deteriorated renal function, as demonstrated using an experimental I/R model. The underlying mechanisms of nicotiflorin might inhibit HK-2 cell apoptosis through ATF3.

Curcumin modulates gut microbiota and improves renal function in rats with uric acid nephropathy.

It is well known that the progression of hyperuricemia disease often contributes to renal dysfunction. However, there have been few studies on uric acid nephropathy (UAN), especially its relationship with gut microbiota. UAN is usually accompanied by disordered intestinal flora, and damaged gut barrier, which are closely related to tubulointerstitial fibrosis, and systemic inflammation. In previous studies, it has been confirmed that curcumin could alleviate tubulointerstitial fibrosis, and improve renal function through its antioxidant, anti-apoptotic, and anti-inflammatory efficacies. However, the effects curcumin exerts on intestinal flora in uric acid nephropathy are still unknown. Therefore, we used next-generation sequencing technology to investigate the effects of curcumin on gut microbiota in a rat model of UAN induced by adenine and potassium oxonate, and rats were randomly divided into control, model or curcumin treatment groups. The results demonstrated that, compared to the model group, the treatment group showed decreased serum uric acid (156.80 ± 11.90 µmol/L vs. 325.60 ± 18.65 µmol/L, p < 0.001), serum creatinine (66.20 ± 11.88 µmol/L vs. 182.20 ± 8.87 µmol/L, p < 0.001) and BUN level (13.33 ± 3.16 mmol/L vs. 36.04 ± 6.60 mmol/L, p < 0.001). The treatment group also displayed attenuated renal pathological lesions and metabolic endotoxemia (25.60 ± 5.90 ng/mL vs. 38.40 ± 4.98 ng/mL, p < 0.01), and improved tightly linked proteins expression. Besides, curcumin altered the gut microbiota structure in UAN rats. More specifically, curcumin treatment protected against the overgrowth of opportunistic pathogens in UAN, including Escherichia-Shigella and Bacteroides, and increased the relative abundance of bacteria producing short-chain fatty acids (SCFAs), such as Lactobacillus and Ruminococcaceae. These results suggest that curcumin could modulate gut microbiota, fortify the intestinal barrier, attenuate metabolic endotoxemia, and consequently protect the renal function in UAN rats.

Malnutrition screening and acute kidney injury in hospitalised patients: a retrospective study over a 5-year period from China.

Malnutrition and acute kidney injury (AKI) are common complications in hospitalised patients, and both increase mortality; however, the relationship between them is unknown. This is a retrospective propensity score matching study enrolling 46 549 inpatients, aimed to investigate the association between Nutritional Risk Screening 2002 (NRS-2002) and AKI and to assess the ability of NRS-2002 and AKI in predicting prognosis. In total, 37 190 (80 %) and 9359 (20 %) patients had NRS-2002 scores <3 and ≥3, respectively. Patients with NRS-2002 scores ≥3 had longer lengths of stay (12·6 (sd 7·8) v. 10·4 (sd 6·2) d, P < 0·05), higher mortality rates (9·6 v. 2·5 %, P < 0·05) and higher incidence of AKI (28 v. 16 %, P < 0·05) than patients with normal nutritional status. The NRS-2002 showed a strong association with AKI, that is, the risk of AKI changed in parallel with the score of the NRS-2002. In short- and long-term survival, patients with a lower NRS-2002 score or who did not have AKI achieved a significantly lower risk of mortality than those with a high NRS-2002 score or AKI. Univariate Cox regression analyses indicated that both the NRS-2002 and AKI were strongly related to long-term survival (AUC 0·79 and 0·71) and that the combination of the two showed better accuracy (AUC 0·80) than the individual variables. In conclusion, malnutrition can increase the risk of AKI and both AKI and malnutrition can worsen the prognosis that the undernourished patients who develop AKI yield far worse prognosis than patients with normal nutritional status.

Acute kidney injury after nephrectomy: a new nomogram to predict postoperative renal function.

BACKGROUND: We aimed to develop a nomogram based on preprocedural features for early prediction of acute kidney injury (AKI) and to assess the prognosis in patients after radical and partial nephrectomy. METHODS: The study included a development cohort of 1111 patients who were treated between June 2012 and June 2017 and an additional validation cohort of 356 patients who were treated between July 2017 and June 2018. Stepwise regression and logistic regression analyses were used to evaluate the association between predictors and AKI. Incorporating all independent predictors, a nomogram for postoperative AKI was developed and externally validated. Patients were followed up for 5 years to assess renal function, acute kidney disease (AKD), chronic kidney disease (CKD), hospital readmission and mortality were key prognosis we focused on. RESULTS: After multivariate logistic regression, radical nephrectomy (odds ratio (OR) = 3.57, p < 0.001), aspirin (OR = 1.79, p = 0.008), systolic blood pressure (OR = 1.41, p = 0.004), triglyceride (OR = 1.26, p = 0.024), and alkaline phosphatase (OR = 1.75, p = 0.034) were independent risk factors for postoperative AKI, while albumin (OR = 0.72, p = 0.031) was a protective factor for postoperative AKI. Patients with a higher estimated glomerular filtration rate (eGFR) (60-90 ml/min/1.73 m2, OR = 0.41, p = 0.004; ≥ 90 ml/min/1.73 m2, OR = 0.37, p < 0.001) were less prone to AKI than those with a lower eGFR (< 15 ml/min/1.73 m2). These predictors were all included in the final nomogram. The area under the receiver operating characteristics curve for the model were 0.77 (p < 0.001) in the development cohort and 0.72 (p < 0.001) in the validation cohort. The incidence of AKD and CKD were 27.12 and 18.64% in AKI group, which were much higher than those in no AKI group (p < 0.001). CONCLUSIONS: The nomogram had excellent predictive ability and might have significant clinical implications for the early detection of AKI in patients undergoing nephrectomy.

A visual risk assessment tool for acute kidney injury after intracranial aneurysm clipping surgery.

OBJECTIVE: The aim of the study was to establish a predictive postoperative nomogram for acute kidney injury (AKI) after intracranial aneurysm clipping surgery, in order to early identify patients with high postoperative AKI risk. METHODS: This is a retrospective study, which included patients who underwent intracranial aneurysm clipping surgery. Multivariate logistic regression was employed to select confound factors that associated with AKI, then incorporated into the nomogram. The predictive accuracy of the model was assessed by concordance index (C-Index). RESULTS: A total of 365 patients after intracranial aneurysm clipping surgery were enrolled in the study eventually, of which 68 (18.63%) suffered postoperative AKI, and the incidence of stage 1, stage 2 and stage 3 were 92.65% (63/68), 5.88% (4/68), and 1.47% (1/68), respectively. Univariate logistic regression revealed that high density lipoprotein (HDL), prothrombin time (PT), estimated glomerular filtration rate (eGFR), size of aneurysm ≥10 mm, and aneurysm ruptured before surgery were associated with AKI after surgery, while multivariate logistic regression showed same results as the size of aneurysm ≥10 mm and aneurysm ruptured were independent AKI risk factors. In addition, the nomogram demonstrated a good accuracy in estimating intracranial aneurysm clipping associated AKI, as a C-Index and a bootstrap-corrected one of 0.772 and 0.737, respectively. Moreover, calibration plots showed consistency with the actual presence of AKI. CONCLUSION: The novel nomogram model can serve as a promising predictive tool to improve the identification of AKI among those who underwent intracranial aneurysm clipping surgery.

Insulin-like growth factor-1 promotes osteogenic differentiation and collagen I alpha 2 synthesis via induction of mRNA-binding protein LARP6 expression.

This study explored the mechanism underlying the stimulation of collagen synthesis and osteoblastic differentiation by insulin-like growth factor 1 (IGF1) in primary mouse osteoblasts. Primary mouse calvarial osteoblasts were cultured and treated with various doses of IGF1 before transfection with siRNA targeting the collagen type I alpha 2 (Col1a2) or La ribonucleoprotein domain family member 6 (Larp6) genes. Alkaline phosphatase (ALP) activity, osteocalcin staining, alizarin red quantification and the expression level of runt-related transcription factor 2 (RUNX2) were performed to assess the differentiation of pre-osteoblasts. Based on Western blot analysis, IGF1 up-regulated COL1A2 protein expression in the primary osteoblasts in a dose- and time-dependent manner. In addition, Col1a2 interference inhibited the differentiation and mineralization of osteoblasts. IGF1 also stimulated the differentiation of mouse primary osteoblasts and increased LARP6 expression during osteogenic differentiation. RNA-Immunoprecipitation (IP) indicated that LARP6 could bind to Col1a2 mRNA after IGF1 stimulation. However, transfection of Larp6-specific siRNA significantly reduced collagen and ALP secretion, mineralization and inhibited the expression of osteocalcin and RUNX2, indicating that Larp6 interference inhibited the differentiation ability of primary mouse calvarial osteoblasts, and these effects could not be reversed by IGF1. Thus, IGF1 could promote COL1A2 expression and osteoblast differentiation in primary mouse calvarial pre-osteoblasts by increasing LARP6 expression via a posttranscriptional mechanism.

Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342.

Insulin promotes bone formation via a well-studied canonical signaling pathway. An adapter in this pathway, insulin-receptor substrate (IRS)-1, has been implicated in the diabetic osteopathy provoked by impaired insulin signaling. To further investigate IRS-1's role in the bone metabolism, we generated Irs-1-deficient Irs-1smla/smla mice. These null mice developed a spontaneous mutation that led to an increase in trabecular thickness (Tb.Th) in 12-mo-old, but not in 2-mo-old mice. Analyses of the bone marrow stromal cells (BMSCs) from these mice revealed their differential expression of osteogenesis-related genes and miRNAs. The expression of miR-342, predicted and then proven to target the gene encoding collagen type Iα2 (COL1A2), was reduced in BMSCs derived from Irs-1-null mice. COL1A2 expression was then shown to be age dependent in osteoblasts and BMSCs derived from Irs-1smla/smla mice. After the induction of osteogenesis in BMSCs, miR-342 expression correlated inversely with that of Col1a2 Further, Col1a2-specific small interfering RNA (siRNA) reduced alkaline phosphatase (ALP) activity and inhibited BMSC differentiation into osteocyte-like cells, both in wild-type (WT) and Irs-1smla/smla mice. Conversely, in Irs-1smla/smla osteocytes overexpressing COL1A2, ALP-positive staining was stronger than in WT osteocytes. In summary, we uncovered a temporal regulation of BMSC differentiation/bone formation, controlled via Irs-1/miR-342 mediated regulation of Col1a2 expression.-Guo, Y., Tang, C.-Y., Man, X.-F., Tang, H.-N., Tang, J., Wang, F., Zhou, C.-L., Tan, S.-W., Feng, Y.-Z., Zhou, H.-D. Insulin receptor substrate-1 time-dependently regulates bone formation by controlling collagen Iα2 expression via miR-342.

Anatomical effects of clear lens extraction by phacoemulsification versus trabeculectomy on anterior chamber drainage angle in primary angle-closure glaucoma (PACG) patients.

PURPOSE: To document the anatomical effects of clear lens extraction by phacoemulsification versus trabeculectomy on anterior chamber angle in patients with primary angle-closure glaucoma (PACG). METHODS: Gonioscopy and ultrasound biomicroscopy (UBM) were performed pre-operatively, and at 1 year after clear lens extraction or trabeculectomy in PACG eyes. RESULTS: Fifty PACG eyes of 50 patients were included. Twenty-six eyes had clear lens extraction by phacoemulsification, while 24 eyes underwent trabeculectomy. The mean extent of synechial angle closure was significantly reduced from 272.3° ± 57.3° to 253.3° ± 70.5° (p = 0.007) by phacoemulsification, but it was only reduced from 285.0° ± 64.6° to 283.1° ± 55.5° (p = 0.32) by trabeculectomy. The mean angle-opening distance at 500 microns from sclera spur (AOD500) measured by UBM was significantly increased from 220.3 ± 93.8 microns to 388.9 ± 134.1 microns (p < 0.001) by clear lens extraction, but decreased from 220.9 ± 79.8 microns to 214.5 ± 70.2 microns (p = 0.11) by trabeculectomy. The mean anterior chamber depth (ACD) measured by UBM was significantly increased from 1,983.8 ± 176.8 microns to 3335.0 ± 174.2 microns (p < 0.001) by clear lens extraction, but decreased from 2,000.2 ± 214.5 microns to 1975.8 ± 218.2 microns (p = 0.001) by trabeculectomy. CONCLUSION: Compared to trabeculectomy, clear lens extraction resulted in a significant reduction in synechial angle closure, and an increase in anterior chamber angle width and anterior chamber depth in PACG eyes without cataract.

Dose-dependent effects of neuropeptide Y on the regulation of preadipocyte proliferation and adipocyte lipid synthesis via the PPARγ pathways.

The objective of this study was to investigate the impact of neuropeptide Y (NPY) on preadipocyte proliferation and differentiation. Preadipocytes were incubated with a range of concentrations of NPY (10(-15)M - 10(-7)M). After NPY-induced differentiation, the extent of preadipocyte adipogenesis was evaluated. The expressions levels of related adipocyte markers such as PPARγ, C/EBPα and DLK-1 were examined by real-time PCR (RT-PCR) or western blot analysis. Furthermore, the mitogen-activated protein kinase (MAPK) signaling pathway proteins were also analyzed by western blot. Our results showed that low doses of NPY stimulated preadipocyte viability and proliferation, while high NPY doses inhibited cell viability. At high concentrations of NPY significantly promoted lipid accumulation and increased the size of lipid droplets. DLK-1 mRNA expression was inhibited, but the expression levels of PPARγ and C/EBPα were increased during differentiation with the presence of high concentration of NPY. High-dose NPY also suppressed the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2 protein. We conclude that NPY has a biphasic effect on preadipocyte proliferation. A high dose inhibits the proliferation of 3T3-L1 cell while promotes adipocyte differentiation, increasing lipid accumulation especially enlarged lipid droplets' size. NPY may lead to a better understanding for drug development to prevent hyperplastic obesity and hypertrophic obesity.

A survey of perceived training differences between ophthalmology residents in Hong Kong and China.

BACKGROUND: To study the differences in ophthalmology resident training between China and the Hong Kong Special Administrative Region (HKSAR). METHODS: Training programs were selected from among the largest and best-known teaching hospitals. Ophthalmology residents were sent an anonymous 48-item questionnaire by mail. Work satisfaction, time allocation between training activities and volume of surgery performed were determined. RESULTS: 50/75 residents (66.7 %) from China and 20/26 (76.9 %) from HKSAR completed the survey. Age (28.9 ± 2.5 vs. 30.2 ± 2.9 years, p = 0.15) and number of years in training (3.4 ± 1.6 vs. 2.8 ± 1.5, p = 0.19) were comparable between groups. The number of cataract procedures performed by HKSAR trainees (extra-capsular, median 80.0, quartile range: 30.0, 100.0; phacoemulsification, median: 20.0, quartile range: 0.0, 100.0) exceeded that for Chinese residents (extra-capsular: median = 0, p < 0.0001; phacoemulsification: median = 0, p < 0.0001). Chinese trainees spent more time completing medical charts (>50 % of time on charts: 62.5 % versus 5.3 %, p < 0.0001) and received less supervision (≥90 % of training supervised: 4.4 % versus 65 %, p < 0.0001). Chinese residents were more likely to feel underpaid (96.0 % vs. 31.6 %, p < 0.0001) and hoped their children would not practice medicine (69.4 % vs. 5.0 %, p = 0.0001) compared HKSAR residents. CONCLUSIONS: In this study, ophthalmology residents in China report strikingly less surgical experience and supervision, and lower satisfaction than HKSAR residents. The HKSAR model of hands-on resident training might be useful in improving the low cataract surgical rate in China.

Mesenchymal Stem Cells Attenuate Sepsis-associated Acute Kidney Injury by Changing the Balance of Th17 cells/Tregs via Gal-9/Tim-3.

OBJECTIVE: The aim of the present study was to investigate the protective effect of MSCs on CLP-induced SA-AKI and determine the mechanisms of this effect. METHODS: The expression of Gal-9 and Tim-3 was assayed by qPCR and western blot. IL-10, IL-17, RORγt, and FOXP3 were assayed by qPCR and TNFα, INFγ, IL-4, and IL-6 were assayed by ELISA in renal samples after CLP with or without MSCs treatment. The expression of Gal-9 in MSCs was knocked down in vivo using RNA interference, and si-Gal-9-MSCs were injected in SA-AKI mice. The effect of MSCs on the differentiation of lymphocytes into Th17 cells and Tregs was evaluated in vitro by FAC in coculture of MSCs and CD4+ T cells and after blockade of the Gal-9/Tim-3 pathway. RESULTS: MSCs decreased serum creatinine and urea nitrogen levels and relieved tubular injury. Additionally, MSCs significantly improved the survival rate and markedly attenuated the infiltration of neutrophils and the levels of TNF-α, IFN-γ, IL-4, and IL-6 in the kidneys of septic mice (P < 0.05). Treatment with MSCs also reduced the proportion of Th17 cells and the levels of IL-17 and RORγt (P < 0.05). In contrast, MSCs increased the proportion of Tregs and the levels of IL-10 and FOXP3 related to these cells (P < 0.05). Furthermore, we determined whether Gal-9/Tim-3 and Th17 cells/Tregs are involved in the protective effects of MSCs in an SA-AKI model. The results of Western blot and real-time PCR indicated that MSCs inhibited the expression of Tim-3 and increased the expression of gal-9 (P < 0.05). Knockdown of gal-9 in MSCs using small interfering RNA blunted the therapeutic effect of MSCs, and blockade of the Gal-9/Tim-3 pathway using α-lactose or anti-Tim-3 inhibited the induction of Tregs and suppressed the inhibition of the differentiation to Th17 cells by MSCs after coculture of MSCs with CD4+ T cells (P > 0.05). CONCLUSION: Treatment with MSCs can protect against SA-AKI. The results suggested that the relieving effect of MSCs against SA-AKI may be partially mediated by the induction of Tregs and inhibition of Th17 cells via the Gal-9/Tim-3 pathway.

Hospitalized patients received furosemide undergoing acute kidney injury: the risk and prediction tool.

PURPOSE: Furosemide, a frequently prescribed diuretic for managing congestive heart failure and edema, remains a topic of debate regarding its potential risk of inducing acute kidney injury (AKI) in patients. Consequently, this study aims to examine the occurrence of hospital-acquired AKI (HA-AKI) in hospitalized patients who are administered furosemide and to investigate potential risk factors associated with this outcome. METHODS: This study encompassed a cohort of 22374 hospitalized patients who either received furosemide treatment or not from June 1, 2012, to December 31, 2017. Propensity score matching was employed to establish comparability between the two groups regarding covariates. Subsequently, a nomogram was constructed to predict the probability of AKI occurrence among patients who underwent furosemide treatment. RESULTS: The regression analysis identified the single-day total dose of furosemide as the most significant factor for AKI, followed by ICU administration, estimated glomerular filtration rate, antibiotic, statin, NSAIDs, ß-blockers, proton pump inhibitor, chronic kidney disease, and 7 other indicators. Subgroup analysis revealed a synergistic effect of furosemide with surgical operation, previous treatment with ß-blockers, ACEI/ARB and antibiotics, leading to an increased risk of AKI when used in combination. Subsequently, a visually represented prognostic nomogram was developed to predict AKI occurrence in furosemide users. The predictive accuracy of the nomogram was assessed through calibration analyses, demonstrating an excellent agreement between the nomogram predictions and the actual likelihood of AKI, with a probability of 77.40%. CONCLUSIONS: Careful consideration of factors such as dosage, concurrent medication use, and renal function of the patient is necessary for clinical practice when using furosemide. Our practical prognostic model for HA-AKI associated with furosemide use can be utilized to assist clinicians in making informed decisions about patient care and treatment.

Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.

INTRODUCTION: Hexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms. METHODS: We assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 µg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin. RESULTS: In this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin's anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments. CONCLUSION: Collectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.

Tilianin Reduces Apoptosis via the ERK/EGR1/BCL2L1 Pathway in Ischemia/Reperfusion-Induced Acute Kidney Injury Mice.

Background: Acute kidney injury (AKI) is a common syndrome impacting about 13.3 million patients per year. Tilianin has been reported to alleviate myocardial ischemia/reperfusion (I/R) injury, while its effect on AKI is unknown; thus, this study aimed to explore if tilianin protects I/R-induced AKI and the underlying mechanisms. Methods: The microarray dataset GSE52004 was downloaded from GEO DataSets (Gene Expression Omnibus). Differential expression analysis and gene-set enrichment analysis (GSEA) were performed by R software to identify apoptosis pathway-related genes. Then, RcisTarget was applied to identify the transcription factor (TF) related to apoptosis. The STRING database was used to construct a protein-protein interaction (PPI) network. Cytoscape software visualized PPI networks, and hub TFs were selected via cytoHubba. AutoDock was used for molecular docking of tilianin and hub gene-encoded proteins. The expression levels of hub genes were assayed and visualized by quantitative real-time PCR, Western blotting, and immunohistochemistry by establishing I/R-induced AKI mouse models. Results: Bioinformatics analysis showed that 34 genes, including FOS, ATF4, and Gadd45g, were involved in the apoptosis pathway. In total, seven hub TFs might play important roles in tilianin-regulating apoptosis pathways. In in vivo, tilianin improved kidney function and reduced the number of TUNEL-positive renal tubular epithelial cells (RTECs) after I/R-induced AKI. Tilianin reduced the activation of the ERK pathway and then downregulated the expression of EGR1. This further ameliorated the expression of anti-apoptotic genes such as BCL2L1 and BCL2, reduced pro-apoptotic genes such as BAD, BAX, and caspase-3, and reduced the release of cytochrome c. Conclusion: Tilianin reduced apoptosis after I/R-induced AKI by the ERK/EGR1/BCL2L1 pathway. Our findings provided novel insights for the first time into the protective effect and underlying molecular mechanisms of tilianin on I/R-induced AKI.