The molecular mechanism that leads to pregnancy-induced hypertension (PIH), a pregnancy-specific syndrome, remains poorly understood. It has been suggested that microRNAs (miRNAs) may be potentially useful biomarkers for severe preeclampsia (PE), which is an important condition associated with PIH. The aim of the present study was to identify miR-204 by verifying differentially expressed serum miRNAs in patients with PIH during pregnancy compared with normal controls. Subsequently, the effects of miR-204 on proliferation and apoptosis of human choriocarcinoma (JAR) cells in hypoxic microenvironment were investigated. Previous studies indicated a number of miRNA candidates and the present study validated the expression of eight miRNAs in serum samples using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A higher expression of miR-204 was identified in patients with PIH. To assess the impact of miR-204 inhibition on hypoxic JAR cells function in vitro, cell proliferation was detected using a Cell Counting Kit-8 assay. The rate of apoptosis and cell cycle progression was then examined by flow cytometry. RT-qPCR confirmed that serum miR-204-5p is more highly expressed in patients with PIH. Further statistical analysis indicated that the survival ratio of JAR cells in hypoxic microenvironments was increased in the miR-204-5p inhibitor group. However, the miR-204-5p inhibitor protected hypoxic JAR cells from apoptosis. The analysis of cell-cycle status demonstrated that the percentage of cells in the G2/G1 phase was larger compared with the control group. The results of the present study suggest that low levels of miR-204-5p may increase cell proliferation and reduce cell apoptosis with cell cycle changes in vitro. Therefore, serum miR-204-5p may be used as a notable biomarker for the diagnosis, prevention and treatment of PIH.
Abstract Background Patients with chronic kidney disease (CKD) exhibited a pronounced burden of cardiac mortality. However, early prediction of cardiovascular mortality risk in CKD patients remains an unmet medical need. Purpose This study aimed to evaluate the performance of machine learning (ML) algorithms and identify the most influential factors in predicting long-term cardiac mortality among CKD patients. Methods Six ML models were developed, with the most effective one chosen for predicting and categorising patients into high-risk and low-risk groups based on the maximal Youden’s index. Differences in survival rates were assessed using the log-rank test on Kaplan-Meier curves. Cox regression analysis was employed to investigate the relationship between ML-predicted risk scores and mortality. Furthermore, the SHapley Additive exPlanations (SHAP) method was implemented to provide personalised explanations for model decisions. Results The auto-encoder (AE) model achieved the highest AUC of 0.94, with a sensitivity of 80.95% and specificity of 96.34%. Compared to individuals in low-risk group, those in high-risk group exhibited a significantly elevated risk of cardiovascular mortality (adjusted hazard ratio [HR]: 48.24; P <0.001). According to the SHAP model, age, C-reactive protein, blood urea nitrogen and hypertension were identified as the four most influential factors in the AE model. Conclusions Our study successfully developed an AE machine learning model for predicting 10-year cardiovascular mortality among CKD patients. The combination of ML model and SHAP aids doctors in understanding key features in the model, improving their insight into decision-making related to disease severity assessment, thus facilitating early preventive strategies in clinical practice.
Abstract Rationale: Tacrolimus-associated neurologic disorders can be found in some cases, mainly in organ transplantation patients. However, epilepsy induced by tacrolimus in primary membranous nephropathy (PMN) patient is scare. Patient concerns: A 63-year-old man experienced 1-year history of foamy urine, and edema of lower extremity. Diagnosis: The patient had proteinuria, hypoalbuminemia, which indicated nephrotic syndrome. Further, we performed renal biopsy for this patient. Combined with the renal biopsy result, the diagnosis of primary membranous nephropathy was established. Intervention: At first, irbesartan was administrated for 6 months. However, the proteinuria had no obvious improvement. Tacrolimus was administrated afterwards. Outcomes: Twenty-two days after tacrolimus treatment, epilepsy occurred. Sodium valproate and carbamazepine were successively given to control epilepsy. However, the epileptic symptoms were not effectively controlled. During the treatment, the concentration of tacrolimus fluctuated greatly. At last, levetiracetam was given to maintain the curative effect. Fortunately, the patient did not suffer from epilepsy again. The concentration of temporary tacrolimus was stable, whereas proteinuria gradually decreased. Lessons: Tacrolimus-induced epilepsy should be considered in patients exhibiting acute neurological symptoms. Early diagnosis and effective treatment play a vital role for favorable prognosis.
The mechanism of Periplaneta americana extracts and rabeprazole in treating gastric mucosal injury were explored through ER stress pathway. Acute gastric mucosal injury model rats were made by intragastric administration of anhydrous ethanol. The rats were then randomly assigned to different groups: model group, Periplaneta americana extracts group, rabeprazole group and combined drug group of rabeprazole and Periplaneta americana extracts, with 6 rats in each group. A normal control group, comprising of six rats, was fed a standard diet. Drug groups were treated with intragastric administration for 3 days. The apparent morphological changes of gastric mucosal injury repair in each group of rats were observed. The length and width of the damaged erosion bands were measured and recorded by vernier caliper, and the index of gastric mucosal damage of rats was calculated using the Guth 57 standard method. Pathological repair of gastric mucosal damage was visualized using hematoxylin-eosin staining (HE). The protein expression of gastric mucosa glucose regulated protein (GRP 78), transcriptional activator 6 (ATF 6), C/EBP (CHOP) and interleukin-6 (IL-6) by protein immunoblot (Western Blot, WB). The content of prostaglandin 2 (PGE 2) in the gastric mucosa and serum was observed by an enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). The results were compared between the other groups and the model group. Intervention treatment in each experimental group demonstrated effective improvement of gastric mucosal injury, reduction in the index of gastric mucosal injury, downregulation of the protein expression of GRP 78, ATF 6, CHOP, and IL-6 in the gastric mucosa. Increasing the content of PGE2 in gastric mucosa and serum, and promoting the repair of inflammation. Notably, the combined drug group exhibited the most significant intervention effect, with a statistically significant difference ( P > 0.05). Periplaneta americana extracts, Rabeprazole alone and in combination have different degrees of protection and repair effect on gastric mucosal injury. The regulation of endoplasmic reticulum stress (ERS) may affect the mechanism of action, reducing the protein expression of inflammatory factors, increasing the expression level of PGE2, and promoting the recovery of normal physiological metabolic environment of gastric mucosa.
Objective
To investigate the clinical, pathological features and risk factors of hyperuricemia in children with IgA nephropathy (IgAN).
Methods
A retrospective study of 269 primary IgAN children diagnosed between January 1, 2006 to December 31, 2017 at the ChildrenKidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University, was performed in the hyperuricemia group (uric acid>350 μmol/L) and the normal uric acid group. The clinical and pathological characteristics were analyzed, and the risk factors of hyperuricemia were analyzed by using multivariate logistic regression analysis.
Results
There were 185 males and 84 females in the 269 IgAN children with age of (9.2±3.1) years old, among whom there were 70 patients (26.0%) accompanied by hyperuricemia. Clinical indicators such as hypertension, urea nitrogen, serum creatinine, blood lipids, urinary protein in hyperuricemia group were higher than those in normal uric acid group (all P 0.05). According to the Katafuchi semi-quantitative score, there was no significant difference in the total scores of renal lesions, glomeruli, and tubulointerstitial scores (all P>0.05), while the hyperuricemia group had higher renal vascular scores than the normal uric acid group (P<0.01). Multivariate logistic regression analysis showed that hypertension (OR=12.596, 95%CI 1.778-89.243, P=0.011), higher total cholesterol (OR=1.192, 95%CI 1.064-1.336, P=0.002), higher urea nitrogen (OR=1.273, 95%CI 1.104-1.468, P=0.001), proteinuria 3+(OR=1.875, 95%CI 1.309-2.684, P=0.001), proteinuria 4+(OR=1.627, 95%CI 1.241-2.134, P<0.001) and CKD stage 3 (OR=3.355, 95%CI 1.376-8.181, P=0.008) were the risk factors of hyperuricemia in children with IgAN.
Conclusions
Twenty-six percent IgAN children patients are accompanied by hyperuricemia, and their clinical parameters and pathological changes are more severe than those in normal uric acid group. Hypertension, higher total cholesterol, higher urea nitrogen, proteinuria 3+/4+ and CKD stage 3 are the risk factors of hyperuricemia in children with IgAN.
Key words:
Glomerulonephritis, IgA; Children; Hyperuricemia; Prevalence; Risk factors
Objective
To observe effects of huaiqihuang on proteinuria in rats with IgA nephropathy (IgAN) and dynamic changes of expression and distribution of nephrin, podocin, and to further explore the mechanism of proteinuria of IgA nephropathy and try to find the approach to the therapy for IgA nephropathy.
Methods
A total of 24 Sprague–Dawley (SD) rats with 6 weeks (n=24) were randomLy divided into 3 groups: Control group (n=8), model group (n=8) and huaiqihuang group (n=8). IgA nephropathy model was induced by the improved method of bovine serum albumin (BSA)+ carbon tetrachloride (CCl4)+ lipopolysaccharide (LPS). At the end of the experiment, hematuria, proteinuria and renal pathology should be noticed. The IgA intensity was examined by direct immunofluorescence. The protein expression and distribution of nephrin and podocin were examined by indirect immunofluorescence. The mRNA expression of nephrin and podocin were examined by real–time PCR.
Results
① The count of urinary red cells and urinary protein in huaiqihuang group were significant less than those of model group (P 0.05), but were still higher than those of control group. In huaiqihuang group, and mRNA of nephrin and podocin expressed markedly higher than those of model group (P<0.01). ④Abnormal discontinuous distribution of nephrin and podocin in huaiqihuang group was slighter than that in model group.
Conclusion
Huaiqihuang is good for decreasing urinary protein by regulating the expression and distribution of nephrin and podocin.
Key words:
huaiqihuang; IgA nephropathy (IgAN); proteinuria; nephrin; podocin
<i>Background:</i>Intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) is effective for refractory systemic lupus erythematosus (SLE). When intensive chemotherapy is immunoablative but nonmyeloablative, ASCT for hematopoietic reconstitution, with the risk of reinfusing autoreactive lymphocytes, is unnecessary. <i>Methods:</i>Four children aged 12–16 years were enrolled, 3 with WHO class IV nephritis, 2 with hemolytic anemia and 1 with thrombocytopenia. Median disease duration prior to the study was 4 years (range 1–6). Previous therapy, including intravenous bolus cyclophosphamide (Cy) with a median accumulated dose of 6.5 g/m<sup>2</sup> and high-dose methylprednisolone with a median accumulated dose of 370 mg/kg, had failed. The protocol included: Cy 1.2 g/m<sup>2</sup> daily for 4 days, fludarabine 30 mg/m<sup>2</sup> daily for 4 days, porcine antilymphocyte globulin 25 mg/kg daily for 3 days. <i>Results:</i>Themedian duration of absolute neutrophil count <0.5 × 10<sup>9</sup>/l was 5.5 days after treatment. The median SLE Disease Activity Index and urine protein decreased from 8.5 and 3.4 to 1.0 and 0.1 g/day at the date of last follow-up (median 20 months), respectively. Two cases with hemolytic anemia and 1 with thrombocytopenia before treatment recovered to normal or near normal hemogram, respectively. All patients achieved complete or partial remission within 10–28 months of follow-up. <i>Conclusion:</i>Intensive chemotherapy leads to rapid hematopoietic reconstitution without ASCT and appears beneficial in refractory childhood SLE. Further study is needed.
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