Risk Factors and Drug Efficacy for Severe Illness in Hemodialysis Patients Infected with the Omicron Variant of COVID-19.

INTRODUCTION: The Omicron variant of the novel coronavirus (COVID-19) has been spreading more rapidly and is more infectious, posing a higher risk of death and treatment difficulty for patients undergoing hemodialysis. This study aims to explore the severity rate and risk factors for hemodialysis patients infected with the Omicron variant and to conduct a preliminary analysis of the clinical efficacy of drugs. METHODS: Clinical and biochemical indicators of 219 hemodialysis patients infected with the Omicron variant were statistically analyzed. The patients were divided into two groups based on whether they were severely ill or not, and multiple regression analysis was conducted to determine the risk factors for severe illness. The severely ill patients were then grouped based on discharge or death, and the treatment drugs were included as influencing factors for multiple regression analysis to determine the risk factors and protective factors for death of severely ill patients, and drug efficacy analysis was conducted. RESULTS: Analysis showed that diabetes, low oxygen saturation, and high C-reactive protein (CRP) were independent risk factors for severe illness in hemodialysis patients infected with the Omicron variant. A history of diabetes and high C-reactive significantly increased the risk of severe illness in patients (aOR: 1.450; aOR: 1.011), while a high oxygen saturation level can reduce this risk (aOR: 0.871). In addition, respiratory distress was an independent risk factor for death in severely patients, significantly reducing the probability of discharge for patients (aOR: 0.152). The drugs thymalfasin and Tanreqing significantly increased the probability of discharge for patients (aOR: 1.472; aOR: 3.104), with the latter having a higher correlation, but with a relatively longer effective course. CONCLUSION: Hemodialysis patients infected with the Omicron variant of COVID-19 should pay special attention to their history of diabetes, CRP, and oxygen saturation levels, as well as respiratory distress symptoms, to reduce the risk of severe illness and death. In addition, thymalfasin and Tanreqing may be considered in treatment.

Inhibition of ALKBH5-mediated m6 A modification of PPARG mRNA alleviates H/R-induced oxidative stress and apoptosis in placenta trophoblast.

The alpha-ketoglutarate-dependent (ALKB) homolog 5 (ALKBH5), an m6 A demethylase, has been reported to be involved in the pathogenesis of preeclampsia (PE), but the exact mechanism requires further investigation. RT-qPCR or Western blotting were used to determine ALKBH5 and peroxisome proliferator-activated receptor gamma (PPARG) expression in placentas from PE patients and normal volunteers, as well as in HTR-8/SVneo cells treated with hypoxia/reoxygenation (H/R). Our results showed that the expression of ALKBH5 was significantly upregulated and PPARG was downregulated in preeclamptic placentas and H/R-treated cells. ALKBH5 interference reduced m6 A levels of PPARG mRNA, and increased PPARG mRNA stability and promoted PPARG translation level. In addition, ALKBH5 silencing increased the cell proliferation, migration, and vimentin protein level, and inhibited cell apoptosis, oxidative stress, and protein levels of endoglin (ENG) and E-cadherin in H/R-treated cells, whereas PPARG interference reversed these effects. Furthermore, PPARG repressed the H3K9me2 levels at activated leukocyte cell adhesion molecule (ALCAM) promoter region by increasing the expression and activity of lysine demethylase 3B (KDM3B). ALCAM inhibition reversed the effects of PPARG overexpression on H/R-treated cell functions. PKF115-584 suppressed the effects of ALKBH5 interference on the behaviors of H/R-treated cells. Finally, inhibition of ALKBH5 alleviates PE-like features in pregnant mice. Inhibition of ALKBH5 promotes KDM3B-mediated ALCAM demethylation by facilitating PPARG mRNA m6 A modification, and further activates the Wnt/ß-catenin pathway, and in turn alleviates PE progression.

Identity-Preserved Human Posture Detection in Infrared Thermal Images: A Benchmark.

Human pose estimation has a variety of real-life applications, including human action recognition, AI-powered personal trainers, robotics, motion capture and augmented reality, gaming, and video surveillance. However, most current human pose estimation systems are based on RGB images, which do not seriously take into account personal privacy. Although identity-preserved algorithms are very desirable when human pose estimation is applied to scenarios where personal privacy does matter, developing human pose estimation algorithms based on identity-preserved modalities, such as thermal images concerned here, is very challenging due to the limited amount of training data currently available and the fact that infrared thermal images, unlike RGB images, lack rich texture cues which makes annotating training data itself impractical. In this paper, we formulate a new task with privacy protection that lies between human detection and human pose estimation by introducing a benchmark for IPHPDT (i.e., Identity-Preserved Human Posture Detection in Thermal images). This task has a threefold novel purpose: the first is to establish an identity-preserved task with thermal images; the second is to achieve more information other than the location of persons as provided by human detection for more advanced computer vision applications; the third is to avoid difficulties in collecting well-annotated data for human pose estimation in thermal images. The presented IPHPDT dataset contains four types of human postures, consisting of 75,000 images well-annotated with axis-aligned bounding boxes and postures of the persons. Based on this well-annotated IPHPDT dataset and three state-of-the-art algorithms, i.e., YOLOF (short for You Only Look One-level Feature), YOLOX (short for Exceeding YOLO Series in 2021) and TOOD (short for Task-aligned One-stage Object Detection), we establish three baseline detectors, called IPH-YOLOF, IPH-YOLOX, and IPH-TOOD. In the experiments, three baseline detectors are used to recognize four infrared human postures, and the mean average precision can reach 70.4%. The results show that the three baseline detectors can effectively perform accurate posture detection on the IPHPDT dataset. By releasing IPHPDT, we expect to encourage more future studies into human posture detection in infrared thermal images and draw more attention to this challenging task.

Influence of therapeutic drugs on different manifestations of renal involvement in 907 Chinese patients with ankylosing spondylitis
.

BACKGROUND: There is no systematic or large-scale study in the published literature in which the relationship between drug therapies and renal involvement in ankylosing spondylitis (AS) has been rigorously evaluated. In addition, the sensitivity of the kidneys to drugs varies significantly between races and regional populations. Therefore, the aim of the present study was to investigate the impact of drugs on renal involvement in Chinese AS patients. MATERIALS AND METHODS: The clinical characteristics and biochemical data of 907 AS patients were collected and analyzed, and the differences between patients who had received drugs and those who had not were analyzed using intergroup comparisons to screen out confounding factors. Multivariate logistic regression analysis that corrected for the confounding factors explored the impact of the AS therapeutic drugs on the clinical manifestations of renal involvement. RESULTS: Renal involvement in Chinese AS patients increased significantly following non-steroidal anti-inflammatory drug (NSAID) or conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy, and combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor. For AS patients, NSAID monotherapy increased the probability of hematuria 2.4-fold and the probability of mixed manifestations of renal involvement 3.0-fold. csDMARD monotherapy increased the probability of proteinuria 2.4-fold; combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor increased the probability of hematuria 4.1-fold. In addition, the study found that TNF-α inhibitor monotherapy and combination therapy with NSAIDs or csDMARDs caused no apparent impact on renal involvement in AS patients. CONCLUSION: NSAID or csDMARD monotherapy may significantly increase renal involvement in Chinese AS patients. Combination therapy with TNF-α inhibitor with NSAIDs and csDMARDs should be used prudently.

Chinese Herbal Formulas Si-Wu-Tang and Er-Miao-San Synergistically Ameliorated Hyperuricemia and Renal Impairment in Rats Induced by Adenine and Potassium Oxonate.

BACKGROUND/AIMS: Hyperuricemia is an independent risk factor for chronic kidney disease and cardiovascular disease. Here, we examined the combined protective effects of Chinese herbal formula Si-Wu-Tang and Er-Miao-San on hyperuricemia and renal impairment in rats. METHODS: Rats were randomly divided into normal rats, hyperuricemic rats, and hyperuricemic rats orally administrated with benzbromarone (4.5 mg·kg⁻¹·d⁻¹), Si-Wu-Tang (3.78 g·kg⁻¹·d⁻¹) and Si-Wu-Tang plus Er-Miao-San (6.48 g·kg⁻¹·d⁻¹) for 4 weeks. Hyperuricemic rats were orally gavaged with adenine (0.1 g·kg⁻¹·d⁻¹) and potassium oxonate (1.5 g·kg⁻¹·d⁻¹) daily for 4 weeks. Serum uric acid, creatinine, total cholesterol (TCH), triglyceride and blood urea nitrogen (BUN) concentrations, as well as urinary uric acid and microalbuminuria were measured weekly. Serum xanthine oxidase (XOD) activity and renal histopathology were also evaluated. The renal expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) was detected by western blot. RESULTS: Si-Wu-Tang plus Er-Miao-San lowered serum uric acid, creatinine, triglyceride and BUN levels to a greater degree than did Si-Wu-Tang alone. Si-Wu-Tang plus Er-Miao-San ameliorated microalbuminuria and renal histopathology, as well as decreased serum TCH concentration and XOD activity in hyperuricemic rats. Combination of Si-Wu-Tang and Er-Miao-San also led to a greater increase in OAT1 and OAT3 expression than did Siwutang alone. CONCLUSION: Si-Wu-Tang and Er-Miao-San synergistically ameliorated hyperuricemia and renal impairment in rats through upregulation of OAT1 and OAT3.

Notoginsenoside R1 ameliorates podocyte adhesion under diabetic condition through α3ß1 integrin upregulation in vitro and in vivo.

BACKGROUND: Decreased expression of α3ß1 integrin may contribute to reduction in podocyte adhesion to glomerular basement membrane (GBM), which represents a novel early mechanism leading to diabetic kidney disease (DKD). Here, we examined the protective effects of Notoginsenoside R1 (NR1) on podocyte adhesion and α3ß1 integrin expression under diabetic condition in vitro and in vivo. METHODS: Conditionally immortalized mouse podocytes were exposed to high glucose (HG) with 10 and 100µg /ml of NR1 for 24 h. Podocyte adhesion, albuminuria, oxidative markers, renal histopathology, podocyte number per glomerular volume, integrin-linked kinase (ILK) activity and α3ß1 integrin expression were measured in vitro and in vivo. RESULTS: HG decreased podocyte adhesive capacity and α3ß1 integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored α3ß1 integrin protein and mRNA expression. These in vitro observations were confirmed in vivo. In streptozotocin(STZ)-induced diabetic rats, treatment with NR1 (5 and 10 mg· kg(-1)· d(-1)) for 12 weeks partially restored the number of podocytes per glomerular volume and glomerular α3ß1 integrin expression, as well as ameliorated albuminuria, histopathology and oxidative stress. NR1 also inhibited glomerular ILK activity in diabetic rats. CONCLUSION: NR1, a novel antioxidant, ameliorated glucose-induced impaired podocyte adhesive capacity and subsequent podocyte depopulation partly through α3ß1 integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.

The expression and significance of dishevelled in human glioma.

BACKGROUND: The proto-oncogene dishevelled (Dvl) is a critical component of the Wnt/ß-catenin signaling pathway, and its elevated expression in various tumor types is associated with malignancy. However, a role for Dvl in glioma has not been explored. MATERIALS AND METHODS: To determine whether Dvl expression is elevated in human glioma, we examined the protein levels in 67 human glioma samples and 3 normal brain specimens by Western blotting and immunohistochemistry. To investigate a possible association of Dvl with the malignant phenotype in glioma, the correlation of the Dvl immunoreactivity score (IRS) with ß-catenin IRS, the tumor proliferation index (PI), and tumor invasion index (II) were determined for each sample. RESULTS: The Dvl IRS, ß-catenin IRS, PI, and II increased significantly with the pathologic grade of glioma (P <0.001) with average scores of 3.46 ± 3.45, 3.92 ± 3.28, 30.93 ± 17.92, and 20.43 ± 11.79, respectively. Furthermore, the PI and II were significantly higher for the Dvl-positive group than the Dvl-negative group (P <0.001). Correlation analysis demonstrated that ß-catenin IRS, PI, and II were positively correlated with Dvl IRS. CONCLUSIONS: Dvl overexpression may contribute to the malignant proliferation and invasion of human glioma.

Astragaloside IV prevents acute kidney injury in two rodent models by inhibiting oxidative stress and apoptosis pathways.

Oxidative stress and apoptosis play key role in the pathogenesis of acute kidney injury (AKI). We hypothesize that Astragaloside IV(AS-IV) prevents AKI through inhibiting oxidative stress and apoptosis. The rats were divided into sham control, saline-,vehicle-, or AS-IV-treated groups. AS-IV (20 mg/kg) was orally administered once daily to the rats for 7 consecutive days before terminating the experiments. In ischemia-induced AKI model, experimental rats were subjected to bilateral clamping of the renal arteries for 45 min, followed by reperfusion for 24 h. In contrast-induced AKI model, iopamidol (2.9 g iodine/kg) was administered intravenously into the rats. Renal function, histopathology, oxidative stress and apoptosis were evaluated in these models. Pretreatment with AS-IV significantly decreased blood urea nitrogen, serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels, as well as urinary kidney injury molecule-1 level and tubular injury. AS-IV also reduced oxidative stress and tubular cell apoptosis. The p38 mitogen-activated protein kinase phosphorylation and caspase-3 activity were elevated in kidney tissues from AKI rats, accompanied by an increase in Bax expression and a decrease in Bcl-2 expression at mRNA and protein levels. These changes were prevented by AS-IV pretreatment. Therefore, AS-IV can be developed as a novel therapeutic approach to prevent AKI through targeting inhibition of oxidative stress and apoptosis pathways.

Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-κB-mediated inflammatory genes expression.

Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n=8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mgkg(-1)d(-1), p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n=8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-κB activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-α, MCP-1 and ICAM-1 in kidney tissues. The α1-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-α, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NF-κB mediated inflammatory genes expression.

LncRNA TCF7 contributes to high glucose-induced damage in human podocytes by up-regulating SEMA3A via sponging miR-16-5p.

AIMS/INTRODUCTION: Long non-coding RNAs (lncRNAs) exert essential functions in the pathogenesis of diabetic nephropathy (DN). LncRNA T-cell factor 7 (TCF7) and semaphorin-3A (SEMA3A) have been found to be involved in the progression of diabetic nephropathy. However, whether the effect of TCF7 on the pathogenesis of diabetic nephropathy is mediated by SEMA3A remains unclear. MATERIALS AND METHODS: TCF7, miR-16-5p, and SEMA3A were quantified by a qRT-PCR or immunoblotting method. A CCK-8 assay gauged the cell viability. Measurement of cell apoptosis was done using flow cytometry. RNA immunoprecipitation (RIP), dual-luciferase reporter, and RNA pull-down assays were utilized to assay the targeted interactions among the variables. RESULTS: The TCF7 and SEMA3A levels were elevated in serum from patients with diabetic nephropathy. TCF7 silencing or SEMA3A depletion ameliorated high glucose (HG)-induced podocyte injury. Moreover, TCF7 silencing protected against HG-induced podocyte injury by down-regulating SEMA3A. TCF7 targeted miR-16-5p, and miR-16-5p targeted SEMA3A. Furthermore, TCF7 affected the expression of SEMA3A by competing specifically for shared miR-16-5p. CONCLUSIONS: These findings suggested that TCF7 silencing attenuated high glucose-induced podocyte damage partially through the miR-16-5p/SEMA3A regulation cascade.

MiRNA-200b level in peripheral blood predicts renal interstitial injury in patients with diabetic nephropathy.

Background: To uncover the diagnostic potential of peripheral blood microRNA-200b (miRNA-200b) in renal interstitial injury in diabetic nephropathy (DN) patients. Methods: A total of 50 diabetes subjects, 50 mild DN subjects, 50 moderate-severe DN subjects and 50 healthy subjects were included. Peripheral blood level of miRNA-200b in every subject was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Serum levels of renal function indicators were determined by enzyme-linked immunosorbent assay (ELISA). Meanwhile, relative levels of fibrosis damage indicators were examined by chemiluminescent immunoassay. Diagnostic potentials of miRNA200b in diabetes, mild DN and moderate-severe DN were assessed by depicting receiver operating characteristic (ROC) curves. Results: Peripheral blood level of miRNA-200b was higher in DN subjects than diabetes subjects without vascular complications, especially moderate-severe DN patients. Peripheral blood level of miRNA-200b in DN subjects was negatively correlated to relative levels of serum creatinine, urinary nitrogen, cystatin, TGF-b, CIV and PCIII. ROC curves demonstrated diagnostic potentials of miRNA-200b in mild and moderate-severe DN. Conclusions: Peripheral blood level of miRNA-200b is closely linked to the degree of renal interstitial injury in DN patients. MiRNA-200b may be a vital indicator in predicting the development of DN.

Upregulated Tripartite Motif 47 Could Facilitate Glioma Cell Proliferation and Metastasis as a Tumorigenesis Promoter.

INTRODUCTION: Tripartite motif 47 (TRIM47) belongs to a category of the TRIM family. It takes part in cancer tumorigenesis, thus demonstrating important functions across numerous carcinomas. Unfortunately, it is still elusive towards TRIM47 expression, characteristic, and biological function in brain gliomas. METHODS: Public database analysis was applied to analyze TRIM47 expression, and quantitative real-time PCR (qRT-PCR) was applied to detect the expression of TRIM47 in 9 paired tissues of glioma. The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were applied to evaluate the overall survival (OS). Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were applied to analyze differentially expressed gene (DEG) functions. In vitro experiments were performed to validate TRIM47-mediated effects on glioma cell proliferation, migration, and invasion. RESULTS: Compared to that in normal tissues, TRIM47 expression was greatly higher in glioma tissues, and its expression level was associated with different grades of glioma. Our data indicated that highly expressed TRIM47 displayed an association with the poor prognosis of glioma patients. Ablating TRIM47 obviously impeded glioma cell invasion and migration. CONCLUSION: TRIM47 could modulate glioma cell proliferation, invasion, and migration. Highly expressed TRIM47 exhibited a correlation with poor prognosis. All data imply that TRIM47 is a probable biomarker for glioma and has the potentiality to become a newly generated target for glioma treatment.

Protocol for thiamine and folic acid in the treatment of cognitive impairment in maintenance haemodialysis patients: a prospective, randomised, placebo-controlled, double-blind, multicentre study.

INTRODUCTION: Cognitive impairment (CI) is the common complications in maintenance haemodialysis (MHD) patients. Recently, the pathogenesis of CI has been discussed and oxidative stress is one of the main mechanisms in these patients. Thiamine and folic acid, which play an important role in relieving the production of reactive oxygen species, reducing homocysteine levels, improving oxidative stress in the nervous system. In pilot study, cognitive function was significantly improved in the group with thiamine and folic supplementation. Based on this result, we hypothesise that thiamine combined with folic acid supplementation may improve cognitive function in patients with MHD. METHODS AND ANALYSIS: In this prospective, randomised, placebo-controlled, double-blind, multicentre study, we will enrol patients undergoing haemodialysis who has the Montreal Cognitive Assessment score lower than 26 to treatment group (thiamine 90 mg/day combined with folic acid 30 mg/day) or control group (thiamine placebo 90 mg/day combined with folic acid placebo 30 mg/day). All subjects will be followed up for 96 weeks. The primary endpoint is the comparison of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score between treatment group and control group at 96 weeks of follow-up. The secondary endpoints include serum thiamine, folate, homocysteine levels, cranial functional MRI and survival. The central randomisation method will be adopted and the principles of placebo-controlled, double-blind randomised control will be followed. The comparisons among ADAS-Cog scores and other secondary endpoints over time within subjects is conducted by using repeated measure analysis of variance (ANOVA) or generalised estimating equations (GEE). Pairwise t-test with Bonferroni adjustment is performed for multiple comparisons. On the other hand, for comparisons between treatment and control group, simple one-way ANOVA, GEE or Wilcoxon rank sum test is used. The χ2 method is used for statistical analysis of the categorical data. Kaplan-Meier survival curve is used for survival analysis. A p<0.05 is considered statistically significant difference. ETHICS AND DISSEMINATION: This trial has been approved by Shanghai Jiao Tong University School of Medicine, Renji Hospital Ethics Committee (KY2019-199). After publication of study results, trial report will be published in peer-reviewed journals and/or in national or international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000029297.

Efficacy and safety of Bailing capsules in the treatment of type 2 diabetic nephropathy: a meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is the main cause of end-stage renal failure (ESRF) in diabetic patients. Chinese medicine plays an extremely important role in controlling the symptoms of DN. At present, the efficacy and safety of Bailing capsules in the treatment of type 2 DN are still unclear. Therefore, the aim of this meta-analysis was to evaluate the clinical efficacy and safety of Bailing capsules in the treatment of type 2 DN. METHODS: A literature search on type 2 DN was conducted using Chinese and English databases. The Chinese databases searched were the CNKI database, Wanfang database, and Weipu database using the following search terms: Bailing capsule and DN. The English databases were PubMed, Embase, and Web of Science using the following search terms: type 2 diabetes mellitus, type II diabetes mellitus, and Bailing capsule. The quality of the literature was evaluated using RevMan 5.3 software. The meta-analysis was performed using the R3.5.1 software meta package. RESULTS: Twenty-four articles with a total of 985 patients in the treatment group and 956 patients in the control group were found. The total effective rate of Bailing capsules in the treatment group was 1.24 times that of the control group [95% confidence interval (CI): 1.11-1.38]. Reductions in 24-h urine total protein, urine albumin excretion rate (UAER), serum creatinine (Scr), and blood urea nitrogen (BUN) levels before and after treatment in the treatment group were significantly lower than that of the control group, with standard mean differences (SMD) of 0.61 (95% CI: -1.01 to -0.22), -1.56 (95% CI: -2.34 to -0.78), -0.58 (95% CI: -0.89 to -0.27), and -0.73 (95% CI: -1.16 to -0.29), respectively. However, there was no significant change in serum potassium between the two groups (P>0.05). No publication bias was found in the metaanalysis (P>0.05). CONCLUSIONS: For type 2 DN patients, the use of Bailing capsules in routine treatment demonstrated higher clinical efficacy and was found to improve the kidney function. However, high-quality randomized controlled trials are required to further explore the safety of Bailing capsules.

High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma.

AIM: To conduct a randomized trial to evaluate the role of using high-dose iodized oil transcatheter arterial chemoembolization (TACE) in the treatment of large hepatocellular carcinoma (HCC). METHODS: From January 1993 to June 1998, 473 patients with unresectable hepatocellular carcinoma were divided into two groups: 216 patients in group A received more than 20 mL iodized oil during the first TACE treatment; 257 patients in group B received 5-15 mL iodized oil in the same way. The Child's classification and ICG-R15 for evaluating the liver function of the patients were done before the treatment. During the TACE procedure the catheters were inserted into the target artery selectively and the tumor vessels were demonstrated with contrast medium in the hepatic angiography.The anticancer drugs mixed with iodized oil (Lipiodol) were Epirubicin and Mitomycin. In group A, 112 cases received 20-29 mL Lipiodol in the first procedure, 85 cases 30-39 mL, 19 cases more than 40 mL. The largest dose was 53 mL and the average dose was 28.3 mL. In group B, 119 cases received 5-10 mL Lipiodol,138 cases received 11-15 mL and the average dose was 11.8 mL. RESULTS: High-dose Lipiodol chemoembolization had tolerable side effects and a little hurt to the liver function in the patients with Child's A or ICG-R15<20. But the patients with child's B or ICG-R15>20 had higher risk of liver failure after high-dose TACE. More type I and type II in CT scan after 4 weeks of TACE were seen in the patients of group A than those in the patients of group B (P<0.01). The resection rate and complete tumor necrosis rate of group A were higher than those of group B (P<0.05). The 1-,2-, 3-year survival rates of group A patients with Child's A were 79.2 , 51.8 and 34.9 , respectively, better than those of group A (P<0.001). CONCLUSION: High-dose Lipiodol can result in more complete tumor necrosis by blocking both arteries and small portal vein of the tumor. High-dose TACE for treatment of large and hypervascular hepatocellular carcinoma is practically acceptable with the better effect than the routine dose. For the patients with large and hypervascular tumor of Child grade A liver function or ICG-R15 less than 20%, oily chemoembolization with 20-40 mL Lipiodol is recommended.

Preventive Effects of a Natural Anti-Inflammatory Agent, Astragaloside IV, on Ischemic Acute Kidney Injury in Rats.

This study investigated the anti-inflammatory effects of astragaloside IV(AS-IV) on ischemia/reperfusion (IR) induced acute kidney injury (AKI) in rats. Experimental model of ischemic AKI was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 12 h and 24 h, respectively. AS-IV was orally administered once a day to rats at 10 and 20 mg·kg(-1)·d(-1) for 7 days prior to ischemia. AS-IV pretreatment significantly decreased serum urea, creatinine, and cystatin C levels at 12 h and 24 h of reperfusion in AKI rats. AS-IV pretreatment also ameliorated tubular damage and suppressed the phosphorylation of p65 subunit of NF- κ B in AKI rats. Moreover, NF- κ B and MPO activity as well as serum and tissue levels of TNF- α , MCP-1, and ICAM-1 were elevated in AKI rats. All of these abnormalities were prevented by AS-IV. Furthermore, AS-IV downregulated the mRNA expression of NF- κ B, TNF- α , MCP-1, and ICAM-1 in AKI rats. These results suggest that AS-IV might be developed as a novel therapeutic approach to prevent ischemic AKI through inhibition of NF- κ B mediated inflammatory genes expression.

Astragaloside IV, a novel antioxidant, prevents glucose-induced podocyte apoptosis in vitro and in vivo.

Glucose-induced reactive oxygen species (ROS) production initiates podocyte apoptosis, which represents a novel early mechanism leading to diabetic nephropathy (DN). Here, we tested the hypothesis that Astragaloside IV(AS-IV) exerts antioxidant and antiapoptotic effects on podocytes under diabetic conditions. Apoptosis, albuminuria, ROS generation, caspase-3 activity and cleavage, as well as Bax and Bcl-2 mRNA and protein expression were measured in vitro and in vivo. Cultured podocytes were exposed to high glucose (HG) with 50, 100 and 200 µg/ml of AS-IV for 24 h. AS-IV significantly attenuated HG-induced podocyte apoptosis and ROS production. This antiapoptotic effect was associated with restoration of Bax and Bcl-2 expression, as well as inhibition of caspase-3 activation and overexpression. In streptozotocin (STZ)-induced diabetic rats, severe hyperglycemia and albuminuria were developed. Increased apoptosis, Bax expression, caspase-3 activity and cleavage while decreased Bcl-2 expression were detected in diabetic rats. However, pretreatment with AS-IV (2.5, 5, 10 mg·kg(-1)·d(-1)) for 14 weeks ameliorated podocyte apoptosis, caspase-3 activation, renal histopathology, podocyte foot process effacement, albuminuria and oxidative stress. Expression of Bax and Bcl-2 mRNA and protein in kidney cortex was partially restored by AS-IV pretreatment. These findings suggested AS-IV, a novel antioxidant, to prevent Glucose-Induced podocyte apoptosis partly through restoring the balance of Bax and Bcl-2 expression and inhibiting caspase-3 activation.