Background Cadmium (Cd) is a highly toxic heavy metal. Chronic low-dose cadmium exposure can lead to renal tubular dysfunction. However, the precise mechanisms by which cadmium induces renal tubular injury through disruption of intracellular metabolic networks remain incompletely understood. Objective To investigate the toxic effects of cadmium exposure on human renal tubular epithelial cells (HK-2) and to elucidate the associated metabolic regulatory network from the perspective of metabolic reprogramming. Methods An in vitro HK-2 cell injury model was established using 5 μmol·L⁻¹ cadmium chloride (CdCl₂). The expression of the renal injury marker kidney injury molecule-1 (KIM-1) was determined by Western blot (WB). Glycolytic capacity was evaluated by metabolic flux analysis. Mitochondrial reactive oxygen species (ROS) production was assessed with a fluorescent probe. Mitochondrial membrane potential (MMP) was evaluated after JC-1 staining. Intracellular adenosine triphosphate (ATP) levels were measured using an ATP assay kit. In addition, untargeted metabolomics analysis was conducted to characterize alterations in the intracellular metabolic fingerprint profile and to explore the metabolic pathway changes underlying cadmium-induced renal tubular epithelial cell injury. Results Cadmium exposure induced injury in HK-2 cells, as indicated by mitochondrial membrane depolarization, increased mitochondrial ROS levels, and decreased intracellular ATP levels. Metabolic flux analysis further revealed significant metabolic reprogramming, characterized by compensatory increases in basal glycolytic rate and maximal glycolytic capacity. Untargeted metabolomics showed depletion of the long-chain acylcarnitine pool and deficiency of key metabolic cofactors, suggesting impaired fatty acid oxidation and mitochondrial energy metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that the differential metabolites were mainly enriched in oxidative phosphorylation and glycerophospholipid metabolism. Correlation analysis showed that acylcarnitines were negatively correlated with nucleic acid metabolism-related metabolites, whereas ATP was positively correlated with lysophosphatidylcholine, suggesting that cadmium exposure-induced mitochondrial dysfunction may be accompanied by abnormal DNA metabolism and lipid peroxidation. Conclusion Cadmium exposure could induce impaired mitochondrial function, and promote glycolytic metabolic reprogramming in renal tubular epithelial cells. These findings provide new insights into the metabolic mechanisms underlying cadmium-induced nephrotoxicity and may help identify potential metabolic targets for intervention.

Objective To explore the clinical effect of fluticasone propionate combined with noninvasive positive pressure ventilation in the emergency treatment of AECOPD .Methods 88 AECOPD patients were selected, and they were divided into two groups by digital random method ,44 cases in each group.The control group received conventional treatment, the observation group received fluticasone propionate and noninvasive positive pressure ventilation treatment.The curative effect of the two groups was compared .Results The total effective rate of the observation group was 100.0%,which was higher than 70.5% of the control group (χ2 =10.827,P =0.000).After treatment,in the observation group,the FVC was (2.50 ±0.32)L,forced expiratory volume in one second (FEV1 ) was (1.36 ±0.20) L,the first second forced expiratory solvent percentage of predicted value ratio (FEV1%) was (51.23 ±4.32),the arterial oxygen pressure(PaO2 ) was (10.51 ±2.10) kPa,arterial partial pressure of carbon dioxide(PaCO2 ) was (5.15 ±1.19) kPa,and in the control group,the FVC was (2.00 ±0.30) L,FEV1 was (1.08 ±0.12)L,FEV1% was (40.6 ±4.03),PaO2 was (9.32 ±2.11) kPa,PaCO2 was (6.06 ±1.23) kPa,the differences between the two groups were statistically significant (t =7.940,9.192,8.102,8.920,9.920,P =0.023, 0.006,0.011,0.008,0.005).The readmission rate of the observation group was 4.5%,which was significantly lower than 13.6% of the control group (χ2 =9.298,P =0.000).Conclusion Fluticasone propionate combined with noninvasive positive pressure ventilation in the treatment of AECOPD patients can effectively improve lung function , reduce the relapse rate of the disease.

Objective:To investigate the regulation effect of endogenous nicotinamide phosphoribosyl transferase (Nampt) on the Vimentin expression of glomerular cells in high concentration glucose,and to clarify the mechanism of formation of diabetic kidney inflammation fibrosis.Methods:The C57/BL6 diabetic mice were selected and the kidney tissues were collected,and the wild C57/L86 mice were used as control group;the pathological section and tissue fluorescence staining were performed.The expression and location of endogenous Nampt and Vimentin in the glomerular cells were detected by immuno-focused technology.The HBZY-1 cells were randomly divided into 4 groups:low concentration of glucose (LG,0.56 mmol · L-1) control group,high concentration glucose (HG,200 mmol · L-1) group,HG +-FK866 group and HG+nicotinamide mononucleotide (NMN) group.In HG group,the cells were treated with FK866 (10 μmol · L-1) and NMN (1 mmol · L-1) for 24 h after cultured with HG for 5 d.The expression levels of Nampt,Vimentin,nuclear factor-kappa B p65 (NF-κBp65) and sirtuin type 1 (Sirt1) were detected by immunofluorescence and Western blotting methods.The expression levels of Nampt and Vimentin were detected by RT-PCR and Western blotting methods.Results:The shape and size of glomerulus had obvious atrophy of the mice in severe diabetic group compared with normal C57/BL6 mice group.The expression level of Vimentin in glomerular cells was increased with the increasing of endogenous Nampt (P＜0.01).When the HBZY-1 cells were cultured in HG condition,the exprssion levels of Nampt,Vimentin and NF-kB p65 were obviously increased while the Sirt1 expression levels was significantly decreased compared with control group (P＜ 0.01).The expression levels of Nampt,Vimentin and NF-κB p65 in glomerular cells in HG+FK866 HG+ NMN groups were singnificartyly decreased compared with control group (P＜0.01).Conclusion:The endogenous Nampt over-expression in glomerular cells can enhance the expression of Vimentin under high concentration of glucose stress through NF-κBp65 and Sirt1 signal pathway.

OBJECTIVE To investigate the mechanism of nicotinamide mononucleotide (NMN) on inflammation and fibrosis between endogenous nicotinamide phosphoribosyltransferase (NAMPT) and bone morphogenetic protein 7 (BMP-7) in diabetic glomerular cells.METHODS ① In vivo,spontaneous diabetic C57/BL6 mice and wild C57/BL6 mice were divided into two groups.When blood glucose was above (34.2±1.9) mmol· L-1,renal histology of diabetic mice became obvious.The protein expressions of Nampt and nuclear transcription factors-kappa B p65 (NF-κB p65),silent mating type information regulation 2 homolog 1 (SIRT1) and BMP7 were analyzed by lengths of immunofluorescence.② In vitro,rats' glomerular cells HBZY-1 were incubated with glucose 200 mmol· L-1 for different lengths of time (0,24,48 and 72 h) and at different concentrations of NMN (0,50,100 and 200 iμmol· L-1).The protein levels of Nampt and BMP7 were detected by Western blotting and the protein expressions of NF-κB p65 and α-SMA were measured by immunofluorescence assay.The protein levels of Nampt,BMP7 and NF-κB p65 were detected by Western blotting after HBZY-1 cells were treated with NMN 100 μmol· L-1 and FK866 10 μmol· L-1 for 24 h.RESULTS ① In vivo,the glomeruli of diabetic C57/BL6 mice showed obvious atrophy.Fluorescence intensity of Nampt was increased (P＜0.05),but that of BMP7 and SIRT1 in renal glomeruli cells was decreased compared with the wild type (P＜0.01).② In vitro,HBZY-1 cells were cultured in glucose 200 mmol· L-1 for 48 and 72 h.The protein expression of NAMPT was increased,but that of BMP7 was decreased (P＜0.05,P＜0.01).Expressions of NF-κB p65 and α-SMA were increased (P＜0.01) by immunofluorescence.The expression of BMP7 was increased after treatment with glucose 200 mmol· L-1,followed by NMN 50,100 and 200 μmol · L-1 for 24 h (P＜0.01).The expressions of NAMPT and NF-κB p65 were decreased (P＜0.01).The expressions of Nampt and NF-κB p65 in glucose 5.6 mmol· L1 +FK866 and glucose 5.6 mmol· L-1+ NMN groups were increased (P＜0.01),but the expression of BMP7 did not change.CONCLUSION Upregulation of endogenous Nampt obviously intervenes in BMP7 expression in the process of glomerular inflammatory fibrosis in severe diabetes.NMN can affect the protein expression of BMP7 via a special Nampt signaling pathway.

Objective To investigate the clinical efficiency of Huayu Xiaozhong Decoction (HXD) on preventing peri-operative deep venous thrombosis (DVT) in lower limbs following artificial total hip replacement. Methods Ninety cases following artificial total hip replacement were randomized into blank control group, Rivaroxaban group and HXD group, 30 cases in each group, and were treated with brown sugar water, Rivaroxaban, HXD respectively. Before operation, and one, 3 and 14 days after operation, we monitored the changes of bleeding volume, DVT incidence, hemoglobin, prothrombin time ( PT) , activated partial thromboplastin time ( APTT) , international normalized ratio (INR), and D-dimer (DD) in the three groups. Results (1) Fifteen cases had DVT, with a total incidence rate of 16.67%. Of the 15 cases, 10 were from blank control group, 2 from Rivaroxaban group, and 3 from HXD group. ( 2) The amount of bleeding volume of Rivaroxaban group was larger than that of the blank control group and HXD group (P<0.05), but the bleeding was mild. (3) One, 3 and 14 days after operation, PT and APTT were shortened in blank control group (P<0.01 compared with those before operation). PT, APTT and INR were prolonged, and coagulation function was improved in Rivaroxaban group and HXD group, the differences being significant as compared with the blank control group ( P<0.05). HXD group had better effect on improving INR than Rivaroxaban group ( P<0.05). ( 4) In the three groups, hemoglobin level began to decrease on postoperative day one, arrived to the bottom on postoperative day 3 (P<0.05), and rose up near to the normal level on postoperative day 14; HXD group had higher hemoglobin level than blank control group and Rivaroxaban group on postoperative day 3 and 14 ( P<0.05). The 3 groups had higher plasma DD level than the normal level before the operation, arrived to the highest level on postoperative day one and 3 ( P<0.05) , and fell down near to the normal level on postoperative day 14. The inter-group comparison results showed that Rivaroxaban group and HXD group had lower DD level than the blank control group on postoperative day 3 and 14 ( P<0.05). Conclusion HXD is effective on preventing DVT in the peri-operation period through reducing bleeding, increasing hemoglobin level and improving postoperative anemia. The efficiency and safety of HXD are similar to Rivaroxaban.

OBJECTIVETo analyze the genetic polymorphism of D16S539, D7S820 and D13S317 in Chinese Kazak ethnic population from Xinjiang.

METHODSOne hundred and two unrelated individuals and a sample of families (n=42) were investigated by multiplex amplification, 6% denaturing PAGE and silver staining. And, the obtained allele frequencies were compared with those of other populations.

RESULTSEight, seven, eight alleles were observed at the 3 STR loci respectively and the genotypes distributions were in accordance with Hardy-Weinberg equilibrium. The expected heterozygosities for these loci were 0.9439, 0.9356 and 0.9304; the calculated polymorphism formation content (PIC) was 0.9905; the discrimination power (DP), 0.9998; the paternity exclusion (PE), 0.9572. In addition, significant difference was found in comparison with other populations, and in the sample of families (n=42) no new mutations could be found.

CONCLUSIONThe multiplex examination of 3 STR loci can be used in forensic identification and population genetics research.

China ; ethnology ; European Continental Ancestry Group ; genetics ; Female ; Gene Frequency ; Genetics, Population ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Tandem Repeat Sequences ; genetics