Pathogenesis, prevention and treatment of acute kidney injury in elderly patients with COVID-19 / 中华老年医学杂志

With the coronavirus disease 2019(COVID-19)pandemic across the world, numerous variants have emerged.As a high-risk group for COVID-19, the elderly are prone to acute kidney injury(AKI), with atypical clinical features and high proportions of patients with critical illness.Its pathogenesis mainly includes direct damage to the kidney via the angiotensin-converting enzyme 2(ACE2)pathway, the extracellular matrix metalloproteinase inducer(CD147)pathway, and age-related renal dysfunction, inflammatory aging, immune aging and other non-specific mechanisms, which significantly increase the risk of adverse prognosis.Therefore, the establishment of an early warning system for AKI, increasing vaccination coverage, nutritional support, treatment of primary diseases, extracorporeal supportive therapy and other control measures are particularly important to prognosis improvement.This review summarized the pathogenesis, early prevention and treatment of AKI in elderly patients with COVID-19.

Correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis / 中华肾脏病杂志

Objective:To investigate the correlation between serum C3 and glomerular microthrombosis in patients with lupus nephritis (LN).Methods:Patients who were diagnosed as LN by renal biopsy hospitalized in Department of Nephrology, the First Affiliated Hospital of Shenzhen University from January 2010 to February 2019 were retrospectively analyzed and they were divided into glomerular microthrombosis group (GMT group) and non-glomerular microthrombosis group (non-GMT group). The demographic data, clinical characteristics, pathology and prognosis of the two groups were compared. Logistic regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and glomerular microthrombosis. Renal prognosis of the two groups were compared by the Kaplan-Meier survival curve.Results:A total of 116 patients were enrolled, aged (32.79±11.43) years old, in which 108 cases (93.10%) were female. Thirty-seven patients (31.90%) were confirmed to be combined with GMT (GMT group) and 79 cases were not (non-GMT group). Compared with the non-GMT group, patients in the GMT group were relatively older ( t=-2.876, P=0.002), with higher proportion of hypertension ( χ2=7.492, P=0.006), higher urine protein quantitation ( Z=-2.115, P=0.003), lower levels of eGFR and serum complement C3 ( Z=3.469, P<0.001; t=1.744, P<0.001), higher systemic lupus erythematosus disease activity index ( t=-2.758, P=0.007). As to the pathological characteristics, type IV LN patients were the majority (72.97%). Proportion of crescents and pathological activity indicators of the GMT group were higher ( Z=-1.866, P=0.002; t=-5.005, P<0.001), nuclear fragmentation, endothelial hyperplasia and renal tubular atrophy were more serious ( χ2=14.987, P<0.001; χ2=15.695, P<0.001; χ2=4.130, P=0.042). Multivariate logistic regression analysis indicated that serum complement C3 was a relational factor of the formation of GMT in LN patients ( OR=0.966, 95% CI 0.938-0.995, P=0.023). Smooth curve fitting of generalized additive mixed model analysis indicated that level of complement C3 had a linear relationship with the changing trend of GMT. The Kaplan-Meier curve showed that there were statistical differences between the two groups in terms of complete remission of urine protein (Log-rank χ2=5.858, P=0.016) and doubled serum creatinine/end-stage renal disease (Log-rank χ2=3.945, P=0.047). Conclusions:Serum C3 is closely related to the formation of GMT in LN patients, and statistical differences were demonstrated in the renal prognosis of GMT group and non-GMT group.

Curative effect and mechanism ofαlipoic acid combined with epalrestat and methylcobalamin in the treatment of type 2 diabetic peripheral neuropathy / 中国医师杂志

Objective To investigate the curative effect and mechanism of α lipoic acid combined with epalrestat and methylcobalamin in patients with type 2 diabetes mellitus (T2DM) complicated with pe-ripheral neuropathy ( DPN) . Methods A total of 160 cases of patients with DPN were randomly divided into the control group ( treated with methylcobalamin and epalrestat) and the observation group ( treated with methylcobalamin, epalrestat and α lipoic acid) , and all patients were treated for 4 weeks. The therapeutic effect, nerve conduction velocity, oxidative stress index and related proteins expression in serum were ob-served in two groups. Results The effective rate of treatment in the observation group was higher than that in the control group (87. 50％ vs 75. 0％) (χ2 = 4. 103,P<0. 05). After treatment, the sensory nerve conduction velocity ( SNCV) and motor nerve conduction velocity ( MNCV) of median nerve and common peroneal nerve were significantly better in the observation group than the control group ( P<0. 05 ) . After treatment, the level of superoxide dismutase ( SOD) was significantly higher in the observation group than the control group, while the level of malondialdehyde ( MDA ) was significantly lower the control group (P<0. 05). After treatment, the level of Bcl-2 protein was significantly higher in observation group than the control group, while the levels of Bax and Caspase-3 proteins were significantly lower than the control group (P<0. 05). Conclusions The application ofαlipoic acid combined to epalrestat and methylcobal-amin in the treatment of DPN can significantly improve the sensory and motor nerve conduction.

Autosomal dominant polycystic kidney disease in children's early identification and outcome / 中华实用儿科临床杂志

Autosomal dominant polycystic kidney disease( ADPKD)is the most common hereditary renal disease,which has an incidence of 1 / 1 000 to 1 / 500 in live births,was characterized by renal enlargement along with renal tubular cystic dilatation,approximately half of affected individuals reach end stage renal disease(ESRD)by 60 years of age,accounting for 7% - 10% of patients with ESRD. ADPKD could be diagnosed in children and even in ute-ro,early identification and intervention in children would ameliorate the progression of ADPKD to ESRD. Therefore,it is imperative for pediatricians to recognize the early clinical manifestations and outcome of the disease. The aim of this re-view will focus on the early identification,management and outcome in childhood.

Interleukin 10 knockout increases renal fibrosis of ischemia-reperfusion injury model mice / 中华肾脏病杂志

Objective To study the effect of interleukin (IL)-10 knockout (IL-10-/-) on renal repair after renal ischemia-reperfusion injury in mice.Methods Eighteen IL-10-/-mice (KO) aged 8-10 weeks and 18 C57BL/6 wild type mice (WT) aged 8-10 weeks were divided into control group (Sham) and renal ischemia-reperfusion injury (IRI) group.The renal tissue morphology change was observed by Hematoxylin and eosin (HE) staining and Masson staining.The expressions of IL-18, Ki67 and TGF-β1 were detected by immunohistochemistry.The expression of TGF-beta1 and IL-18 were detected by Western blotting.Results Compared with that in WT-IRI group, in KO-IRI group renal pathological damage was more severe, renal interstitial fibrosis was visible, Ki67 expression of renal tubular epithelial cells decreased distinctly (P＜0.01), the expression of TGF-betal increased significantly (P＜0.01).Conclusion Repair slows down significantly after kidney ischemia-reperfusion injury and fibrosis occurs gradually in IL-10-/-mice, eventually progressing to chronic kidney disease.

Significance of combined analysis of autoantibodies in diagnosis of primary biliary cirrhosis / 临床肝胆病杂志

ObjectiveTo evaluate the significance of combined analysis of different autoantibodies in the diagnosis of primary biliary cirrhosis (PBC). MethodsTwo-hundred and forty-five patients with liver diseases were randomly selected. According to the disease type, patients were divided into PBC group (n=162), autoimmune hepatitis (AIH) group (n=42), and liver disease control (LDC) group (n=41). ELISA assay was used to detect serum anti-mitochondrial antibody (AMA-M2) and antibodies against SP100 and GP210. Western blot assay was employed to detect serum anti-SLA antibodies. Indirect immunofluorescence assay was performed to detect serum AMA. Comparison of antibody positive rates between groups was carried out using the chi-square test and Fisher′s test. ResultsSerum AMA, AMA-M2, and anti-GP210 positive rates of the PBC group were 93.21%, 87.65%, and 19.75%, respectively, significantly higher than those of the AIH group, i.e., 19.05%, 7.14%, and 9.52%, respectively (χ2=97.311, P=0.001; χ2=98264, P=0001; χ2=10.312, P=0.012). The AMA, AMA-M2, and anti-GP210 positive rates of the PBC group were also significantly higher than those of the LDC group, i.e., 9.76%, 2.44%, and 7.32%, respectively (χ2=142.745, P=0.003; χ2=112.574, P=0.002; χ2=15.217, P=0.042). ConclusionSerum AMA has a remarkable meaning to PBC diagnosis, anti-SP100 gives a hint of PBC progression, and anti-GP210 plays a role in the diagnosis of AMA-negative PBC.

A study of reference intervals for serum thyrotropin and thyroid hormones during the neonatal period for the healthy term newborns in Suqian / 中华内分泌代谢杂志

Objective To establish thyrotropin( TSH) and thyroid hormones reference ranges during the neonatal period for the healthy term newborns in Suqian. Methods Blood samples from a heel-prick were collected from 500 healthy newborns 72 hours after birth to determine the level of TSH. 200 healthy newborns were chosen to determine the levels of serum TSH and thyroid hormones on the 14th day of life, and then compared with the results from 120 healthy adults. Results The reference range of TSH at 72 hours after birth was 0. 46-6. 59 mIU/ L. The reference ranges of TT3 , TT4 , TSH, FT3 , FT4 on the 14th day of life were 1. 10-2. 62 nmol/ L, 81. 10-158. 28 nmol/ L, 0. 83-6. 39 mIU/ L, 3. 76-6. 66 pmol/ L, and 10. 67-22. 27 pmol/ L, respectively. There was no significant difference in the interval of TSH between newborns and adluts, whereas there were significant difference in the intervals of TT3 , TT4 , FT3 , and FT4 between the two groups. Conclusions The establishment of TSH and thyroid hormone reference ranges during the neonatal period for the healthy term newborns could improve our understanding of the thyroid function during the neonatal period for the healthy term newborns, and our data suggests lowing the initiatory screening cut-off point of congential hypothyroidism.

Expression of stromal cell-derived factor 1 in the acute ischemia-reperfusion injury and its relationship with macrophages / 中华肾脏病杂志

Objective To observe the expression of stromal cell-derived factor 1 (SDF-1) in the kidney after ischemic reperfusion injury (IRI),and explore its relationship with macrophage during the IRI kidney.Methods A total of 28 healthy C57BL/6 male mice were used to establish renal IRI model by clamping both pedicles for 35 min followed by reperfusion.Kidney tissue samples were collected at indicated time points.Renal histological changes were estimated.The expression of SDF-1 was determined by immunohistochemistry,ELISA and real-time PCR.After the liposomal clodronate was injected intraperitoneally,the location of CD68 was observed by immunofluorescence.Renal histology and protein expression of SDF-1 were also detected.Results Compared with sham-operated group,classical tubular damage was found in IRI group,accompanied by a large number of inflammatory cells.The expression of total renal SDF-1 peaked on day 1 and decreased to control levels in the following days.SDF-1 in healthy kidney was localized at cortex,but spread to the corticomedullary area of the kidney during IRI.Compared with IRI groups,elimination of macrophage by injection of liposomal clodronate alleviated renal IRI and down-regulated the expressions of CD68 while up-regulating SDF-1.Conclusions SDF-1 expression is up-regulated in IRI kidney and is associated with macrophage.SDF-1 may play a role in the early phase of acute kidney injury and it may be a new marker in diagnosis of AKI.

Role of inhibitor of nuclear factor kappa B kinase alpha on renal inflammation after ischemia-reperfusion injury and its associated mechanism / 中华肾脏病杂志

Objective To reveal the role of inhibitor of nuclear factor kappa B kinase alpha (IKKα) in renal inflammation after renal ischemia-reperfusion (IR) injury and its potential associated mechanism.Methods Ischemia-reperfusion injury models were induced in a total of 24 healthy C57BL/6 male mice.Renal function and histological changes were estimated.The expression and site of IKKα,p52,RelB,IL-10 and IL-18 were determined by immunohistochemistry and Western blotting.After the short hairpin RNA(shRNA)targeting IKKα was injected into renal parenchyma,renal function and protein expressions of IKKα,p52,RelB,IL-10,IL-18 were detected.Results Compared with sham-operated group[Scr(7.30±0.13) μmol/L,BUN (8.39± 0.30) mmol/L],levels of Scr [(29.80± 2.10)μmol/L,(27.00±3.40) μmol/L,(23.00±3.70) μmol/L] and BUN [(9.47±3.50) mmol/L,(11.68 ±4.30)mmol/L,(13.12±2.10) mmol/L] were higher on day 1,3,7 and the injury of kidney was serious in IR injury group.Immunohistochemical expression of both IL-18 and IL-10 were increased.Markedly increased IKKα,p52 and RelB protein expression were noted in experiments from day 1 to day 7 during kidney recovery period,with a peak on day 3 and then decreasing toward baseline after day 7.Compared with IR injury group,low-expression of IKKα by injection of shRNA up-regulated the expression of IL-18 and down-regulated the expression of IKKα,p52,RelB and IL-10.Conclusions The NF-κB pathway is activated and IKKα expression is up-regulated during the kidney ischemiareperfusion injury,low-expression of IKKα may block inflammation resolution via down-regulation of alternative NF-κB pathway family members of both p52 and RelB.

Association of urinary neutrophil gelatinase-associated lipocalin and interleukin 18 with acute kidney injury after cardiac surgery / 中华肾脏病杂志

Objective To examine the association of urinary neutrophil gelatinase-associated lipocalin(NGAL) and interleukin 18(IL-18) with acute kidney injury (AKI) in patients after cardiac surgery. Methods Thirty-three patients undergone cardiac surgery were divided into AKI group and non-AKI group according to the AKI criteria. The Scr, urinary NGAL and IL-18 were measured at different time points. Results Nine of 33 patients (27.27%)developed postoperative AKI, and Scr concentration in AKI group reached its peak within 12-48 hours after cardiac surgery. Urinary concentrations of NGAL and IL-18 at 2 h and 4 h after cardiac surgery were significantly higher than those before operation in AKI patients (P<0.01). The urinary concentrations of NGAL at each time point and that of IL-18 at 2 h and 4 h after cardiac surgery in AKI patients were significantly higher than those in non-AKI patients. After correction by urinary creatinine, the differences of NGAL/Ucr and IL-18/Ucr ratios were still significant (P< 0.01). For concentrations of urinary NGAL, IL-18 and ratios of NGAL/Ucr, IL-18/Ucr at 2 h after surgery, sensitivities and specificities were good with cutoff values at 250 μg/L, 250 μg/mmol and 1800 ng/L, 1800 ng/mmol, respectively. Urinary concentration of NGAL at 2 h after cardiac surgery was positively correlated with Scr at 12 h postoperation in AKI group (r=0.638, P<0.05).Conclusions The incidence of AKI in patients after cardiac surgery is quite high. Urinary concentrations of NGAL, IL-18 and ratios of NGAL/Ucr, IL-18/Ucr at 2 h after cardiac surgery are the early diagnostic markers for AKI, among which urinary NGAL/Ucr is the most sensitive one.

Abnormal DNA-binding abilities of NF-?B and glucocorticoid receptor in cortex of kindey from rats with Adriamycin-induced nephrosis / 中国医师杂志

Objective To explore the role of transcription factors such as nuclear factor-kappa B(NF-?B) and glucocorticoid receptor(GR) in the pathogenesis of Adriamycin(ADM)-induced nephrosis in rats and the therapeutic effects of dexamethasone(Dex) and cyclosporin(CsA) on these animals.Methods The DNA-binding abilities of NF-?B and GR in cortex of kindey were examined with electrophoretic mobility shift assay(EMSA) and isotopic radioautography on the 7th,14th,21th and 28th day after a single intravenous injection of ADM,and the therapeutic effects of Dex and CsA were estimated.The biochemistry parameters from blood and urine of rats and the urine protein excretion were also measured.Results The NF-?B DNA-binding ability was significantly increased after 7 days and achieved maximum after 28 days(P0.05).Conclusion The DNA-binding ability of NF-?B is abnormally increased and that of GR is decreased in cells from cortex of kindey in Adriamycin-induced nephrotic rats.The NF-?B DNA-binding ability can be inhibited and the urine protein excretion is decreased by the treatment of CsA.

A Modified Method for Transfection to SKOV3 Cells with Protamine-DOT-AP/Chol Liposome-Oligodeoxynuleotides Complex / 中国肿瘤生物治疗杂志

Objective: To observe the transfer efficiency of protamine-DOTAP/Chol liposome-oligodeoxynuleotides complex to SKOV3 cells. Methods; Synthesized NF-?B decoy ODNs or scrambled ODNs labeled by FITC on the 5'ends was mixed with rationic DOTAP/cholesteral liposome and protamine, making the charge ratio of positive: negative 4. SK-OV3 cells were transfected by the complex (1 ?mol/L) and the efficiency were measured by flow cytometry ( FCM) and fluorescence meter. The direct effect of NF-KB decoy ODNs transfer on the growth of SKOV3 cell line in vitro was measured by MTT method. Results: The efficiency of LPD transfer to SKOV3 cell line was 96. 41% , significantly higher than that of naked DNA transfer which was 12. 86%. The growth of SKOV3 cell line was not affected by 48h incubation after NF-KB decoy ODNs or scrambled ODNs transfection. Conclusion: LPD method is the one with high transfer efficiency not affected by NBS( newborn bovine serum) with possibility of use in vivo.