Hypoxia is associated with the occurrence and development of many diseases in clinical settings.Cell hypoxia not only serves as a vital marker for disease advancement,but also plays a pivotal role in exacerbating the disease process,and improving tissue hypoxia may thus provide new strategies for the treatment of related diseases.Further investigation of these diseases at the cellular and molecular levels requires the establishment of a cellular hypoxia model.Current extensively employed hypoxic cell models can be categorized primarily into three types:chemical hypoxia,physical hypoxia,and glucose deprivation hypoxia models.This article reviews the various types of hypoxic cell models and scrutinizes their applications and limitations in disease research.

Hypoxia is associated with the occurrence and development of many diseases in clinical settings.Cell hypoxia not only serves as a vital marker for disease advancement,but also plays a pivotal role in exacerbating the disease process,and improving tissue hypoxia may thus provide new strategies for the treatment of related diseases.Further investigation of these diseases at the cellular and molecular levels requires the establishment of a cellular hypoxia model.Current extensively employed hypoxic cell models can be categorized primarily into three types:chemical hypoxia,physical hypoxia,and glucose deprivation hypoxia models.This article reviews the various types of hypoxic cell models and scrutinizes their applications and limitations in disease research.

Clinical data of a case of Epstein-Barr virus-associated smooth muscle tumor with non-human immunodeficiency virus/transplantation admitted in the Department of Nephrology and Rheumatology, Hunan Children′s Hospital in May 2020 were retrospectively analyzed.The 6 years and 7 months old girl presented with bilateral hip pain for more than 1 year.Imaging examination revealed multiple nodular lesions in the central nervous system and lungs.Arthritis was the first manifestation in this case, and as a result, the patient was misdiagnosed as juvenile idiopathic arthritis.Finally, the patient was pathologically diagnosed as Epstein-Barr virus-associated smooth muscle tumor, which was a rare tumor associated with immunosuppression.

Objective:To explore the role of the fat mass and obesity-associated protein (FTO) in human renal tubular epithelial cells (HK-2) suffering ischemia-reperfusion injury (IRI).Methods:The in vitro IRI mo-del was established in HK-2 cells by induction with antimycin A, A23187 and 2-deoxy-D-glucose.The cells were divided into control group and ischemia-reperfusion group (I/R group). The mRNA and protein expressions of FTO, B-cell lymphoma / leukemia 2(Bcl-2)-associated X(Bax), Bcl-2 and cleaved cysteinyl aspartate specific proteinase(cleaved Caspase-3) in HK-2 cells before and after IRI were detected by real-time fluorescent quantitative PCR(qPCR) and Western blot, respectively.Cell apoptosis was measured using flow cytometry.The level ofe N 6-methy-ladenosine (m 6A) RNA was detected by colorimetry. Results:(1) The mRNA expressions of FTO (0.15±0.05 vs.1.00±0.23) and Bcl-2 (0.14±0.07 vs.1.02±0.25) in I/R group were significantly lower than those in control group; While those of Bax (3.10±0.35 vs.1.00±0.13) and cleaved Caspase-3 (4.21±0.56 vs.1.00±0.09) were significantly higher ( t=6.28, 5.84, -9.83, and -9.84, respectively, all P<0.01). (2) The protein expressions of FTO (0.69±0.14 vs.1.37±0.02) and Bcl-2 (0.50±0.12 vs.1.25±0.21) were significantly lower in I/R group than those of control group; While those of Bax (1.04±0.08 vs.0.57±0.06) and cleaved Caspase-3 (0.99±0.05 vs.0.36±0.07) were significantly higher ( t=8.10, 5.49, -8.22, and -12.09, respectively, all P<0.05). (3) Compared with the control group, the apoptosis rate of HK-2 cells in I/R group was significantly higher [(61.70±1.01)% vs.(0.16±0.10)%, t=63.80, P<0.01]. (4) Compared with the control group, the percentage of m 6A modification level in total RNA in I/R group was significantly higher [(3.13±0.21)% vs.(1.10±0.26)%, t=-10.61, P<0.01]. Conclusions:FTO-mediated RNA m 6A modification may affect renal IRI by regulating the apoptosis of HK-2 cells.

Pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare autoinflammatory bone disease, which caused by proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) gene mutations.Due to a lack of awareness of it among clinicians, PAPA syndrome is hard to diagnose and easy to be misdiagnosed or miss-diagnosed clinically.In this paper, twin brothers with recurrent fever and joints pain were reported.They were diagnosed with suppurative arthritis by many hospitals, but after receiving the joint cavity incision operation with negative pressure drainage for several times and antibiotics treatment, their conditions were not improved.Genetic tests showed that the twin brothers had a heterozygous mutation p. E250K (NM003978.3; c.748 G>A; p.Glu250Lys) on the PSTPIP1 gene.They were finally diagnosed with PAPA syndrome and improved with glucocorticoid therapy.

Objective:To investigate the risk factors for prolonged acute post-streptococcal glomerulonephritis(APSGN) in children, and to provide evidence for the prevention and treatment of chronic kidney diseases in children.Methods:A retrospective analysis was performed on the patients who were diagnosed as APSGN and hospitalized in the Department of Nephrology and Rheumatology of Hunan Children′s Hospital from January 2005 to August 2017 with complete clinical data, and follow-up time of more than 12 months.The patients were divided into the non-prolonged group and the prolonged group according to whether the disease course of the children exceeded 1 year. Logistic regression analysis of the high-risk factors for the prolonged disease was conducted. Results:Among 271 children included in the study, 197 cases were males, 74 cases were females; with the median age of 9.91 (7.66, 11.33) years old; there were 154 cases in the non-prolonged group (course of disease < 1 year) and 117 patients in the prolonged group (course of disease ≥1 year). Logistic regression analysis showed that duration of proteinuria ≥8 weeks, acute kidney injury, a large amount of proteinuria, and female were the risk factors for the prolonged APSGN (all P<0.05). Giving 1 point to the acute kidney injury duration of proteinuria ≥8 weeks and female, and 2 points to a large amount of proteinuria, the receiver operating characteristic curve analysis showed that for patient whose risk score was 3 points or more, the sensitivity of APSGN to be belonged was 43.6%, specificity was 86.4%, and positive predictive value and negative predictive value were 70.8% and 66.8%. Conclusions:Patients with a large amount of proteinuria accompanied by acute kidney injury or proteinuria duration ≥8 weeks, or female patients with a large amount of proteinuria, or female patients with acute kidney injury and proteinuria duration ≥8 weeks, but without a large amount of proteinuria, have a higher risk of prolonged APSGN.

OBJECTIVE: To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS: A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
Carcinoma, Hepatocellular ; blood ; diagnosis ; virology ; Case-Control Studies ; Chromatography, High Pressure Liquid ; DNA, Viral ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; virology ; Humans ; Liver Cirrhosis ; virology ; Liver Neoplasms ; blood ; diagnosis ; virology ; Mass Spectrometry ; Metabolome ; Metabolomics ; ROC Curve

With the increasing use of contrast agents,contrast medium-induced acute kidney injury(CI-AKI)has become one of the most important causes of hospital-acquired AKI.The study of adult population showed that the incidence of CI-AKI was approximately 11.0%,CI-AKI extend the patient's prolonged hospitalization,in-creased mortality and increased rates of cardiovascular events.However,little research is available regarding CI-AKI incidence,risk factors,prognostic impact and preventive measures in the pediatric population.How to improve the pre-vention and treatment level of CI-AKI in children is a challenge for pediatricians.

Objective To investigate the protective effect of ischemia preconditioning(IPC)on apoptosis in-duced by renal ischemia - reperfusion(IR)and relations to the changing expressions of Bcl - 2,Bax in rat kidney. Methods Ischemia models were induced by clipping bilateral renal pedicles for 30 min by using the artery clamp;IPC group was induced by clipping bilateral renal pedicles for 15 min,4 days later IR was performed again by clipping bila-teral renal pedicle for 30 min. Rats were randomly divided into 5 groups with 5 animals in each group:control group(C group),sham - operation group(S group),IR group,IPC group(IPC ﹢ IR group),sham IPC group(S ﹢ IR group),all groups were randomly divided into 9 sub groups(0 h,3 h,6 h,12 h,24 h,48 h,3 d,5 d,7 d)except C group according to the time points after reperfusion. Occurrence of apoptosis was detected by terminal deoxynuleotidyl transferase media-ted dUTP nick end and labeling(TUNEL)method;the mRNA expression and protein levels of Bax and Bcl - 2 were de-tected by reverse transcriptase - polymerase chain reaction and quantitave immunohistochemisty. Results (1)Com-pared with S group and S ﹢ IR group,serum creatinine,blood urea nitrogen,kidney pathological damage scores in IR group gradually increased after IR,and peak point was 24 h after reperfusion;among all the subgroups there was a sig-nificant difference(all P ﹤ 0. 01). The expression of Bax,Bcl - 2 mRNA raised sharply in IR group after reperfusion, peaking at 6 h,24 h of reperfusion respectively,2. 66 ± 0. 12,2. 70 ± 0. 10,and among all the subgroups there was a sig-nificant difference(all P ﹤ 0. 01);the expression of Bax,Bcl - 2 protein had significant difference(all P ﹤ 0. 05). TUNEL immunofluorescence staining showed C group and S group had no obvious apoptosis cells in renal tubular epi-thelium;epithelial cell apoptosis after IR gradually increased in IR group,peaking at 24 h of reperfusion[(25. 07 ± 2. 29)% ].(2)Compared with IR group and S ﹢ IR group,pathological injury was significantly decreased in IPC ﹢ IR group;the expression of Bax,Bcl - 2 mRNA and protein,apoptosis cells were significantly decreased in IPC ﹢ IR group (all P ﹤ 0. 05). Conclusions Bax,Bcl - 2 are closely associated with kidney injury induced by IR. IPC may regulate acute kidney injuries by regulating Bax/ Bcl - 2.

Objective To investigate the expression and significance of microRNA - 21(miR - 21)in acute kidney injury mice model at the different time points following ischemic/ reperfusion. Methods C57BL/ 6J mice were divided into 3 major groups:the control group(C group),sham operation group(S group)and ischemia - reperfusion group(IR group). Later 2 groups were divided into 9 sub - groups respectively according to the time following reperfu-sion. Automatic biochemical analyzer detected serum creatinine(Scr),blood urea nitrogen(BUN)level. HE staining detected renal pathological damage. Renal tubulointerstitial pathological score accessed pathological damage. Real time - PCR tested the expression of miR - 21 and mitogen - activated protein kinase kinase 3(MKK3)mRNA in renal respectively. Immunohistochemistry staining tested expression of MKK3. Results IR group's Scr,BUN levels gradually increased following reperfusion,24 h reached its peak,then gradually declined. The Scr,BUN level had statistically sig-nificant difference between IR group and S group at the same time subgroup from 3 h to 168 h following reperfusion(all P ﹤ 0. 01). The change of kidney damage and pathological changes of interstitial and tubular injury score consensus with renal function. miR - 21 increased gradually in renal ischemia after reperfusion,24 h peaked and then stabilized at this high level. miR - 21 was positively correlated with pathological tubulointerstitial injury from 0 h to 168 h after reperfu-sion(r = 0. 969,P ﹤ 0. 05). IR group's MKK3 mRNA and protein expression rose sharply following ischemia/ reperfu-sion,24 h peaked,and then gradually decreased. From 3 h to 168 h,the expression of MKK3 mRNA and proteins had significant difference at each same time points subgroups between IR group and S group(all P ﹤ 0. 01). Conclusions miR - 21 increases gradually in renal ischemia after reperfusion,24 h peaked and then stabilized at this high level. miR - 21 is positively correlated with pathological tubulointerstitial injury,which may be associated with the negative regulated relationship between miR - 21 and MKK3.