Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-induced cytokine storms constitute the primary cause of coronavirus disease 19(COVID-19)progression,severity,criticality,and death.Gluco-corticoid and anti-cytokine therapies are frequently administered to treat COVID-19,but have limited clinical efficacy in severe and critical cases.Nevertheless,the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection.We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory interleukin(IL)-6,upregulated anti-inflammatory IL-10,and ameliorated acute inflammatory lung injury caused by mul-tiple infectious agents.Inosine significantly improved survival in mice infected with SARS-CoV-2.It indirectly impeded TANK-binding kinase 1(TBK1)phosphorylation by binding stimulator of interferon genes(STING)and glycogen synthase kinase-3β(GSK3β),inhibited the activation and nuclear trans-location of the downstream transcription factors interferon regulatory factor(IRF3)and nuclear factor kappa B(NF-κB),and downregulated IL-6 in the sera and lung tissues of mice infected with lipopoly-saccharide(LPS),H1N1,or SARS-CoV-2.Thus,inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19.Moreover,targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

Objective:The purpose of this study was to investigate the relationship between genotypes and clinical phenotypes of primary distal renal tubular acidosis (dRTA) in children.Methods:Clinical information, genetic testing information and follow-up data (until March 2021) of children with dRTA from Children′s Hospital of Chongqing Medical University (from January 2010 to December 2020) were analyzed retrospectively. According to different pathogenic genes, patients were divided into SLC4A1 gene and ATP6V0A4+ATP6V1B1 gene groups. Age at onset, clinical manifestations and laboratory findings were compared. Self-comparisons of height standard deviation score (HtSDS), weight standard deviation score (WtSDS), blood pH and serum potassium before and after treatment were tested. T-test, Fisher′s exact test and rank sum test were used to analyze among groups. Results:Among 27 children with dRTA (16 boys and 11 girls), the age of onset was 33.4 (10.0, 36.0) months.There were 22 patients (81%) with SLC4A1 gene variation, 3 patients (11%) with ATP6V1B1 gene variation and 2 patients (8%) with ATP6V0A4 gene variation. Totally 22 patients (81%) with renal calcium deposition, 19 patients (70%) hypokalemia, 18 patients (67%) short stature, 16 patients (59%) malnutrition, 16 patients (59%) rickets, and 15 patients (56%) polydipsia and polyuria. Noteworthily, the genotyping results indicated that the age at onset in SLC4A1 gene group was older than that in ATP6V0A4+ATP6V1B1 gene group, with a statistically significant difference (27.3 (12.0, 36.0) vs. 8.2 (2.5, 15.0) months, H=6.33, P=0.012). However, there were no significant differences in clinical manifestations or laboratory test results (all P>0.05). Furthermore, the course of disease was 3.9 (1.3, 6.0) years and the follow-up period was 3.1 (1.0, 4.5) years in 27 patients. In addition, there were no significant differences in recovery rate of clinical manifestations and last laboratory findings between SLC4A1 gene group and ATP6V0A4+ATP6V1B1 gene group (all P>0.05). HtSDS and WtSDS of those patients significantly increased after treatment (-3.2±1.9 vs. -2.1±1.1, -2.5±1.5 vs. 0±1.9, t=-2.94, -5.44, both P<0.01). Serum K + and blood pH were restored eventually ((3.2±0.5) vs. (4.0±0.5) mmol/L, 7.27±0.07 vs. 7.37±0.07, t=-4.92, -5.25, both P<0.01). Totally 14 patients had normalized serum potassium, 12 patients had normalized blood pH, but only 4 patients had normalized serum bicarbonate concentration and normal base excess. Conclusions:The age of onset of patients who had SLC4A1 gene mutation was older than that of patients with ATP6V0A4 gene and ATP6V1B1 gene mutations. However, there was no obvious correlation between the condition and prognosis of the dRTA patients and pathogenic genes. Early diagnosis, early treatment, regular follow-up and timely adjustment of the dosage of medication can significantly improve the prognosis of dRTA in children. Serum bicarbonate concentration and actual base excess might not be the necessory indicators to assess clinical recovery.

Objective:To investigate the effect of high glucose on scavenger receptor-A (SR-A) in human glomerular mesangial cells (HMC) and explore the mechanism of inflammatory injury mediated by SR-A in HMC cultured in high-glucose medium.Methods:According to the concentration of D-glucose in culture medium, HMC were divided into normal glucose group (5.5 mmol/L) and high glucose group (30 mmol/L), with mannitol group as hypertonic control. High glucose group was transfected with SR-A small interfering RNA (siSR-A) and the transfection control (siNC) group were set up. Western blotting technology was used to detect the levels of SR-A, NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-1β (IL-1β) protein. Immunofluorescent staining was applied to measure the SR-A in HMC. The mRNA of NLRP3, Caspase-1, IL-1β, FN, ColⅣ, α-SMA and GRP78 were detected by real-time quantitative PCR. The relative activity of Caspase-1 was detected by enzyme method and the concentration of IL-1β in culture medium was detected by enzyme linked immunosorbent assay. Flow cytometry was used to measure the cell cycles of HMC. One-way ANOVA and SNK-q test were used for statistical analysis.Results:The protein level of SR-A in high glucose group was higher than that in normal glucose group and mannitol group (1.23±0.21 vs. 0.68±0.10, 1.23±0.21 vs. 0.78±0.13, all P<0.05). In addition, mean fluorescence intensity of SR-A, protein levels of NLRP3 and IL-1β, mRNA of NLRP3, Caspase-1 and IL-1β, relative activity of Caspase-1 as well as the concentration of IL-1β in high glucose group were all significantly higher than those in normal glucose group and mannitol group (all P<0.05).After transfection induced silencing, SR-A protein in high glucose siNC group was higher than that in high glucose siSR-A group and normal glucose siNC group (1.23±0.10 vs. 0.20±0.01, 1.23±0.10 vs. 0.87±0.01, all P<0.01). In high glucose siNC group, the NLRP3, IL-1β proteins, the NLRP3, Caspase-1 and IL-1β mRNA, all of the mRNA levels of FN, ColⅣ, α-SMA, GRP78 and the proportion of DNA synthesis phase were all higher than those in high glucose siSR-A group and normal glucose siNC group (all P<0.05). Conclusion:High glucose can promote abnormal cell proliferation, increase mesangial matrix production and enhance oxidative stress response through upregulating SR-A expression, and ultimately aggravate cellular inflammatory damage in HMC, which may be associated with NLRP3-Caspase-1-IL-1β pathway regulated by SR-A expression.

Objective:To explore the differences in clinical indicators of different pathological types of children with hematuria as the main manifestation, and to establish a BP neural network prediction model based on clinical data.Methods:The clinical data and renal pathological results of children who were referred to Children′s Hospital of Chongqing Medical University from June 2003 to December 2018 for evaluation of hematuria as the main manifestation were collected, the significant differences in these clinical indicators were analyzed, and a BP neural network model for predicting renal pathology in children with hematuria as the main manifestation was established.Results:A total of 438 cases were enrolled in this study, including 232 males and 206 females, with the onset age of (7.00±3.15) years old.According to different clinical manifestations, the children were divided into microscopic hematuria group(179 cases), gross hematuria group(81 cases), microscopic hematuria and proteinuria group (44 cases), and gross hematuria and proteinuria group(134 cases). There were significant differences in sex ratio, onset age, course of disease, inducement, Addis count of urinary red cells, 24-hour proteinuria, blood urea nitrogen, serum creatinine, serum albumin and serum IgA levels among different clinical manifestations (all P< 0.05). Pathological grouping indicated that there were significant differences in sex ratio, onset age, course of disease, family history, Addis count of urinary red cells, 24-hour proteinuria, blood urea nitrogen, serum creatinine, serum albumin, serum IgA and C 3 levels among different pathological groups (all P< 0.05). The BP neural network prediction model was then constructed based on the above indicators, and the accuracy of the prediction model was measured to be 61.19% by using the leave one out method. Conclusions:By comparing the differences of various indicators under different clinical manifestations and pathological types, a BP neural network prediction model for renal pathology in children with hematuria as the main manifestation is established.The model can accurately predict renal pathology with the help of related indicators, and provides a basis for determining the time of kidney biopsy.

Objective: To establish the pathological grades of Henoch-Schönlein purpura nephritis(HSPN) in children with diagnostic prediction models by stepwise Fisher discriminant in children. Methods: Based on the investigation of 28 clinical indicators from 144 cases with HSPN came from Children′s Hospital of Chongqing Medical University, the sensitive indicators were found and stepwise Fisher discriminant model was established and its accuracy in predicting the pathological classification of HSPN was tested. Results: There were 5 laboratory indicators and clinical manifestations with different pathological grades of HSPN.In children with pathological grade Ⅱ, Ⅲ and Ⅳ, 5 indicators were screened (P<0.05) and stepwise Fisher discriminant models were established.And the correct rate of comprehensive diagnosis was (61.371±8.740)% in 100 random sampling diagnostic simulations; in children with pathological grade Ⅲa and Ⅲb, 5 indicators were also screened (P<0.05) and stepwise Fisher discriminant models were established.And the correct rate of comprehensive diagnosis was (68.015±5.736)% in 100 random sampling diagnostic simulations. Conclusions The stepwise Fisher discriminant models established in this research have a better diagnostic accuracy in forecasting for pathological grade of HSPN, and have a certain guiding value on early treatment and prognosis evaluation of children with newly diagnosed HSPN.

Objective: To systematically analyze the risk factors for urinary tract infection (UTI) in children with primary nephrotic syndrome (PNS), in order to provide scientific evidence for clinical prevention. Methods: Eight databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang Database, Chinese Science and Technology Periodical Database and Chinese Biological Medical Literature Database were retrieved for the case-control studies on PNS complicated with UTI in children.According to the inclusion and exclusion criteria, eligible studies were selected for meta-analysis by using RevMan 5.3 software. Results: Finally, 12 case-control studies were included, 917 children in the case group and 2 784 children in the control group.Compared with children without UTI, statistically significant difference existed in children with UTI of elevated 24-hour urine protein [standardized mean difference (SMD)=0.45, 95% CI: 0.02-0.88], decreased serum albumin (SMD=-1.06, 95%CI: -1.14--0.97), elevated serum cholesterol [weighted mean difference (MD)=2.28, 95%CI: 1.61-2.95], elevated serum low density lipoprotein (SMD=0.57, 95%CI: 0.37-0.77), decreased plasma IgG (SMD=-0.76, 95%CI: -0.94 to-0.58), elevated plasma IgM (MD=0.28, 95%CI: 0.11-0.46), high-dose hormone (MD=0.75, 95%CI: 0.58-0.92), and long time hormone use[<15 d odds ratio (OR)=-0.20, 95%CI: 0.10-0.42; ≥15 d OR=5.00, 95%CI: 2.38-10.50]. Conclusions Massive proteinuria, hypoalbuminaemia, hypercholesterolemia, high level of low density lipoprotein, decreased plasma IgG, high-dose hormone and long time hormone use are risk factors for UTI in children with PNS.

Objective To provide a reference for early detection and diagnosis of nutcracker syndrome(NCS) by analyzing the clinical features of children with NCS in different age groups and different gender groups.Methods Data of 112 children with simple NCS diagnosed at the Department of Nephrology of Chongqing Children's Hospital from January 2008 to January 2018 were analyzed retrospectively.Follow-up was conducted.Results In children with NCS,71 girls accounted for 63.4％,mainly in preschool age(82.4％,28 cases);41 boys accounted for 36.6％,mainly in school age(48.5％,8 cases) and adolescence(42.2％,7 cases).Fifty-one point two percent (21/41 cases) of boys presented with both hematuria and proteinuria after activities,60.6％ (43/59 cases) of girls presented with isolated hematuria after activities,while 46.7％ (21/45 cases) children in adolescence were most likely to appear lumbar and abdominal pain after activities,and the incidence of boys(63.2％,12 cases) was higher than girls (34.6％,9 cases),and the differences above were all statistically significant (x2 =6.939,P ＜ 0.05).The 24-hour urinary protein level in adolescent group was significantly higher than that in 2 groups of younger children,and the male children[0.09 (0.02-0.21) g/d] in this group were significantly higher than that in female children[0.06 (0.01-0.21) g/d] (x2 =6.48,P ＜ 0.05).The detection rate of CT angiography (CTA) (95.7 ％,67/70 cases) was significantly higher than that of color Doppler ultrasound (82.4％,75/91 cases),and the difference was statistically significant (x2 =6.721,P ＜ 0.05).Children with NCS in adolescence had smaller aortomesenteric angles (AMA) and larger ratios of the internal diameter of left renal vein(LRV) 's dilation part (a) to the stenosis part(b) (a/b) than those in preschool age and school age,and the difference was statistically significant (F =4.797,P ＜ 0.05).By follow-up of 96 cases for 3 months-7 years,there were 51 cases(58.0％) whose urine was back to normal in 88 cases who had reexamination of urine,and among the 54 patients who underwent color doppler ultrasound,25 cases(46.3％) showed relief of LRV compression.Conclusions There are more girls with NCS than boys,and girls are mainly in preschool age and always present with isolated hematuria,while boys are mainly in school age and adolescence and always presented with both hematuria and proteinuria.Children in adolescence were most likely to appear lumbar and abdominal pain,and boys have a higher incidence rate than girls.Children in school age and adolescence have the relatively higher quantitation level of proteinuria,and the smaller AMA and the larger a/b ratio,the more serious compression of LRV,and it's especially obvious in adolescence.

Objective To investigate whether follicular helper T(Tfh) cells were involved in the development of Henoch-Sch?nlein purpura(HSP) and Henoch-Sch?nlein purpura nephritis(HSPN) in chil-dren through affecting CD40/CD40L axis. Methods Fifty-five subjects were enrolled in this study and di-vided into four groups as follows:22 children with HSP but without renal involvement(Group A),11 chil-dren with HSPN presenting with microhematuria(Group B),11 children with HSPN presenting with micro-hematuria and proteinuria (Group C) and 11 healthy children (control group). Flow cytometry was per-formed to detect the percentages of CD19+B cells and their subsets,CD19+B cells and CD19+CD38+B cells secreting different Ig classes,CD19+CD40+B cells and their subsets and Tfh cells expressing CD40 ligand (CD40L). Results Compared with the control group,the percentages of CD19+CD86+B,CD19+CD138+B and CD40L+Tfh cells significantly increased in Group C(P<0.05) and slightly increased in Groups A and B (P>0.05). No significant difference in the percentages of CD19+B cells, CD19+CD27+B cells, CD19+B cells or CD19+CD38+B cells expressing IgG, IgM, IgD, CD19+B cells or CD19+B cell subsets secreting CD40 was found between the control group and Groups A,B and C(P>0.05). Moreover,the percentages of CD19+B and CD19+CD38+B cells secreting IgA and IgE in Groups A,B and C were higher than those in the control group(P<0.05). Secretion of IgA by CD19+B and CD19+CD38+B cells were positively correla-ted with the expression of CD40L by Tfh cells(P<0.05). Conclusion Tfh cell-mediated abnormal expres-sion of CD40/CD40L might play an important role in the development of HSP and be related to the clinical severity of renal involvement in HSPN.

Objective To explore the risk factors of acute kidney injury (AKI) in very low birth weight (VLBW) infants. Method The clinical data of 313 VLBW newborns aged under 3 days from January 2012 to December 2016 were retrospectively analyzed. According to the improved KDIGO standard of neonatal AKI, the difference between AKI (group AKI) and non AKI (group NAKI) newborns was compared, and the risk factors of AKI and mortality of AKI infants were analyzed. Results In the 313 VLBW infants, 126 had AKI and the incidence rate was 40.3％. There were 53 cases at stage 1 (42.1％), 43 cases at stage 2 (34.1％), and 30 cases at stage 3 (23.8％). Compared with NAKI group, patients in AKI group were lower in gestational age, birth weight, 5-minute Apgar score, critical score and mean arterial pressure. Furthermore, AKI group was higher in mother's age, incidence of premature rupture of membranes and respiratory failure. Also, white blood cells number and procalcitonin level were higher; albumin and sodium levels were lower; more cases had invasive mechanical ventilation after birth; time of mechanical ventilation was longer; mortality were higher in AKI group. There were statistically differences (P<0.05). Multivariate logistic regression analysis showed that gestational age, respiratory failure and invasive mechanical ventilation at birth were independent risk factors for AKI in VLBW infants. More severe acidosis and associated pulmonary hemorrhage at admission were the independent risk factors for the death caused by AKI in children. Conclusions Short gestational age, respiratory failure, and invasive mechanical ventilation at birth significantly increased the risk of AKI in VLBW infants. The more severe metabolic acidosis and pulmonary hemorrhage increased the risk of death in AKI children .

Objective To explore the clinical characteristics and influencing factors of primary nephrotic syndrome (PNS) combined with hypercoagulability in children. Methods The clinical data of 57 children with primary PNS were analyzed retrospectively. The clinical features and treatment were compared among high coagulation state group, non high coagulation state group and control group (20 children). At the same time, the differences between the simple nephrotic syndrome group (SNS) and nephritic syndrome group (NNS) in hypercoagulable state were analyzed. In addition, the correlation analysis was performed. Results Among 57 patients, there were 50 patients in high coagulation state group and 7 in non high coagulation state group. There was no significant difference in gender, age and clinical manifestations between two groups (P>0.05). The platelet (PLT) count, platelet aggregation (PCT), albumin (Alb), fibrinogen (Fib), D-dimer (D2) were significantly higher than those in the control group, and there were statistically significant differences (P all<0.01). There were significant differences in the levels of PLT, Fib, D2 and complement C4 between hypercoagulable state group and non hypercoagulable state group (P all<0.05). There were significant differences in HCT, TC, LDL, PT and complement C3 levels between SNS group (n = 32) and NNS group (n =18) in 50 patients with high coagulation state (P<0.05). There was positive correlation between HCT and complement C3 (r=0.30, P<0.05), while there was no correlation between PLT and other indices (P>0.05). All of the 57 patients were improved and has no thrombosis after the treatment. Conclusion Children with primary PNS were usually associated with different degrees of hypercoagulable state, and PLT, Fib, D2 could be used as reference indices for the severity of hypercoagulable state, and the activation of complement system might be related to the occurrence and development of hypercoagulable state.