Objective:To discuss the ameliorative effect of total flavonoids from corn silk(TFCS)on kidney injury in the rats with urate nephropathy,and to clarify the possible mechanism.Methods:Sixty male Wistar rats were randomly divided into control group,model group,positive control group[benzbromarone(BZM)group,5 mg·kg-1·d-1],low dose of TFCS group(20 mg·kg-1·d-1),medium dose of TFCS group(40 mg·kg-1·d-1),and high dose of TFCS group(80 mg·kg-1·d-1),and there were 10 rats in each group.Except for control group,the rats in the other groups were administered potassium oxonate(350 mg·kg-1)and adenine(70 mg·kg-1)by gavage for 4 weeks to establish the hyperuricemic nephropthy models.The rats in different doses of TFCS groups were treated with TFCS for 2 weeks.Speckle blood flow imager was used to detect the renal blood perfusion of the rats in various groups and the kidney coefficients of the rats in various groups were caculated;HE staining and Masson staining were used to observe the pathomorphology and fibrosis degrees of kidney tissue of the rats in various groups and enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of uric acid(UA),creatinine(Cr),blood urea nitrogen(BUN),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the serum and levels of β2-microglobulin(β2-MG)and microalbumin(ALB)in the urine of the rats in various groups;Western blotting method was used to detect the expression levels of urate transporter 1(URAT1),glucose transporter 9(GLUT9),and ATP-binding cassette transporter G2(ABCG2)proteins in kidney tissue of the rats in various groups.Results:Compared with control group,the renal blood perfusion volume of the rats in model group was significantly decreased(P<0.01).Compared with model group,the renal blood perfusion volumes of the rats in BZM group and low,medium,and high doses of TFCS groups were significantly increased(P<0.05 or P<0.01).Compared with control group,the kidney weight of the rats in model group was increased,with visible white granular spots on the surface,absence of blood color,and kidney volume was increased.Compared with model group,the kidney volumes of the rats in BZM group and medium and high doses of TFCS groups were decreased,with color tending toward that in control group,and the white granular spots on the surface were significantly reduced.Compared with model group,the kidney coefficients of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).The HE staining results showed there were no abnormalities in kidney tissue structure in control group,while there were a small amount of brown-yellow urate crystal deposition and interstitial connective tissue hyperplasia in model group;compared with model group,the kidney tissue damage and inflammatory infiltration were alleviated to varying degrees in BZM group and different doses of TFCS groups.The Masson staining results revealed no obvious collagen fiber deposition in control group,whereas significant blue collagen fiber deposition in kidney tissue of the rats was found in model group,and the collagen volume fraction(CVF)was increased compared with control group(P<0.01);compared with model group,the CVFs of the rats in BZM group and different doses of TFCS groups were decreased(P<0.01).The ELISA results showed that compared with control group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in model group were increased(P<0.01);compared with model group,the levels of UA,Cr,BUN,IL-6,and TNF-α in serum of the rats in BZM group and medium and high doses of TFCS groups were decreased(P<0.01).Compared with control group,the levels of β2-MG and ALB in urinary in model group were increased(P<0.01);compared with model group,the levels of β2-MG and ALB in urinary of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01).The Western blotting results showed that compared with control group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in BZM group and model group were increased(P<0.01),while the expression level of ABCG2 protein was decreased(P<0.01).Compared with model group,the expression levels of URAT1 and GLUT9 proteins in kidney tissue of the rats in different doses of TFCS groups were decreased(P<0.05 or P<0.01),and the expression level of ABCG2 protein was increased(P<0.01).Conclusion:TFCS can significantly alleviate the kidney injury in the rats with urate nephropathy model,and its mechanism may be related to the downregulation of expression of URAT1 and GLUT9 proteins and upregulation of ABCG2 protein expression in kidney tissue.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Pasteurella multocida(Pm)type A is an important pathogen responsible for respiratory diseases,such as bovine pneumonia,which seriously restricts the development of cattle industry in China.Currently,the prevention of Pm infection-related diseases primarily relies on vaccination in production.However,the diverse Pm serotypes result in inadequate cross-immunological protection from vaccines.Therefore,it is of great significance to develop vaccines with cross-protection for the prevention and control of Pm infectious diseases.The previous studies conducted by our team have demonstrated that PmCQ2△cra exhibits a strong immune protective effect against Pm type A(PmA),Pm type B(PmB),and Pm type F(PmF).Transcriptomic sequencing results suggest that the cross-immunoprotective effect of PmCQ2△cra may be attributed to high expression levels of bacterial surface protective antigens.Consequently,four putative immune protective antigens,namely PmCQ2-5175,PmCQ2-6290,PmCQ2-0275 and PmCQ2-2640,were screened through bioin-formatics analysis in this study.Subunit vaccines formulated with these potential antigenic proteins exhibited protective efficacy of 62.5％,25％,12.5％and 10％against PmA-infected mice,respectively.Importantly,PmCQ2-5175,one of the most protective single-component antigen vac-cines,demonstrating a 75％cross-protection against PmB infection in mice.Furthermore,the pro-tective efficacy of the PmCQ2-5175 protein screened in this study was superior to that of the previ-ously reported Pm antigen protein plpE.Moreover,the fusion expression protein PmCQ2-5175-PLPE exhibited better protective effects against PmA compared to a single protein.The findings of this study will establish a theoretical foundation for the advancement of Pm subunit vaccines with broad-spectrum immune protection.

Pasteurella multocida(Pm)type A is an important pathogen responsible for respiratory diseases,such as bovine pneumonia,which seriously restricts the development of cattle industry in China.Currently,the prevention of Pm infection-related diseases primarily relies on vaccination in production.However,the diverse Pm serotypes result in inadequate cross-immunological protection from vaccines.Therefore,it is of great significance to develop vaccines with cross-protection for the prevention and control of Pm infectious diseases.The previous studies conducted by our team have demonstrated that PmCQ2△cra exhibits a strong immune protective effect against Pm type A(PmA),Pm type B(PmB),and Pm type F(PmF).Transcriptomic sequencing results suggest that the cross-immunoprotective effect of PmCQ2△cra may be attributed to high expression levels of bacterial surface protective antigens.Consequently,four putative immune protective antigens,namely PmCQ2-5175,PmCQ2-6290,PmCQ2-0275 and PmCQ2-2640,were screened through bioin-formatics analysis in this study.Subunit vaccines formulated with these potential antigenic proteins exhibited protective efficacy of 62.5％,25％,12.5％and 10％against PmA-infected mice,respectively.Importantly,PmCQ2-5175,one of the most protective single-component antigen vac-cines,demonstrating a 75％cross-protection against PmB infection in mice.Furthermore,the pro-tective efficacy of the PmCQ2-5175 protein screened in this study was superior to that of the previ-ously reported Pm antigen protein plpE.Moreover,the fusion expression protein PmCQ2-5175-PLPE exhibited better protective effects against PmA compared to a single protein.The findings of this study will establish a theoretical foundation for the advancement of Pm subunit vaccines with broad-spectrum immune protection.

A retrospective data collection was conducted on 16 patients who underwent secondary resection of bladder cancers using β-knife resection. The postoperative follow-up period is 12(10, 15)months, and no perioperative complications were detected. Among them, there were 3 cases of tumor recurrence, 2 cases continued to undergo β-knife resection, and 1 case underwent radical cystectomy. The safety of β-knife secondary electric cutting is high, and it can correct the insufficient first TURBT.

A retrospective data collection was conducted on 16 patients who underwent secondary resection of bladder cancers using β-knife resection. The postoperative follow-up period is 12(10, 15)months, and no perioperative complications were detected. Among them, there were 3 cases of tumor recurrence, 2 cases continued to undergo β-knife resection, and 1 case underwent radical cystectomy. The safety of β-knife secondary electric cutting is high, and it can correct the insufficient first TURBT.

Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.

Objective:To investigate the clinical characteristics, diagnosis and treatment of mycoplasma pneumoniae(MP) pneumonia in children with pseudo-macrocytic erythrocytes.Methods:The clinical data of 50 children with mycoplasma pneumoniae pneumonia with pseudo-macrocytic erythrocytes in the Department of Pediatrics at Shengjing Hospital of China Medical University from January 2019 to August 2020 were analyzed retrospectively.Results:Among the 50 cases, there were 32 boys and 18 girls.The blood routine examination showed that pseudo-macrocytic erythrocytes, red blood cells decreased significantly, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration increased significantly, as well as MP-IgM was positive.Sixteen cases were complicated with herpes simplex virus infection, one with Epstein Barr virus infection, and six with both herpes simplex virus and Epstein Barr virus infection at the same time.All 50 cases were MP pneumonia, pulmonary imaging showed lobar pneumonia, and 25 cases were complicated with pleural effusion, including 32 cases of refractory MP pneumonia.The clinical symptoms of three cases were extrapulmonary manifestations, hemolytic anemia and diagnosed with cold agglutinin syndrome.In 36 children with D-dimer more than 252 μg/L, one case had femoral vein thrombosis and one case had pulmonary embolism.Conclusion:Pseudo-macrocytic phenomenon may play important roles in clinical etiological diagnosis, severity of disease and refractory MP pneumonia.The children with hemolytic anemia suggest cold agglutinin syndrome, and the hypercoagulable state of MP infection may be related to the aggregation of red blood cells caused by cold agglutinin in MP infection.

Objective:To investigate the clinical features, risk factors, treatment and prognosis of dermatomyositis (DM) patients with positive anti-melanoma differentiation associated gene 5(MDA5) antibody with rapidly progressive interstitial lung disease (RPILD).Methods:The clinical data of 88 DM patients from June 2019 to June 2020, at the rheumatology department of Guangdong Provincial People's Hospital were collected and retrospectively analyzed. T-test, non-parametric Mann-Whitney U test, Chi-squared test, Fisher exact probability and Logistics regression analysis were used for data analysis. Results:① 37%(36/88) DM patients were positive for anti-MDA5 antibody. The frequency of ulcerative rash, Gottron's sign, arthritis, clinically amyopathic dermatomyositis (CADM), and erythrocyte sedimentation rate (ESR) was significantly higher in patients with anti-MDA5 antibody ( P<0.05). The cell count of white blood cell, neutrophil, lymphocyte, and serum creatine kinase (CK) level were significantly lower in the anti-MDA5 antibody positive group than those in the negative group ( P<0.05). Of anti-MDA5 antibody positive DM patients, 100% developed ILD, 34% (11/32)developed RP-ILD, 16%(5/32) died, which were significantly higher than those of anti-MDA5 antibody negative patients ( P<0.05). ② Of anti-MDA5 antibody positive DM patients, the C reactive protein (CRP) level, positive rate of anti-Ro-52 antibody and mortality rate were significantly higher RPILD group than those in the non-RPILD group [15.70(4.49, 29.00) vs 3.22 (1.66, 7.15), Z=-2.440, P=0.014; 91% vs 43%, P=0.011; 46% vs 0, P=0.002]. Logistics regression analysis indicated that positive anti-Ro-52 antibody [ OR=4.561, 95% CI (1.797, 11.580), P=0.001] might be a risk factor for anti-MDA5 antibody positive DM-RPILD. ③ Among patients with anti-MDA5 antibody with RPILD, serum ferritin and D-dimer level was significantly higher and oxygenation index was significantly lower in the non-survival group than those in the survival group [1 931 (1 377, 7 379) vs 638(196, 876), Z=-2.556, P=0.009; 2 760(1 995, 4 854) vs 985(533, 1 588), Z=-2.379, P=0.017; 230(140, 256) vs 309(262, 382), Z=2.191, P=0.030]. In addition, the delayed intensive treatment time was significantly longer in the non-survival group than those in the survival group [(14.0±2.6) vs (4.5±1.4), t=7.899, P<0.01]. Furthermore, the proportion of combined therapy with two disease modifying antirheumatic drug (DMARDs) was significantly lower in the non-survival group than those in the survival group (0 vs 83%, P=0.015). Conclusion:Anti-MDA5 antibody may be associ-ated with characteristic clinical manifestations of DM, ILD, RPILD and high mortality rate. Positive anti-Ro-52 antibody may be a risk factor for anti-MDA5 antibody positive DM-RPILD. High serum ferritin and D-dimer level and low oxygenation index in RPILD patients may be associated with poor prognosis. Early treatment with two DMARDs may improve the prognosis of RPILD.

With the rapid changes in lifestyle, natural and social environment, the reproductive health status of couples in childbearing age continues to decline, and long-term outcomes of the rapidly increasing offspring conceived by assisted reproductive technology (ART) needs to be evaluated urgently. Therefore, the focus of research now needs to be extended from death and severe diseases to full life cycle and full disease spectrum. In order to meet the demand for such research, we launched the China National Birth Cohort (CNBC) study, an ongoing prospective and longitudinal study aiming to recruit 30 000 families underwent ART and 30 000 families with spontaneous pregnancies. Long-term follow-up programs will be conducted for both spouses and their offspring. Data of couples and their offspring, such as environmental exposure, reproductive history, psychological and behavioral status, will be collected during follow-up. Peripheral blood, urine, umbilical blood, follicular fluid, semen were also collected at different follow-up nodes. Based on high-quality data and biological samples, CNBC will play an extremely important supporting role and have a far-reaching impact on maternal and children's health care and reproductive health in China. This paper is exactly a brief introduction to the construction and basic design of CNBC.