In recent years, rituximab has been gradually used in the treatment of idiopathic membranous nephropathy (IMN). Compared with traditional treatments, the safety and effectiveness of rituximab in the treatment of IMN have been confirmed, which induces remission in 60%-80% of patients. For the remaining 20%-40% patients, several mechanisms can explain rituximab resistance: decreased rituximab bioavailability; internalized by targeted B cells; the generation of anti-rituximab antibody; chronic and irreversible damage to the glomerular filtration barrier; autoreactive B-cell clones in secondary lymphoid organs that cannot be effectively eliminated. The treatment of patients with rituximab-refractory IMN remains controversial and challenging. The recognition of IMN as an antibody-mediated autoimmune disease has rationalized the use of immunosuppressive drugs such as B cell-targeted therapies, plasma cell-targeted therapies, and complement inhibitors. This review mainly summarizes recent advances in the understanding of the physiological mechanisms of rituximab resistance, and in the management of rituximab-refractory IMN, aiming to aid in the clinical management of IMN.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

From Early May 2022, monkeypox broke out in many countries around the world.By July 15, 2022, monkeypox has spread to more than 60 countries, causing more than 10 thousands human infections, and there have been death cases in countries with non-endemic regions.Monkeypox is caused by monkeypox virus which was belong to the Orthopoxvirus as smallpox, it is necessary for us to review the history of the fight against smallpox virus in humans and to develop measures to deal with monkeypox virus.

Monkeypox is a zoonotic disease.Previous studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications.In order to improve pediatricians′ understanding of monkeypox and achieve early detection, early diagnosis, early treatment and early disposal, the committee composed of more than 40 experts in the related fields of infectious diseases, pediatrics, infection control and public health formulate this expert consensus, on the basis of the latest clinical management and infection prevention and control for monkeypox released by the World Health Organization (WHO), the guidelines for diagnosis and treatment of monkeypox (version 2022) issued by National Health Commission of the People′s Republic of China and other relevant documents.During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis and differential diagnosis, treatment, discharge criteria, prevention, case management process and key points of prevention and control about monkeypox.

Group A Streptococcus (GAS) is a very important pathogen, especially for children.On a global scale, GAS is an important cause of morbidity and mortality.But the burden of disease caused by GAS is still unknown in China and also has not obtained enough attention.For this purpose, the expert consensus is comprehensively described in diagnosis, treatment and prevention of GAS diseases in children, covering related aspects of pneumology, infectiology, immunology, microbiology, cardiology, nephrology, critical care medicine and preventive medicine.Accordingly, the consensus document was intended to improve management strategies of GAS disease in Chinese children.

OBJECTIVETo detect disease-causing mutations in a patient with hereditary elliptocytosis.

METHODSSodium dodecyl sulfate polyacrylamide gel electropheresis (SDS-PAGE) was used to identify the type of erythrocyte membrane protein defect. Potential mutations of the exons and adjacent introns of relevant genes were analyzed by Sanger sequencing.

RESULTSSDS-PAGE has failed to detect any difference between the patient and healthy controls. However, Sanger sequencing has detected three mutations in the SPTA1 gene in the patient, which included c.5077A>C (p.Lys1693Gln) missense mutation in exon 36, c.5572C>G (p.Leu1858Val) missense mutation in exon 40, and a IVS45nt-12C>T in intron 45. The father and grandmother of the patient were both heterozygous for c.5077A>C mutation, while her mother was heterozygous for c.5572C>G and IVS45nt-12C>T mutations.

CONCLUSIONThe hereditary elliptocytosis in the patient may be attributed to the synergistic action of c.5077A>C, c.5572C>G and IVS45nt-12C>T mutations of the SPTA1 gene.

Objective: To analyze the clinical characteristics, diagnosis and treatment of bronchopulmonary foregut malformation(BPFM). Method: The clinical manifestations, imaging findings and treatment of 8 patients with BPFM were analyzed retrospectively from January 2006 to May 2016 in Beijing Children′s Hospital. Result: The age of children varied from 2 months to 7 years and 3 children were male while 5 female. Symptoms showed cough in 6 cases, fever in 4 cases, bucking when intaking of fluids or foods in 3 cases, tachypnea in 1 case, wheezing in 1 case, vomiting in 1 case, haematemesis in 1 case Pulmonary signs were decreased breath sounds in 4 cases, phlegm rale in 3 cases, shortness of breath in 2 cases, wheeze in 1 case, and retraction in 1 case. The upper gastrointestinal series showed abnormal fistulous tracts arising from the esophagus or the gastric fundus and extending into the mass in the lung. CT showed pulmonary sequestration and prompted the tube between lung and esophagus. Six children underwent pneumonectomy and esophageal fistula repair. They were discharged and their symptoms were improved. Two cases of children were discharged from a hospital without surgery. Conclusion Bronchopulmonary foregut malformation usually has its onset in early stage of life. The most common symptoms include recurrent pneumonia or bucking when intaking of fluids or foods. CT can demonstrate the bronchopulmonary sequestration and evaluate the communication with the gastrointestinal tract. The upper gastrointestinal series can demonstrate the abnormal tract directly. Pneumonectomy and esophageal fistula repair are the treatment of this disease.

Objective To investigate the potential role of CXC chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway in the progression of diabetic nephropathy (DN). Methods 8?week old male db/db mice were randomly divided into DN group and DN inflamed group. 10% casein was subcutaneously injected to induce the DN mouse model with inflammation. In vitro, HK?2 cells were treated with high glucose (HG), and IL?1β+HG to investigate the effect of inflammatory stress on HK?2 cells. Further knockdown CXCL16 was mediated by RNA interference to determine the effects of CXCl16, then cells were divided into HG+IL?1βgroup, HG+IL?1β + siCXCL16 group and HG + IL?1β + vehicle group. Changes of renal function in mice were assessed by 24 h proteinuria and N?acetyl?β?D?glucosaminidase (NAG) during 8 weeks. The ultra?microstructure was checked by electron microscopy at 8th week. Lipid accumulation in kidneys and HK?2 were observed by Filipin staining and quantitative assay of intracellular free cholesterol. The protein expressions of CXCl16, CXCR6, a disintegrin and metalloproteinase?10 (ADAM10), fibronectin and α smooth muscle actin (α?SMA) in renal tissue were detected by immunohistochemistry and Western blotting. The mRNA and protein expressions of CXCl16, CXCR6, ADAM10, fibronectin andα?SMA in HK?2 cells were detected by real?time PCR and Western blotting, and protein expressions of CXCl16, CXCR6 and ADAM10 in HK?2 cells were also tested by cell immunofluorescence. Results Mice in DN inflamed group had higher 24 h proteinuria and NAG than those in DN group, and the differences between two groups shown statistical significance at 8th week (all P<0.05). Compared with DN mice, DN inflamed mice had more vacuoles within renal tubular cells, with mitochondrial swelling, deformation and decrease. Lipid accumulation and protein expressions of fibronectin and α?SMA were increased in DN inflamed group when compared with DN group (all P<0.05). Further, the expressions of CXCL16, CXCR6, ADAM10 were significantly increased in DN inflamed group (all P<0.05). In vitro, the mRNA and protein expressions of CXCL16, CXCR6, ADAM10, fibronectin and α?SMA, and lipid accumulation were increased in high glucose plus IL?1βgroup when compared with high glucose group (all P<0.05). However, after siRNA of CXCL16 transfection, the mRNA and protein expressions of CXCL16, CXCR6, ADAM10, fibronectin andα?SMA were down?regulated in HG+IL?1β+siCXCL16 group as compared with high glucose+IL?1βgroup (all P<0.05). Furthermore, lipid accumulation was decreased (P<0.05). Conclusion Inflammation accelerates tubulointerstitial injury in DN partly through the activation of CXCL16 pathway, which may facilitate the lipid accumulation in tubular epithelial cells.

Objective To explore the effect of irbesartan on cardiac endothelial-mesenchymal transition (EndMT) in diabetic rats.Methods The model of diabetic rat was induced by intraperitoneal injection with streptozotocin (STZ,35 mg/kg) in spontaneous hypertensive rats (SHR).Diabetic rats were divided into diabetic group and the Irbesartan treated group.The pathological changes were investigated by fluorescence microscope and electron microscope.The EndMT was studied in human aortic endothelial cells (HAEC) exposure to high glucose.The concentration of angiotensin Ⅱ in the supernatant was detected by radioimmunoassay.Immunofluorescence staining was performed to detect the co-localization of CD31 and FSP1.Results The significant myocardial fibrosis was presented in the diabetic group.Endothelial protrusions were prominent feature in myocardial microvascular of diabetic rat compared with the control group rats.Double staining of HAEC showed co-localization of CD31 and FSP1,which was decreased by the treatment of Irbesartan (P ＜ 0.05).When HAEC was exposed to high glucose,it showed some cells acquired spindle-shaped morphology and lost CD31 staining,and FSP1 and α-SMA protein expression levels were markedly upregulated,which attenuated by the treatment of Irbesartan.Conclusion Irbesartan might prevent diabetes from myocardial fibrosis via inhibition of EndMT in diabetic rats.

Objective To investigate the effects of low density lipoprotein receptor (LDLr) pathway on podocyte injury in diabetic nephropathy (DN) under inflammatory stress.Methods Male db/db mice and db/m mice were randomly divided into four groups (8 mice in each group):db/m group (control),casein injected db/m group (db/m + casein),db/db group (db/db),and casein injected db/db group (db/db + casein).An inflamed model of DN was established according to our previous study.24-hour urinary protein was measured every week.The plasma lipid profile was detected by clinical biochemistry assay.Podocyte changes were evaluated by electron microscope and immunofluorescent staining.Lipid accumulation in the kidney was evaluated by oil red O staining and intracellular cholesterol quantitative assay.The protein expression of Wilm's tumor-1 (WT-1),nephrin,α-smooth muscle actin (t-SMA),and molecules correlated with LDLr pathway were examined by immunohistochemical staining or Western blotting.The colocalized protein expression of LDLr with WT-1 was examined by immunofluorescent staining and laser confocal microscopy.Results There were no differences in plasma levels of LDL and HDL among four groups.Compared with db/db group,the db/db+ casein group showed markedly increased 24-hour urinary protein,more significant podocyte foot process effacement and podocyte damage,increased lipid droplet accumulation in kidneys,increased protein expressions of LDLr,SCAP and SREBP-2 in kidneys (all P ＜ 0.05).Interestingly,increased LDLr protein expression in kidneys of db/db mice was negatively correlated with decreased nephrin protein expression (r =-0.855,P ＜ 0.01) and positively correlated with increased α-SMA protein expression (r=0.768,P ＜ 0.01).Conclusions The disruption of LDLr pathway induced by inflammation contributes to podocyte injuries in diabetic nephropathy.