Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

To analyze the correlation between the duration of hyperbaric oxygen (HBO) therapy and oral medication clonazepam reduction in patients with paroxysmal sympathetic hyperactivity (PSH).

OBJECTIVE: To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin. METHODS: Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×10⁹/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71⁺ erythrocytes and hemoglobin. RESULTS: The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717). CONCLUSION CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.
Male ; Humans ; Altitude Sickness/metabolism* ; Glucose Transporter Type 1 ; 2,3-Diphosphoglycerate ; Hemoglobins ; Chronic Disease ; RNA, Messenger ; Phenotype ; Glucose

Pediatric idiopathic nephrotic syndrome (INS) is characterized by massive albuminuria, hypoproteinemia, edema and hyperlipidemia, with a long course and high probability of relapse and prolongation. Long-term complications caused by long-term usage of hormones and immunosuppressants in children with INS seriously affect their physical and mental health and quality of life. Most children with steroid-sensitive nephrotic syndrome can be cured before adulthood, while some of them relapse in adulthood. Long-term prognosis of children with steroid-resistant nephrotic syndrome is poor. There have been few studies in China followed the long-term outcomes and its related factors of children with INS over 10 years. The paper reviewed the literatures on the long-term outcomes of children with INS, including renal survival, growth, mental health, learning and work, marriage and fertility, disease recurrence and long-term related complications, to explore the factors related to the poor long-term outcomes of children with INS and to assist in clinical decision-making and follow-up management.

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that affects multiple systems and organs throughout the body. Thrombotic microangiopathy (TMA) is a rare clinical syndrome that can lead to multiple organ dysfunction and even threaten life. Clinically, SLE patients with TMA are relatively rare, especially in children, but the mortality of SLE patients with TMA is significantly increased. The article reports 2 cases of successful remission of SLE complicated with TMA after treatment with eculizumab, and discusses the diagnosis, clinical manifestations and treatment of SLE complicated with TMA in children, so as to provide clinical basis for the diagnosis and treatment of SLE complicated with TMA in children.

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA_1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA_1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.
Aged ; Blood Pressure ; China/epidemiology* ; Cholesterol, LDL/therapeutic use* ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/drug therapy* ; Glycated Hemoglobin A/analysis* ; Humans ; Male ; Middle Aged

In recent years, it has been demonstrated in some studies that adrenocorticotropic hormone (ACTH) is effective in the treatment of certain steroid-resistant nephrotic syndrome, including membranous nephropathy, focal segmental glomerular sclerosis, minimal change nephropathy and so forth.ACTH can effectively relieve proteinuria and protect renal function, suggesting that there may be other mechanisms in addition to the adrenocorticotropic effect.This article mainly introduces the biological characteristics of ACTH, in combination with the clinical and basic studies on the treatment of nephrotic syndrome by ACTH, and clarifies several possible mechanisms, in an attempt to provide basis for clinical application.

C3 glomerulopathy is a rare disease of glomeruli mediated by abnormal activation of alternative complement pathway secondary to congenital genetic defects and acquired autoantibodies.Renal biopsy is the gold standard for diagnosing C3 glomerulopathy.C3 glomerulopathy encompasses both dense deposit disease and C3 glomerulonephritis.The main glomerular immunofluorescence staining is C3, with few or without immunoglobulins deposition, which is the obvious pathological feature.The clinical manifestations of C3 glomerulopathy are usually various, with limited detection methods and therapies and poor prognosis.This article mainly reviews the progress of C3 glomerulopathy in recent years, in order to improve clinical understanding of C3 glomerulopathy, and choose individualized therapy.

Objective:To investigate the clinical characteristics and electron transfer flavoprotein dehydrogenase ( ETFDH) genetic mutations in patients with riboflavin responsive lipid storage myopathy (RR-LSM). Methods:A retrospective analysis was performed. The clinical data and muscular pathology of 26 patients with RR-LSM, admitted to our hospital from January 2009 to June 2021, were collected. Peripheral venous blood DNA was extracted, and the mutations of ETFDH gene were detected and analyzed by whole exome sequencing. Results:These 26 patients had onset of proximal limb myasthenia, 17 patients had difficulty in raising their head, 12 patients had mastication weakness, 6 had dysphagia, 5 had nausea and vomiting, and one was complicated with rhabdomyolysis and one was with reversible splenic lesion syndrome. Muscle biopsy indicated pathological deposition of lipid droplet, which type I fibers were involved mainly; degenerative necrotic muscle fibers were seen in a few cases. ETFDH gene mutations were detected in 26 patients; 23 patients had compound heterozygous mutation, two had single heterozygous mutation and one had homozygous mutation; 25 different mutation sites were found, mainly missense mutations; the C.770A>G frequency was the highest, accounting for 20% alleles (10/50); two novel mutation sites were found: c.1115A>G and c.1781T>C. Conclusion:RR-LSM is mainly characterized by proximal limb muscle weakness and fatigue intolerance, often accompanied by neck extensor and masticatory weakness; c. 770A>G is the hot site of ETFDH genetic mutations in RR-LSM patients.

Objective:To investigate the efficacy and safety of adrenocorticotropic hormone (ACTH) in treating primary nephrotic syndrome in children with dual resistance to glucocorticoids and calcineurin inhibitors (CNIs).Methods:Clinical data of 6 children with primary nephrotic syndrome treated with ACTH in the Children's Hospital of Zhejiang University School of Medicine from January 1, 2015 to December 31, 2019 were retrospectively collected. All the enrolled patients were children with primary nephrotic syndrome with dual resistance to glucocorticoids and CNIs. All the 6 children were given 0.4-1.0 IU·kg -1·d -1 ACTH (total ≤25 IU)+5% glucose 500 ml intravenous infusion for 8 h during the hormone reduction process, with a course of treatment for 5 days, once a month, and continuous treatment for 3-6 months. Clinical data such as 24 h urinary protein quantification, serum albumin, serum cholesterol, estimated glomerular filtration rate (eGFR) level and glucocorticoid dosage were collected at equal time points at 6 months before treatment, at the beginning of treatment, at the end of treatment and at 6 months of follow-up after treatment of ACTH to evaluate the efficacy and adverse reactions. Results:The onset age of 6 children was (4.89±1.77) years, and the age of the first treatment with ACTH was (9.49±3.06) years. All the 6 children completed 3 to 6 months of ACTH treatment, with 2 cases of complete remission, 2 cases of partial remission and 2 cases of no remission. At the end of ACTH treatment, 24 h urinary protein was significantly decreased ( P=0.026), serum albumin level was significantly increased ( P=0.003), and glucocorticoid dosage was significantly decreased ( P<0.001) than before treatment. At 6 months after the end of ACTH treatment, there was no statistical significance in 24 h urinary protein, serum albumin and hormone dosage compared with the end of ACTH treatment (all P>0.05), and the blood cholesterol level continued to decrease ( P=0.039). There was no significant change in eGFR during observation period ( P>0.05). In the process of ACTH infusion, all the 6 children showed transient decrease in urine output, rash in 2 cases, and elevated blood glucose in 1 case, which could be spontaneously relieved after drug withdrawal. There were no serious cardiovascular events, renal impairment, infection and other adverse reactions. Conclusions:ACTH has a good effect on children with primary nephrotic syndrome who are dual resistant to glucocorticoids and CNIs. ACTH can reduce proteinuria, decrease the dosage of glucocorticoids, improve the clinical remission rate, and has good security.