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.

The paper reports a case of Fabry disease in a child with non-singular nocturnal enuresis as the first symptom. The boy developed unexplained nocturnal enuresis with frequent daytime urination since the age of 6. Fabry disease was detected and diagnosed by chance through high-risk screening. The activity of α-galactosidase A by dry blood spot was 1.97 μmol·L -1·h -1 , and there was c.640-801G>A mutation in GLA gene. Urine routine, urinary microprotein and renal function were normal. However, there were mulberry bodies found in urine deposition microscopy, suggesting the presence of kidney injury. This case suggests that enuresis can be the first symptom of Fabry disease, and mulberry bodies can be seen in the urine at the early stage of the disease.

Toxic encephalopathy is a term used to describe a group of diseases that are caused by poisoning with a variety of harmful substances. The main clinical manifestation of these diseases is damage to the central nervous system. Previously reported cases of selenium poisoning had only general clinical manifestations, and head imaging changes were rarely reported. This article reports a 58 year-old selenium-poisoned female patient who had been taking a selenium-containing dietary supplement for a long period of time and subsequently developed neurological impairment. The head magnetic resonance imaging indicated the presence of irregular and abnormal signals in the midbrain and cerebellum. The objective of reporting this case is to show the neurological manifestations of selenium toxic encephalopathy and to provide references for the clinical diagnosis and treatment of this disease, as well as the standardized utilisation of selenium-containing supplements.

Objective To explore the mechanism of Shanggan granules in suppressing pulmonary inflammation in mice infected with H1N1 influenza virus.Methods A mouse model of pulmonary influenza virus infection was established by nasal inoculation with H1N1 influenza virus.Mice were divided into a normal control group,model group,positive control group,and low-,medium-,and high-dose Shanggan granules groups.Mice were treated for 7 days and then sacrificed,and the body weight and lung wet weight were measured.Pathological changes in the lung tissues were detected by hematoxylin/eosin(HE)staining.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,and transforming growth factor-β(TGF-β)levels in lung tissues were detected by enzyme-linked immunosorbent assay,and superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected using appropriate kits.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)inflammatory signaling pathways were detected by real-time polymerase chain reaction,and TANK-binding kinase 1(TBK1)/interferon regulatory factor(IRF)signaling pathway proteins were detected by Western blot.Results Both Shanggan granules and oseltamivir phosphate reduced the lung wet weight(P＜0.05,P＜0.001)in mice infected with influenza virus H1N1 compared with the model group,decreased the infiltration of inflammatory cells in lung tissue,reduced levels of the inflammatory factors TNF-α,IL-6,IL-8,and TGF-β(P＜0.05,P＜0.01,P＜0.001),decreased levels of SOD and GSH-Px in lung tissue(P＜0.05,P＜0.01),and increased MDA levels(P＜0.05,P＜0.01).Shanggan granules and oseltamivir phosphate also reduced TLR4,MyD88,and p38 mRNA levels(P＜0.05,P＜0.01)and expression of TBK1/IRF3/7/NF-κB signaling pathway proteins(P＜0.05,P＜0.01,P＜0.001).Conclusions Shanggan granules may effectively reduce lung injury,lung inflammation,and oxidative stress,via a mechanism related to the down-regulation of TLR4/NF-κB inflammatory signaling pathways.

Objective To explore the mechanism of Shanggan granules in suppressing pulmonary inflammation in mice infected with H1N1 influenza virus.Methods A mouse model of pulmonary influenza virus infection was established by nasal inoculation with H1N1 influenza virus.Mice were divided into a normal control group,model group,positive control group,and low-,medium-,and high-dose Shanggan granules groups.Mice were treated for 7 days and then sacrificed,and the body weight and lung wet weight were measured.Pathological changes in the lung tissues were detected by hematoxylin/eosin(HE)staining.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,and transforming growth factor-β(TGF-β)levels in lung tissues were detected by enzyme-linked immunosorbent assay,and superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected using appropriate kits.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)inflammatory signaling pathways were detected by real-time polymerase chain reaction,and TANK-binding kinase 1(TBK1)/interferon regulatory factor(IRF)signaling pathway proteins were detected by Western blot.Results Both Shanggan granules and oseltamivir phosphate reduced the lung wet weight(P＜0.05,P＜0.001)in mice infected with influenza virus H1N1 compared with the model group,decreased the infiltration of inflammatory cells in lung tissue,reduced levels of the inflammatory factors TNF-α,IL-6,IL-8,and TGF-β(P＜0.05,P＜0.01,P＜0.001),decreased levels of SOD and GSH-Px in lung tissue(P＜0.05,P＜0.01),and increased MDA levels(P＜0.05,P＜0.01).Shanggan granules and oseltamivir phosphate also reduced TLR4,MyD88,and p38 mRNA levels(P＜0.05,P＜0.01)and expression of TBK1/IRF3/7/NF-κB signaling pathway proteins(P＜0.05,P＜0.01,P＜0.001).Conclusions Shanggan granules may effectively reduce lung injury,lung inflammation,and oxidative stress,via a mechanism related to the down-regulation of TLR4/NF-κB inflammatory signaling pathways.

The paper reports a case of Fabry disease in a child with non-singular nocturnal enuresis as the first symptom. The boy developed unexplained nocturnal enuresis with frequent daytime urination since the age of 6. Fabry disease was detected and diagnosed by chance through high-risk screening. The activity of α-galactosidase A by dry blood spot was 1.97 μmol·L -1·h -1 , and there was c.640-801G>A mutation in GLA gene. Urine routine, urinary microprotein and renal function were normal. However, there were mulberry bodies found in urine deposition microscopy, suggesting the presence of kidney injury. This case suggests that enuresis can be the first symptom of Fabry disease, and mulberry bodies can be seen in the urine at the early stage of the disease.

Toxic encephalopathy is a term used to describe a group of diseases that are caused by poisoning with a variety of harmful substances. The main clinical manifestation of these diseases is damage to the central nervous system. Previously reported cases of selenium poisoning had only general clinical manifestations, and head imaging changes were rarely reported. This article reports a 58 year-old selenium-poisoned female patient who had been taking a selenium-containing dietary supplement for a long period of time and subsequently developed neurological impairment. The head magnetic resonance imaging indicated the presence of irregular and abnormal signals in the midbrain and cerebellum. The objective of reporting this case is to show the neurological manifestations of selenium toxic encephalopathy and to provide references for the clinical diagnosis and treatment of this disease, as well as the standardized utilisation of selenium-containing supplements.

Objective:To explore the combination of high risk screening and family screening for potential patients with Fabry disease in adult hemodialysis population, and to improve the diagnostic efficiency of the disease.Methods:It was a cross-sectional investigation study. High-risk screening for Fabry disease was performed on adult hemodialysis patients with end-stage kidney disease who were admitted to Yongkang First People's Hospital of Zhejiang Province between November 2022 and February 2023. Dry blood paper α-galactosidase A (α-Gal A) detection assay was performed in males, or glycosphingolipids (Lyso-GL-3) detection assay was performed in females. GLA genetic assay was performed for further diagnosis after abnormal screening results. Family screening was carried out on the family members of the confirmed Fabry disease patients, and α-Gal A activity and Lyso-GL-3 of peripheral blood were measured. Additionally, urine routine, blood biochemistry, eye examination, hearing test, cranial magnetic resonance imaging, and electrocardiogram were performed to assess organ damage. Results:Among 244 hemodialysis patients, 139 (56.97%) were males and 105 (43.03%) were females. The age ranged from 25 to 81 years (with median age of 61 years). One female patient with Fabry disease was identified GLA IVS4+919G>A mutation, resulting in a total prevalence of 0.41%. Pedigree screening was conducted on 41 family members of the patient, leading to the confirmation of 12 patients (including the proband), including 3 males and 9 females. Among them, 9 patients were abnormal in enzyme examination, 10 patients were abnormal in substrate, and 11 patients were abnormal in gene sequencing. None of the 12 patients exhibited limb pain, hypohidrosis, angiokeratoma, corneal opacity, and hearing impairment. Eight patients had heart abnormalities. Nine patients had abnormal urine routine (albuminuria or hematuria) and one patient had abnormal renal function. Four patients had abnormal cranial magnetic resonance imaging findings. Conclusions:One GLA IVS4+919G>A mutation family is successfully identified through the combination of high-risk screening and family screening in adult hemodialysis patients, with a total of 12 cases of Fabry disease. The combination of high-risk screening and family screening proves to be effective in detecting potential patients with Fabry disease, and improve the screening efficiency of Fabry disease.

Objective:To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A.Methods:It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed.Results:The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband′s father had knee joint pain. The proband′s elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband′s fifth aunt with a GLA variant had decreased vision.Conclusions:High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Type 2 diabetes mellitus(T2DM)is a serious public health issue in China.Poor glycemic control is closely related to increased risks of microvascular,macrovascular events and mortality.Self-management ability and treatment adherence are key factors affecting glycemic control.Based on this,this review summarizes the findings on medication adherence related to different glucose-lowering regimens,analyzes the factors affecting patient treatment adherence and discusses the roles of drug characteristics,patient factors and shared decision-making in optimizing T2DM management strategies,in the hope of improving clinical outcomes.