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.

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:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

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.

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.

A case of cirrhosis with spontaneous spinal cord hemorrhage is reported. The patient was a 57-year-old male, whose main clinical symptoms were acute onset, sudden progressive decline of lower limb muscle strength, and incontinence. Magnetic resonance imaging+magnetic resonance angiography+susceptibility-weighted imaging of thoracic spinal cord showed that thin strip like equal and slightly high signal could be seen in the spinal cord of T 1WI sequence, a few low signal foci could be seen in the corresponding part of T 2WI sequence, and there was no obvious change in enhanced scanning. Obvious long strip like low signal foci were shown in the spinal cord of susceptibility-weighted imaging, and the range was significantly larger than that of T 2WI sequence. Spinal cord hemorrhage was diagnosed before operation, and no obvious improvement was found after drug treatment. Spontaneous spinal cord hemorrhage was diagnosed after surgical incision.

Objective To investigate the application value of pre-implantation genetic testing(PGT)in patients with Turner syndrome.Methods The clinical data,embryonic development,PGT results and pregnancy outcome of 18 patients with Turner syndrome who underwent PGT in the reproductive center of 900th Hospital from January 2016 to June 2023 were retrospectively analyzed.Results All 18 patients had spontaneous puberty development,of which 4 patients had primary ovarian insufficiency(POI).A total of 24 oocyte retrieval cycles were performed in 18 patients,of which 6 patients had no biopsied embryos for 10 cycles.Sixty-one embryos were biopsied and 60 embryos were clearly diagnosed,including 25 with chromosomal abnormalities.Seven patients with mosaic Turner syndrome obtained clinical pregnancies after transplantation,including 4 healthy boys had already been delivered and 3 are in pregnancy.Conclusion There are numerous types of karyotype in Turner syndrome.The clinical phenotypes vary greatly in individuals with Turner syndrome,and prognosis of PGT is significant different.Patients with Turner syndrome who had biopsied embryos can obtain available embryo using PGT,and achieve ideal clinical outcomes.

Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction (柴胡龙骨牡蛎汤, CHLGMLD) in rats with temporal lobe epilepsy (TLE). Methods A total of 80 Sprague-Dawley (SD) male rats were randomized into control (CON), model (MOD), carbamazepine (CBZ, 0.1 g/kg), CHLGMLD low dose (CHLGMLD-L, 12.5 g/kg), and high dose (CHLGMLD-H, 25 g/kg) groups, with 16 rats in each group. TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group. After the successful establishment of TLE models, all drugs were administered through gavage, and distilled water was given to rats in the CON and MOD groups for four weeks. The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-146a-3p and miR-146a-5p. The expression levels of toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TAK1-binding protein (TAB), nuclear factor-kappa B (NF-κB), and interleukin-1 beta (IL-1β) in hippocampus were tested by immunofluorescence assay. Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately. Results CHLGMLD decreased the frequency (P < 0.05) and duration (P < 0.01) of seizures in rats. CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p (P < 0.05), and inhibited the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β (P < 0.01). The correlation analysis revealed that the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR, respectively (P < 0.01). Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats, thus relieving seizures.

Objective:To evaluate the clinical efficacy of multi-disciplinary single center's CCCG-HB-2016 regimen in the treatment of hepatoblastoma (HB) in children.Methods:Clinical data of 36 HB patients treated with CCCG-HB-2016 program from Aug 2016 to March 2020 were analyzed.Results:These 36 patients included 20 boys and 16 girls. The serum AFP was all higher than 2 792 ng/ml,there was a correlation between AFP and tumor risk stratification ( H=14.973, P<0.05). Twenty eight cases (77.78%) were epithelial type and 8 cases (22.22%) were mixed epithelial mesenchymal type.All children were treated by tumor resection combined with chemotherapy, and there was a correlation between tumor risk stratification and surgical resection of liver lobe ( H=8.847, P<0.05). The probability of bone marrow suppression in the low-risk group was 58.33% (35/60),that in the intermediate-risk group was 73.49% (61/83) and in the high-risk group was 80.23% (69/86).All 36 cases were followed up to March 31, 2020,with an average follow-up of 21.9 months and the median survival was 22.5 months.The overall survival rate (OS) and event-free survival rate (EFS) were 97.2% and 83.3% respectively. Conclusions:The multidisciplinary CCCG-HB-2016 regimen was with a high success rate and along with a high incidence of bone marrow suppression.