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

Objective:To explore the early identification, diagnosis and pathogenesis of childhood acute lymphoblastic leukemia (ALL) complicated with cytokine release syndrome(CRS).Methods:The clinical data of childhood ALL complicated with CRS admitted to Shenzhen Children's Hospital in February 2021 were retrospectively analyzed. The relevant literature was reviewed.Results:The little girl was 2 months and 11 days of age and was diagnosed with ALL with MLL rearrangement positive by bone marrow aspiration because of abdominal mass and abnormal hemogram. She had recurrent high fever with pulmonary imaging characteristic changes during the early intensive induction chemotherapy, accompanied by the elevated interlukin (IL)-2, IL-6, IL-10 and interferon (IFN)-γ. Finally, she was diagnosed with ALL complicated with CRS. Glucocorticoid therapy showed a good efficacy and her clinical symptoms improved.Conclusions:ALL complicated with CRS is essentially induced by cytarabine syndrome drugs in the chemotherapy. The main clinical manifestations include recurrent high fever accompanied by the elevated IL-2, IL-6, IL-10 and IFN-γ. The symptomatic and supportive therapy is usually based on glucocorticoids. Early identification and diagnosis can reduce adverse drug reactions and improve the life quality of children.

Objective:To investigate the risk factors and prognosis of varicella zoster virus (VZV) infection in children with thalassemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The clinical data of 446 children with thalassemia who underwent allo-HSCT from January 2012 to December 2020 in the Department of Hematology and Oncology, Shenzhen Children′s Hospital were retrospectively collected.The clinical features of the patients with VZV infection were analyzed.The patients were divided into different groups according to whether they had VZV infection.Categorical variables between groups were compared using the chi- square tests to investigate the risk factors that were associated with the development of VZV.Survival time was analyzed by the Kaplan-Meier method. Results:VZV incidence was 4.3% (19/446 cases), and the median onset time was 5 months (1.5-11.0 months) after allo-HSCT.Of the 19 cases with VZV infection, 5 cases were complicated with VZV encephalitis.All cases were treated with antiviral agents (Acyclovir alone, or both Acyclovir and Foscarnet), intravenous immunoglobulin and external use of Acyclovir ointment.After 7-28 days of treatment (median treatment time: 14 days), all of their herpes subsided, and the neurological symptoms of patients with VZV encephalitis disappeared.One of the 19 children died.The death was not directly caused by VZV infection, but by secondary graft dysfunction and severe pneumonia 5 months after VZV infection.The incidence of VZV infection following allo-HSCT in children with thalassemia was related to the age of the donor ( P=0.010), but not to the age of the patient ( P=0.378), gender ( P=0.653), disease grade of thalassemia ( P=0.912), type of the donor ( P=0.205), source of stem cells ( P=0.624) and acute graft versus host disease ( P=0.277). VZV infection had no significant effect on the prognosis of thalassemia children after allo-HSCT ( P=0.241). Conclusions:Thalassemia children with VZV infection after allo-HSCT are prone to be complicated with VZV encephalitis.Cord blood transplantation is a high risk factor.VZV infection may not have an impact on survival of children with thalassemia after allo-HSCT.

Objective:To study the effectiveness of noninvasive embryo chromosome screening (NICS) based on blastocyst culture medium and cystic fluid in preimplantation genetic detection (PGT) of embryos in different age groups.Methods:A retrospective analysis of 62 couples who underwent PGT assisted pregnancy in Shenzhen Hospital of Peking University from January 2019 to June 2021. A total of 310 blastocysts were biopsied. At the same time, D3-6 blastocyst culture medium and blastocyst cavity fluid were collected for NICS. According to the age of the patients, they were divided into three groups: <35 years old group, 35≤age<40 years old group and ≥40 years old group. The results of NICS were compared with those of embryonic trophoblast (TE) biopsy in each group, and the consistency, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Then the consistency, sensitivity, specificity, positive predictive value and negative predictive value of NICS and TE among the three age groups were statistically analyzed.Results:There was no statistically significant difference in the consistency rate of NICS and TE among the three age groups ( P>0.05), but there was an upward trend in the elderly group (35≤age<40 years and ≥40 years). There was no statistically significant difference in specificity, sensitivity and PPV among the three age groups ( P>0.05). There was significant difference in NPV between the ≥40 years group and the other two groups ( P<0.05). Conclusions:There was no statistical difference in the effectiveness of NICS among different age groups, However, there was an increasing trend in people ≥35 years of age.

Objective To investigate effect of high glucose on the function of endothelial and the underlying mechanisms in human umbilical vascular endothelial cells (HUVECs).Methods The experiment was divided into 4 groups: normal group (NG), low dose group (LG), middle dose group (MG) and high dose group ( HG) .The concentration of glucose in the culture medium was 5.5, 10, 20, 30 mmol/L in the 4 groups, respectively.The HUVECs was cultured for 0, 24, 48 h.At different time point, the cell viability were measured by MTT.The secretary content of nitric oxide (NO) in the supernatant were detected using test kit.The extraction of protein were extracted for Western blot analysis to detect the expression of endothelial nitric oxide synthase (eNOS).ResuIts Compared with normal group at same time point (cultured for 24 h), the cell viability and the content of NO were significantly decreased in LG, MG(P<0.05).The expression of eNOS in HG were markedly reduced (P<0.01).Compared with normal group at same time point (cultured for 48 h), the cell viability decreased significantly in HG (P <0.05).The expression of eNOS were markedly decreased 11.91, 25.72 and 34.50% in LG, MG and HG, respectively.A rising trend of cell viability were found in NG, LG and MG, but a descending trend were found in HG within 48 h.ConcIusion The cell viability were significantly affected by high glucose.The endothelial dysfunction induced by high glucose may be associated with the reduction of eNOS and NO production.

Objective To discuss the important role of clinical pharmacists in medication reconciliation through the prac‐tice of clinical pharmacists of nephrology department .Methods The medication reconciliation serviced for the patients newly admitted to nephrology department was carried out through the way of interrogation .The difference and the causes between the results of pharmacist′s interrogation and the doctors′were analyzed .Results 20 patients were enrolled .The quantity was not consistent with what hospital doctor′s advice rate (60% ) ,drugs produced in different areas (55% ) ,different producing areas pharmacist had higher accuracy .Conclusion It had certain effect on medication management and could reduce the ADR .Clinical pharmacists and doctors should pay more attention on the medication reconciliation ,strengthen the ability of interrogation to im‐prove patient compliance and establish a complete medication reconciliation system .

A large number of literatures at home and abroad in recent years about Schisandrin B were viewed and its pharmacological effects were summarized. Schisandrin B has a variety of pharmacological activities, which can reduce transaminase activity in liver cells, inhibit lipid peroxidation, anti-oxidant, hepatoprotection, anti-tumor and so on. Its pharmacological effects are accurate and worthy of research and development as a potential drug.

Objective:To observe the effect and evaluate the necessity of reducing nurse-students' psychological pressure before practice.Methods:To making measures to help 318 nurse-students of grade 2004 reduce psychological pressure two months before practice,investigate and contrast the psychological situations of nurse-students before and after reducing psychological pressure.Result:58.8 percent of nurse-students are under psychological pressure in varying degrees before practice.The students from one-child families are under higher pressure than those from non-one-child families.The percentage was reduced from 58.8 percent to 18.2 percent after taking the measures.The difference is notable(P

AIM: To investigate the clinical utilization of antihypertension agents in a hospital. METHODS: By the method of retrospective study, 301 medical records (286 was selected) of discharged patients with hypertension who were admitted from June 2003 to June 2004 were investigated. RESULTS: The angiotensin converting enzyme inhibitors (ACEI) and calcium antagonists were used with the highest frequency, and the use frequency from high to low listed as enalapril, metoprolol, felodipine, benazapril and losartan. All drugs were administrated in combined therapy. CONCLUSION: The usage of antihypertensive drugs is rational in this hospital, and the tendency of drug utilization is similar to international standard.