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 evaluate the economics of utidelone combined with capecitabine compared with capecitabine in the second-line treatment of metastatic breast cancer from the perspective of Chinese health-care system. METHODS A partitioned survival model was established using clinical trial data and relevant literature data, with the cycle of 3 weeks and the time horizon of 15 years. Cost and utility data were discounted using a discount rate of 5%. The model output was the incremental cost-effectiveness ratio(ICER), and the willingness-to-pay threshold(WTP) was set to 1-3 times per capita gross domestic product(GDP) in China in 2021(80 976 yuan/QALY-242 928 yuan/QALY). One-way sensitivity analyses and probabilistic sensitivity analyses were performed to evaluate the stability of model results when the model parameters were changed. RESULTS The results of base-case analysis showed that utidelone combined with capecitabine was a high-cost and high-health benefit regimen, and the ICER was 393 949.83 yuan/QALY. One-way sensitivity analyses showed that the price of utidelone was the most influential factor of the ICER, and the probabilistic sensitivity analyses showed that the model results were robustness. CONCLUSION Utidelone combined with capecitabine has no economic advantage compared with capecitabine alone in the second-line treatment of metastatic breast cancer, but in areas with per capita GDP of more than 131 316 yuan, utidelone combined with capecitabine can be considered the cost-effective regimen.

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.
Humans ; Angioedemas, Hereditary/drug therapy*

Alleles ; Amelogenin/genetics* ; Chromosomes, Human, Y ; Humans ; Male ; Sex Determination Analysis

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

OBJECTIVE: To investigate the effect of high mobility group protein 1(HMGB1) on the proliferation and cytokine expression of human bone marrow mesenchymal stem cells (MSC). METHODS: Different concentrations of recombinant human HMGB1 protein (100, 200, 400, 800 and 1000 ng/ml) were incubated with MSC for 24, 48, 72 h and the proliferation of MSC were detected respectively by using the CCK-8 method and flow cytometry. The best concentrations of HMGB1 incubated with MSC was determined (200 ng/ml, 1000 ng/ml), and the flow cytomerty was used to determine the effect of HMGB1 on the proliferation of MSC. The mRNA expression levels of IL-10, TGF- β1, TSG-6 and IFN-γ in MSC incubated with HMGB1 protein were detected by real-time quantitative PCR and ELISA. RESULTS: The result of MSC identification and flow cytometry showed that the CD105, CD73 and CD90 were expressed, but did not expression CD45, CD34, CD11b, CD19 and HLA-DR; CCK-8 showed that HMGB1 at the concentrations of 100 ng/ml, 200 ng/ml and 400 ng/ml could promote the proliferation of MSC incubated for 24, 48 and 72 h as compared with the control group (P<0.05), and the most effective concentration was 200 ng/ml; flow cytometry showed that the compared with the control group, HMGB1 200 ng/ml could induce MSC from G1 phase to S phase to promote the proliferation of MSC; QPCR showed that the mRNA expression of MSC cytokines IL-10, TGF-β1, TSG-6 increased while IFN-γ decreased at the concentration of 200 ng/ml HMGB1 as compared with the control group. ELISA experiments showed that the HMGB1 200 ng/ml acting on MSC for 48 h could significantly promoted the secretion of IL-10, TGF-β 1 and TSG-6(P<0．05), while IFN-γ showed no significant difference as compared with control group. CONCLUSION Recombinant human HMGB1 can promote the proliferation and secretion of MSC in healthy people.
Bone Marrow Cells ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; HMGB1 Protein ; Humans ; Mesenchymal Stem Cells

SARS-CoV-2 can cause multiple organ injuries in some susceptible people in a short time, which seriously threatens the health and safety of people, and intensive care and multiple extracorporeal organ support are important means of treatment. Although many experts’ consensus and clinical guidelines have been published, a series of clinical problemsstill exist during the treatment procedure, and no consensushas not been reached until now. Therefore,in this paper wemake some reflections and explorations to provide experience and help for clinicians.

Objective　To explore the repair effect of curcumin on injured neurons in Parkinson’s model rats and the related mechanisms.Methods　Forty SD healthy male rats were selected,10 were group,the remaining 30 were established Parkinson’s model,divided into model group,low and high dose groups,and the four groups of rats were intervened separately.The learning and memory abilities of rats in each group were tested.HE staining was performed on brain tissue specimens of rats in each group.The size and number of neurons were counted.The levels of IL-6,IL-1β and TNF-α were detected by enzyme-linked immunosorbent assay.Results　Compared with model group and low dose group,the size and number of neurons in high dose group were higher (P<0.05).Compared with model group and low dose group,rats in high dose group had shorter escape latency and higher number of times crossing the platform at each time point (P<0.05).Compared with model group and low dose group,the levels of IL-6,IL-1β and TNF-α were lower in high dose group (P<0.05).Conclusion　Intervention with curcumin in Parkinson’s model rats can improve the learning and memory ability of rats,increase the size and number of neurons in rat brain tissue,and play a role in neuronal damage repair.Its function may be related to alleviating the inflammatory response in brain tissue,regulating the expression of apoptosis protein.

Uveal melanoma (UM) is one of most common ocular cancers and is extremely malignant; so far there is no effective treatment. Moreover, the survival period is only 2-7 months after metastasis. It has been proven that more than 83% of uveal melanomas harbor mutations in G protein subunit α q (GNAQ) or G protein subunit α 11 (GNA11), among which 95% are a Q209P/L single-site mutation. Q209P/L mutations lead to dysfunction of guanine triphosphatase (GTPase) in the G protein and result in constitutive activation of downstream pathways including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), Ras homologue (Rho)/ Rho-associated kinase (Rock)/Yes-associated protein (YAP) and others. Therefore, targeting GNAQ/GNA11 mutations are potential strategies for UM treatment. This review will focus on roles of G protein mutations in UM progression, and the potential therapeutic effects of GNAQ/GNA11 inhibitors, and will provide insights into basic and clinical research on UM treatment.