ArchiveAmyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease characterized by the degeneration of upper and lower motor neurons. Clinically, it manifests as progressive muscle weakness and atrophy, ultimately leading to death, imposing a significant burden on patients’ families and society. The pathogenesis of ALS remains unclear. Currently, several ALS treatment drugs have failed to significantly extend survival or alter the outcome. In recent years, cell therapy has been increasingly applied to refractory or incurable diseases. Various types of stem cell therapies have been developed for ALS treatment, undergoing preclinical research and clinical trials. This article provides an overview of the application of cell therapy in ALS, with a detailed examination of the research and development history of the representative cell therapy NurOwn in ALS. And the achievements and challenges of current ALS cell therapy, suggesting the optimization of cell type selection and efficacy evaluation metrics in future ALS cell therapy research were further discussed. This optimization aims to guide the development, approval, and market entry of ALS cell therapies, benefiting patients and their families.
Preeclampsia is a common hypertensive disorder of pregnancy, which seriously endangers the health of mothers and infants. The early application of low-dose aspirin can effectively prevent preeclampsia, and effectively reduce the probability of hemolysis, elevated liver function and low platelet count syndrome, placental abruption, and fetal distress. In recent years, with the deepening of research, more experimental evidences show that there is a correlation between gene polymorphisms and aspirin resistance. Because some patients have gene polymorphisms, the expected therapeutic effect cannot be achieved. This paper reviewed the research progress of precision medication of aspirin in high-risk pregnant women with preeclampsia, in order to guide the medication of aspirin in special groups such as pregnant women with preeclampsia and improve pregnancy outcomes.
Alzheimer’s disease (AD) is the most common form of irreversible dementia. In addition to assessing of patients’ memory abilities, positron emission tomography (PET), as a non-invasive diagnostic modality with high sensitivity and qualitative or quantitative imaging of the target sites, can qualitatively and quantitatively evaluate β-amyloid (Aβ), tau proteins, synaptic proteins, and other related biomarkers, which is of great significance in the diagnosis of AD. As PET imaging approved by FDA, [18F]-flutemetamol, a derivative of 18F labelled thioflavin-T, and [18F]-florbetaben, [18F]-florbetapir, which are phenylpyridine derivates, have high specificity in their affinity for Aβ plaque binding. Other radionuclides such as 68Ga and 64Cu labeled radiotracers also showed high affinity with Aβ plaques. Quinoline derivatives [18F]-THK5351, [18F]-PPQ8, benzimidazolopyrimidine and pyridine-indole derivatives [18F]-T807, and lansoprazole derivatives [11C]-NML as PET imaging agents, can quantify tau protein tangles. And the structural derivatives of levetiracetam [11C]-UCB-J and [18F]-SDM-8 can measure synaptic density, while the structural derivatives [18F]-FPEB of 3-fluoro-4-acetylidene-benzylnitrile can assist in the diagnosis of AD by binding with mGluR5. The fluorobenzoyl derivative [18F]-altanserin, with ketoserin as its structural parent, acts on 5-hydroxytryptamine to study the molecular changes of early AD.
CD34+ cells have microcirculatory regenerative potential and paracrine anti-inflammatory effects, but the number and function of CD34+ cells involved in vascular repair are decreased in patients with heart failure. Multiple trials have found that CD34+cell transplantation therapy in patients with chronic heart failure can improve myocardial performance, reduce neurohumoral activation, improve exercise capacity and quality of life, and even improve the survival rate in patients with heart failure. CD34+ cell transplantation may be a future treatment option for patients with chronic heart failure.
Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor that occurs in the biliary system, with a hidden onset, poor overall prognosis and high mortality. Futibatinib is a fibroblast growth factor receptor (FGFR) 1-4 inhibitor, which was approved by the U.S. Food and Drug Administration in 2022 for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic ICC with FGFR2 gene fusions or other rearrangements. Phase Ⅰ and Ⅱ clinical trials have shown that futibatinib has good clinical effect on ICC, which can significantly improve the objective response rate and prolong the survival time of ICC patients. The common adverse events include hyperphosphatemia, diarrhea, constipation, and dry mouth, with a high incidence of adverse events.
The new antidepressant toludesvenlafaxine, also known as ansofaxine, is a triple monoaminergic reuptake inhibitor independently developed in China. It can play an antidepressant effects by blocking the reuptake of the three neurotransmitters by combining with the serotonin transporter, noradrenaline, and dopamine transporter. Toludesvenlafaxine has a rapid effect, which can significantly improve the low mood, anhedonia, lack of motivation and other symptoms of patients with depressive disorders, relieve the associated anxiety symptoms, and is not easy to lead to sexual dysfunction and other adverse reactions in the treatment process. While using toludesvenlafaxine, clinicians should start titration with a low dose and assess the risk of mania during the course of treatment, and pay attention to whether the drug could cause psychotic symptoms, since it acts on the dopamine pathway.
To analyze the usage of “dual channel” drugs in designated pharmacies and medical institutions, and to provide a basis for better implementation of the national negotiation drug “dual channel” management mechanism.
The relevant policies of the “dual channel” management mechanism for Shanghai medical insurance were reviewed. The growth rate and coverage of “dual channel” drug costs, the proportion of different types of drug costs, and the ranking of drug costs within the Shanghai medical security intelligent supervision system from January 2022 to December 2023 were analyzed.
The cost of medication costs have increased significantly with the expansion of the scope of “dual channel” management drugs. Antitumor drugs account for the highest cost proportion among all “dual channel” drugs. There were some problems in the implementation of the policy, such as difficulties in prescription circulation, security vulnerabilities in medical insurance funds caused by paper prescriptions.
Since the implementation of the“dual channel” management mechanism, the supply guarantee level of the national negotiation drug has been effectively improved through two different channels of designated pharmacies and medical institutions. To further demonstrate policy effects, it is recommended to strengthen the allocation of “dual channel” drugs, increase the service layout of designated pharmacies and strengthen the supervision of drug usage.
As a new therapeutic modality, gene therapy drugs (GTDs) play a therapeutic role and also have many risks, which brings challenges to the regulation of GTDs. The United States (US) and the European Union (EU) have established a relatively perfect system in terms of the regulatory body, regulatory basis and listing regulation, which is worthy of China’s reference. China’s regulation of GTDs still exists in the regulatory basis level is not detailed, the regulatory content is not mature and transparent, the main body of the regulatory implementation and the body of the responsibility is not clear enough and other issues. It is suggested that our country can learn from the advanced experience of the US and the EU, divide and control the risk of GTDs, set up an expert technical team, establish an advisory committee, and strengthen international communication and exchange, so as to improve the regulatory system of GTDs and enhance the safety of such drugs in China.
To investigate the potentially inappropriate medications (PIM) in elderly patients with hypertension combined with cerebral infarction and to develop a nomogram model based on Lasso-logistic regression of the influencing factors.
A total of 105 patients with hypertension combined with cerebral infarction and multi-drug therapy discharged from January to December 2020 were included，and the PIM was evaluated by the criteria of potentially inappropriate medications for older adults in China. The PIM influencing factors were analyzed by Lasso-logistic regression, Nomogram model of factors influencing the PIM risk was developed, and the discrimination and accuracy of the model were evaluated.
The incidence of PIM in 105 patients of hypertension complicated with cerebral infarction was 85 cases (81.0%) and 184 times, involving 26 drugs. The 1st drug was clopidogrel with 48 times (26.1%). A statistically significant effect of the number of drugs (P=0.003, OR=1.412, 95% CI: 0.582 to 2.868) and diabetes (P<0.001, OR=0.081, 95% CI: -3.899 to -1.129) on PIM was suggested by the Lasso-logistic regression. Of the model, a good accuracy and discrimination was suggested by the area under the ROC curve (AUC), which was 85.3% (95% CI: 0.772 to 0.933), and an acceptable predictive power was suggested by internal validation with Bootstrap method (B=1 000).
The nomogram model based on Lasso-logistic regression can better identify the risk of PIM. Elderly patients with hypertension complicated with cerebral infarction and multi-drug therapy have a high risk of PIM, and it is necessary to reduce the number of medications to reduce the risk of PIM.
To explore the effects of berberine on intestinal injury in sepsis rats and its mechanism.
Forty male healthy SD rats were randomly divided into sham group, model group, berberine low, medium, and high dose (25, 50, 100 mg·kg-1) groups, with 8 rats in each group, and the corresponding dose was given by gavage for 7 d. Sepsis model was prepared by cecum ligation and perforation (CLP). After 24 h of modeling, the rats were anesthetized and the ileum specimens were collected. The pathological changes of the ileum were observed and scored under light microscope. The contents of serum heme oxygenase-1 (HO-1), diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), interleukin (IL) -6 and IL-1β were detected by ELISA. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in ileum were detected by colorimetric analysis. The protein levels of HO-1, nuclear factor E2-related factor 2 (Nrf2) and IL-1β in ileum were detected by Western blot.
Compared with the sham group, ileum histopathological score was significantly increased in the model group (P<0.01), and contents of HO-1, IL-1β, IL-6, TNF-α, DAO, iFABP in serum, and MDA in intestinal tissue were increased, while SOD activity was decreased, and the expressions of Nrf2, HO-1 and IL-1β protein in the model group were significantly increased (P<0.01). Compared with the model group, the ileum histopathologic score of the berberine high dose group was significantly decreased (P<0.01), the contents of IL-1β, IL-6, TNF-α, DAO, iFABP in serum and MDA in intestinal tissue were also decreased (P<0.05), while the HO-1 content in serum and SOD activity in intestinal tissue were increased (P<0.01), and the protein expressions of Nrf2 and HO-1 in the berberine high dose group were significantly increased, but the IL-1β protein expression was decreased (P<0.05).
Berberine can effectively improve intestinal damage caused by sepsis, and its mechanism may be related to the up-regulation of Nrf2/HO-1 expression.
To investigate the effect of canagliflozin on liver cancer cells and its regulatory mechanism.
The effects of canagliflozin on the proliferation of liver cancer cell HepG2, Huh7 and HCCM were detected by cell clone formation assay and CCK-8 assay. Flow cytometry was used to measure changes in reactive oxygen species (ROS) levels, both intracellular and mitochondrial ROS levels, as well as alterations in mitochondrial membrane potential. Western blot was employed to assess the expression of proteins related with proliferation and cGAS-STING pathway. Mitochondrial DNA (mtDNA) release and inflammatory factor mRNA expression level were detected by RT-qPCR.
Compared with human normal liver cell MIHA, the inhibitory effect of canagliflozin on HepG2 cell proliferation was more significant (P<0.05，semi-inhibitory concentrations were >40 μmol·L-1 and 15 μmol·L-1, respectively). Compared with the control group, the clone number of liver cancer cells and the expression of proliferation-related proteins in the canagliflozin group were decreased in a concentration dependent manner (P<0.05). Additionally, the intracellular and mitochondrial ROS levels were increased, the mitochondrial membrane potential was decreased, and the cytoplasmic mtDNA release level, cGAS-STING pathway-related protein expression and pro-inflammatory factor mRNA levels were increased (all P<0.05). Compared with the canagliflozin group, the intracellular and mitochondrial ROS levels, cytoplasmic mtDNA release levels, cGAS-STING pathway-related protein expression and pro-inflammatory factor mRNA levels in the N-acetyl-L-cysteine (NAC) +canagliflozin group were decreased (all P<0.05). Compared with the canagliflozin group, the proliferation activity and the expression of proliferation-related proteins in the cGAS inhibitor RU.521 + canagliflozin group were significantly increased (all P<0.05).
Canagliflozin induces oxidative stress in liver cancer cells, leading to the accumulation of ROS within cells and mitochondria, impairment of mitochondrial function, leakage of mtDNA into the cytoplasm, activation of the cGAS-STING pathway, and subsequent release of intracellular pro-inflammatory factors. These processes collectively contribute to the modulation of liver cancer cells proliferation.
To investigate the protective mechanism of berberine against Polygonum multiflorum thunb.induced liver injury.
SD rats were randomly divided into sham group, PM (Polygonum multiflorum thunb. 40 g·kg-1) group, PM+NS (saline 1 mL) group, PM+BBR (berberine 50 mg·kg-1) group (n=12 in each group). Another 24 rats were divided into PM+BBR+sh-PPAR-γ group and PM+BBR+sh-NC group, which were injected with 100 μL of shRNA-PPAR-γ and 100 μL of shRNA-NC into the tail vein. The administration of each group lasted for 8 weeks. HE staining was used to observe the pathological changes in liver tissue, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) levels and the levels of IL-1β, IL-6 and IL-10 in liver tissues were detected by ELISA. PPAR-γ expression was knockdown by transfecting shRNA-PPARγ into rats. The expression levels of PPAR-γ in rat liver tissues was detected by RT-qPCR and Western blot.
Compared with the sham group, the levels of serum ALT, AST, ALP were significantly increased, the levels of IL-1β, IL-6 in liver tissue were increased and IL-10 level was decreased, and PPAR-γ expression was significantly downregulated in the PM group and PM+NS group (all P<0.05). Compared with the PM+NS group, serum ALT, AST, ALP levels were significantly decreased, IL-1β and IL-6 levels were significantly decreased, IL-10 level was significantly increased, and PPAR-γ expression was significantly increased in the PM+BBR group (all P<0.05). Compared with the PM+BBR+sh-NC group, PPAR-γ expression was significantly decreased, serum ALT, AST, ALP levels were significantly increased, IL-1β and IL-6 levels were significantly increased, IL-10 level was significantly decreased in the PM+BBR+sh-PPAR-γ group (all P<0.05).
Berberine may alleviate hepatic injury induced by Polygonum multiflorum thunb. by up-regulating PPAR-γ expression.
To investigate the use of new oral anticoagulants (NOACs) and clinically relevant drug-related problems (DRPs) in hospitalized patients, in order to provide a reference for promoting the rational use of NOACs.
A total of 586 medical records of inpatients using NOACs at the First Affiliated Hospital of Anhui Medical University from October 2021 to September 2022 were collected. Retrospective reviews were conducted according to relevant guidelines and regulations. The summary analysis of the observed DRPs was performed with reference to the criteria used in the Chinese Classification System for Drug-Related Problems (V1.0), which is adapted to the Chinese population and healthcare model.
Among the 586 cases, the majority were females (52.4%), and the average age was (69.5±12.6) years old. The most common indication for the use of NOACs was nonvalvular atrial fibrillation (272 cases, 46.4%), which involved three varieties and eight criteria. DRPs occurred in 358 patients, with a total of 389 DRPs identified, including 213 (54.8%) DRP1.1, 72 (18.5%) DRP2.1, 4 (1.0%) DRP3.1, 65 (16.7%) DRP3.2, and 35 (9.0%) DRP3.3.
The use of NOACs in our hospital are mainly manifested as low single doses, infrequent administration, and lack of indication for medication.
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