As a common neurological disease in China, stroke has an extremely high rate of death and disability, of which 80% is ischemic stroke (IS), causing a serious burden to individuals and society. Neuronal death is an important factor in the pathogenesis of stroke. Studies have shown that mitochondrial dynamics, as a key mechanism regulating intracellular energy metabolism and cell death, plays an important role in the pathogenesis of IS. In recent years, targeting mitochondrial dynamics has become an emerging therapeutic tool to improve neurological impairment after stroke. This paper reviews the research advance in recent years in IS mitochondrial dynamics, summarizing and discussing the overview of mitochondrial dynamics, the role of mitochondrial dynamics in IS, and the studies on mitochondrial dynamics-based treatment of IS. This paper helps to explore the mechanism of the role of mitochondrial dynamics in IS and effective interventions, and provides a theoretical strategy for targeting mitochondrial dynamics to treat IS in the clinic.
Humans ; Mitochondrial Dynamics/physiology* ; Ischemic Stroke/metabolism* ; Mitochondria/physiology* ; Animals ; Brain Ischemia/physiopathology* ; Energy Metabolism

OBJECTIVE: To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms. METHODS: CCK-8 method was used to screen AML cell lines (MV4-11, MOLM13, OCI-AML2) that were relatively sensitive to venetoclax. Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines. Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry. BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients. RESULTS: Venetoclax-resistant cell lines of MV4-11, MOLM13, and OCI-AML2 were successfully established, with IC₅₀ values exceeding 10-fold. Under the same concentration of venetoclax, the apoptosis rate of resistant cells decreased significantly (P < 0.05). BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins (such as BIM,BID and NOXA). RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines. Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results. CONCLUSION The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax. The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM, BID, and NOXA, which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.
Humans ; Sulfonamides/pharmacology* ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Leukemia, Myeloid, Acute/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis ; Antineoplastic Agents/pharmacology*

Post-stroke cognitive impairment(PSCI)is a prevalent functional impairments following stroke that seriously affects patients'quality of life and daily activities.Studies indicate a close relationship between intestinal microflora dysbiosis and central nervous system diseases.Intestinal microflora profoundly impacts on human physiological health,contributing to the stability of nervous,metabolic and immune systems through regulation of the gut-brain axis.An increasing number of studies confirmed the important role of the gut microbiome-gut-brain axis in the occurrence and development of stroke and its associated PSCI,and regulation of microbiome-gut-brain could be potential target to treatment of PSCI.This review summarizes research progress on gut microbiome-gut-brain axis and PSCI to provide a reference for exploration of related mechanisms and clinical prevention and treatment strategies.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To explore the characteristics of pulmonary blood flow perfusion imaging of single photo emission computer tomography/computer tomography (SPECT/CT) in chronic pulmonary vascular Stenosis (CPVS) caused by different etiological factors. Methods: This is a retropective study. Present study screened 50 consecutive cases diagnosed with chronic pulmonary vascular stenosis from January 2019 to January 2020 in the department of cardiology of Gansu Provincial Hospital and underwent SPECT/CT pulmonary blood flow perfusion examination. Thirteen patients were excluded because of pulmonary vascular lesions with a disease course of less than 3 months and poor image quality. According to the etiology, patients were divided into fibrosing mediastinitis (FM) group, Takyasu's arteritis (PTA) group, and chronic thromboembolic pulmonary hypertension/chronic thromboembolic pulmonary disease (CTEPH/CTED) group. The severity of pulmonary blood flow perfusion was evaluated in accordance with the Begic scoring principle in the three groups. The overall Begic score, lung lobe scores among three groups were compared. CT signs of lung SPECT/CT, such as enlargement of hilar lymph node, atelectasis, bronchial stenosis, were also analyzed in three groups. Results: A total of 37 patients with chronic pulmonary vascular stenosis were finally enrolled (18 in the FM group, 5 in the PTA group, and 14 in the CTEPH/CTED group). The total Begic score of pulmonary perfusions was similar among the three groups (F=0.657,P>0.05). There was a statistically significant difference in the left upper lobe Begic score among the three groups (H=4.081, P<0.05). The left upper lobe Begic score was higher in the FM group than in the PTA group (3.44±2.50 vs. 1.60±0.55, P<0.05). As compared to other two groups, patients in FM group were featured with CT signs of higher percent of hilar enlargement (FM group vs. PTA group: 16/18 vs. 1/5, P=0.008; FM group vs. CTEPH/CTED group: 16/18 vs. 3/14, P=0.000 2), enlargement of the pulmonary hilum lymph nodes (FM group vs. PTA group: 14/18 vs. 1/5, P=0.033; FM group vs. CTEPH/CTED group: 14/18 vs. 2/14, P=0.001), and calcification of mediastinal soft tissue (FM group vs. PTA group: 11/18 to 0/5, P=0.037; FM group vs. CTEPH/CTED group: 11/18 vs. 1/14, P=0.003). The proportion of CT signs of bronchial stenosis (9/18 vs. 0/14, P=0.002) and atelectasis (9/18 vs. 1/14, P=0.002) was also higher in the FM group than in the CTEPH/CTED group. In case of abnormal pulmonary blood flow perfusion, the diagnostic accuracy of CT signs hilar enlargement, hilar lymph node enlargement, mediastinal soft tissue calcification, bronchial stenosis, and atelectasis for the diagnosis of FM were 81.1%, 83.8%, 78.4%, 75.7%, and 73.0%, respectively. Conclusion: There is no significant difference in the Begic score of SPECT/CT pulmonary blood flow perfusion imagines among the three groups of patients. Impaired pulmonary blood flow perfusion combined with typical CT signs is useful for identifying patients with FM.
Humans ; Constriction, Pathologic/diagnostic imaging* ; Perfusion ; Pulmonary Atelectasis ; Mediastinitis ; Calcinosis ; Lung/diagnostic imaging* ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

Objective: To analyze the phenotype and genotype of two pedigrees with inherited fibrinogen (Fg) deficiency caused by two heterozygous mutations. We also preliminarily probed the molecular pathogenesis. Methods: The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and plasma fibrinogen activity (Fg∶C) of all family members (nine people across three generations and three people across two generations) were measured by the clotting method. Fibrinogen antigen (Fg:Ag) was measured by immunoturbidimetry. Direct DNA sequencing was performed to analyze all exons, flanking sequences, and mutated sites of FGA, FGB, and FGG for all members. Thrombin-catalyzed fibrinogen polymerization was performed. ClustalX 2.1 software was used to analyze the conservatism of the mutated sites. MutationTaster, PolyPhen-2, PROVEAN, SIFT, and LRT online bioinformatics software were applied to predict pathogenicity. Swiss PDB Viewer 4.0.1 was used to analyze the changes in protein spatial structure and molecular forces before and after mutation. Results: The Fg∶C of two probands decreased (1.28 g/L and 0.98 g/L, respectively). The Fg∶Ag of proband 1 was in the normal range of 2.20 g/L, while it was decreased to 1.01 g/L in proband 2. Through genetic analysis, we identified a heterozygous missense mutation (c.293C>A; p.BβAla98Asp) in exon 2 of proband 1 and a heterozygous nonsense mutation (c.1418C>G; p.BβSer473*) in exon 8 of proband 2. The conservatism analysis revealed that Ala98 and Ser473 presented different conservative states among homologous species. Online bioinformatics software predicted that p.BβAla98Asp and p.BβSer473* were pathogenic. Protein models demonstrated that the p.BβAla98Asp mutation influenced hydrogen bonds between amino acids, and the p.BβSer473* mutation resulted in protein truncation. Conclusion: The dysfibrinogenemia of proband 1 and the hypofibrinogenemia of proband 2 appeared to be related to the p.BβAla98Asp heterozygous missense mutation and the p.BβSer473* heterozygous nonsense mutation, respectively. This is the first ever report of these mutations.
Humans ; Afibrinogenemia/genetics* ; Codon, Nonsense ; Pedigree ; Phenotype ; Fibrinogen/genetics* ; Genotype

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective:To explore the difference of clinical characteristics between senile Parkinson's disease(PD)with depression and unipolar depression.Methods:From March 2019 to March 2020, 53 patients with Parkinson's disease depression and 57 patients with unipolar depression who were admitted to the neurology department of Beijing Hospital were continuously collected.The gender, age and education level of the patients were recorded.The course of disease and other general data of the patients with Parkinson's disease were also recorded.Depression and anxiety of the patients were evaluated by Beck Depression Inventory(BDI)and Generalized Anxiety Disorder Scale(GAD-7). Quality of life of patients with Parkinson's disease was evaluated by 8-item Parkinson's disease questionnaire(PDQ-8). Differences in the assessment results and quality of life scores between the two groups were analyzed.Results:The incidence of depression comorbid with anxiety in elderly PD patients was 52.8%(28/53), lower than that in elderly unipolar depression patients comorbid with anxiety [84.2%(48/57)]( χ2=12.664, P<0.001). The scores of activity inhibition [(1.8±0.8)points]and hyposexuality [(0.4±1.0)points]in elderly PD patients with comorbid depression were higher than that in patients with unipolar depression [(1.1±0.8)points, (0.0±0.0)points]( t=4.399, 2.942, P<0.001, =0.005). Moreover, the incidence of activity inhibition(98.1%)and hyposexuality(15.1%)in PD patients with comorbid depression was higher than that in patients with unipolar depression(78.9%, 0.0%)( χ2=9.680, 9.279, both P=0.002). The scores of self-blame [(1.0±0.8)points]and pain [(1.0±0.8)points]in elderly patients with unipolar depression were higher than those in PD patients with comorbid depression [(0.5±0.7)points, (0.9±0.7)points]( t=-3.902, -2.486, P<0.001, =0.014). Moreover, the incidence of self-blame(66.7%), irritability(78.9%)and image distortion(56.1%)in elderly patients with unipolar depression was higher than that in PD patients(35.8%, 56.6%, 35.8%)( χ2=10.447, 6.320, 4.547, P=0.001, 0.012, 0.033). The scores of PDQ-8 in PD patients with comorbid depression and anxiety [14.8(10.8, 19.0)points]( Z=-3.544, P<0.001)were higher than those in PD patients with depression only [7.0(4.8, 11.0)points]. Conclusions:The focus of depression in elderly PD patients is different from that in elderly unipolar depression patients.Elderly patients with unipolar depression are more likely to be comorbid with anxiety.Depression reduces the quality of life in PD patients, and the comorbidity of anxiety further reduces the overall quality of life in PD patients with depression.