OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective: To analyze the nucleic acid load of human parvovirus B19 in major commercially available blood products in China, including human albumin, human intravenous immunoglobulin, human rabies immunoglobulin and various coagulation factor products, aiming to provide evidence for improving blood product manufacturing processes and quality control of source plasma. Methods: A total of 98 batches of coagulation factor products were tested for human parvovirus B19 nucleic acid using real-time fluorescent quantitative PCR, including 42 batches of human prothrombin complex, 35 batches of human coagulation factor Ⅷ, and 21 batches of human fibrinogen. Additionally, 6 batches of human albumin, 6 batches of human intravenous immunoglobulin, and 38 batches of human rabies immunoglobulin were tested for human parvovirus B19 nucleic acid. Results: Human parvovirus B19 nucleic acid were undetectable in human albumin, human intravenous immunoglobulin and human rabies immunoglobulin. Among the 98 batches of coagulation factor products tested for human parvovirus B19 nucleic acid, B19 nucleic acid reactivity rate was 69.0% (29/42) for human prothrombin complex batches, but nucleic acid concentration were all significantly lower than 10 IU/mL. The reactivity rate of B19 nucleic acid in 35 batches of human coagulation factor Ⅷ was 48.6% (17/35), with nucleic acid concentration all below 10 IU/mL. The reactivity rate of B19 nucleic acid in 21 batches of human fibrinogen was 61.9% (13/21), with nucleic acid concentration all below 10 IU/mL. Conclusion: No human parvovirus B19 has been detected in human albumin, human intravenous immunoglobulin, or human rabies immunoglobulin. Human parvovirus B19 nucleic acid may exist in commercially available coagulation factor products, highlighting the need for enhanced screening of human parvovirus B19 nucleic acid in these products. It is also recommended that B19 viral nucleic acid testing be conducted on source plasma, particularly for coagulation factor products.

Objective:To preliminarily assess the biocompatibility and durability of the TruDelta TM transcatheter mitral valve replacement (TMVR) system. Method:Six adult sheep were divided into 3 groups based on the duration of follow-up: 30 days ( n=1), 90 days ( n=3) and 180 days ( n=2). The TruDelta TM TMVR system was implanted through a transapical approach under transesophageal echocardiographic guidance. The operability of the TMVR system was evaluated using an instrument performance evaluation scale (consisting of 39 items), with scores ranging from 1 (worst) to 10 (best) assigned by the operator. Echocardiography was conducted preoperatively, immediately after surgery, and at 30, 90, and 180 days post-implantation. At the last follow-up time point, the intervention mitral valve membrane and major organs were dissected for observation. The artificial valves were taken for hematoxylin eosin (HE) staining and observed under a scanning electron microscope. Result:All six procedures were successfully completed using 29S size TruDelta TM TMVR device. At the final follow-up, echocardiogram demonstrated good valve function without obvious paravalvular leakage, with a transvalvular gradient of (7.8±3.2) mmHg (1 mmHg=0.133 kPa) and a mitral valve orifice area of (1.8±0.2) cm 2. Autopsy findings revealed no structural valve failure and almost complete endothelialization (>75%) with 90 to 180 days. Both HE staining and scanning electron microscopy confirmed optimal endothelialization of the valve stent. Conclusion:The preclinical animal study indicates that the TruDelta TM device exhibits favorable biocompatibility and durability.

Treatment-resistant depression(TRD)is a severe psychiatric disorder with a high incidence bringing heavy burden of disease,and better treatment options still need to be explored.In recent years,the antidepressant effects of nitrous oxide(N2O)and its application in TRD have attracted attention.N2O exerts unique rapid onset of action and has comparative advantages in terms of adverse reactions and tolerability and may become a new therapeutic drug for TRD.N2O may exert effects through mechanisms such as antagonizing N-methyl-D-aspartate(NMDA)receptors,regulating serotonin and dopamine,brain-derived neurotrophic factor(BDNF)signaling pathways,and the opioid receptor system.In clinical studies,the efficacy and safety of N2O for TRD have shown promise,displaying advantageous characteristics compared to existing therapies,and the limitations of N2O,such as its side effects,can often be improved via modification of the therapeutic regimen.Future research will mainly focus on validating the long-term efficacy and safety of standardized N2O treatment regimens through larger sample clinical trials,as well as further exploring its individualized or comprehensive treatment,and in-depth neurobiological mechanisms,in order to provide new choices and optimization strategies for clinical treatment practices suitable for relevant populations.

Objective:To preliminarily assess the biocompatibility and durability of the TruDelta TM transcatheter mitral valve replacement (TMVR) system. Method:Six adult sheep were divided into 3 groups based on the duration of follow-up: 30 days ( n=1), 90 days ( n=3) and 180 days ( n=2). The TruDelta TM TMVR system was implanted through a transapical approach under transesophageal echocardiographic guidance. The operability of the TMVR system was evaluated using an instrument performance evaluation scale (consisting of 39 items), with scores ranging from 1 (worst) to 10 (best) assigned by the operator. Echocardiography was conducted preoperatively, immediately after surgery, and at 30, 90, and 180 days post-implantation. At the last follow-up time point, the intervention mitral valve membrane and major organs were dissected for observation. The artificial valves were taken for hematoxylin eosin (HE) staining and observed under a scanning electron microscope. Result:All six procedures were successfully completed using 29S size TruDelta TM TMVR device. At the final follow-up, echocardiogram demonstrated good valve function without obvious paravalvular leakage, with a transvalvular gradient of (7.8±3.2) mmHg (1 mmHg=0.133 kPa) and a mitral valve orifice area of (1.8±0.2) cm 2. Autopsy findings revealed no structural valve failure and almost complete endothelialization (>75%) with 90 to 180 days. Both HE staining and scanning electron microscopy confirmed optimal endothelialization of the valve stent. Conclusion:The preclinical animal study indicates that the TruDelta TM device exhibits favorable biocompatibility and durability.

Treatment-resistant depression(TRD)is a severe psychiatric disorder with a high incidence bringing heavy burden of disease,and better treatment options still need to be explored.In recent years,the antidepressant effects of nitrous oxide(N2O)and its application in TRD have attracted attention.N2O exerts unique rapid onset of action and has comparative advantages in terms of adverse reactions and tolerability and may become a new therapeutic drug for TRD.N2O may exert effects through mechanisms such as antagonizing N-methyl-D-aspartate(NMDA)receptors,regulating serotonin and dopamine,brain-derived neurotrophic factor(BDNF)signaling pathways,and the opioid receptor system.In clinical studies,the efficacy and safety of N2O for TRD have shown promise,displaying advantageous characteristics compared to existing therapies,and the limitations of N2O,such as its side effects,can often be improved via modification of the therapeutic regimen.Future research will mainly focus on validating the long-term efficacy and safety of standardized N2O treatment regimens through larger sample clinical trials,as well as further exploring its individualized or comprehensive treatment,and in-depth neurobiological mechanisms,in order to provide new choices and optimization strategies for clinical treatment practices suitable for relevant populations.

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.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

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*