ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

Investigator initiated trial （IIT） represents a primary format for clinical research in traditional Chinese medicine （TCM）. As key implementation sites for TCM-based IIT targeting malignant tumors， western medicine institutions often face unique challenges in conducting such studies， which limit their feasibility and standardization. This paper reviews the registration status of TCM-based IIT for malignancies conducted in western medical institutions and analyzes key difficulties， including complex project initiation and management processes， limited TCM knowledge and skills among western medicine physicians， and relatively low patient acceptance of TCM. From a practical perspective， the study proposes several optimization strategies. These include improving the review and management mechanisms of TCM-related IIT within western medical institutions， establishing multidisciplinary clinical research teams that integrate TCM and western medicine， and enhancing investigators' training in TCM theory and clinical skills. Additionally， the study suggests standardizing IIT operational procedures， objectifying the collection of TCM diagnostic information， refining subject recruitment methods， and increasing TCM involvement in patient follow-up and management. These investigator-oriented， TCM-featured， and operable strategies aim to promote the high-quality development of TCM-based IIT in western medicine institutions and enhance the clinical application of TCM.

ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

OBJECTIVE To establish a quantitative analysis model for the contents of tussilagone， moisture， ethanol-soluble extract and total ash in Farfarae Flos based on near-infrared spectroscopy （NIRS）， providing a new idea for the rapid quality evaluation of Farfarae Flos and its preparations. METHODS Referring to the 2020 edition of the Chinese Pharmacopoeia， the contents of the main quality control indexes tussilagone， moisture， ethanol-soluble extract and total ash in 130 batches of Farfarae Flos from 19 producing areas were determined by HPLC， drying method， hot dip method and ash assay， respectively. The NIRS data information of the medicinal herbs of Farfarae Flos was collected， and then NIRS combined with the partial least squares method was used to establish the individual quantitative analysis models of the above quality control indexes in the samples， and the predictive model of the NIRS content was obtained after sample validation with validation set. RESULTS The range for the contents of tussilagone， moisture， ethanol-soluble extract and total ash in 130 batches of Farfarae Flos were 0.051 4%-0.103 5%， 7.75%-10.93%， 20.17%-31.12%， and 7.68%-12.10%， respectively. The internal cross-validation coefficients of determination （R2） of the established models for the quantitative analysis of tussilagone， moisture， ethanol-soluble extract and total ash in Farfarae Flos were 0.985 8， 0.968 4， 0.973 4， 0.988 0， respectively； the root mean square errors of calibration （RMSEC） were 0.001 54， 0.187， 0.478， 0.127， respectively； the root mean square errors of prediction （RMSEP） were 0.001 81， 0.212， 0.543， 0.149， respectively； RMSEP/RMSEC were 1.175 3， 1.133 7， 1.136 0 and 1.173 2， respectively， which were all within a reasonable range （1＜RMSEP/RMSEC≤1.2）. The mean absolute errors between the true and model-predicted values of the above four quality control indexes in the validation set of samples were －0.000 36， 0.061 43， 0.144 00， and 0.010 43， respectively，and the mean predicted recoveries were 99.65%， 100.72%，100.66%， and 100.15%， respectively. CONCLUSIONS The established NIRS quantitative analysis model has high stability and reliable results， which can be used for the rapid batch prediction of the content of relevant quality control indexes in Farfarae Flos.

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 investigate the changes and clinical significance of peripheral blood mucosal-associated invariant T(MAIT)cells in children with influenza.Methods Children with influenza who received treatment in the outpatient and inpatient departments of a children's hospital from January to May 2023 were selected and divided into the common type group and the severe type group.Healthy children who underwent physical examination in this hospital during the same period were selected as the healthy control group.Within 24 hours after admission,children's venous blood was drawn for testing;ratios of MAIT cells(CD3+CD161+TCRVα7.2+cells)and MAIT cells expressing PD-1,CD69,perforin,and CD107 α were tested by flow cytometry,respectively.Differences among all the groups were compared.Results Compared with the control group,the proportion of peripheral blood MAIT cells in children with common and severe influenza gradually decreased,while the proportion of CD69-ex-pressing and perforin-positive MAIT cells increased gradually.Differences were statistically significant(all P＜0.05).There was no statistically significant difference in the proportion of MAIT cells expressing CD107(P＞0.05).The proportion of PD-1 positive MAIT cells increased(P＜0.05),but there was no statistically significant difference be-tween the common type and severe type groups(P＞0.05).Conclusion The decrease of peripheral blood MAIT cells accompanied with immune activation plays a role in the pathogenesis of influenza.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B₂ （TXB₂）， prostacyclin I₂（PGI₂） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.

Humans ; Angina, Stable ; COVID-19 ; Risk Factors ; Patients

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.
Rats ; Animals ; Berberine/pharmacokinetics* ; Tissue Distribution ; Chromatography, Liquid ; Tandem Mass Spectrometry/methods* ; Drugs, Chinese Herbal/pharmacokinetics* ; Alkaloids/pharmacokinetics* ; Chromatography, High Pressure Liquid/methods* ; Arthritis