Objective To investigate the value of carvedilol or propranolol in preventing rebleeding in patients with esophageal variceal bleeding(EVB)in liver cirrhosis.Methods Patients with EVB in liver cirrhosis were divided into the treatment group and the control group.The treatment group was treated with oral administration of carvedilol dispersible tablets,with an initial dose of 6.25 mg,bid.The control group was treated with oral administration of propranolol hydrochloride tablets,with an initial dose of 20 mg,bid.The treatment course of two groups was 1 year.The effects between two groups were compared.The rebleeding rate,and hemodynamics between two groups were compared treated after 6 months and 1 year of treatment.Safety that occurred during treatment were observed.Results The treatment group consisted of 64 patients,while the control group consisted of 61 patients.After treatment,the overall response rate in the treatment group was 93.75％(60 cases/64 cases),while the control group was 91.80％(56 cases/61 cases),without statistically significant difference between the groups(all P＞0.05).After 6 months of treatment,rebleeding rates in the treatment group and the control group were 4.69％(3 cases/64 cases)and 9.84％(6 cases/61 cases),without statistically significant difference between the groups(P＞0.05).After 1 year of treatment,rebleeding rates in the treatment group and the control group were 10.94％(7 cases/64 cases)and 24.59％(15 cases/61 cases),without statistically significant difference between the groups(P＜0.05).After 6 months of treatment,portal vein diameter(PVD)in the treatment group and the control group were(12.39±2.41)and(13.88±1.76)mm;splenic vein diameter(SVD)were(7.56±1.52)and(8.35±1.69)mm;mean blood flow velocity of portal vein(Vp)were(35.26±7.04)and(38.12±7.60)cm·s-1;mean blood flow velocity of splenic vein(Vs)were(20.03±4.11)and(22.34±4.69)cm·s-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.05).After 1 year of treatment,PVD in the treatment group and the control group were(11.87±2.52)and(13.15±2.04)mm;SVD were(7.33±1.48)and(8.22±1.55)mm;Vp were(33.96±6.75)and(37.46±6.83)cm·s-1;Vs were(19.26±4.33)and(21.55±4.47)cm·s-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,dizziness,nausea and vomiting,while adverse reactions in the control group included bradycardia,hypotension,dizziness,drowsiness,nausea and vomiting,and skin rash.The total incidence of adverse drug reactions in the treatment group was 12.50％,while the control group was 27.87％,the differences were statistically significant(P＜0.05).Conclusion Compared to propranolol,carvedilol can better prevent rebleeding and relieve esophageal varices.

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

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 observe the therapeutic effect and mechanism of Guhuaisi Kangfu Pills on rats with steroid-induced osteonecrosis of the femoral head(SONFH).Methods Sixty rats were randomly divided into blank group,model group,Xianling Gubao Capsules group and Guhuaisi Kangfu Pills low-,medium-and high-dose groups,10 rats in each group.Except for the blank group,the SONFH model was established by lipopolysaccharide combined with Glucocorticoid induction method in all other groups of rats.At the end of the intervention,for the femoral head,blood vessel radiography was performed to observe the microvascular changes in the bone marrow,and hematoxylin-eosin(HE)staining and calculation of the empty bone trap rate,Micro-CT scanning analysis,and compression experiments were carried out,and the real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the gene expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt)1,vascular endothelial growth factor(VEGF)and platelet endothelial cell adhesion molecule 1(CD31)in whole blood.Results Compared with the blank group,the blood supply in the femoral head medullary cavity of the model group was poor,the empty bone lacuna rate was increased(P＜0.05),the bone mineral density and bone volume fraction were significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were decreased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in whole blood were decreased(P＜0.05).Compared with the model group,the blood supply in the femoral head medullary cavity was relatively good,the empty bone lacuna rate was decreased(P＜0.05),the bone mineral density,bone volume fraction,trabecular number and trabecular thickness were significantly increased(P＜0.05),the trabecular separation was significantly decreased(P＜0.05),the maximum load and elastic modulus of the femoral head were increased(P＜0.05),and the mRNA expression levels of Akt1,PI3K,VEGF and CD31 in the whole blood were increased(P＜0.05)in the high-dose group of Guhuaisi Kangfu Pills and Xianling Gubao Capsules group.There was no significant difference in the above indexes between the high-dose group of Guhuaisi Kangfu Pills and the Xianling Gubao Capsules group(P＞0.05).Conclusion Guhuaisi Kangfu Pills improves SONFH in rats,and its mechanism is related to the promotion of VEGF/PI3K/Akt pathway gene expression,thereby promoting angiogenesis.

Lactic acid bacteria(LAB)were isolated and cultivated from the intestinal contents of rabbits by MRS-CaCO3 solid medium.Identification was achieved through morphological observa-tion,Gram staining,physiological and biochemical characterisation,16S rDNA sequence analysis,and ERIC-PCR analysis.Strains displaying typical Lactobacilli characteristics were exanimated for their biological characteristics,resistance properties,adherence capacity in vitro,colonization abili-ty in vivo,and safety profile.In this study,a total of four strains of Lactobacillus reuteri were iso-lated from rabbits,all of which exhibited typical biological characteristics of LAB.These strains demonstrated inhibitory effects on common pathogenic bacteria in the gastrointestinal tract,with the primary inhibitory substance being bacteriocin.Furthermore,they showed sensitivity to chlor-amphenicol,rifampicin,and erythromycin,and displayed a degree of tolerance to gastrointestinal conditions and high temperature.These stains were capable of successful colonization in rabbits with a higher degree of safety.This study lays a foundation for the development of LAB prepara-tions for the prevention and treatment of rabbit intestinal diseases.

Objective:To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma(MM)bone disease(MBD)patients with different blood separation results.Methods:A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group[119 cases,serum,colloid and red blood cell(RBC)from top to bottom of sample]and abnormal group(15 cases,serum,mixed layer of RBC and serum,colloid and RBC from top to bottom of sample)according to the results of blood separation.According to the imaging findings,MBD was classified into grade 0-4,grade 0-2 was mild,and grade 3-4 was severe.The MBD grade of patients in the two groups was analyzed.The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated.The correlation between β 2-microglobulin(MG)and bone metabolic indexes was analyzed by Pearson correlation analysis.Results:In the control group,there were 69 cases of grade 0-2 and 50 cases of grade 3-4,while in the abnormal group,there were 5 cases of grade 0-2 and 10 cases of grade 3-4,the difference was statistically significant(P＜0.05).The serum β 2-MG,β-CTX levels in abnormal group were both significantly higher than those in control group,while the levels of P1NP and osteocalcin(OC)were significantly lower(all P＜0.001).In the control group,there were 95 patients with ≥ partial response(PR)and the blood separation results were not changed,while 24 patients with＜PR and 5 of them had abnormal blood separation results.In the abnormal group,9 patients with efficacy≥PR showed normal blood separation results,while 6 patients with efficacy＜PR and 5 of them still remained abnormal blood separation results.Compared with before treatment,β-CTX and β 2-MG of patients with efficacy ≥ PR were significantly decreased but P1NP and OC increased in the control group(all P＜0.00 1),which was the same as abnoraml group(both P＜0.001,P＜0.01).There were no significant changes in the levels of all indexes in the two groups of patients with efficacy＜PR(P＞0.05).Compared with before treatment,the levels of β-CTX and β 2-MG in the control group with unchanged blood separation results were significantly decreased(both P＜0.00l),while the levels of P1NP and OC were significantly increased(P＜0.01,P＜0.001),and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change(P＞0.05);the levels of β-CTX and β 2-MG in the abnormal group transformed to normal blood separation result were significantly decreased(both P＜0.01),while the levels of P1NP and OC were significantly increased(P＜0.001,P＜0.01),and the level of each index in patients with unchanged blood separation results did not significantly change(P＞0.05).Pearson correlation analysis showed that serumβ 2-MG was positively correlated with β-CTX(r=0.709,P＜0.001),and negatively correlated with P1NP and OC(r=-0.410,r=-0.412,both P＜0.001).Conclusion:MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis,which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels,leading to more serious bone metabolic homeostasis disorder.The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition,efficacy monitoring and prognosis evaluation of MBD patients.

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(β-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly β-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.
Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Excipients ; Solubility ; Nonprescription Drugs ; Biological Products

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 μg·mL~(-1), respectively.
Hedyotis/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Magnetic Resonance Spectroscopy ; Salicylic Acid

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.