This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

A dry suspension of Indigo Naturalis (IN) based on lactose-IN composite particles was designed by powder modification technology to meet the clinical needs of IN. The contact angle was used as an evaluation index to investigate the effects of the type of modifier lactose, the amount of lactose, and the co-grinding time of lactose and IN on the hydrophilicity of IN. The difference between IN before and after modification was compared through physical properties such as particle size and scanning electron microscope, as well as hydrophilic properties such as surface free energy and multiple light scattering. The optimal process of lactose-IN composite particles is as follows: after lactose is ground alone for 2 minutes, it is co-ground with IN at a ratio of 1∶1 for 6 minutes. The results of the investigation of powder properties show that the particle size d_0.9 of IN is reduced from 112.75 μm to 87.30 μm after modification. The BET and Langmuir specific surface areas decreased by 8.661 m²·g^-1 and 12.512 m²·g^-1, respectively. SEM shows that lactose is attached to the surface of modified IN (MIN); surface element analysis shows that Si, Ca, and Mg elements of MIN are smaller than IN, and O elements are larger. The infrared spectrum shows that the MIN possesses the characteristic peaks of both IN and lactose. Compared MIN with IN, the contact angle and the non-polar surface free energy decreased by 35.1° and 9.975 mJ·m^-2, respectively; the polar surface free energy and the surface free energy increased by 36.956 and 26.950 mJ·m^-2, respectively. The results of multiple light scattering showed that the light transmittance of MIN was 35% lower than that of IN, and the backscattered light intensity was increased by about 25%. Only one excipient was used to successfully prepare IN dry suspension with good wettability and suspending property, which provided a basis for the development of new preparations of IN.

Humans ; Factor XIII/genetics* ; Factor XIII Deficiency/genetics* ; Mutation ; Pedigree

Objective:To investigate the clinical manifestations and prognosis of severe coronal virus disease 2019(COVID-19)pneumonia combined with coronary artery disease(CAD)in the elderly.Methods:A total of 351 old patients(&ge;60 years)with severe COVID-19 pneumonia combined with CAD admitted to Tongji Hospital of Wuhan from February 2020 to March 2020 were enrolled in this retrospective study.The patients were divided into CAD group(n=52)and non-CAD group(n=299). The clinical data, the changes of blood tests and cardiovascular complications were observed.Results:Compared with non-CAD group, CAD group showed a longer time of stay in hospital[(12.3±2.6)d and(9.3±2.1)d, t=3.24, P=0.002], and higher incidence of cardiovascular complications, such as myocardial infarction(7.7% and 0.0%, χ2=21.6, P<0.001), heart failure(15.4% and 0.3%, χ2=34.7, P<0.001), arrhythmia(50.0% and 12.4%, χ2=24.45, P<0.001)and all-cause mortality(15.4% and 4.3%, χ2=7.94, P=0.005). The serum levels of interleukin-2 receptor, interleukin 6, CK-MB, cTnI, NT-proBNP, D-dimer and fibrinogen were higher in CAD group than in non-CAD group.The oxygenation index was significantly lower and the blood lactic acid level was higher in CAD group than in non-CAD group. Conclusions:The aged patients with severe COVID-19 pneumonia combined with CAD show obvious inflammatory reaction, high incidence of cardiovascular complications and high mortality.

OBJECTIVE To explore the clinical effects of Shuangxin Decoction in treating coronary heart disease accompa-nied with psychological disorder.METHODS 80 cases with coronary heart disease manifested as chest pain,chest distress plus psychological disorders like depression and anxiety were randomly divided into treatment group and control group.Patients in both groups were treated with routine western medicine plus psychological counseling.Based on which,patients in the treat-ment group were further given Chinese medicine Shuangxin Decoction,while those in the control group were added deanxit, with the course lasting for 6 weeks.Chest pain(distress) integral score scale,traditional Chinese medicine(TCM) syndrome score scale and comprehensive hospital anxiety and depression scale were evaluated to explore the therapeutic effects of chest pain,psychological disorder and clinical TCM syndromes before and after treatment of both groups,together with the changes of electrocardiogram test results and cardiac markers.RESULT Chest pain(distress) integral scores of treatment group were lower than those of control group(P <0.05),with the total curative rate being 82.50%,notably higher than 52.5% of the control group(P <0.01).The anxiety and depression scores of both groups were evidently reduced after treatment(P <0.01). The comparison of the two groups was P >0.05.TCM syndrome scores of both groups were notably declined(P <0.01).The total curative rate was 75%,which was superior to 20% of the control group(P <0.01).Both electrocardiogram test results and cardiac markers in both groups experienced an evident improvement than before(P <0.05).The comparison of the two groups showed P >0.05.No abnormality was detected in blood,urine,stool or liver and kidney function test in patients of both groups.CONCLUSION Shuangxin Decoction can efficiently improve chest pain,chest distress symptoms as well as TCM clinical syndromes due to coronary heart disease accompanied with psychological disorder.Also,it is helpful for improving de-pression and anxiety,which has been considered as a safe and effective formula for treating these two disorders,worthy of clin-ical application and promotion.

OBJECTIVETo investigate the protective effects of hepatocyte growth factor (HGF) on hypoxic human pulmonary microvascular endothelial cells (HPMECs).

METHODSHPMECs were cultured in vitro, and the hypoxic model was established by the physical method. Cells were divided into 4 groups: the control group, the hypoxic group, HGF group, and phytohemagglutinin (PHA) group. The 7(th) generation of HPMECs was evaluated by the method of immunocytochemistry. The persistence rate of HPMECs was measured by MTT assay and the adhesive cells were counted by the microscopy. The expression of intercellular adhesion molecule-1 (ICAM-1) protein was determined by immunofluorescence staining.

RESULTSThe adherence percentage of cells significantly decreased after hypoxia, whereas the expression of the ICAM-1 protein was significantly higher in the hypoxia group than in control group (P<0.01). Compared with the hypoxia group, the persistence and adherence percentage of cells in the HGF group significantly increased (P<0.01), whereas the expression of the ICAM-1 protein significantly dropped (P<0.01). In the PHA group, the persistence and adhesion rate were significantly different from those in the hypoxia group and HGF group (P<0.01), and the expression of the ICAM-1 protein increased significantly (P<0.01).

CONCLUSIONHGF could inhibit the hypoxic damage of HPMECs by decreasing the persistence and the adhesive capacity of these cells and inducing the expression of ICAM-1.

Cell Adhesion ; drug effects ; Cell Hypoxia ; Cell Survival ; drug effects ; Cells, Cultured ; Endothelial Cells ; drug effects ; Endothelium, Vascular ; cytology ; metabolism ; Hepatocyte Growth Factor ; pharmacology ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Lung ; blood supply

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP &ge; 140 mmHg and/or diastolic BP &ge; 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

BACKGROUNDPneumonia is the most common cause of morbidity and mortality in lung transplant (LT) recipients. The aim of the present study was to evaluate the incidence, etiology, risk factors and prognosis of pneumonia in LT recipients.

METHODSThe LT cohort consisted of 28 recipients receiving LT in Beijing Chao-Yang Hospital from August 2005 to April 2011. Data collected included demographic data, underlying disorders, time and type of transplant, follow-up information, date of last follow-up, and patient status. A retrospective analysis was made of observational data that were prospectively collected.

RESULTSTwenty-two patients of 28 LT recipients had 47 episodes of pneumonia throughout the study period. Thirtyeight episodes of pneumonia in 19 recipients occurred post-LT with a median follow-up of 257.5 days (1-2104 days), the incidence of pneumonia was 192.4 episodes per 100 LT/year and its median time of onset was 100.5 days (0-946 days) post-transplantation. Bacteria, virus and fungi accounted for 62%, 16% and 15% of the microbial pathogens, respectively. The most frequent were Pseudomonas aeruginosa (20%), cytomegalovirus (CMV) (15%), and Aspergillus fumigatus (10%). A total of 29% (11/38) of pneumonias occurred in the first month post-LT, and then the incidence decreased gradually. The incidence of CMV pneumonia was 25% (7/28) with a median time of 97 days (10-971 days). More than one bacterial infection and CMV infection were independent risk factors for aspergillus infection. The incidence of pulmonary tuberculosis (TB) was 18% (5/28), and the history of TB was a risk factor for TB relapse. There were 58% (7/12) of recipients who died of infection, and 71% (5/7) of these died in the first year after LT.

CONCLUSIONSPneumonia is still a major cause of morbidity and mortality in LT recipients. The most frequent microorganisms were Pseudomonas aeruginosa, CMV, and Aspergillus fumigates. The incidence of CMV pneumonia decreases with a delayed median time of onset. More than one incidence of bacterial infection and CMV infection are independent risk factors for aspergillus infection. LT recipients are at high risk for TB, and the history of TB is a risk factor for TB relapse.

Aspergillus fumigatus ; pathogenicity ; Cytomegalovirus ; pathogenicity ; Humans ; Lung Transplantation ; adverse effects ; Pneumonia ; etiology ; microbiology ; virology ; Prospective Studies ; Pseudomonas aeruginosa ; pathogenicity

This study was purposed to investigate the incidence of mixed lineage leukemia (MLL) gene rearrangement and partner gene types as well as the clinical features and prognosis of acute leukemia (AL) with this rearrangement through detection in adult AL using combination of 3 techniques, and to evaluate the clinical value of this combination detection. The MLL gene rearrangement in 183 cases of adult AL was detected by combination of conventional cytogenetics, split signal FISH and multiplex nested PCR. The results showed that the incidence of MLL rearrangements in adult patients with AL was low (8.2%), and MLL-AF4 fusion gene was most common and predominant in acute lymphoblastic leukemia (ALL), while the MLL-AF6 and MLL-AF9 were most frequent in acute myeloid leukemia (AML). Extramedullary involvements were found in 40% of MLL-rearranged AL patients, and 33.3% of patients with MLL-rearranged AL reached to complete remission within 30 days during induction chemotherapy. In addition, in this cohort of MLL-rearranged adult AL patients, the 3-month relapse rate and 6-month overall survival rate were 50.0% and 50.0% respectively. It is concluded that the rate of missed diagnosis of CC technique for patients with MLL-rearranged AL reached to 60% in this study, while the combination of CC, FISH and multiplex nested PCR has been confirmed to have important significance for evaluating prognosis and conducting clinical therapy of patients with MLL-rearranged AL.
Adolescent ; Adult ; Aged ; Female ; Gene Rearrangement ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Oncogene Proteins, Fusion ; genetics ; Young Adult