This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

Objective:To investigate the correlation between morphological typing and monoclonality of bone marrow plasma cells,and explore the diagnostic value of plasma cell morphological typing for high-risk smoldering multiple myeloma(HR-SMM).Methods:The correlation between the morphological characteristics and the monoclonality of bone marrow plasma cells was analyzed in 84 patients with HR-SMM who treated in our hospital.The consistency of morphologically abnormal bone marrow plasma cells with serum free light chain(sFLC)ratio,next-generation sequencing(NGS)detection results,and its correlation with monoclonal plasma cells detected by flow cytometry(FCM)were further verified.The immunoglobulin types and levels of non-involved immunoglobulins in serum of the patients were detected,and the distribution of plasma cell clusters in patients with different disease was observed.Results:The mean percentage of mature plasma cells were decreased successively in the order of reactive plasmacytosis(RP)group,monoclonal gammopathy of undetermined significance(MGUS)group,smoldering multiple myeloma(SMM)group,HR-SMM group and multiple myeloma(MM)group;while the mean percentage of immature,primitive,reticular and flaming plasma cells were increased successively in the order of RP group,MGUS group,SMM group,and HR-SMM group,and the difference between any two groups was statistically significant(P＜0.05).The average proportion of abnormal plasma cells in the bone marrow of HR-SMM patients was 96.2％of the total plasma cells.The proportion of abnormal plasma cells were in good agreement with the sFLC ratio and the results of NGS detection in HR-SMM patients(kappa=0.879 and kappa=0.891,both＞0.75),and showed good correlation with the monoclonal plasma cells with immunophenotype of CD45-/CD38+/CD138+/CD56+/CD19-(γ=0.825).The levels of non-involved immunoglobulin in IgG,IgA and IgM type HR-SMM patients were all decreased by more than 25％compared with the normal reference range,and the differences were statistically significant(P＜0.05).There was no significant difference in the distribution ratio of plasma cell clusters among different disease groups(P＞0.05).Conclusion:In HR-SMM patients,the immature,primitive,reticular and flaming plasma cells in bone marrow are considered as abnormal plasma cells,and they are correlated with monoclonal plasma cells.The proportion of abnormal plasma cells in total plasma cells of bone marrow and the reduction extent of non-involved immunoglobulin level in patients have certain reference value for the diagnosis of HR-SMM.

Since the end of 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has swept the world,bringing great harm to human society and significantly increasing the health burden.Due to stron-ger infectivity,faster transmission,and higher reinfection rate of the Omicron variant,it has now replaced the Delta variant as the main epidemic strain for both imported and local outbreaks in China.Chinese Diagnosis and treatment protocol for SARS-CoV-2 infection(10th trial version)emphasizes"strengthening the protection of key popula-tions,"which includes the increasing number of immunocompromised population.These people have a high inci-dence of severe diseases and a high fatality rate after infected with SARS-CoV-2,and belong to the high-risk popula-tions of severe or critical diseases.Moreover,due to underlying diseases,these people take immunosuppressants and other related drugs chronically.The interactions between anti-SARS-CoV-2 infection treatment drugs and origi-nal drugs are complicated,thus bring significant challenges to the treatment after the SARS-CoV-2 infection.Cur-rently,there is a lack of guidelines or consensus on the diagnosis and treatment of SARS-CoV-2 infection among im-munocompromised population.Therefore,the Guangzhou Institute of Respiratory Health and National Center for Respiratory Medicine organized experts from multiple disciplines(respiratory and critical care medicine,organ transplantation,rheumatology and immunology,hematology,infection,critical care medicine,etc.)in China.Af-ter multiple rounds of discussions,13 items of recommendations are made as the reference for peers based on evi-dence-based medical evidence,so as to provide a theoretical and practical reference for the diagnosis and treatment strategies of this population.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45⁺ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3⁺ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

OBJECTIVE: To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR). METHODS: Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting. RESULTS: Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction. CONCLUSION Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.
Humans ; Aurora Kinase A/metabolism* ; Cell Line, Tumor ; Mitosis ; Cell Cycle ; Radiation, Ionizing ; RNA, Small Interfering/metabolism* ; Cyclin-Dependent Kinase Inhibitor p21/metabolism*

Aim To study the mechanism of anti-plate- let aggregation of sorghum root active parts. Methods The effects of active fraction (WEAE-M 30%) from sorghum roots on platelet aggregation induced by collagen, thrombin and adenosine diphosphate were investigated in vitro. Western blot, enzyme-linked immunoas-say, flow cytometry and fluorescence techniques were used to explore the mechanism of the antiplatelet aggregation effect of WEAE-M 30% . Results WEAE-M 30% had a significant inhibitory effect on platelet aggregation induced by the three agonists mentioned above. The inhibitory effect on platelet aggregation induced by collagen was the most significant, with an inhibitory rate of (72. 91 ±2. 42)%. It was found that WEAE-M 30% had a significant inhibitory effect on the collagen- mediated platelet (IPVI signaling pathway protein Src, MAPK signaling pathway protein p38 and ERK phosphorylation. It also significantly inhibited the levels of ATP, P-selection and Ca2+ in platelets. Conclusions It is suggested that the mechanism of WE-AE-M 30% antiplatelet aggregation may be related to the inhibition of platelet activation pathway GPV1, MAPK and the release of typical platelet representative particles.

Objective:To analyze the death rate of asthma among Chinese people aged 0-19 years in 2018 and the trend of asthma mortality between 2008 and 2018, in order to guide the research of asthma control management and prevention strategy, and reduce the mortality of childhood asthma in China.Methods:Data from the national disease surveillance points system (DSPs) was adopted.The mortality rates of 0-19-year-old people in different age groups, genders, places of residence and geographical regions from 2008 to 2018 were calculated, and the national death toll of asthma was estimated as well.The annual percentage change (APC) and average annual percentage change (AAPC) were calculated, and the death rate of asthma among Chinese people aged 0-19 years in 2018 and change trend of asthma mortality from 2008 to 2018 were analyzed.Results:In 2018, there was no significant gender diffe-rence in asthma mortality among Chinese people aged 0-19 years among different age groups, places of residence and geographical regions(all P>0.05). From 2008 to 2018, the mortality rate of people aged 0-19 fluctuated from 0.023/100 000 to 0.046/100 000, the highest mortality rate was in 2009 and 2012, and the lowest was in 2018. It was estimated that the total number of deaths among people aged 0-19 years reached the highest in 2009 (148 cases) and the lowest in 2018 (70 cases). It is estimated that the total number of deaths among people aged 0-19 years in China from 2008 to 2018 was 1 158 cases.From 2008 to 2018, the total mortality rate of asthma in Chinese population aged 0-19 years decreased significantly (AAPC=-7.6%, 95% CI: -10.4%--4.7%). There was a significant decrease in male group(AAPC=-7.4%, 95% CI: -12.5%--2.0%), female group(AAPC=-7.5%, 95% CI: -12.7%--2.0%), 1-<5 years old group(AAPC=-11.4%, 95% CI: -17.9%--4.5%), 15-19 years old group(AAPC=-14.4%, 95% CI: -24.8%--2.6%), rural group(AAPC=-9.0%, 95% CI: -13.1%--4.8%) and central areas(AAPC=-13.1%, 95% CI: -24.0%--0.5%), with statistical significance(all P<0.05). Conclusions:The total mortality of asthma in 0-19-year old population decreased significantly from 2008 to 2018.The mortality rate of asthma in 0-19-year old people in China is at the low level around the world.

Objective:To analyze the long-term prognosis and prognostic factors of allergic bronchopulmonary aspergillosis(ABPA) in children suffering from cystic fibrosis (CF).Methods:An observational study was performed.All children who were admitted to the Department of Respiratory, Beijing Children′s Hospital, Capital Medical University from August 2014 to June 2018, with more than 2 years of followed up for the diagnosis of CF accompanied by ABPA were involved.Results:Three children met the inclusion criteria, with 2 boys and 1 girl, and their diagnostic age were 14, 8 and 9 years old, respectively.The follow-up duration ranged from 2 to 6 years.All the 3 cases were treated with systemic corticosteroids and antifungal agent.In case 1, the initial dose of prednisone was 0.75 mg/(kg·d), and the course of treatment was more than 5 years.The corticosteroid-dependent patient suffered from expectoration and chest pain, and radiographic findings indicated exacerbation, while his lung function was normal.Treating with initial dose of prednisone 2 mg/(kg·d) for 9 months, case 2 had normal serum immunoglobulin E(IgE) concentration, but his pulmonary artery was infiltrated by lesions, thus leasing to lobectomy.In case 3, the initial dose of prednisone was 0.6 mg/(kg·d), and the course of treatment was 18 months.And she developed persistent hypoxemia, and decreased pulmonary function, so lung transplantation was necessary 2 years after diagnosis.Conclusions:Systemic glucocorticoid combined with antifungal therapy is the main treatment for CF with ABPA, but there are individual differences in the efficacy.The level of serum total IgE is not always consistent with lung function and chest images.The overall prognosis is poor, and it is infeasible to evaluate the prognosis by single factor.

Objective:To explore the significance of US lung allocation score (LAS) in Chinese lung transplant recipients.Methods:The clinical data were analyzed for 173 lung recipients from May 2005 to March 2018. The LAS of each patient was calculated by an online LAS calculator of Organ Procurement and Transplantation Network (OPTN).Results:The mean age was (56.49±12.64) years and the mean LAS (56.63±18.39)(32.79-90.70). The underlying diseases were chronic obstructive pulmonary disease (COPD, n=62), interstitial lung disease (n=85), bronchiectasis (n=11), pulmonary arterial hypertension (n=8) and others (n=7). And the value of LAS was (47.85±15.22) vs. (61.89±18.63) vs. (56.58±18.91) vs. (55.23±10.74) vs. (72.45±16.41). LAS of COPD patients was significantly lower than that of interstitial lung disease ( P<0.001). Mean LAS was the highest in endotracheal intubation or ECMO group (79.15±7.95), then non-invasive ventilation group (48.42±11.58) and lowest in oxygen inhalation group (44.11±8.81)( P<0.001). Recipients were divided into three groups of LAS <50 for low-risk, 50-75 for moderate-risk and >75 for high-risk. Survivals at 90 days and 1 year were 90.5% vs. 81.8% vs. 71.1% and 85.4% vs. 74.4% vs. 57.8% ( P=0.002). Conclusions:LAS can not only reflect the urgency of recipients waiting for lung transplantation but also predict postoperative period. LAS score should be employed for selecting suitable lung transplant recipients in China and the optimal LAS lies between 30 and 75.