Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.

Platelet adhesion is a key process in thrombosis. Anti-platelet adhesion effect of some Chinese medicines for promoting blood circulation and removing blood stasis (PBCRBS) has been reported, but their relative efficacies as a whole and specific targets remained unclear. This paper combined activity screening, drug compatibility analysis, pathway clustering, target prediction, and molecular docking to explore the mechanism of anti-platelet adhesion by PBCRBS Chinese medicine. Screening the activity of anti-platelet adhesion of 58 commercially available PBCRBS Chinese patent medicines showed that about 50.0% significantly inhibit ADP-induced platelet adhesion in vitro, and about 96.6% significantly inhibit thrombin-induced platelet adhesion in vitro. The animal experiment involved was approved by the Animal Ethics Committee of Tianjin International Biomedical Research Institute. Combined with the auxiliary platform for TCM (V2.0) inheritance showed that the compatibility of Danshen-Chuanxiong was used most frequently among the top 20 active proprietary Chinese patent medicines. IPA network analysis revealed that IL-1, APP and CCL2 might be the key targets for anti-platelet adhesion function of Danshen-Chuanxiong against atherosclerosis, neuroinflammation and chemokine signaling pathways as the main mechanisms. Molecular docking analysis confirmed the interaction between one of the active compounds shared by Danshen and Chuanxiong, i.e. chlorogenic acid, with its target CCL2. This study provides TCM theory guidance and experimental support for targeting platelet adhesion in anti-thrombosis therapy by Chinese medicine for promoting blood circulation and removing blood stasis.

Objective To observe the clinical efficacy and safety of sorafenib tablets combined with transcatheter arterial chemoembolization (TACE) in the treatment of unresectable liver cancer. Methods A total of 164 patients with unresectable liver cancer were randomly divided into control and treatment groups with 82 cases per group. Control group was treated with TACE alone, once every 4 weeks. Treatment group was given sorafenib tablets 400 mg per time from 5 d after TACE treatment, bid, orally, on the basis of control group. Two groups were treated for 12 weeks. The clinical efficacy, serum tumor markers, serum vascular endothelial growth factor (VEGF) , levels of basic fibroblast growth factor (bFGF) , and adverse drug reactions were compared between two groups.Results After treatment, the objective remission rates of treatment and control groups were 52. 44％ (43 cases/79 cases) and 28. 05％ (23 cases/79 cases) , the disease control rates were 87. 80％ (72 cases/79 cases) and 68. 29％ (56 cases/79 cases) , the progression free survival time were (15. 32 ± 2. 04) and (10. 83 ± 1. 43) months, the overall survival time were (15. 32 ± 2. 04) and (10. 83 ± 1. 43) months, the differences were statistically significant (all P < 0. 05) . After treatment, the alpha fetoprotein of treatment and control groups were (71. 38 ± 10. 04) and (152. 36 ± 20. 37) ng·m L-1, the carcinoembryonic antigen were (2. 02 ± 0. 27) and (2. 94 ± 0. 34) μg·L-1, the VEGF were (317. 87 ± 32. 76) and (442. 45 ± 35. 09) pg·m L-1, the differences were statistically significant (all P < 0. 05) . The adverse reactions of treatment group and the control group were nausea and vomiting (71. 95％ vs63. 41％) , diarrhea (35. 37％ vs 42. 68％) , myelosuppression (43. 90％ vs 40. 24％) and fever (84. 15％ vs90. 24％) , oral mucositis (32. 93％ vs 6. 10％) , hand-foot skin reaction (69. 51％ vs 2. 44％) , the differences were statistically significant (all P < 0. 05) . Conclusion Sorafenib tablets combined with TACE have a definitive clinical efficacy in the treatment of unresectable liver cancer, which can effectively inhibit the release of tumor markers, decrease the levels of serum VEGF and other cytokines. Although the incidence of adverse drug reactions is high, they can be controlled.

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients' overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion: Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.
Adult ; B-Lymphocytes ; DNA Mutational Analysis ; Humans ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis

OBJECTIVETo investigate the effect of recombinant adenovirus (phosphatidylinositol-3-kinases(PI3K)(I()-RNAi-AD which blocks the class I( PI3K signaling pathway on gastric carcinoma cells xenografts in nude mice.

METHODSSubcutaneous tumor models of nude mice were established with SGC7901 cells and randomly divided into PI3K(I()-RNAi-AD group, NC-RNAi-GFP-AD group and control group. The tumor size and the inhibitory rate of tumor growth on days 3, 6, and 9 after cell transplantation were measured. The expression of TNF-α, COX2, P53, PCNA, E-cadherin and nm23/DNPK in tumor tissues were detected by immunohistochemistry.

RESULTSTumor growth was significantly inhibited in the PI3K(I()-RNAi-AD group(14.2%, 21.0%, and 28.1%) on days 3, 6, 9 compared with NC-RNAi-GFP-AD group(1.3%, 1.9%, and 2.0%, all P<0.05). The expressions of TNF-α, P53, E-cadherin and nm23/DNPK were up-regulated, and the expressions of COX2 and PCNA were down-regulated in the PI3K(I()-RNAi-AD group by immunohistochemical staining(all P<0.05).

CONCLUSIONSPI3K(I()-RNAi-AD can inhibit the growth of SGC7901 cell transplantation tumor in vivo in nude mice by inhibiting cell growth, reducing the capacity of tumor invasion and inhibiting tumor angiogenesis.

Adenoviridae ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Class I Phosphatidylinositol 3-Kinases ; Heterografts ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; Phosphatidylinositols ; Stomach Neoplasms

OBJECTIVETo delineate the characteristics of the clinical manifestation, pathology of skeletal muscle and gene mutations of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) in children.

METHODThe clinical manifestation, laboratorial data, brain images, muscle pathology and mitochondrial gene mutations were analyzed in 24 patients with MELAS who were diagnosed in Department of Pediatrics, Peking University First Hospital. Their prognosis was evaluated by following up.

RESULTSymptoms of central nervous system such as stroke-like episodes, vomiting, convulsion and headache were present in all the 24 cases. Nine cases had the symptoms of myopathy. Twenty cases had developmental delay. Short stature, being thin and hairy was very common in these cases. Serum lactate level increased in all the cases, pyruvate increased in 17 cases. Elevated CSF lactate was found in 2 cases. Magnetic resonance imaging (MRI) was performed on 24 cases, out of them 23 were abnormal. The lesions mainly involved cerebral lobes. Occipital lobe was the most common site of lesions. Computed tomography (CT) was performed on 13 cases, low density lesions were present in 10 cases, basal ganglia calcifications in 5 cases. Muscle biopsy was performed on 8 cases, ragged-red fibers (RRF) were found in 4/8 cases, and abnormal accumulation of mitochondria were found in 3/8 cases. The mtDNA gene mutational analysis showed A3243G mutation in these patients. The mutation rates varied from 11.6% to 75.0%. The same mutation were found in 4/5 mothers who had the genetic tests, and the mutation rates of the mothers varied from 15.0% to 23.6%. The clinical information of 11 cases was available through recent following up. Three cases died, the others had some degrees of mental retardation.

CONCLUSIONChildren with MELAS had various clinical manifestations. Central nervous system and skeletal muscle were usually involved. Short stature and hypertrichosis were common signs. The prognosis of this disease was disappointing. mtDNA A3243G was the most common mutation in MELAS. Fully understanding the characteristics of its clinical manifestation, laboratory tests, brain image, muscle pathology and molecular features can be helpful to the early diagnosis and treatment.

Acidosis, Lactic ; blood ; Adolescent ; Brain ; diagnostic imaging ; pathology ; Child ; Child, Preschool ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Electroencephalography ; Female ; Follow-Up Studies ; Humans ; Infant ; MELAS Syndrome ; diagnosis ; genetics ; pathology ; Magnetic Resonance Imaging ; Male ; Muscle, Skeletal ; diagnostic imaging ; pathology ; Point Mutation ; Pyruvic Acid ; blood ; Stroke ; diagnostic imaging ; genetics ; pathology ; Syndrome ; Tomography, X-Ray Computed

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 ≥ 140 mmHg and/or diastolic BP ≥ 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

Acquired Immunodeficiency Syndrome ; epidemiology ; virology ; Adolescent ; Adult ; China ; epidemiology ; Drug Resistance, Viral ; Female ; HIV-1 ; drug effects ; Humans ; Male ; Young Adult

Objective To observe the prognostic value of admission B-type natriuretic peptide (BNP) on outcome for patients with congestive heart failure (CHF).Methods Blood BNP levels,routine echocardiography and tissue Doppler image were obtained in 162 CHF patients [95 male,mean age:(71.8 ±3.7 ) years] at admission.Patients were divided into high BNP ( BNP ＞ 1500 ng/L,n =104) and low BNP (BNP≤ 1500 ng/L,n =58 ) groups.All patients were followed up for 2 years and clinical characteristics,echocardiography including Doppler image and cardiovascular events results were analyzed.Data were also compared between patients with ( n =48 ) or without ( n =107 ) cardiovascular events.Results Left ventricular ejection fractions (LVEF) was significantly lower [ (40.9 ±5.6)％ vs.(44.0 ±5.9)％,P ＜0.01 ] while the total cardiovascular events rate (49.1％ vs.21.0％,P ＜0.01 ) and cardiac mortality rate (25.5％ vs.9.0％,P＜0.01) were significantly higher in high BNP group than in low BNP group.BNP level at admission in event group was significantly higher than in event-free group [ (2875.4 ±325.7) ng/Lvs.(1136.9±298.6) ng/L,P＜0.000].BNP level was positively related to Tei-index (r=0.793,P＜0.001 ) and negatively correlated with LVEF ( r =-0.57,P ＜0.001 ).Multiple logistic regression analysis demonstrated that BNP,LVEF,Tei-index and β-blocker use were independent risk factors for cardiovascular events.The area under the ROC curve for predicting cardiovascular death within 2 years in event group by BNP was 0.795 (95％ CI 0.693 - 0.935,sensitivity:72.31％ and specificity:84.62％,cut-off BNP value:1910 ng/L).The event risk was 2.17 times higher in CHF patients with admission BNP ＞ 1910 ng/Lcompared CHF patients with admission BNP ≤ 1910 ng/L ( 95％ CI:1.852 - 2.954,P =0.000 ).Conclusion Admission BNP level,LVEF,Tei-index and β-blocker use are independent risk factors for cardiovascular events in patients with CHF.Patients with higher admission BNP level ( ＞ 1910 ng/L) is linked with worse prognosis in this patient cohort.

Objective To investigate the changes of open probability (Po) of large conductance Ca2+ -activated K + channel (BK channel ) in diabetic coronary smooth muscle cells and elucidate the underlying cellular electrophysiology mechanisms of coronary dysfunction.Methods Rat coronary smooth muscle cells were isolated from control group and diabetic group.BK single channel currents were recorded by patch clamp technique in inside-out configuration.Open probabilities were calculated and compared between two groups.After exposure to DHS-1,a specific BK channel activator,Po at 0.2 and 1 μmoL/L free Ca2+ were compared between control and diabetic groups.Results In the presence of 0.2 μmol/L free Ca2+,the Po at baseline was significantly lower in diabetic rats than in control rats (0.0032 ± 0.0012 vs.0.095 ±0.036,P ＜ 0.05).Cytoplasmic application of DSH-1 significantly increased the Po to 0.335 ±0.096 (P ＜0.05 vs.baseline) in control rats,whereas DSH-1 had no effect in diabetic rats ( Po =0.022 ±0.018,P＞0.05 vs.baseline).In the presence of 1 μmol/L free Ca2+,the Po at baseline was also significantly lower in diabetic rats than in control rats (0.210 ± 0.055 vs.0.458 ± 0.077,P ＜ 0.05 ).Cytoplasmic application of DHS-1 further robustly enhanced Po to 0.823 ± 0.019 (P ＜ 0.05 vs.baseline) in control rats and to 0.446 ± 0.098 in diabetic rats ( P ＜ 0.05 vs.baseline of diabetic rats; P ＜ 0.05 vs.control rats with DHS-1 ).Conclusion The decrease of Po of BK single channel in coronary smooth muscle cells may be a potential cause for coronary dysfunction in diabetic rats.