Objective To explore the rule of traditional Chinese medicine (TCM) syndrome differentiation of coronavirus disease 2019 (COVID-19) patients. Methods The symptoms of 756 cases with COVID-19 in Guanggu Branch of Maternity and Child Healthcare Hospital of Hubei Province were collected by cross sectional survey. The incidence rates of the symptoms were recorded by frequency method at different courses of the disease: prodromal stage (onset), middle stage (7-30 days), and later stage (>30 days). The common symptoms (incidence rate>5.0%) were analyzed by systematic clustering. With expert experience, the rule of TCM syndrome differentiation of COVID-19 patients was summarized. Results Fever (52.25%, 395 cases), cough (43.25%, 327 cases), asthenia (27.25%, 206 cases), chest distress (26.72%, 202 cases), asthma (17.59%, 133 cases) and expectoration (5.03%, 38 cases) were the most common symptoms in the prodromal stage (756 cases) of the disease, which were clustered into one category except expectoration, indicating the pathogenesis of both lung and body surface suppressed by dampness. In the middle stage (383 cases), the 19 common symptoms including greasy fur (64.49%, 247 cases), yellow fur (43.86%, 168 cases), thick fur (40.21%, 154 cases), cough (34.73%, 133 cases), red tongue (32.38%, 124 cases), poor stool (25.85%, 99 cases), asthma (25.33%, 97 cases), asthenia (25.07%, 96 cases), poor appetite (23.76%, 91 cases), bitterness of mouth (14.36%, 55 cases), dry fur (12.01%, 46 cases), purple tongue (12.01%, 46 cases), perspiration (11.49%, 44 cases), constipation (10.18%, 39 cases), white phlegm (8.62%, 33 cases), insomnia (7.31%, 28 cases), nausea (7.05%, 27 cases), diarrhea (6.79%, 26 cases) and yellow phlegm (6.27%, 24 cases), were clustered into three groups, indicating the pathogenesis of damp-heat accumulation, obstruction of lung and spleen by dampness, and dryness due to dampness-heat. In the later stage (373 cases), the 13 common symptoms including greasy fur (50.94%, 190 cases), asthenia (39.41%, 147 cases), cough (37.80%, 141 cases), red tongue (33.78%, 126 cases), asthma (32.17%, 120 cases), perspiration (23.86%, 89 cases), dry mouth (22.79%, 85 cases), poor appetite (20.11%, 75 cases), poor stool (19.30%, 72 cases), bitterness of mouth (15.01%, 56 cases), white phlegm (10.72%, 40 cases), palpitation (8.31%, 31 cases) and little fur (8.04%, 30 cases), were clustered into two groups, indicating the pathogenesis of deficiency of Qi and Yin with residual dampness, and deficiency of lung Qi and spleen Qi with residual dampness. Conclusion The TCM syndromes of COVID-19 patients in different stages have its own typical characteristics, with a regular change from exterior to interior, from dampness to dampness-heat and from excess to deficiency..

To silence the expression of K-RASAsn12 in human pancreatic cancer cell line by vector-based RNAi(RNA interference) technique,two single-strand DNA sequences encoding mutant-specific shRNA (short haipin RNA) for K-RASAsn12 were synthesized and then inserted into pSilenCircle. The recombinant plasmid was called pSC-K-RASAsn12. According to the same method, pSC-GFP encoding shRNA for GFP was gained. Both recombinant plasmids were transfected into human pacreatic cancer cell line AsPC-1 and BxPC-3. The expression level of K-RASAsn12 was detected by semi-quantitative RT-PCR and Western blot. The result indicated that the recombinant plasmid edcoding mutant-specific shRNA for K-RASAsn12 can inhibit significantly the expression of K-RASAsn12 without affection of wild-type K-RAS(K-RASWT)in Human Pancreatic Cancer Cell Line.

OBJECTIVENovel stents loaded with antibody against CD105 were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting activated endothelial cell.

METHODSThirty Stents coated with antibody against CD105, thirty unloaded polymer, and thirty bare metal stents were deployed in 90 coronary arteries of 30 minipigs. Oral aspirin (300 mg before operation and 100 mg post operation) and clopidogrel (300 mg before operation and 75 mg post operation) were orally administrated. Coronary artery quantitative analysis was completed by coronary arteriography, the vascular endothelium changes were observed under scanning electron microscope and the vascular morphological changes were observed under light microscope 7 and 14 days after operation.

RESULTSComplete procedural and angiographic success was achieved in all 30 minipigs. There were no major adverse cardiac and cerebrovascular events. At 7 days, there was no difference for mean neointimal area and percent area stenosis among various groups. At 14 days, endothelialization scores were significantly higher in the CD105 antibody-loaded stents and bare metal stents group than in sirolimus-eluting stents group (1.78 ± 0.49, 1.50 ± 0.67 vs. 1.08 ± 0.29, all P < 0.05), mean percent area stenosis in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(23.8 ± 4)%, (24.2 ± 2)% vs. (38.0 ± 3)%, all P < 0.05], mean angiographic late luminal loss in the CD105 antibody-loaded stents, sirolimus-eluting stents group were less than that in bare metal stents group [(0.29 ± 0.28) mm, (0.28 ± 0.02) mm vs. (0.41 ± 0.01) mm, all P < 0.05]. There was no difference for mean percent area stenosis in the CD105 antibody-loaded stents and sirolimus-eluting stents group. The mean neointimal area in the CD105 antibody-loaded stents, and sirolimus-eluting stents group were less than that in bare metal stents group [(0.88 ± 0.08) mm(2), (0.89 ± 0.12mm)(2) vs. (1.00 ± 0.14) mm(2), all P < 0.05] and there was no difference for the mean neointimal area in the CD105 antibody-loaded stents and sirolimus-eluting stents group. At 7 and 14 days, there was no difference for the injury score and the inflammation score among various groups, scanning electron microscopy evidenced enhanced endothelial coverage on CD105 antibody-loaded stents compared to sirolimus-eluting stents group.

CONCLUSIONStent coated with antibody against CD105 could effectively reduce in-stent restenosis and accelerate endothelialization in the minipigs.

Animals ; Antibodies ; pharmacology ; Antigens, CD ; immunology ; Aspirin ; pharmacology ; Coronary Restenosis ; prevention & control ; Endothelial Cells ; drug effects ; Neointima ; prevention & control ; Stents ; Swine ; Swine, Miniature ; Thrombosis ; prevention & control ; Ticlopidine ; analogs & derivatives ; pharmacology

Objectives: To investigate whether remote ischemic conditioning (RIC) applied to patients with ST-segment elevation myocardial infarction (STEMI) before percutaneous coronary intervention (PCI) could affect circulating miR-208b level or not. Methods:Patients diagnosed with STEMI undergoing PCI from January 2016 to July 2017 were enrolled from the Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University.The patients were randomly allocated to two groups: (1) control group (n=25), PCI alone; (2) RIC group (n=50), PCI combined with RIC (three cycles of 5 min inflation and 5 min deflation of the right lower limb with blood pressure cuff performed before reperfusion). Serum miR-208b was measured before and immediately, at 24 h, and 48 h after PCI with real-time quantitative polymerase chain reaction. Results: The expression of miR-208b was significantly higher immediately post PCI than that before operation in the control group (84.1±9.0 vs 77.8±9.4; P=0.032), while it was significantly lower immediately post PCI than that before operationin RIC group (71.0±9.3 vs 77.4±8.8; P=0.028).miR-208b level was similar before PCI between the control and RIC groups (P=0.874), which was significantly reduced immediately post PCI in RIC group as compared with the control group (P=0.021).The peak value of creatine kinase isoenzyme (CK-MB) in the limb RIC group was significantly lower than that in the control group ([135.2±18.6] U/L vs [167.7±17.2] U/L; P=0.038).The area under the CK-MB curve of the RIC group was significantly smaller than that of the control group ([3 060.7±17.1] U/L vs [3 635.9±15.1] U/L); P=0.047]. The left ventricular ejection fraction (LVEF) in RIC group was significantly higher than that in the control group ([57.8±7.8]% vs [51.9±7.9]%; P=0.003) post PCI. The expression level of serum miR-208b was positively correlated with CK-MB AUC in RIC group (r=0.498, P<0.001). Conclusions: RIC of the lower limb prior to PCI could reduce miR-208b level and improve cardiac functionin STEMI patients.

OBJECTIVETo explore the immune tolerance induction (ITI) in a severe hemophilia A patient with inhibitor, and to improve the therapeutic efficacy for patient.

METHODSThe FVIII:C was assayed by one-stage method and FVIII antibody by Bethesda method. Mutation screening of FVIII gene intron 22 inversion was performed using LD-PCR.

RESULTSFVIII gene intron 22 inversion was detected in this patient. Clinical tolerance to FVIII was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FVIII recovery (> 66%) was normalized. The patient had no bleeding episode in the following 6 months.

CONCLUSIONThis is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.

Autoantibodies ; immunology ; Factor VIII ; genetics ; Hemophilia A ; genetics ; Humans ; Immune Tolerance ; drug effects ; Immunosuppression

BACKGROUNDRandomized studies have shown beneficial effects of drug-eluting stent (DES) in reducing the risk of repeated revascularization. Other studies have shown higher proportion of death, myocardial infarction (MI) and increased cost concerning DES. However the long term safety and effectiveness of DES have been questioned recently.

METHODSTo compare long term clinical outcomes, health-related quality of life (HRQOL) and cost-utility after sirolimus-eluting stent (SES) and bare metal stent (BMS) implantation in angina patients in China, 1241 patients undergoing percutaneous coronary revascularization (PCI) with either SES (n = 632) or BMS (n = 609) were enrolled continuously in this prospective, nonrandomized, multi-center registry study.

RESULTSTotally 1570 stents were implanted for 1334 lesions. Follow-up was completed in 1205 (97.1%) patients at 12 months. Rates of MI, all causes of death were similar between the two groups. Significant differences were found at rate of cardiovascular re-hospitalization (136 (22.4%) in BMS group vs. 68 (10.8%) in SES group, P = 0.001) and recurrent angina (149 (24.5%) vs. 71 (11.3%), P = 0.001). Dramatic difference was observed when compared the baseline and 9-month HRQOL scores intra-group (P < 0.001). However no significant difference was found inter-group either in baseline or follow-up HRQOL. Compared with SES, the total cost in BMS was significantly lower on discharge (62 546.0 vs. 78 245.0 Yuan, P = 0.001). And follow-up expenditure was remarkably higher in the BMS group than that in the SES group (13 412.0 vs. 8 812.0 Yuan, P = 0.0001).

CONCLUSIONSThere were no significant differences on death, in-stent thrombosis, MI irrespective of stent type. SES was superior to BMS on improvement of life quality. SES was with higher cost-utility compared to BMS.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; economics ; mortality ; Coronary Angiography ; Drug-Eluting Stents ; economics ; Female ; Health Care Costs ; Humans ; Immunosuppressive Agents ; administration & dosage ; Male ; Metals ; Middle Aged ; Prospective Studies ; Quality of Life ; Sirolimus ; administration & dosage ; Stents ; economics ; Treatment Outcome

To establish a relation between an protein amino acid sequence and its tendencies to generate antibody response, and to investigate an improved in silico method for linear B-cell epitope (LBE) prediction. We present a sequence-based LBE predictor developed using deep maxout network (DMN) with dropout training techniques. A graphics processing unit (GPU) was used to reduce the training time of the model. A 10-fold cross-validation test on a large, non-redundant and experimentally verified dataset (Lbtope_Fixed_ non_redundant) was performed to evaluate the performance. DMN-LBE achieved an accuracy of 68.33% and an area under the receiver operating characteristic curve (AUC) of 0.743, outperforming other prediction methods in the field. A web server, DMN-LBE, of the improved prediction model has been provided for public free use. We anticipate that DMN-LBE will be beneficial to vaccine development, antibody production, disease diagnosis, and therapy.
Amino Acid Sequence ; Computational Biology ; methods ; Epitopes, B-Lymphocyte ; chemistry ; immunology ; ROC Curve

OBJECTIVETo observe the incidence and the predictors of upper gastrointestinal haemorrhage (UGH) in patients underwent percutaneous coronary interventions (PCI).

METHODSUGH occurred in 21 out of 2279 PCI patients (0.92%). The clinical characteristics, procedural and prognostic status of all UGH patients were analyzed.

RESULTSThe incidence of UGH was significantly higher in patients aged more than 70 years, female, diabetes mellitus, peptic ulcer history, admission with ACS than patients without above factors. Platelet glucoprotein IIb/IIIa receptor antagonist use during the procedure and primary PCI also contributed to the development of UGH. Hospitalization time was significantly longer in patients with UGH compared with patients without UGH (13.8 versus 5.1 days, P < 0.001). The total MACCEs including myocardial infarction, TVR and death rate in patients with UGH were higher than that in patients without UGH (23.0% versus 9.3%, P < 0.01). Stepdown multivariate logistic regression analysis revealed that age more than 70 years (OR 2.23, 95% CI 1.01 - 4.13, P < 0.01), admission with acute coronary syndrome (OR 1.91, 95% CI 0.57 - 2.52, P < 0.05) and history of peptic ulcer (OR 1.02, 95% CI 0.17 - 2.25, P < 0.05) were the predictors of in-hospital UGH post PCI.

CONCLUSIONAge more than 70 years, admission with ACS and peptic ulcer history were closely related to the development of in-hospital UGH post PCI and hospitalization was prolonged in UGH patients.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; adverse effects ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage ; etiology ; Humans ; Incidence ; Male ; Middle Aged ; Postoperative Hemorrhage ; etiology ; Stents

Objective:To explore the biological basis underlying the different syndromes of nontraumatic osteonecrosis of the femoral head (NONFH) according to the molecular interaction network associated with syndromes and the corresponding prescriptions. Method:A total of 30 NONFH patients and 10 healthy controls were enrolled in the present study. The gene expression profiles associated with different syndromes of NONFH were detected by microarray analysis. Then, the molecular interaction networks of the differentially expressed genes of different syndromes were constructed to identify the crucial syndrome-related genes. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of different syndromes from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 (http://www.tcmip.cn/), the molecular interaction network associated with syndromes and the corresponding prescriptions were constructed and the biological basis of each syndrome was analyzed by functional enrichment analysis. Result:The crucial genes associated with the phlegm-stasis blocking collateral syndrome were mainly involved into the bone and lipid metabolism, and the regulation of immune-inflammation balance and circulation. Consistently, the candidate targets of the corresponding prescription-Jianpi Huogu prescription might play roles in the metabolism of osteogenesis, dissipating phlegm, activating circulation to remove blood stasis, relieving pain and inflammatory response. In addition, our data revealed that the stagnation of meridians syndrome-related genes could be mainly involved into the regulation of circulation and inflammatory response, as well as the metabolism of lipid and bone. Accordingly, the corresponding prescription of this syndrome-Huoxue Tongbi Formula could exert the regulatory effects on osteogenesis and inflammatory response, as well as the activation of the circulation and qi-invigorating. Moreover, the crucial genes associated with the liver and kidney deficiency syndrome played roles in various pathological processes during NONFH, such as the abnormal bone and lipid metabolisms, the immune-inflammation imbalance, and the blocked blood circulation, which were in line with our findings on the pharmacological mechanisms of the corresponding prescription of this syndrome-Bushen Zhuanggu formula. Conclusion:The current study indicated that the phlegm-stasis blocking collateral syndrome may be mainly associated with the abnormal bone and lipid metabolisms. The molecular mechanisms underlying the stagnation of meridians syndrome may be the imbalance of "immune-inflammation" and the blocking circulation. Furthermore, the liver and kidney deficiency syndrome may be not only associated with the abnormal bone and lipid metabolisms, but also implicated into various biological pathways-related to inflammation and circulation. Interestingly, the pharmacological mechanisms of the corresponding prescriptions may be in accord to the biological basis of each syndrome.