OBJECTIVETo study the effects of combined use of total alkaloids (TA) of Uncaria rhynchophylla (UR) and Coryadlis ambailis migo (CAM) on cerebral ischemia/reperfusion injury in rats.

METHODSRat model of middle cerebral artery ischemia/reperfusion was established, the changes of neurological state was scored before and after treatment with the two kinds of TA, single or combined, and the changes of cerebral infarcted volume, cerebral water content, activities of NOS and SOD and content of MDA in rats' brain were estimated as well.

RESULTSAfter being treated with the combination of both TA, the average neurological score, cerebral infracted volume, cerebral water content, activity of NOS and content of MDA in the model rats significantly decreased, and the activity of SOD was significantly increased (all P < 0.05). The effect of combined use of the two TA was higher than that of use TA of UR or CAM alone (P <0.05). Moreover, the central nervous system inhibitory effect induced by combined TA was significantly weaker than that of UR.

CONCLUSIONCombined use of TA of UR and CAM may facilitate the protection against cerebral ischemia/reperfusion damage, the action mechanism might be relevant to reducing the lipid peroxidation injury of brain cells through inhibiting the NOS activity and increasing the SOD activity.

Alkaloids ; pharmacology ; therapeutic use ; Animals ; Brain ; blood supply ; drug effects ; enzymology ; Brain Ischemia ; complications ; Corydalis ; chemistry ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Male ; Mice ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Nitric Oxide Synthase Type I ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; prevention & control ; Superoxide Dismutase ; metabolism ; Uncaria ; chemistry

Objective To investigate the effects of small volume resuscitation on hemodynamics and visceral perfusion in dog model of hemorrhagic shock. Methods Twenty-four dogs were hemorrhaged to hold mean arterial blood pressure at 45-55 nun Hg for 45 minutes, and then eight dogs were resuscitated with 6 ml/kg of hypertonic saline (HS group) solution and the other eight resuscitated with 6 ml/kg of hypertonic saline-hydroxyethyl starch (HSS group) solution. The rest eight dogs were set as control and resuscitated with normal saline (NS). Hemodynamics and gastrointestinal intramucosal pH (pHi) were detected after fluid resuscitation. Results (1) All three kinds of solutions could improve early hemodynamics and visceral perfusion. But 30 minutes after fluid resuscitation, the hemodynamics of dogs in HS group, HSS group and NS group began to decrease, with more obvious decrease HS group and NS group compared with HSS group. (2) pHi of three groups began to decrease 120 minutes after fluid resuscitation, but the level of arterial lactate remained unchanged. Conclusions (1) HS has the similar effect as NS in aspect of resuscitation, and HSS is better than HS and NS.(2) pHi is an ideal marker in monitoring the visceral perfusion and has higher sensitivity than arterial lactate.

AIMTo search for new artemisinin derivatives with higher immunosuppressive activity.

METHODSTwo kinds of new artemisinin derivatives containing polyethylene glycol group were synthesized from dihydroartemisinin via condensation and esterification. These compounds were assayed for their inhibitory activity on ConA-induced T cell proliferation and LPS-induced B cell proliferation.

RESULTSTwenty three new compounds (2a - 2f, 3a - 3d, 4a - 4f, 6a, 6b and 7a - 7g) were synthesized and identified by 1H NMR and elemental analysis.

CONCLUSIONThese compounds had immunosuppressive activity in vitro. Among them, the symmetrical substituted compound 2 and 6 had higher activity than mono-substituted compound 3, 4 and 7. Especially, compounds 2a - 2f remarkably exhibited higher inhibition in comparison with artemisinin and artesunate.

Animals ; Artemisinins ; chemical synthesis ; pharmacology ; B-Lymphocytes ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Immunosuppressive Agents ; chemical synthesis ; pharmacology ; Molecular Structure ; Polyethylene Glycols ; Sesquiterpenes ; chemical synthesis ; pharmacology ; T-Lymphocytes ; drug effects

To develop a Huntington’s disease(HD) cell model in vitro to screen drugs targeting the aggregation of polyQ,different length of CAG repeat fragments were amplified by random primer PCR, identified by DNA sequencing and were fused to the N-terminus of CAT in the pCAR system respectively which had been constructed and identified before. Recombinant plasmids were transformed into and induced to express in the host E.coli. SDS-PAGE and chloramphenicol resistance test were done to determine the solubility of the polyQ and chloramphenicol resistance levels of the fusions. With different length of CAG repeat fragments cloned and expressed in the CAT-fusion protein reporting system, it is found that when the length of the fragments increased over 40, their encoding polyQ expressed as insoluble protein and chloramphenicol resistance levels are lower, while under 40, the polyQ expressed as soluble ones and chloramphenicol resistance levels are higher. A in vitro HD model that could minimize the pathological process of the HD thus has been developed. With which by measure the recombinant bacteria’s resistance to chloramphenicol, the polyQ’ solubility and folding state in vitro by quality and quantity could be determined. Thus this model can be used to screen drugs or bioactivity materials that can inhibit aggregation of the polyQ, which thereby shedding new light on the prevent, diagnosis and therapy of HD.

Objective: To investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma. Methods: A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T. Results: Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×10⁶/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group. Conclusions: CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.
Antigens, CD19 ; Humans ; Lymphoma, B-Cell ; Neoplasm Recurrence, Local ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; T-Lymphocytes

Isotemporal substitution model is a powerful tool to explore the real association between physical behavior and health outcomes, which has the potential of the application in large-scale cohort study. This paper systematically introduces the principle of isotemporal substitution model and its implementation method in specific analysis to provide analytical ideas for the epidemiological research related to physical behavior in China. The baseline data of Regional Ethic Cohort Study in Northwest China conducted in Shaanxi province were used to analyze the relationship between physical behavior and cardiovascular disease with single-factor model, partition model and isotemporal substitution model. The advantages and disadvantages of different models were compared, and the advantages of isotemporal substitution model in quantifying physical activity health risk were introduced. Isotemporal substitution model could qualify physical behavior and health outcomes, which has wide application value in epidemiological research.
Humans ; Cohort Studies ; Epidemiologic Studies ; Cardiovascular Diseases ; China/epidemiology*

Objective To evaluate diagnosis and preoperative management of cases with interrupted aortic arch(IAA)in infancy.Methods Fifty-three infants who were admitted to our hospital from Jan.2001 to Nov.2007 were involved.Clinical data,findings of echocardiogram(Echo),spiral CT,MRI,angiocardiography,preoperative management,surgical repair and postoperative outcome were analyzed retrospectively.Results There were 38 boys and 15 girls,weighted 2.18-10.0(4.32?1.60)kg,aged 1 day to 12(3.05?3.53)months,of which 50.94% were neonates.Symptoms at presentation were 90.57% with tachypnea and 83.02% with difficulty in feeding.Eighty three point zero two percentage cases had different degree of congestive heart failure,37.74% of which were in grade Ⅲ heart function.All cases had weakened femoral pulse.All cases were performed Echo,38 cases of them diagnosed as IAA,6 cases as IAA or severe coarctation of aorta(CoA);they were diagnosed as IAA by CT,and 9 as severe CoA who were diagnosed as IAA via CT or operation.Thirty-three cases were performed CT,of which 15 underwent surgical repair,cardiovascular abnormalities revealed by CT were the same as those in surgical findings.Three cases were taken MRI,and 7 cases were performed angiocardiography.According to the results of Echo,CT,MRI,angiocardiography and surgical findings,35 cases were type A,15 cases were type B and 3 cases were type C.Preoperative treatment included maintaining patent ductus areriosis,management of heart failure and supportive treatment.After proper preoperative management of medication,most cases with congestive heart failure were improved.Twenty-six cases underwent surgical repair,16 survived,10 died du-ring perioperative stage.Main cause of death was severe low cardiac output.Conclusions Value of Echo in diagnosis of IAA is limi-ted.Combination of Echo with CT or MRI is a convenient and safe way to diagnose IAA,it can replace the traditional method of Echo combined with angiocardiography.Proper preoperative management is helpful to patients with IAA to pass to surgical repair,and makes for successful operation.

This study was aimed to investigate the c-kit mutation in acute myeloid leukemia (AML) patients with AML1-ETO and analyze its relation with clinical and laboratorial features and prognosis. PCR and sequencing methods were used to detect the c-kit 17 exon mutations in 31 AML patients with AML1-ETO. The relation of the c-kit mutation with clinical features, results of laboratorial examination and prognosis of disease were analyzed. The results showed that the c-kit mutation was found in 14 out of 31 AML patients and the mutation frequency was 45.16%. Male patients had a higher incidence of c-kit mutation than that of female patients (P = 0.020). The proportion of patients with newly diagnosed white blood cell>10×10(9)/L and with extramedullary infiltration in mutated group were higher than those in unmutated group respectively. No significant difference was observed at the age (P = 0.437) and the rate of bone marrow blasts(P = 0.510) between the above mentioned two groups. The difference in complete remission rate (64.29% vs 80%, P = 0.344)and relapse rate (58.33% vs 21.43%, P = 0.054) between c-kit mutated and c-kit unmutated groups were not significant. While the c-kit mutated group had a significant higher death rate as compared with c-kit unmutated group (57.14% vs 20%, P = 0.039). It is concluded that the c-kit mutation is frequent in AML patients with AML1-ETO and the c-kit mutated patients have a poor prognosis. It is important to detect c-kit mutation in routine clinical practice for patient's risk stratification, evaluation of prognosis and selection of effective treatment.
Adolescent ; Adult ; Aged ; Core Binding Factor Alpha 2 Subunit ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Oncogene Proteins, Fusion ; genetics ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; RUNX1 Translocation Partner 1 Protein ; Treatment Outcome ; Young Adult

OBJECTIVETo screen the molecular markers for refractory anemia with excess blasts in transformation (RAEB) in myelodysplastic syndromes (MDS) by serum proteome profiling.

METHODSThe serum protein were isolated from patients with RAEB, acute myeloid leukemia or normal subjects by 2-dimensional electrophoresis (2-DE), and the electrophoresis gels were obtained to identify the differentially reacting protein spots. The replica gels of the differentially reacting proteins were analyzed to locate the matching protein spots, which were identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF-MS) and database searching.

RESULTSSeven differentially expressed proteins in RAEB were found by 2-DE. Of the 7 proteins, 4 were identified by MALDI-TOF-MS to have significantly differential expression in RAEB, including dipeptidyl peptidase (DPP/CD26), polymerase (DNA directed) kappa, PRO2044 and an albumin-like protein.

CONCLUSION2-DE-based serum proteome profiling helps identify serum proteomic biomarkers related to MDS. DDP/CD26 has increased expression in the serum in RAEB subtype MDS, suggesting its possible role in advanced MDS.

Anemia, Refractory, with Excess of Blasts ; blood ; genetics ; Bone Marrow ; pathology ; DNA-Directed DNA Polymerase ; blood ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ; blood ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; blood ; classification ; genetics ; Proteomics

OBJECTIVETo evaluate the diagnostic value and safety of flexible bronchoscopy in congenital great vessel diseases complicated with airway compression.

METHODThe medical records of patients with great vessels abnormalities who were admitted to the neonatal intensive care unit (NICU) from October 2005 to June 2009 were retrospectively reviewed; 34 cases were diagnosed as airway compression by flexible bronchoscopy, 10 cases as vascular ring, 24 cases as aortal arch obstruction. The age of the patients was 6 d - 11 m, body weight 2.2 - 8.7 kg [(4.6 +/- 1.4) kg]. Recorded airway abnormalities detected by bronchoscopy and CT, cardiac vascular defects and airway compression were consistent with the findings on operation. The relation between the airway compression and cardiac vascular abnormalities, treatment of the airway compression and outcome were analysed.

RESULTBronchoscopic assessment was successfully performed in NICU or operating room for all the patients. (1) Initial presentation of the 34 cases were tachypnea, stridor, refractory lung infection and prolonged mechanical ventilation. (2) Extrinsic compression was found in all the 10 cases with vascular ring by bronchoscopy initially which indicated vascular ring, airway compression was mainly of lower part of trachea. Diagnosis of 9 cases was consistent with CT diagnosis and in 1 case the diagnosis was confirmed by surgery; among these cases, 7 had congenital tracheal stenosis. (3) In the 24 cases with aortic obstructive lesion, 5 were detected to have tracheal stenosis by CT before correction of vascular abnormality, among whom one case was indicated to have tracheal stenosis by bronchoscopy, the other 19 cases were found with airway compression by bronchoscopy during or after vascular correction. Among the 24 cases, 21 had left main bronchial stenosis, 2 had congenital tracheal stenosis. Airway compression diagnosed by bronchoscopy agreed with the findings of CT. Two cases developed transient decrease of oxygen saturation, 5 cases developed transient tachycardia.

CONCLUSIONFlexible bronchoscopy plays an important role in assessment of the airway compression complicated with great vessel abnormalities. Bronchoscopy is an accurate, convenient, safe and rapid way for airway assessment, but further examination of the peripheral structure and vascular malformation need combined examination with CT.

Airway Obstruction ; diagnosis ; etiology ; Bronchoscopy ; methods ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Retrospective Studies ; Vascular Malformations ; complications ; diagnosis