It is unanimously accepted that stroke is a highly heterogeneous disorder.Different subtypes of ischemic stroke may have different risk factors,clinical features,and prognoses.The aim of this study was to evaluate the risk factors,clinical characteristics,and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment (TOAST) criteria.We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period.Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria.Patients were followed up till 30 and 90 days after stroke onset.It was found that large-artery atherosclerosis was the most frequent etiology of stroke (37.4％),and showed the highest male preponderance,the highest prevalence of previous transient ischemic attack,and the longest hospital stay among all subtypes.Small artery disease (36.4％) was associated with higher body mass index,higher plasma triglycerides,and lower plasma high-density lipoprotein cholesterol than cardioembolism.Cardioembolism (7.7％),which was particularly common in the elderly (i.e.,individuals aged 65 years and older),showed the highest female preponderance,the highest prevalence of atrial fibrillation,the earliest presentation to hospital after stroke onset,the most severe symptoms on admission,the maximum complications associated with an adverse outcome,and the highest rate of stroke recurrence and mortality.Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder.Studies involving risk factors,clinical features,and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes.

Objective:To observe the effect of electroacupuncture (EA) pretreatment on adenine nucleotides in the myocardial tissues of the myocardial ischemia-reperfusion injury (MIRI) rats, and to explore the mechanism of EA pretreatment on myocardial prevention and protection in MIRI rats. Methods:Forty SPF male Sprague-Dawley (SD) rats were randomly divided into 5 groups: a blank group, a sham operation group, a model group, an EA at Neiguan (PC 6) group and an EA at Hegu (LI 4) group, with 8 rats in each group. Rats in the blank group only received binding to the rat plate, 30 min/time, once a day for 7 d; on the 7th day, rats in the sham operation group were subjected to threading for 40 min at the left anterior descending coronary artery without ligation, and then the rats were allowed to stand for 60 min before collection of the specimens; on the 7th day, rats in the model group were subjected to threading at the left anterior descending coronary artery with ligation, for 40 min before the blood flow was restored, and then the rats were allowed to stand for 60 min before collection of the specimens; on the 7th day of pretreatment with EA at Neiguan (PC 6) or Hegu (LI 4) for 30 min per day (once a day for 7 d), rats in the EA at Neiguan (PC 6) group and EA at Hegu (LI 4) group were subjected to modeling and sample collection same as in the model group. The left ventricular myocardium of the lower left anterior descending coronary artery was collected from rats in all 5 groups. Hematoxylin-eosin (HE) staining and transmission electron microscope (TEM) were used to observe the changes in myocardial pathological morphology. The change in the adenine nucleotide level of myocardial tissue was measured by high performance liquid chromatography (HPLC). Results:The HE staining and ultrastructure showed that the myocardial injury was severer in the model group compared with the sham operation group. Compared with the model group, the myocardial injury in the EA at Neiguan (PC 6) and the EA at Hegu (LI 4) groups was mild or hardly any. The adenine nucleotide levels in the sham operation group and the model group were all decreased compared with the blank group (allP<0.05); compared with the sham operation group, the adenine nucleotide level of the model group was also decreased, but the difference was not statistically significant (P>0.05); compared with the model group, the adenine nucleotide level in the EA at Neiguan (PC 6) group was increased (P<0.05), and the adenine nucleotide level in the EA at Hegu (LI 4) group was significantly increased (P<0.01). The adenine nucleotide level in the EA at Hegu (LI 4) group was higher than that in the EA at Neiguan (PC 6) group, but the difference was not statistically significant (P>0.05). Compared with the EA at Neiguan (PC 6) group, the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in the EA at Hegu (LI 4) group were significantly increased (allP<0.01). Conclusion:Both EA at Neiguan (PC 6) and Hegu (LI 4) can alleviate the pathological damage to myocardium in MIRI rats, and increase the adenine nucleotide level in myocardial tissues, and thus protect MIRI rats. EA at Hegu (LI 4) has a better protective effect than Neiguan (PC 6).

Objective To study the influence on the tumor after percutaneous intra-tumor injection of ~(32)P-GMS in liver cancer as well as its suitable dose.Methods 24 New Zealand rabbits were used to establish the animal model of VX-2 liver cancer,and divided into A,B,C and D groups with individually 37,74,111 and 148 MBq of ~(32)P-GMS being injected,respectively;and then pathological changes of tumor were observed by light and electron microscope respectively.Result The dose of ~(32)P-GMS was obviously correlated with the radioactivity damage of tumor cells.In the A and B groups,the tumor cells were not observed to disappear completely after injection of ~(32)P-GMS,but in C group,tumor cells were almost completely disappeared and surrounded by a lot of connective tissue.Although the tumor cells were found to disappear completely in D group,normal liver tissues were also involved.Conclusion Percutaneous intra-tumor injection of ~(32)P-GMS with suitable dose that may induce the tumor tissue to be maximally damaged and may also provide some significances to prevent the tumor metastasis.

OBJECTIVEThis study is to verify the use of rich BHI medium to substitute synthetic media for gene regulation studies in Yersinia pestis.

METHODSThe transcriptional regulation of rovA by PhoP or via temperature upshift, and that of pla by CRP were investigated when Y. pestis was cultured in BHI. After cultivation under 26 °C, and with temperature shifting from 26 to 37 °C, the wild-type (WT) strain or its phoP or crp null mutant (ΔphoP or Δcrp, respectively) was subject to RNA isolation, and then the promoter activity of rovA or pla in the above strains was detected by the primer extension assay. The rovA promoter-proximal region was cloned into the pRW50 containing a promoterless lacZ gene. The recombinant LacZ reporter plasmid was transformed into WT and ΔphoP to measure the promoter activity of rovA in these two strains with the β-Galactosidase enzyme assay system.

RESULTSWhen Y. pestis was cultured in BHI, the transcription of rovA was inhibited by PhoP and upon temperature upshift while that of pla was stimulated by CRP.

CONCLUSIONThe rich BHI medium without the need for modification to be introduced into the relevant stimulating conditions (which are essential to triggering relevant gene regulatory cascades), can be used in lieu of synthetic TMH media to cultivate Y. pestis for gene regulation studies.

Bacterial Proteins ; genetics ; metabolism ; Bacteriological Techniques ; Culture Media ; pharmacology ; Gene Expression Regulation, Bacterial ; drug effects ; physiology ; Yersinia pestis ; metabolism ; physiology

Biodegradable four-arm star-shaped poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (sPEG-b-PLLA), four-arm star-shaped poly(L-lactic acid) (sPLLA), linearly poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (PEG-b-PLLA) and linearly poly(L-lactic acid) (PLLA) were synthesized from L-lactice acid, pentaerythritol, poly(ethylene glycol) and star-shaped poly(ethylene glycol), using the method of melt polycondensation, and the products were characterized and confirmed by 1H NMR spectroscopy, FT-IR and GPC. Four types of ibuprofen loaded microspheres based on the above four types of polymers, i.e., IBU/PLLA, IBU/sPLLA, IBU/PEG-b-PLLA, and IBU/sPEG-b-PLLA microspheres were prepared using the method of solvent evaporation, and the optimized preparation technology was obtained via orthogonal experiments, and the drug-encapsulating properties and in vitro drug-releasing properties were studied. The results showed that compared with IBU/PLLA and IBU/PEG-b-PLLA microspheres, the drug encapsulate efficiency of IBU/sPLLA and IBU/sPEG-b-PLLA microspheres were higher and the in vitro drug releasing rate slowed down, which mainly due to the faster degradation of sPLLA and sPEG-b-PLLA for the star-shaped structure and the block copolymerization of sPEG. The drug releasing curves of these three types of microspheres could be fit by first-order equation, and the releasing mechanism was non-Fickian diffusing, i.e., the synergetic effect of polymer degradation and drug diffusion.
Analgesics, Non-Narcotic ; administration & dosage ; chemistry ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Ibuprofen ; administration & dosage ; chemistry ; Lactates ; chemistry ; Lactic Acid ; chemistry ; Magnetic Resonance Spectroscopy ; Microspheres ; Particle Size ; Polyesters ; Polyethylene Glycols ; chemistry ; Polymers ; chemistry ; Spectroscopy, Fourier Transform Infrared

OBJECTIVETo investigate the efficiency and safety of two-dose steroid combined with two-dose daclizumab and tacrolimus (FK506) regimen in liver transplant recipients.

METHODSThere were 74 patients who treated in the First Affiliated Hospital of Sun Yat-Sen University from September 2006 to March 2008. Expect for 7 patients who didn't measure up, 67 adult liver transplant recipients were randomized into two groups: conventional protocol group (n = 35) in which steroid was withdrawn in 3 months after operation, and two-dose steroid group (n = 32). Comparison of rejection, infection (bacteria, fungal and cytomegalovirus) and metabolic complications rates were studied between two groups.

RESULTSThere were significant differences between two groups in the rate of early postoperation hyperglycemia, the average dosage of insulin consumption among hyperglycemia recipients as well as the rate of diabetes mellitus, hypertension and infection during the follow-up period (P < 0.05). The rate of hypertension in early postoperation period, hyperlipemia and rejection rate during the follow-up period were similar in two groups (P > 0.05).

CONCLUSIONSTwo-dose steroid combined with two-dose daclizumab and tacrolimus would be a safe and efficient immunosuppression strategy without increase the acute rejection rate hazard, that could reduce post-transplant infection and other complications from side-effect of long-term usage of steroid.

Adult ; Aged ; Antibodies, Monoclonal ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Female ; Graft Rejection ; prevention & control ; Humans ; Immunoglobulin G ; administration & dosage ; therapeutic use ; Immunosuppression ; methods ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Liver Transplantation ; Male ; Methylprednisolone ; administration & dosage ; therapeutic use ; Middle Aged ; Steroids ; administration & dosage ; therapeutic use ; Tacrolimus ; administration & dosage ; therapeutic use

Objective:To investigate the clinical, cerebrospinal fluid (CSF) and neuroimaging characteristics and their associations with prognosis in cerebral amyloid angiopathy(CAA)-related inflammation (CAA-ri).Methods:Seventeen patients with CAA-ri, 59 patients with CAA-related intracerebral hemorrhage (ICH) and 15 patients with CAA-related cognitive decline were recruited from Huashan Hospital, Fudan University from November 2015 to May 2020 and the First Affiliated Hospital of University of Science and Technology of China from January 2018 to May 2020. Vascular risk factors and imaging features of cerebral small vessel disease were compared among three groups. Clinical manifestations, CSF results, lesion features on magnetic resonance imaging, treatment options and follow-up data were collected in patients with CAA-ri. The good prognosis was defined by clinical and radiographic improvement with no disease recurrence. The associations between clinical characteristics and the immunosuppressive therapy or the good prognosis were analyzed by binary Logistic regression models.Results:Patients with CAA-ri showed earlier disease onset [(61.5±11.7) years vs (70.9±8.6) years, t=9.428, P=0.001] and more lobar cerebral microbleeds [69.0 (43.5, 134.3) vs 10.0 (5.0, 59.0), H=3.363, P=0.002] compared to patients with CAA-ICH, and higher prevalence of male (14/17 vs 6/15, χ2=6.099, P=0.014) and lower white matter hyperintensity Fazekas score [4.0 (2.0, 6.0) vs 6.0 (5.0, 6.0), H=2.461, P=0.042] compared to patients with CAA-related cognitive decline. In patients with CAA-ri, the immunosuppressive therapy was positively correlated with CSF protein>600 mg/L (odds ratio 16.50, 95% confidence interval 1.09-250.18, P=0.043), and during a follow-up of (3.0±1.9) years, the good prognosis was positively correlated with CSF protein<1 000 mg/L plus immunosuppressive therapy (odds ratio 20.00, 95% confidence interval 1.39-287.60, P=0.028). Conclusions:CAA-ri is a special subtype of CAA with earlier disease onset and higher prevalence of hemorrhagic imaging makers compared to CAA-ICH and CAA-related cognitive decline. CAA-ri patients with normal or slightly elevated CSF protein receiving immunosuppressive therapy are more likely to have good prognosis.

OBJECTIVETo investigate bone defect healing by true bone ceramic complex carrying core binding factor a1 (Cbfa1) gene modified rabbit skin fibroblasts.

METHODSTransfect rabbit skin fibroblasts (RSF) with both eukaryotic expression vector pSG5 which could express Cbfa1 gene and pSG5. After being cultured for 48 h, the transfected RSF were seeded into true bone ceramic (TBC) of 2 cm in length and 4 mm in diameter to construct pSG5-Cbfa1/RSF/TBC complex and pSG5/RSF/TBC complex. Forty-eight bone defect model rabbits were randomized into four groups, each has 6 rabbits (12 radius), due to different treatment. group I: with pSG5-Cbfa1/RSF/TBC complex, group II: with pSG5/RSF/TBC complex, group III: with TBC, Group IV: empty control. After being seeded and cultured for about 24 h the complexes were implanted into 2 cm long bone defects in the middle of bilateral radius of rabbits. The radius were inspected by X-ray and then the specimens were collected at the end of the fourth and twelfth weeks after operation. Then, the specimens were decalcified and histologically investigated with Hematoxylin eosin staining and Masson staining methods. Newly synthesized trabecular bone was inspected by image analysis system and the strength of bone defect area treated with graft-implantation was tested with biomechanical method-three point bending test.

RESULTSIn group I, trabecular bone was actively synthesized to generate a great amount of trabecular bone and osteon. Preliminary union and bone defect healing were completed with good biomechanical characteristics. There were no newly synthesized trabecular in the other three groups, and bone defect healing were not discovered. The amount of newly synthesized trabecular bone and the results of biomechanical testing differed significantly between group I and the other three (P < 0.01). The efficacy of group I was significantly better than that of the other three groups.

CONCLUSIONTrue bone ceramic complex composed with Cbfa1 gene modified rabbit skin fibroblasts can effectively heal bone defect in rabbits.

Animals ; Bone Regeneration ; Bone Substitutes ; Bone Transplantation ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit ; genetics ; Disease Models, Animal ; Fibroblasts ; cytology ; metabolism ; Plasmids ; genetics ; Rabbits ; Radius ; injuries ; physiopathology ; surgery ; Random Allocation ; Skin ; cytology ; Tissue Engineering ; methods ; Transfection

OBJECTIVE: To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF). METHODS: Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting. RESULTS: The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs. CONCLUSIONS STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.
Rats ; Animals ; Matrix Metalloproteinase 2/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; RNA-Seq ; Transcriptome/genetics* ; Heart Failure/drug therapy* ; Collagen ; Collagen Type I/metabolism* ; Fibrosis ; Myocardium/pathology*