Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; Phytotherapy ; Tablets

Objective To analyze the effect of minimally invasive puncture combined with continuous lumbar subarachnoid drainage in the treatment of thalamic expanding hematoma. Methods Seventy-eight patients with thalamic expanding hematoma admitted in our department from 2004 to 2008 underwent minimally invasive puncture combined with continuous lumbar subarachnoid drainage according to the size of intracranial hematoma and the involvement of the cerebral ventricles. Results Of the 78 cases, death occurred in 10 cases, with a mortality rate of 12.8%. The other 68 (87.2%) patients exhibited postoperative recovery of different degrees. Follow-up of the 68 patients for over 6 months after the operation showed that 30 patients had grade 1 Activity of Daily Living (ADL) with independence in daily living, 25 had grade 2 ADL (partially independent in daily living), 19 had grade 3 ADL (capable of assisted walking), 3 had grade 4 ADL (bedridden but conscious), and one patient had grade 5 ADL (in persistent vegetative state). Conclusion This combined treatment with individualized operations reduces the surgical trauma to the minimum and lowers the cost for effective elimination of the hematoma. This procedure also effectively lowers the intracranial pressures and promotes the neurological recovery of the patients with thalamic expanding hematoma.

Heat shock protein 70 (HSP70), which evidences important functions as a molecular chaperone and anti-apoptotic molecule, is substantially induced in cells exposed to a variety of stresses, including hypertonic stress, heavy metals, heat shock, and oxidative stress, and prevents cellular damage under these conditions. However, the molecular mechanism underlying the induction of HSP70 in response to hypertonicity has been characterized to a far lesser extent. In this study, we have investigated the cellular signaling pathway of HSP70 induction under hypertonic conditions. Initially, we applied a variety of kinase inhibitors to NIH3T3 cells that had been exposed to hypertonicity. The induction of HSP70 was suppressed specifically by treatment with protein kinase C (PKC) inhibitors (Go6976 and GF109203X). As hypertonicity dramatically increased the phosphorylation of PKC micron, we then evaluated the role of PKC micron in hypertonicity-induced HSP70 expression and cell viability. The depletion of PKC micron with siRNA or the inhibition of PKC micron activity with inhibitors resulted in a reduction in HSP70 induction and cell viability. Tonicity-responsive enhancer binding protein (TonEBP), a transcription factor for hypertonicity-induced HSP70 expression, was translocated rapidly into the nucleus and was modified gradually in the nucleus under hypertonic conditions. When we administered treatment with PKC inhibitors, the mobility shift of TonEBP was affected in the nucleus. However, PKC micron evidenced no subcellular co-localization with TonEBP during hypertonic exposure. From our results, we have concluded that PKC micron performs a critical function in hypertonicity-induced HSP70 induction, and finally cellular protection, via the indirect regulation of TonEBP modification.
Animals ; Carbazoles/pharmacology ; Cell Line ; Flavonoids/pharmacology ; HSP70 Heat-Shock Proteins/*biosynthesis ; Humans ; Indoles/pharmacology ; Isoquinolines/pharmacology ; MAP Kinase Signaling System/physiology ; Maleimides/pharmacology ; Mice ; NFATC Transcription Factors/metabolism ; Phosphorylation ; Promoter Regions, Genetic ; Protein Kinase C/antagonists & inhibitors/*physiology ; Protein Transport ; Saline Solution, Hypertonic/*pharmacology ; Signal Transduction ; Sulfonamides/pharmacology

OBJECTIVETo investigate the dynamic distribution of human bone marrow mesenchymal stem cells (hBM-MSCs) in mdx mice.

METHODSTwenty-four 8-10-week-old immunocompromised mdx mice were transplanted with 1 x 10(7) passage 5 hBM-MSCs labeled with bromodeoxyuridine (BrdU) by means of injection into the tail vein. The mice were euthanized 48 hours and 2, 4, 8, 12, 16, 20, and 24 weeks after transplantation. BrdU-positive cells in tissue and organs of the mice were detected by immunofluorescence analysis. Skeletal muscle was stained for anti-human nuclei mouse monoclonal antibody (anti-Hu) and analyzed for human dystrophin (Dys) expression by immunohistochemistry and reverse transcription-polymerase chain reaction.

RESULTSAfter transplantation, BrdU-positive cells were found in most organs (especially in bone marrow, liver, and lung) within 4 weeks, and these cells in liver and lung decreased gradually after 4 weeks. At 48 hours after transplantation, BrdU-positive cells were found in bone marrow, which reached a peak level after 2 weeks and were still detectable after 16 weeks. BrdU-positive cells in skeletal muscle increased gradually over time of transplantation. A small number of anti-Hu positive cells were detected in skeletal muscle 2 weeks after transplantation. A small number of Dys positive cell were seldom found at 4 weeks and small Dys mRNA expression detected 4 weeks after transplantation. The proportion of anti-Hu in parallel with Dys positive cells and Dys mRNA in skeletal muscle of mdx mice increased gradually over time of transplantation.

CONCLUSIONAfter being transplanted into mdx mice, hBM-MSCs are mainly distributed in bone marrow, liver, and lung during the early time (2-4 weeks) , and then in bone marrow and skeletal muscle (after 4 weeks).

Animals ; Bone Marrow Cells ; cytology ; Dystrophin ; genetics ; metabolism ; Humans ; Immunocompromised Host ; Immunohistochemistry ; Mesenchymal Stem Cell Transplantation ; methods ; Mice ; Mice, Inbred mdx ; Muscle, Skeletal ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUNDThere were some papers published in the Jonrnal of Science, December 2000 suggesting that one or more important susceptibility genes for late onset Alzheimer's disease (LOAD) were located on the long arm of chromosome 10. Linkage analysis showed maximum lod score close to D10S1225 loci, which indicated the loci might contribute to the etiology of Alzheimer's disease (AD).

METHODSFifty-nine LOAD patients and 107 controls were recruited. Apolipoprotein E (ApoE) genotypes were determined by reverse dot blotting hybridization assay. The D10S1225 was genotyped by 12% nondenaturing polyacrylamide gels electrophoresis and analyzed by silver staining. Statistical analysis was used to compare genotype and allele distributions between LOAD group and control group for ApoE and D10S1225 polymorphisms.

RESULTSApoE epsilon 4 was significantly higher in LOAD group in comparison with the control group (chi(2) = 6.530, P = 0.011). Seven different alleles of D10S1225 have been identified. The length of these gene fragments were 178 bp, 181 bp, 184 bp, 187 bp, 190 bp, 193 bp, and 196 bp, respectively. A total of 21 different genotypes were observed. There was no relationship between D10S1225 polymorphism and LOAD (chi(2) = 4.488, P > 0.05). Conclusion This study suggests that ApoE epsilon 4 is a risk factor for LOAD, however, the results indicated that there is not any possible linkage for disequilibria with a nearby AD risk gene near D10S1225.

Aged ; Aged, 80 and over ; Alleles ; Alzheimer Disease ; genetics ; Apolipoproteins E ; genetics ; Female ; Genotype ; Humans ; Linkage Disequilibrium ; Male ; Middle Aged ; Polymorphism, Genetic

OBJECTIVETo investigate the effect of bone marrow stem cell transplantation (BMT) on the diaphragm muscles of mdx mice, a mouse model of Duchenne muscular dystrophy (DMD).

METHODSThe bone marrow-derived stem cells form male SD rats was transplanted through the tail vein into 18 female 8-week-old mdx mice, which were sacrificed at 4, 8 and 12 weeks after BMT (6 at each time point), respectively. The diaphragm muscles of the mice were subjected to HE staining, immunofluorescence detection of dystrophin, reverse transcription (RT)-PCR analysis of dystrophin mRNA transcripts and PCR analysis of Sry (sex-determining region on the Y chromosome) gene, with age-matched female C57 mice and untreated mdx mice as the controls.

RESULTSThe proportion of centrally nucleated fibers (CNF) in the diaphragm muscle of the recipient mdx mice was (15.58+/-0.91) %, (12.50+/-1.87) % and (10.17+/-1.17) % at 4, 8 and 12 weeks after BMT, respectively, significantly smaller than that of untreated mdx mice [(19.5+/-1.87) %], and the fibers after BMT showed less inflammatory infiltration. Compared with the untreated mice, the recipient mdx mice showed green fluorescence on significantly more diaphragm muscle cell membranes [with the proportion of dystrophin-positive fibers of (1.00+/-0.32) %, (6.00+/-1.05) % and (11.92+/-1.11) % at 4, 8, and 12 weeks after BMT]. RT-PCR of dystrophin mRNA also demonstrated significantly higher relative levels of dystrophin in the recipient mdx mice (0.19+/-0.05, 0.26+/-0.06 and 0.36+/-0.04 at 4, 8 and 12 weeks after BMT) than in untreated mdx mice, and Sry gene was present in the recipient mice.

CONCLUSIONBMT can partially restore dystrophin expression and ameliorate the pathology in the diaphragm muscles of mdx mice, and has great potential to produce general therapeutic effect in patients with DMD.

Animals ; Bone Marrow Transplantation ; methods ; Diaphragm ; metabolism ; pathology ; Dystrophin ; biosynthesis ; genetics ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred mdx ; Muscular Dystrophy, Duchenne ; metabolism ; pathology ; surgery ; Rats ; Rats, Sprague-Dawley ; Transplantation, Heterologous

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07–0.68; p=0.010). Women in their 40s–50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03–1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.
Atypical Squamous Cells of the Cervix* ; Biopsy ; Cervical Intraepithelial Neoplasia* ; Cohort Studies* ; Colposcopy ; Cryotherapy ; Curettage ; Diagnosis ; Ethics Committees, Research ; Female ; Humans ; Incidence ; Mass Screening ; National Health Programs ; Proportional Hazards Models ; Risk Reduction Behavior ; Taiwan ; Uterine Cervical Neoplasms ; Vaginal Smears

BACKGROUNDIt has been proved that sevoflurane postconditioning (SpostC) could protect the heart against myocardial ischemia/reperfusion injury, however, there has been few research focused on the electrophysiological effects of SpostC. The objective of the study was to investigate the effects of SpostC on action potential duration (APD) and L-type calcium current (I(Ca, L)) in isolated cardiomyocytes.

METHODSLangendorff perfused SD rat hearts were randomly assigned to one of the time control (TC), ischemia/reperfusion (I/R, 25 minutes of ischemia followed by 30 minutes of reperfusion), and SpostC (postconditioned with 3% sevoflurane) groups. At the end of reperfusion, epicardial myocytes were dissociated enzymatically for patch clamp studies.

RESULTSSevoflurane directly prolonged APD and decreased peak I(Ca, L) densities in epicardial myocytes of the TC group (P < 0.05). I/R injury shortened APD and decreased peak I(Ca, L) densities in epicardial myocytes of the I/R group (P < 0.05). SpostC prolonged APD and increased peak I(Ca, L) densities in epicardial myocytes exposed to I/R injury (P < 0.05). SpostC decreased intracellular reactive oxygen species (ROS) levels, reduced the incidence of ventricular tachycardia and ventricular fibrillation, and decreased reperfusion arrhythmia scores compared with the I/R group (all P < 0.05).

CONCLUSIONSSpostC attenuates APD shortening and I(Ca, L) suppression induced by I/R injury. The regulation of APD and I(Ca, L) by SpostC might be related with intracellular ROS modulation, which contributes to the alleviation of reperfusion ventricular arrhythmia.

Action Potentials ; drug effects ; Animals ; Calcium ; metabolism ; Electrocardiography ; Methyl Ethers ; therapeutic use ; Patch-Clamp Techniques ; Pericardium ; drug effects ; metabolism ; Rats ; Reactive Oxygen Species ; metabolism ; Reperfusion Injury ; drug therapy ; metabolism

OBJECTIVETo verify the improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke.

METHODSEighty cases were randomly divided into a warming-reinforcing acupuncture combined with rehabilitation training group (group A) and a rehabilitation training group (group B), 40 cases in each group. Both groups were treated with internal routine treatment. The Motor Relearning Program rehabilitation was used in group B, while warming-reinforcing acupuncture combined with Motor Relearning Program rehabilitation were used in group A. Jianyu (LI 15), Quchi (LI 11), Hegu (LI 4), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP 6) were selected, and warming-reinforcing method was used in these points, they were treated for 3 weeks. The neurological functional deficits scores of hemiparalysis patients, Fugl-Meyer Score, Motor Function Assessment Score (MAS), Barthel Index and Mini-mental State Examination (MMSE) were used to evaluate the condition of hemiparalysis patients before and after treatment.

RESULTSThe effective rate of group A (87.5%, 35/40) superior to that of group B (67.5%, 27/40) (P < 0.05). The neurological functional deficit scores, Fugl-Meyer score, MAS and Barthel Index of both groups were improved after treatment (P < 0.01, P < 0.05), and the improved degree of group A was better than that of group B (P < 0.01, P < 0.05).

CONCLUSIONThere is obvious improvement function of warming-reinforcing acupuncture combined with rehabilitation training on the early motor function of hemiparalysis patients caused by ischemic brain stroke, and the function is better than that of simple rehabilitation training.

Activities of Daily Living ; Acupuncture Therapy ; Adult ; Aged ; Aged, 80 and over ; Brain Ischemia ; complications ; Hemiplegia ; physiopathology ; rehabilitation ; therapy ; Humans ; Male ; Middle Aged ; Motor Activity ; Stroke ; complications ; Treatment Outcome

Cancer cell vaccine-based immunotherapy has received increasing interest in many clinical trials involving patients with breast cancer. Combining with appropriate adjuvants can enhance the weak immunogenic properties of tumor cell lysates (TCL). In this study, diphtheria toxin (DT) and two tandem repeats of mycobacterial heat shock protein 70 (mHSP70) fragment 407-426 (M2) were conjugated to TCL with glutaraldehyde, and the constructed cancer cell vaccine was named DT-TCL-M2. Subcutaneous injection of DT-TCL-M2 in mice effectively elicited tumor-specific polyclonal immune responses, including humoral and cellular immune responses. High levels of antibodies against TCL were detected in the serum of immunized mice with ELISA and verified with Western blot analyses. The splenocytes from immunized mice showed potent cytotoxicity on Ehrlich ascites carcinoma cells. Moreover, the protective antitumor immunity induced by DT-TCL-M2 inhibited tumor growth in a mouse breast tumor model. DT-TCL-M2 also attenuated tumor-induced angiogenesis and slowed tumor growth in a mouse intradermal tumor model. These findings demonstrate that TCL conjugated with appropriate adjuvants induced effective antitumor immunity in vivo. Improvements in potency could further make cancer cell vaccines a useful and safe method for preventing cancer recurrence after resection.
Adjuvants, Immunologic ; Animals ; Bacterial Proteins ; genetics ; immunology ; Cancer Vaccines ; immunology ; Carcinoma, Ehrlich Tumor ; immunology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Diphtheria Toxin ; genetics ; immunology ; Female ; HSP70 Heat-Shock Proteins ; genetics ; immunology ; Immunoglobulin G ; immunology ; Immunotherapy ; Mice ; Neovascularization, Pathologic ; Peptide Fragments ; genetics ; immunology ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Tandem Repeat Sequences