OBJECTIVETo study the effects of intrahippocampal injection of cellular prion protein (PrP) antibody on cognitive deficits of APPswe/PSEN1 transgenic mice.

METHODSEight-month-old male APPswe/PSEN1 transgenic mice were subjected to bilateral intrahippocampal injection of a single dose (2 µL) of anti-PrP monoclonal antibody (EP1802Y) or PBS, with wild-type C57Bl/6J mice serving as the control group. After two months, the mice were tested for cognitive behaviors using open filed (OF) test, Morris water maze (MWM) test, fear conditioning (FC) test, and novel object recognition (NOR) test, and immunohistochemistry was used to examine the changes in hippocampal expression of Aβ.

RESULTSThe EP1802Y-treated and PBS-treated mice showed no significantly differences in the performance in OF test in terms of central activity time or total distance of activity (P>0.05), nor in NOR test in terms of novel object recognition index (P>0.05). In MWM test, the EP1802Y-treated and PBS-treated mice showed significantly reduced crossings of the hidden platform as compared with the wild-type mice (P<0.05), but EP1802Y-treated mice had a significantly shorter swimming distance to find the platform than PBS-treated mice (P<0.05). No significant differences were found in the results of FC test among the 3 groups. Immunohistochemistry revealed a significantly reduced expression of Aβ in the hippocampus of EP1802Y-treated mice.

CONCLUSIONIntrahippocampal injection of PrP antibody can improve cognitive deficits of APPswe/PSEN1 transgenic mice, which sheds light on a novel therapeutic approach for Alzheimer's disease that targets PrP to lower the toxicity of Aβ oligomer.

BACKGROUND/AIMS: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. METHODS: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. RESULTS: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [OR(adjusted)], 5.445; 95% confidence interval [CI], 3.075 to 9.643; OR(adjusted), 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (OR(adjusted), 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. CONCLUSIONS: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.
Carcinogenesis ; Case-Control Studies ; China* ; Colorectal Neoplasms* ; DNA Methylation ; Freezing ; Fruit ; Humans ; Leukocytes ; Methylation* ; Odds Ratio

BACKGROUNDLower extremity bursae are very vulnerable to injury during strenuous physical exercises. Understanding the imaging characteristics of normal bursae is essential for early diagnosis of morphological abnormalities. Therefore, we evaluated the normal range of lower extremity bursae in healthy young men using high-resolution ultrasound (HR-US) imaging.

METHODSBursae in the lower extremities were examined by HR-US in 290 Chinese healthy young men with a median age of 18 years (range, 18-23 years). The bilateral suprapatellar bursa (SPB), deep infrapatellar bursa (DIPB), popliteal bursa (PB), and retrocalcaneal bursa (RCB) were imaged and measured for analysis.

RESULTSThe HR-US identification rates of the SPB, DIPB, PB, and RCB were 89.0% (517/580), 55.0% (319/580), 29.4% (171/580), and 49.5% (287/580), respectively. With the assumption that the bursae were normal in 95% of the study participants, the length and width values at the maximal cross-section of the SPB, DIPB, PB, and RCB were ≤18.00 and 6.09 mm, 8.10 and 2.11 mm, 7.67 and 3.93 mm, and 7.82 and 2.04 mm, respectively.

CONCLUSIONSUsing HR-US imaging, we were able to analyze lower extremity bursae with high detection rates in healthy young men. The normal ranges of lower extremity bursa dimensions in healthy young men measured by HR-US in this study could be used as reference values for evaluation of bursa abnormalities in the lower extremity.

Adolescent ; Adult ; Bursa, Synovial ; pathology ; Cross-Sectional Studies ; Humans ; Lower Extremity ; pathology ; Male ; Young Adult

BACKGROUNDEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an effective technique used to precisely detect enlarged mediastinal lymph nodes. The efficacy of EBUS-TBNA versus standard modalities for the diagnosis of sarcoidosis remains to be elucidated. In this meta-analysis, we compared the efficacies of these methods.

METHODSWe searched PubMed, Embase, The Cochrane Library, Wanfang, Cpvip, CNKI, and the bibliographies of the relevant references. We analyzed the data obtained with Revman 5.2 (Nordic Cochrane Center, Copenhagen, Denmark) and Stata 12.0 software (Stata Corporation, College Station, TX, USA). The Mantel-Haenszel method was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs).

RESULTSSixteen studies with a total of 1823 participants met the inclusion criteria, and data were extracted regarding the diagnostic yield of each approach. The ORs for EBUS-TBNA versus transbronchial lung biopsy (TBLB) for the diagnosis of sarcoidosis ranged from 0.26 to 126.58, and the pooled OR was 5.89 (95% CI, 2.20-15.79, P = 0.0004). These findings indicated that EBUS-TBNA provided a much higher diagnostic yield than TBLB. The pooled OR for EBUS-TBNA + TBLB + endobronchial biopsy (EBB) versus TBNA + TBLB + EBB was 1.54 (95% CI, 0.61-3.93, P = 0.36), implying that there was no significant difference between their diagnostic yields. However, clinical heterogeneity was reflected in the nature of the studies and in the operative variables.

CONCLUSIONSThe results of this meta-analysis suggest that EBUS-TBNA + TBLB + EBB could be used for the diagnosis of sarcoidosis, if available. At medical centers without EBUS-TBNA, TBNA + TBLB + EBB could be used instead.

Biopsy, Fine-Needle ; methods ; Bronchoscopy ; methods ; Endosonography ; methods ; Female ; Humans ; Image-Guided Biopsy ; methods ; Male ; Sarcoidosis, Pulmonary ; diagnosis ; Ultrasonography ; methods

OBJECTIVETo compare the incidence rates of postoperative urinary incontinence between transurethral bipolar plasmakinetic enucleation and resection of the prostate (PKERP) and transurethral bipolar plasmakinetic resection of the prostate (PKRP), and provide evidence for the clinical application of PKERP.

METHODSTotally, 180 BPH patients were equally and randomly assigned to undergo PKERP and PKRP, respectively. We measured the urinary incontinence of the patients by pad test at 24 hours after extubation and every week after surgery for 4 weeks. Meanwhile, we recorded and compared the PSA level, prostate volume, Qmax, residual urine, IPSS, QOL, and the results of pad test between the two groups before and after surgery.

RESULTSThe incidence rates of urinary incontinence in the PKERP and PKRP groups were 35.56% and 18.89% (P < 0.01) at 24 hours after extubation, 20.00% and 7.78% at 1 week after surgery (P < 0.05), and 3.33% and 2.22% at 2 weeks. There was no significant difference in the severity of urinary incontinence between the two groups at any time point (P > 0.05). No permanent urinary incontinence was observed in either group.

CONCLUSIONCompared with PKRP, PKERP has a higher incidence rate of short-term urinary incontinence in the treatment of BPH, but not that of genuine incontinence, with similar severity and recovery time.

Aged ; Humans ; Incidence ; Male ; Postoperative Complications ; epidemiology ; Prostatic Hyperplasia ; surgery ; Single-Blind Method ; Transurethral Resection of Prostate ; adverse effects ; methods ; Urinary Incontinence ; epidemiology

OBJECTIVETo investigate the safety, feasibility, perioperational information and post-operational pathology of the modified abdominal operation of extralevator abdominoperineal excision (ELAPE), meaning transpelvic levator dissection under direct visualization.

METHODSFrom January 2010 to March 2013, 36 patients with rectal tumors(≤5 cm distance to anal verge) underwent extralevator abdominoperineal excision with transpelvic levator dissection by laparoscopic or open surgery, without position change during the perineal operation. The preliminary result of this modified technique was summarized.

RESULTSThe levator ani muscles of all the patients were successfully dissected with transpelvic levator dissection and the extent of levator dissection was determined individually according to its involvement. No position was changed during the perineal operation. No conversion to open approach in laparoscopic surgery group was observed, and only 1 case of rectum perforation occurred in open surgery group. The mean operation time was (220.9±36.8) min, and mean intraoperative blood loss was(121.6±99.7) ml. All the specimens had levator ani muscles attached to the mesorectum and positive rate of circumferential resection margin was 5.6%(2/36).

CONCLUSIONSTranspelvic levator dissection simplifies the procedure of ELAPE and achieves individualized dissection of levator. This technique is effective without position change during perineal operation, with shorter operation time and acceptable oncologic outcomes.

Adult ; Aged ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Male ; Middle Aged ; Pelvic Floor ; Perineum ; surgery ; Rectal Neoplasms ; surgery ; Rectum ; surgery

OBJECTIVETo explore an optimal model of hypothetical work injury insurance scheme, which is in line with the wishes of workers, based on the problems in the implementation of work injury insurance in China and to provide useful information for relevant policy makers.

METHODSMultistage cluster sampling was used to select subjects: first, 9 small, medium, and large enterprises were selected from three cities (counties) in Zhejiang Province, China according to the economic development, transportation, and cooperation; then, 31 workshops were randomly selected from the 9 enterprises. Face-to-face interviews were conducted by trained interviewers using a pre-designed questionnaire among all workers in the 31 workshops.

RESULTSAfter optimization of hypothetical work injury insurance scheme, the willingness to participate in the scheme increased from 73.87%to 80.96%; the average willingness to pay for the scheme increased from 2.21% (51.77 yuan) to 2.38% of monthly wage (54.93 Yuan); the median willingness to pay for the scheme increased from 1% to 1.2% of monthly wage, but decreased from 35 yuan to 30 yuan. The optimal model of hypothetical work injury insurance scheme covers all national and provincial statutory occupational diseases and work accidents, as well as consultations about occupational diseases. The scheme is supposed to be implemented worldwide by the National Social Security Department, without regional differences. The premium is borne by the state, enterprises, and individuals, and an independent insurance fund is kept in the lifetime personal account for each of insured individuals. The premium is not refunded in any event. Compensation for occupational diseases or work accidents is unrelated to the enterprises of the insured workers but related to the length of insurance. The insurance becomes effective one year after enrollment, while it is put into effect immediately after the occupational disease or accident occurs.

CONCLUSIONThe optimal model of hypothetical work injury insurance scheme actually realizes cross-regional mobility of workers, minimizes regional differences, and embodies the fairness. The proposed model will, to some extent, protect the rights and interests of enterprises, as well as the healthy rights and interests of workers when they are unemployed.

Accidents, Occupational ; economics ; China ; Insurance, Health ; Models, Theoretical ; Occupational Diseases ; economics

OBJECTIVETo investigate the efficacy and safety of sunitinib on the management of gastrointestinal stromal tumors (GIST) patients with imatinib resistance.

METHODSClinical data of 48 patients with imatinib-resistant GIST received sunitinib therapy from May 2008 to April 2012 in the Union Hospital of Fujian Medical University were analyzed retrospectively. Eighteen patients received 50 mg/d of sunitinib in a protocol of 4/2 (4 weeks on and 2 weeks off) [50 mg/d (4/2)], and 30 patients received a protocol of 37.5 mg of sunitinib continuous daily dose (37.5 mg/d CDD).

RESULTSThe median duration of sunitinib administration of all the 48 patients was 56 weeks, and the short-term efficacy was evaluated at 24 weeks after the initial treatment according to the Choi criteria. The response rate was 27.1% (13/48), including 1 case with complete response (CR), 12 cases with partial response (PR), and 21 cases with stationary disease (SD). The disease control rate was 70.8% (34/48). The mean follow-up time of 48 patients was 89 weeks. The median progression-free survival (PFS) and overall survival (OS) were 48 weeks and 92 weeks respectively. Stratified analyses indicated that the median PFS of patients previously treated by imatinib 400 mg/d and >400 mg/d were 53 weeks and 35 weeks respectively (P=0.018), and the median OS of these two groups were 157 weeks and 71 weeks respectively (P=0.003). Patients with exon 11 mutations had a significantly shorter OS compared with those with exon 9 mutations (71 weeks vs 157 weeks, P=0.008). Hand-foot syndrome was the most common adverse effect (25/48, 52.1%), followed by nausea (24/48, 50.0%), fatigue (23/48, 47.9%), neutropenia(21/48, 41.7%). The sub-group analysis of two protocols of sunitinib administration showed that the incidence of diarrhea and hand-foot syndrome were higher in 50 mg/d (4/2) group than those in 37.5 mg/d CDD group (P=0.027, P=0.048).

CONCLUSIONSSunitinib is effective for the patients with imatinib-resistant GIST. After 400 mg/d imatinib treatment failure, sunitinib should be prescribed instead of increased dosage of imatinib. Patients with KIT exon 9 mutations present better prognosis than those with KIT exon 11 mutations. The protocol of sunitinib 37.5 mg/d CDD possesses better safety.

Adult ; Aged ; Benzamides ; therapeutic use ; Drug Resistance, Neoplasm ; Female ; Gastrointestinal Neoplasms ; drug therapy ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Indoles ; therapeutic use ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Pyrroles ; therapeutic use ; Retrospective Studies ; 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

Cardiomyocytes can resist ischemia/reperfusion (I/R) injury through ischemic postconditioning (IPoC) which is repetitive ischemia induced during the onset of reperfusion. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a member of the WD-40 family proteins, we previously showed that MIP2 was up-regulated during ischemic preconditioning (IPC). As IPC and IPoC engaged similar molecular mechanisms in cardioprotection, this study aimed to elucidate whether MIP2 was up-regulated during IPoC and contributed to IPoC-mediated protection against I/R injury. The experiment was conducted on two models, an in vivo open chest rat coronary artery occlusion model and an in vitro model with H9c2 myogenic cells. In both models, 3 groups were constituted and randomly designated as the sham, I/R and IPoC/hypoxia postconditioning (HPoC) groups. In the IPoC group, after 45 min of ischemia, hearts were allowed three cycles of reperfusion/ischemia phases (each of 30 s duration) followed by reperfusion. In the HPoC group, after 6 h of hypoxia, H9c2 cells were subjected to three cycles of 10 minute reoxygenation and 10 minute hypoxia followed by reoxygenation. IPoC significantly reduced the infarct size, plasma level of Lactate dehydrogenase and creatine kinase MB in rats. 12 h after the reperfusion, MIP2 mRNA levels in the IPoC group were 10 folds that of the sham group and 1.4 folds that of the I/R group. Increased expression of MIP2 mRNA and attenuation of apoptosis were similarly observed in the HPoC group in the in vitro model. These effects were blunted by transfection with MIP2 siRNA in the H9c2 cells. This study demonstrated that IPoC induced protection was associated with increased expression of MIP2. Both MIP2 overexpression and MIP2 suppression can influence the IPoC induced protection.
Animals ; Blotting, Western ; Cell Hypoxia/genetics/physiology ; Cell Line ; Cell Survival/genetics/physiology ; Flow Cytometry ; Ischemic Preconditioning, Myocardial/*methods ; Male ; Myocytes, Cardiac/*metabolism/*pathology ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Reperfusion Injury/*metabolism/*prevention & control