Objective To investigate the underlying mechanisms of Miller-Fisher syndrome (MFS) and Bickerstaff' s brainstem encephalitis (BBE) by studying their clinical and electrophysiological characteristics.Methods The clinical and electrophysiological characteristics of 13 MFS and 7 BBE cases in Peking Union Medical College Hospital between 2000 and 2011 were retrospectively analyzed.The electrophysiological parameters included sensory and motor nerve conduction,electromyography,F wave,sympathetic skin response and brainstem auditory evoked potential and blink reflex.Results MFS and BBE had similar clinical characteristics:respiratory symptoms were the most common infectious symptoms before disease onset; Ophthalmoplegia,facial palsy and bulbar symptoms were common; They both had cerebrospinal fluid albuminocytological dissociation and positive serum anti-GQ1b antibody.However,BBE had more central nervous system lesion signs clinically such as conscious disturbance,positive Babinski' s sign and central facial palsy.Electrophysiologically,MFS and BBE also had similar electrophysiological features:sensory nerve abnormality ratios were 6/13,2/7 respectively,with prominently reduced sensory nerve active potential amplitude,normal or slightly slowed sensory conduction velocity; Motor nerves abnormality ratios were 2/13,1/7 respectively,with slightly prolonged distal motor latency and normal compound muscle action potential; Electromyography abnormality ratios were 1/7,0/4 respectively; F wave frequency abnormality ratios were 3/13,5/7 respectively,and in some cases,F wave frequency would restore; Sympathetic skin response abnormality ratios were 1/2,1/3 respectively; Blink reflex abnormalityratios were 1/2,1/1 respectively,with central involvement in BBE; Brainstem auditory evoked potential abnormality ratios were 3/5,1/4 respectively,with wave Ⅰ latency or amplitude abnormality.Conclusion The similarities of clinical and electrophysiological features suggest that MFS and BBE have the same mechanism and they form a continuous spectrum with variable central nervous system and peripheral nervous system involvement.

BACKGROUNDCathespin-B (cath-B) is an important proteolytic enzyme involved in the disease course of invasion in many types of cancer. Cath-B expression in subcutaneous heteroplastic pancreatic carcinoma in nude mice has not been studied. We investigated the role of cath-B in a model of heteroplastic pancreatic carcinoma in BALB/c nude mice.

METHODSThirty-two six-week-old female BALB/c nude mice were equally divided into four groups. PANC-1 cells were inoculated subcutaneously in the left axillary region. Besides volume, weight of subcutaneous tumor, and change in body weight, cath-B expression in each group was measured by immunohistochemical staining, PCR and Western blotting. Its relationship to microvessel density (MVD), CD44v6, and placenta growth factor (PLGF) was also examined. CA-074Me, a specific inhibitor of cath-B, was injected intraperitoneally (i.p.) at different stages of tumor growth in group B and C. Gemcitabine (GEM), was also injected (i.p.) in group D to compare anti-tumor efficacy with CA-074Me.

RESULTSExpression of cath-B at different levels was related to tumor growth, MVD, and PLGF expression. In group A (control group), cath-B expression was enhanced more than that seen in other groups. CA-074Me clearly inhibited cath-B expression and tumor growth in group B. There was no difference between group C and D with respect to anti-tumor effect.

CONCLUSIONSCath-B correlates with the growth and angiogenesis of tumors, but not with the adhesion induced by CD44v6. CA-074Me clearly inhibited cath-B expression and demonstrated an anti-neoplastic and anti-angiogenesis effect.

Animals ; Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Body Weight ; Cathepsin B ; antagonists & inhibitors ; genetics ; metabolism ; physiology ; Cell Line, Tumor ; Dipeptides ; therapeutic use ; Female ; Humans ; In Vitro Techniques ; Mice ; Mice, Nude ; Pancreatic Neoplasms ; drug therapy ; metabolism ; Placenta Growth Factor ; Pregnancy Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous

OBJECTIVETo provide more detailed information on the roles of lipid peroxidation in the pathogenesis of chronic pancreatic injuries in a pre-clinical rat model.

METHODSTotally 72 rats were divided into 6 groups (12 in each group) Rats in 5 experimental groups (n = 12) were fed with a high-fat diet (1% cholesterol, 10% lard, 0.3% sodium tauroglycocholate, 87.3% standard rodent chow as the control group) for 2, 4, 6, 10 and 16 weeks, respectively. Morphological studies in the pancreas tissue samples from rats were investigated by using various histological methods. Pancreatic stellate cells (PSCs) were identified by immunohistochemical staining for Desmin and α-smooth muscle actin (α-SMA). The expression of the lipid peroxidation was detected by immunostaining for 4-hydroxy-2-nonenal (4-HNE) and thromboxane A2 receptor (TxA2r). The co-localization of α-SMA and 4-HNE or α-SMA and TxA2r in PSCs was also analyzed in this study.

RESULTSPancreatic cells with positive staining for Desmin and α-SMA in HFD rats were distributed in a more extensive way when compared to that in the control group. The levels of pancreatic 4-HNE and TxA2r were increased in rats from HFD groups significantly. The co-localization of 4-HNE and TxA2r were also found within activated PSCs in both of groups.

CONCLUSIONThe results showed that a chronic HFD feeding may increase the lipid peroxidation process and collagen synthesis through a critical signaling pathway of activated PSCs following pancreatic injuries in rats.

Actins ; metabolism ; Aldehydes ; metabolism ; Animals ; Collagen ; biosynthesis ; Desmin ; metabolism ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Lipid Peroxidation ; Male ; Oxidative Stress ; Pancreas ; metabolism ; pathology ; Pancreatic Diseases ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Thromboxane A2, Prostaglandin H2 ; metabolism

BACKGROUND: Pancreatic stellate cells (PSCs) activation plays a critical role in the development of chronic pancreatitis. Previous studies confirmed that thromboxane A2 receptor (TxA2r) was overexpressed in activated PSCs in rats. The purpose of this study was to investigate the role of TxA2r in the activation of PSCs induced by 8-epi-prostaglandin F2α (8-epi-PGF2α). METHODS: TxA2r expression in both quiescent and activated PSCs was detected by immunocytochemistry and immunoblot assay. Isolated PSCs were treated with 8-epi-PGF2α (10, 10, 10 mol/L) for 48 h, and SQ29548 (10, 10, and 10 mol/L), a TxA2r-specific antagonist for 48 h, respectively, to identify the drug concentration with the best biological effect and the least cytotoxicity. Then isolated PSCs were treated with SQ29548 (10 mol/L) for 2 h, followed by 10 mol/L 8-epi-PGF2α for 48 h. Real-time polymerase chain reaction was performed to detect the messenger RNA (mRNA) levels of α-smooth muscle actin (α-SMA) and collagen I. Comparisons between the groups were performed using Student's t test. RESULTS: TxA2r was up-regulated in activated PSCs in vitro compared with quiescent PSCs (all P < 0.001). Compared with the control group, different concentrations of 8-epi-PGF2α significantly increased mRNA levels of α-SMA (10 mol/L: 2.23 ± 0.18 vs. 1.00 ± 0.07, t = 10.70, P < 0.001; 10 mol/L: 2.91 ± 0.29 vs. 1.01 ± 0.08, t = 10.83, P < 0.001; 10 mol/L, 1.67 ± 0.07 vs. 1.00 ± 0.08, t = 11.40, P < 0.001) and collagen I (10 mol/L: 2.68 ± 0.09 vs. 1.00 ± 0.07, t = 24.94, P < 0.001; 10 mol/L: 2.12 ± 0.29 vs. 1.01 ± 0.12, t = 6.08, P < 0.001; 10 mol/L: 1.46 ± 0.15 vs. 1.00 ± 0.05, t = 4.93, P = 0.008). However, different concentrations of SQ29548 all significantly reduced the expression of collagen I (10 mol/L: 0.55 ± 0.07 vs. 1.00 ± 0.07, t = 10.47, P < 0.001; 10 mol/L: 0.56 ± 0.10 vs. 1.00 ± 0.07, t = 6.185, P < 0.001; 10 mol/L: 0.27 ± 0.04 vs. 1.00 ± 0.07, t = 15.41, P < 0.001) and α-SMA (10 mol/L: 0.06 ± 0.01 vs. 1.00 ± 0.11, t = 15.17, P < 0.001; 10 mol/L: 0.28 ± 0.03 vs. 1.00 ± 0.11, t = 11.29, P < 0.001; 10 mol/L: 0.14 ± 0.04 vs. 1.00 ± 0.11, t = 12.86, P < 0.001). After being treated with SQ29548 (10 mol/L) and then 8-epi-PGF2α (10 mol/L), the mRNA levels of α-SMA (0.20 ± 0.08 vs. 1.00 ± 0.00, t = 17.46, P < 0.001) and collagen I (0.69 ± 0.13 vs. 1.00 ± 0.00, t = 4.20, P = 0.014) in PSCs were significantly lower than those of the control group. CONCLUSIONS The results show that 8-epi-PGF2α promoted PSCs activation, while SQ29548 inhibited PSCs activation induced by 8-epi-PGF2α. The result indicated that TxA2r plays an important role during PSC activation and collagen synthesis induced by 8-epi-PGF2αin vitro. This receptor may provide a potential target for more effective antioxidant therapy for pancreatic fibrosis.

Objective To compare the ability and influence factors of three platelet function tests:light transmission aggregometry (LTA),thrombelastograph (TEG) and VerifyNow.Methods A total of 174 patients underwent percutaneous coronary intervention (PCI) and platelet function test were enrolled.Platelet function were tested by LTA,TEG and VerifyNow.Results Patients were found to be high platelet reactivity (HPR) by LTA (56.64％,64 cases/113 cases),TEG(60.38％,32 cases/52 cases),VerifyNow (17.24％,15 cases /87 cases).There were no significant differences observed between TEG and LTA (P ＞0.05).VerifyNow identified lower HPR proportion compared with TEG and LTA (all P ＜ 0.001).Conclusion Compared with LTA and TEG,VerifyNow identified lower HPR proportion and may overestimate the effectiveness of clopidogrel.We will follow the patients to study the predictive capability of three tests.

Objective To find the causes of poor treatment compliance and demands for the health education to guide the health education by nursing staff and improve the treatment compliance of chronic hepatitis B patients.Methods A self-designed "causes of poor treatment compliance and demands for health education of chronic hepatitis B patients questionnaire" was applied to survey 76 chronic hepatitis B patients.Results Poor treatment compliance was found in middle-aged chronic hepatitis B patients. The relapse rate was 72.4％.36.8％ of the patients showed no knowledge of chronic hepatitis B.39.5％ of patients had limited knowledge and misunderstanding.42.1％ of the patients never received health education for hepatitis B and 19.7％ of the patients received incorrect education.The major cause of poor treatment compliance was majority of the patients did not aware of the goal of the treatments and the indication of drug withdrawal.46.1％ of the patients believed their poor treatment compliance resulted from the financial factor.Patients hoped to receive health education from medical staff ( 82.9％ ) and to obtain knowledge of the medicine for hepatitis B ( 75.0％ ) and wished media support for against discrimination (63.2％).Conclusions Nursing staff should educate chronic hepatitis B patients accordingly to improve the poor treatment compliance.

OBJECTIVETo investigate the effects and related mechanisms of Tumstatin 185-191 as a single agent or in combination with cisplatin on proliferation and apoptosis in a cisplatin-resistant human lung adenocarcinoma cell line A549-DDP cells.

METHODSA549-DDP cells were treated with Tumstatin185-191 and cisplatin at varying concentrations. Cell viability was assessed by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 50% inhibiting concentration (IC(50)) values of the chemotherapeutic drugs were analyzed by MTT assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and ERK was evaluated by Western blotting.

RESULTSTumstatin185-191 inhibited the proliferation of A549-DDP cells and its IC(50) value was 80.25 micromol/L. After cotreatment with 20 micromol/L Tum185-191, the IC(50) value of cisplatin in A549-DDP cells reduced from 77.16 micromol/L to 57.97 micromol/L, the reverse index was 1.33, while with 40 micromol/L Tumstatin185-191 the IC(50) was reduced from 77.16 to 26.40 micromol/L and the reverse index was 2.92. The early apoptosis rate was 19.5% +/- 1.1% in the cotreatment group, while 13.3% +/- 1.5% in cisplatin group and 10.2% +/- 2.0% in Tum185-191 group (F = 4.09, P < 0.05). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549-DDP cells were remarkably lower after treatment with Tumstatin 185-191. The Tumstatin 185-191 treatment alone or in combination with cisplatin had a similar effect on the protein levels of p-Akt and p-ERK in A549-DDP cells.

CONCLUSIONOur data suggest that Tumstatin185-191 may promote apoptosis, downregulate proliferation and partly reverse the drug resistance of A549-DDP cells to cisplatin. The effects induced by Tum185-191 may be mediated through inactivation of the Akt and ERK pathways.

Adenocarcinoma ; pathology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Autoantigens ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Collagen Type IV ; pharmacology ; Drug Resistance, Neoplasm ; Drug Synergism ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Lung Neoplasms ; pathology ; Peptide Fragments ; pharmacology ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism

Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.

Objective:To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China.Methods:The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated.Results:A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs.Conclusions:The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epige-netic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive pri-mary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors. In contrast, the TET protein expression and DNA 5hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors. Through genome-wide analysis of 8 sets of primary tumors, we identified 100 high-confidence metastasis-associated 5hmC signatures, and it is found that increased levels of DNA 5hmC and gene expression of MAP7D1 associate with high risk of lymph node metastasis. Furthermore, we demonstrate that MAP7D1, regulated by TET1, promotes tumor growth and metastasis. In conclusion, the dynamic 5hmC profiles during lymph node metastasis suggest a link between DNA 5hmC and lymph node metastasis. Meanwhile, the role of MAP7D1 in breast cancer progression suggests that the metastasis-associated 5hmC signatures are potential biomarkers to predict the risk for lymph node metastasis, which may serve as diagnostic and therapeutic targets for metastatic breast cancer.