The vagus nerve is involved in the regulation of human inflammation, mood and pain. Stimulation of the vagus nerve has assured therapeutic effects on intractable epilepsy and refractory depression. On the surface of the human body, the ear is the only area in which vagal afferent fibers distribute. According to the "bottom-up" mechanism of the signal processing, the central nervous system can be modulated by stimulating the peripheral nerve. Therefore, stimulation of the vagus nerve can regulate the activities of brain stem, thalamus, cerebral cortex and other related areas to produce therapeutic effects. Transcutaneous vagus nerve stimulation is a safe, low-cost, non-invasive physical therapy modified from vagus nerve stimulation. This review focuses on the regulation of organ function by transcutaneous vagus nerve stimulation and its application to diseases treatment.

China ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Kidney Diseases ; drug therapy ; Prospective Studies ; Retrospective Studies ; Tripterygium

Objective To evaluate the effect of pacing in different parts of the ventricle on left ven-tricular mechanical asynchrony using myocardial metabolic imaging.Methods A total of 56 elderly patients undergoing permanent pacemaker implantation in our hospital from January to November 2023 were recruited and randomly divided into left bundle branch pacing(LBBAP)group and right ventricular pacing(RVP)group,with 28 patients in each group.Another 28 elderly patients who did not undergo pacemaker implantation surgery were selected as the control group.Within 1 week after pacemaker implantation,18F fluorodeoxyglucose(18F-FDG)positron emission tomo-graphy(PET)/CT myocardial metabolism imaging was performed to analyze PET myocardial metabolism images and evaluate left ventricular mechanical synchrony.Results The LVEF was significantly higher in the control group than the LBBAP group and RVP group[(67.68±9.61)％vs(62.71±11.33)％vs(57.36±16.07)％,P=0.012],but no such difference was seen between the LBBAP group and the RVAP group(P＞0.05).The LBBAP group had obviously lower pat-tern standard deviation(PSD),phase histogram bandwidth(PHBW),entropy,summed motion score(SMS),summed thickening score(STS),extent of abnormal motion(Mot Ext)and thicken-ing extent(Thk Ext)when compared with the RVP group(P＜0.01).There were no statistical significant differences in the terms of PSD,PHBW,Entropy,SMS,STS,Mot Ext,and Thk Ext between the LBBAP group and the control group(P＞0.05).Conclusion 18F-FDG PET/CT myo-cardial metabolic imaging can be used to evaluate left ventricular mechanical synchrony in pacing different parts of the ventricle,and LBBAP can obtain better left ventricular synchrony parame-ters than RVP,similar to the control group.

OBJECTIVETo explore the existence of vasculogenic mimicry (VM) in ovarian carcinoma and its correlationship with the clinicopathologic features and prognosis of the tumor.

METHODSA total of 84 ovarian carcinoma cases were collected with complete clinical and prognostic data. CD31 immunohistochemistry and PAS special stain were used to investigate VM in the tumor tissue. Immunohistochemical staining of VEGF, MMP-2, MMP-9, E-cadherin, beta-catenin, and Vimentin were used to explore the pathogenesis of VM.

RESULTSTotally 36 of 84 cases exhibited evidence of VM. FIGO classification, pathologic grades and histological types were significantly different between the VM and non-VM groups. Expression of VEGF, MMP-2, MMP-9, E-cadherin and beta-catenin were higher in the VM group than in the non-VM group. Kaplan-Meier survival curve analysis showed that cases of the VM group had a lower survival rate than that of the non-VM group (P = 0.04).

CONCLUSIONSVasculogenic mimicry exists in ovarian carcinoma. Ovarian carcinomas with a high grade malignancy have a high incidence of VM formation, a higher incidence of metastases and a lower survival rate. High expression of MMP-2 and MMP-9 may contribute to the formation of VM in the ovarian cancer.

Cadherins ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Neoplasm Metastasis ; Neovascularization, Pathologic ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism ; beta Catenin ; metabolism

The latent membrane protein 2 (LMP2) is a kind of protein expressed by EBV-infected cells. This study was aimed to investigate whether the stimulation of peripheral blood mononuclear cells with peptides induces EBV-specific cytotoxic T lymphocytes (CTL). The peptides were mixture of LMP2 protein and available for people with different HLA types. Peripheral blood sample was collected from a patient with EBV-associated hemophagocytic syndrome. The mononuclear cells were isolated and cultured to obtain dendritic cells (DCs). Immature DCs were pulsed with MIX-LMP2 and added with different maturation-promoting factors. The auto-T lymphocytes were stimulated weekly with the harvested mature DCs loaded with MIX-LMP2, and totally for two times. Part of isolated lymphocytes was cultured without any stimulation as control. T-cell receptor (TCR) beta spectratyping was used to analyze the distribution of different T cell subgroups before and after culture. The phenotype of T lymphocytes was determined by flow cytometry. The IFN-gamma assay was used to estimate specific cytoxic activity of the cultured T cells. The results showed that the distribution of TCRbeta was changed according to analysis of TCR spectratypes. From the distribution of gene families of TCRbeta, the T lymphocytes were oligoclonal before culture, but shifted to a polyclonal after culture in vitro like the normalization of TCR diversity, suggesting the subgroups of lymphocyte could return to normal. The percentage of CD3+, CD3+CD8+ CD3+ CD45RA- CD45 RO+ on T lymphocytes from freshly isolated mononuclear cells were 70.73%, 42.99%, 27.56% respectively. After being stimulated twice with DC loaded with MIX-LMP2, they further increased to 95.17%, 52.54% and 81.41%. The percentages of CD3-CD56+ NK cells and CD4+CD35+ FOXP3+ regulation T cells seldom changed, from 2.12%, 0.03% to 2.35%, 0.02% respectively. The increase of CD3+CD45RA-CD45RO+ cells obviously indicated that most naive T cells could be activated. ELISA for IFN-gamma showed that when DCs loaded with LMP2 peptide were used as target cells, IFN-gamma level secreted by the T cells stimulated with LMP2 peptide-pulsed DCs was 805+/-16 pg/ml and 1729+/-49 pg/ml, the IFN-gamma level secreted by T cells stimulated twice with LMP2 peptide-pulsed DCs was 956+/-23 pg/ml and 2325+/-58 pg/ml respectively at effector-target ratios of 10:1 and 10:2. They were both significantly higher than that secreted by T cells without any stimulation (441+/-27 pg/m and 557+/-19 pg/ml) (p<0.05). But DCs unpulsed with LMP2 peptide were used as target cells, there were no significant differences between the T cells stimulated with LMP2 peptide-pulsed DCs and the T cells without stimulation (p>0.05). It is concluded that the antigen specific T cells recognizing EBV epitopes can be obtained by using DCs pulsed with MIX-LMP2 peptide in vitro, meanwhile the distribution of T cell subgroups can be changed and normalized.
Antigens, Viral ; immunology ; Cells, Cultured ; Coculture Techniques ; Cysteine Endopeptidases ; immunology ; metabolism ; Dendritic Cells ; immunology ; metabolism ; Epitopes, T-Lymphocyte ; immunology ; Epstein-Barr Virus Infections ; immunology ; Herpesvirus 4, Human ; immunology ; Humans ; Leukocytes, Mononuclear ; cytology ; T-Lymphocytes ; cytology ; immunology

BACKGROUNDPigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization.

METHODSMicrodissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays.

RESULTSCells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However, the concentration of PEDF which we used has little effect on normal CECs.

CONCLUSIONSPEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell. These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.

Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Choroid ; blood supply ; drug effects ; Choroidal Neovascularization ; drug therapy ; Endothelial Cells ; cytology ; drug effects ; Eye Proteins ; pharmacology ; Humans ; Nerve Growth Factors ; pharmacology ; Serpins ; pharmacology ; Vascular Endothelial Growth Factor A ; pharmacology

Objective: To investigate the predictive value of neutrophil-to-lymphocyte Ratio (NLR) in 30-day mortality of patients with acute paraquat poisoning. Methods: We respectively reviewed the clinical parameters of 115 patients with acute paraquat poisoning. They were divided into survival (n=64) and non-survival (n=51) groups based on their 30-day outcome. Multivariate logistic regression was performed to identify risk factors of 30-day mortality. Receiver operating curve (ROC) test was applied to analysis to the predictive value of NLR in 30-day mortality ofacute paraquat poisoning patients. The correlations between NLR and severity index of paraquat poisoning (SIPP) were analyzed using Spearman’s rank correlation coefficient. Results: Of the 115patients included in the study, 54 (46.96%) patients were males and 61 (53.04%) were females with a mean age of 38.96±13.58 years. The total mortality in 30-day was 44.35% (51/115) . The NLR at admission was an independently risk factor of 30-day mortality of patients with acute paraquat poisoning (OR 1.477, 95%CI 1.035-2.107, P<0.05) . The NLR to predict the death of the area under the ROC curve was 0.894 (95%CI: 0.8212-0.9663, P<0.01) ; the optimal cutoff threshold was 11.71; the sensitivity was 71.79% and the specificity was 94.29%; the positive predictive value was 93.33%and negative predictive value of 75.00%. Meanwhile, the positive likelihood ratio was 12.57 and the negative likelihood ratio was 0.30. The NLR was significantly associated with SIPP (Spearman rho 0.525; P<0.01) and it was significantly higher in patients with SIPP of ten or higher than in those with an SIPP less than 10 (15.02±12.40 vs. 6.19±2.54, P<0.05) . Conclusion The increased NLR at admission was an independently risk factor of 30-day mortality of patients with acute paraquat poisoning and it was significantly correlated with SIPP score. Therefore, NLR was useful for predicting prognosis of patients with acute paraquat poisoning.

Objective To assess the nutritional status and dietary quality of medical students and its influencing factors.Methods Students from Shanghai Medicial College of Fudan University were recruited to complete the 7-day and 24-hour dietary records,with food consumption measured by weight.A comprehensive evaluation of the students'dietary quality was carried out by comparing their actual nutrient intake against recommended levels and calculating the component score of the Chinese Healthy Eating Index(CHEI).Factor analysis was used to extract dietary patterns.All subjects were further divided into high score group and low score group based on total CHEI.Binary Logistic regression was used to determine the factors influencing dietary quality.Results The study participants had an average daily energy intake of(2 057.02±501.87)kcal/d,80%from on-campus canteen meals.Carbohydrates,proteins and fats contributed to 48.90%,16.55%and 36.07%of the total energy intake,respectively.The CHEI median score was 67.55.Component scores for tubers,vegetables,fruits,dairy,fish and seafood,and nuts were below 60%,indicating an unbalanced diet.Being in the graduate stage(OR=0.53,95%CI:0.28-0.98)and having unreasonable body weight expectations(OR=0.37,95%CI:0.17-0.81)were associated with lower CHEI scores.Conversely,higher CHEI scores were associated with the fruit-dairy dietary pattern(OR=8.20,95%CI:3.39-19.84),the tuber-vegetable dietary pattern(OR=3.41,95%CI:1.58-7.32),and lower rates of on-campus dining(OR=1.92,95%CI:1.02-3.59).Conclusion The energy intake of students at Shanghai Medical College of Fudan University appears to be adequate.However,a relatively high proportion of energy supply from fat intake indicates a need for improvement in their dietary structure.The dietary quality of students is mainly influenced by their educational level,weight expectations and dietary patterns.

Acute mitral regurgitation(MR)in the setting of myocardial infarction(MI)may be the result of papillary muscle rupture(PMR).The clinical presentation can be catastrophic,with refractory cardiogenic shock.This condition is associated with high morbidity and mortality.Transcatheter edge-to-edge repair(TEER)has become increasingly common in treating severe mitral regurgitation.This case details a successful TEER is feasible and safe in patients with acute MR following MI.TEER is an emerging treatment option in this clinical scenario that should be taken into consideration.

Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients (P=0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.