Liver transplantation(LT)is the only effective treatment for hepatopulmonary syndrome(HPS).Moreover,perioperative refractory hypoxemia(pRH)is a prevalent life-threatening condition and has extremely limited treatment options.Here,we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies,ephedrine inhalation,intravenous use of methylene blue with nitric oxide(NO)inhalation,and NO inhalation alone.The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury.Early initiation of NO inhalation,rather than ephedrine,can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications.Therefore,based on the response to these exploratory salvage treatments,we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS.We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.

Objective:To investigate the prevalence of influenza, pneumococcal, hepatitis B virus (HBV), human papillomavirus (HPV), and varicella zoster virus (VZV) vaccination in patients with systemic lupus erythematosus (SLE), and to analyze the factors related to vaccination.Methods:Data were obtained from 1 203 patients with SLE, via a multi-center web-based survey using an online questionnaire. Data about their social conditions, clinical presentations, willingness for being vaccinated, vaccination within 5 years were collected. Demographic data were shown by descriptive analysis. Chi-square and logistic regression analysis were used to assess the power of related indexes as predictors of vaccination.Results:The vaccination rates of influenza, pneumococcal, HBV, HPV, and VZV were 5.49% (66/1 203), 0.66% (8/1 203), 2.08% (25/1 203), 3.82% (46/1 203), and 0.17% (2/1 203), respectively. Data analysis showed that higher education ( χ2=30.94, P<0.001) and higher income ( χ2=10.70, P=0.001) had greater effects on influenza vaccination. There was a relationship between HPV vaccination and higher education ( χ2=20.96, P<0.001), higher income ( χ2=20.56, P<0.001), younger age ( χ2=8.54, P=0.001), and single ( χ2=5.63, P=0.018). Male ( χ2=10.27, P=0.001) and higher education ( χ2=4.52, P=0.034) were associated with HBV vaccination. The multivariate logistic regression analysis revealed that higher education [ OR (95% CI)=2.14 (1.10, 4.18), P=0.026], having children under 18 years-old [ OR(95% CI)=1.802(1.02, 3.18), P=0.042], and hydroxychloroquine usage [ OR(95% CI)=2.55(1.06, 6.15), P=0.037], had a positive correlation with influenza vaccination. Male [ OR(95% CI)=4.24(1.37, 13.08), P=0.012], had an impact on HBV vaccination. The factors related to HPV vaccination included age <45 [ OR (95% CI)=0.93(0.89, 0.97), P=0.001], higher education [ OR(95% CI)=2.28(1.11, 4.65), P=0.024], higher income [ OR(95% CI)=2.68(1.32, 3.41), P=0.006] and the usage of immunosuppressive agents [ OR(95% CI)=1.92(1.03, 3.59), P=0.041]. Conclusion:The prevalence of vaccination in patients with SLE is low. Patients with higher education and income are more likely to being vaccinated.

Objective : To explore the relationship between geriatric nutritional risk index( GNRI) and perioperative nutritional status，postoperative recovery and complications in elderly patients with gastric cancer． Methods : In this retrospective study，212 elderly patients ( aged ≥60 years ) with gastric cancer who underwent gastrectomy were recruited．GNRI was used to retrospectively assess the patients' preoperative nutritional status ，and analyze the relationship between GNRI and perioperative nutritional status，postoperative recovery and complications．The ROC curve was applied to explore the value of GNRI in predicting postoperative complications. Results : The inci- dence of preoperative nutritional risk in elderly patients undergoing gastric cancer surgery was 45. 07%．Compared with the patients whose GNRI＞98 points，the patients whose GNRI≤98 points had different degrees of decrease in serum total protein，albumin，prealbumin，hemoglobin and lymphocyte counts before surgery，day 1 and day 5－8 after surgery (P ＜0. 05) ．The patients whose GNRI ＜92 points had longer postoperative hospital stay than those with GNRI＞98 points (P＜0. 05) ．With the decrease of GNRI scores，the incidence of complications showed an upward trend(P＜0. 001) ．The multivariate analysis of the relationship between GNRI and postoperative complica- tions showed that TNM staging of III －IV and GNRI ＜92 points were independent risk factors for complications. GNRI had a good predictive value for the occurrence of complications (AUC = 0. 639，95% CI : 0. 570－0. 703，P = 0. 001，Cut-off value : 92. 21) ． Conclusion GNRI can be used for preoperative nutritional assessment for eld- erly gastric cancer patients．Patients with GNRI＜92. 21 points should be actively given nutritional therapy to im- prove perioperative nutritional status，speed up postoperative recovery，and reduce the occurrence of complications.

Objective To explore the effect of miRNA-146a on the proliferation and apoptosis of vascular smooth muscle cells and its mechanism.Methods Taking the SDP grade healthy male SD rats as the experimental subjects,After the digestion of vascular smooth muscle cells(VSMC),50 nmol/L transfected miRNA-146a antisense oligonucleotides,missense chain and the same dose of phosphate buffer(PBS)were compared.Results The number and absorbance value of VSMC in the experimental group were lower than those in the other two groups after transfection with 48 h,the apoptosis rate was significantly higher than that of the other two groups,the expression level of nuclear factor κBp65 and PCNA was lower than the other two groups,and the difference was statistically significant(P＜0.05).Conclusion miRNA-146a can promote the proliferation of VSMC,inhibiting the apoptosis of the cells,the mechanism of action is related to the increase of nuclear factor κBp65 and PCNA expression.

Objective To approach the mechanisms and myocardial protective effect of Qishen Yiqi dropping pills on rats with myocardial infarction. Methods Sixty clean healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and observation group (each n = 20). The rat model of acute myocardial infarction (AMI) was established by ligation of left anterior descent (LAD) branch of coronary artery. After modeling, the rats in observation group were given 0.135 g/kg of Qishen Yiqi dropping pills, and sham operation group and model group were administered the same amount of normal saline, once a day for consecutive 28 days. At the end of treatment, the levels of serum inflammatory factors of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA); the changes of the indexes of hemodynamic [left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximal rate of increase/decrease in left ventricular pressure (±dp/dt max)], the ratio of the heart weight/body weight, and the ratio of the left ventricular weight/heart weight (LVW/HW), the myocardial infarction area, myocardial histopathological changes were observed in the three groups; myocardial tissues inflammatory related factors [the mRNA and protein expressions of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX)], and the expression levels of transforming growth factor-β (TGF-β)/Smads signal transduction pathway related protein (TGF-β1, Smad2/3, Collagen Ⅰ, Collagen Ⅲ ) and cell apoptosis related factors (Bcl-2, Bax) protein were measured. Results Compared with the sham operation group, levels of serum inflammatory factors, the index of LVEDP, the ratio of the heart weight/body weight, LVW/HW, myocardial infarction area, the mRNA and protein expression levels of inflammatory factors in myocardium, the expression levels of TGF-β/Smads signal transduction pathway related protein and the cell apoptosis related factors protein in model group were all significantly elevated, while LVSP and ±dp/dt max were obviously decreased in model group. Compared with the model group, the levels of inflammatory factor in serum [LTB4 (ng/L): 370.11±46.98 vs. 633.23±83.37, PGE2 (ng/L):48.75±26.35 vs. 131.25±29.75, TNF-α (μg/L): 177.28±22.65 vs. 248.47±16.21, IL-6 (μg/L): 493.22±165.99 vs. 638.41±191.66], LVEDP [mmHg (1 mmHg = 0.133 kPa): -2.03±2.98 vs. 7.03±1.39], the ratio of the heart weight/body weight [(6.53±0.11)% vs. (7.14±0.24)%], LVW/HW (0.26±0.01 vs. 0.32±0.02), myocardial infarction area [(27.21±2.87)% vs. (44.98±1.52)%], mRNA and protein expression of myocardial inflammatory factors, the expression of TGF-β/Smads signal transduction pathway related protein, and the protein expression of Bax were all significantly decreased in observation group (all P < 0.05), LVSP (mmHg: 129.01±11.93 vs. 108.11±12.69), the +dp/dt max (mmHg/s: 3101.3±378.6 vs. 2105.3±245.9), the -dp/dt max (mmHg/s: 2612.4±249.7 vs. 1654.4±188.1), while the protein expression of Bcl-2 in observation group were obviously increased (all P < 0.05). It was demonstrated by hematoxylin-eosin (HE) staining that there were no obvious pathological changes in the sham operation group; obvious infiltration of inflammatory factors in myocardium was shown in model group; pathological changes in the observation group were significantly improved as compared with those in the model group. It was shown by Masson staining that there were slight hyperplasia of myocardial fibers and no obvious pathological changes in the sham operation group. Severe collagen hyperplasia was found in model group, and the degree of fibrosis in the observation group was significantly improved. Conclusions Qishen Yiqi dropping pills can reduce the degree of myocardial fibrosis and inhibit the ventricular remodeling via TGF-β/Smads signal transduction pathway. The dropping pills can also suppress the release of inflammatory factors by reducing cPLA2 to decrease the inflammatory response and inhibit apoptosis and alleviate myocardial injury by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.

Objective To evaluate the clinical and radiographic characteristics and function of erosive hand osteoarthritis (EOA) patients. Methods Data were obtained from 19 patients with EOA, including their social conditions, clinical conditions, radiographic scores and hand function evaluation. The number of hand osteoarthritis (HOA) patients was 312. The control group consisted of non-EOA patients with hand osteoarthritis with a ratio of 4:1 to EOA patients. A non-parameter test analysis was performed. All data were analyzed by SPSS 23.0 statistical analysis, t test, χ2 test, Fisher exact probility and Spearman's correlations analysis were used for statistical analysis. Results Totally data of 19 patients were collected. Eighteen were female. Onset age was (56±8). Average duration was 56 (12~120) months. FIHOA scores of all the EOA patients were at least 5. All the erosions of 39 joints were characteristically central and erosive changes in 7 joints (18%) showed up as gull-wing. Among 39 erosive joints, including 12 (31%) E and 27 (69%) R, 34 (87%) distal interphalangeal joints were involved. Data analysis found out that EOA patients had longer disease duration (Z=2.610, P=0.009), more severe K-L level (44 ±11 vs 26 ±7, t=7.134, P<0.01), higher AUSCAN total score (28±6 vs 21±7, t=3.781, P<0.01) and higher AUSCAN function score (18±6 vs 12±6, t=4.042, P<0.01). The differences of ESR and CRP were not significant between EOA and non-EOA patients. Conclusion Erosions seen in EOA patients are centrally located gull-wing in the DIP joints. EOA patients have longer duration, more severe radiographic damage and worse joint function.

Background Retinal neovascularization (RNV) occurs in multiple eye diseases,which can lead to bleeding and retinal detachment.Therefore,inhibition of pathological RNV is becoming crucial to the treatment of ocular diseases.Research has shown that α-melanocyte-stimulating hormone (α-MSH) inhibits retinal angiogenesis during physiological development;however,the effects of α-MSH on pathological RNV remain unknown.Objective This study was to investigate the effects of intravitreal injection of α-MSH at different concentrations on pathological RNV in a mouse model of oxygen-induced retinopathy (OIR).Methods Forty healthy clean C57BL/6J mice were randomly divided into OIR+0.33 μg/μl α-MSH,OIR+ 1.67 μg/μl α-MSH,OIR+3.30 μg/μl α-MSH,OIR,and normal control groups at postnatal day 7 (P7),with 8 pups in each group.The α-MSH intervention groups and OIR group were exposed to high oxygen (75 ±2)％ for 5 days,then maintained under normal air condition for another 5 days;whereas the normal control group was raised under normoxia for 10 days.Retro-orbital injection of high molecular weight fluorescein isothiocyanate-dextran (FITC-dextran) was performed on P17 mice.The retina whole mounts were prepared to reveal retinal vasculature and quantify relative area of vessel obliteration.The mouse eyeballs were subjected to paraffin sections and hematoxylin-eosin staining,and the average number of pre-retinal nuclei per section was quantified.Results FITC-dextran labeled retinal whole mounts showed that the relative vessel obliteration area in normal control,OIR,OIR+0.33 μg/μl α-MSH,OIR+ 1.67 μg/μl α-MSH,and OIR+3.30 μg/μl α-MSH groups were (0.00±0.00) ％,(23.01 ±3.39) ％,(18.14±7.20) ％,(15.64±7.07) ％,and (7.62±6.52) ％,respectively.There was a statistical significance in the relative avascular area among the groups (F=19.635,P＜0.05).The relative avascular area in the OIR group was significantly higher than that in the OIR+3.30 μg/μl α-MSH group (t=4.293,P＜0.01).The results of histopathological examinations showed that the average number of pre-retinal nuclei per section in normal control,OIR,OIR+0.33 μg/μl α-MSH,OIR+1.67 μg/μl α-MSH,and OIR+3.30 μg/μl α-MSH groups were 0.00±0.00,11.45 ±4.26,6.35 ±2.34,4.96 ± 1.79 and 1.03 ± 1.25,respectively.There was a statistical significance in the average number of pre-retinal nuclei per section among the groups (F =147.87,P＜0.05).The average number of pre-retinal nuclei per section in the OIR group was significantly higher than that in the OIR+0.33 μg/μl α-MSH,OIR+ 1.67 μg/μl α-MSH,and OIR+3.30 μg/μl α-MSH groups,the differences between the groups had statistical significances (all at P＜0.001).Conclusions α-MSH reduces the relative area of vessel obliteration and the average number of pre-retinal nuclei in the retinas of OIR mouse model.The inhibitory effects of α-MSH on the pathological RNV are dose-dependent.

AIM:To select an efficient way of promoting induced pluripotent stem cells ( iPSC) to differentiate into neural stem cells (NSC) by comparing 2 methods.METHODS:The culture system in method A contained SB431542 (5 mmol/L) and drosomophorin (5 mmol/L) with 100%initial cell density, while that in method B contained SB431542 (5 mmol/L) and drosomophorin (1 mmol/L) with 30%~50% initial cell density.For comparison and identification of the 2 methods, the growth state was observed under microscope , and the expression of Pax6, nestin, Sox1 and Sox2 was quantitatively detected by real-time PCR and flow cytometry .The related protein expression and the ability of spontaneous differentiation were determined by immunofluorescence analysis .RESULTS: The cells derived from method A with 5 mmol/L of SB431542 and drosomophorin and 100% initial cell density achieved the higher expression of Pax 6, nestin, Sox1 and Sox2.The growth state was better and the cells differentiated into neurons and astrocytes normally .CONCLU-SION:The method A was superior to method B , and we recommend the method A with 5 mmol/L of SB431542 and droso-mophorin and 100%initial cell density as the method for differentiating NSC .

BACKGROUNDThe MAPK phosphatases (MKPs) are a family of dual-specificity phosphatases (DUSPs) that can dephosphorylate both phosphothreonine and phosphotyrosine residues, thus inactivating MAPK signaling. DUSP6 is a cytoplasmic MKP that can inactivate ERK. DUSP6 has been implicated in the development of some tumors. The aim of this research was to investigate the expression of DUSP6 in hepatocellular carcinoma (HCC) and the correlation of DUSP6 with mitogen-activated protein kinases (MAPKs), clinicopathological characteristics, and prognosis.

METHODSTissues from 305 patients who had undergone hepatectomy for HCC was used in this study. The expression of DUSP6, p-ERK, p-JNK, and p-p38α was determined using tissue microarrays for immunohistochemical analysis. The prognostic value of DUSP6 and other clinicopathological factors were evaluated.

RESULTSThe expression of DUSP6 was significantly higher in the tumor tissue when compared to the peritumor or normal liver tissue (P < 0.001). Tumor DUSP6 expression was significantly associated with disease-free survival (DFS) (P = 0.013). Tumor DUSP6 expression was an independent prognostic factor for DFS (Hazard ratio = 1.635, P = 0.006).

CONCLUSIONSDUSP6 is over expressed in tumor tissue compared to peritumor or normal liver tissue. Higher expression of DUSP6 in tumor tissue, than in peritumor tissue, is associated with the recurrence after curative resection of HCC, and the relative tumor DUSP6 expression has good power to predict the recurrence of HCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; metabolism ; Dual Specificity Phosphatase 6 ; metabolism ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; metabolism ; Tissue Array Analysis ; Young Adult

BACKGROUND:Many studies have showed that neural stem cells therapy is a new strategy for hypoxic-ischemic encephalopathy.
OBJECTIVE:To review and analyze the status of research, transplantation strategies and mechanism of neural stem cells therapy for treatment of hypoxic-ischemic encephalopathy.
METHODS:A computer-based retrieval was performed in PubMed and CNKI database to search papers published from August 2000 to August 2013 using the key words of“hypoxic-ischemic encephalopathy, neural stem cells”in English and Chinese. The papers with objective-independent and repetitive contents were excluded, and final y 39 papers were included for final analysis.
RESULTS AND CONCLUSION:Neural stem celltransplantation can promote recovery of neurological function, which brings new hope to hypoxic-ischemic encephalopathy patients. But the study is at a primary stage and limited in laboratory. There are many critical factors that hinder the clinical transplantation, such as delivery path, transplantation time, single or combined transplantation, mechanisms of action. Application of neural stem cells requires further investigation.