Autophagy is a special cellular process, which can participate in regulating cell survival, growth, differentiation and homeostasis maintenance by transporting damaged organelles and macromolecular substances to lysosomes for degradation. Autophagy plays a very important role in all aspects of life process. Research results show that autophagy plays an important role in tumor occurrence, development and metastasis. The synergistic effect of autophagy and vascular endothelial growth factor promotes tumor angiogenesis and cell repair, and may play an important role in the development of tumor resistance to anti-vascular drug therapy. Targeted therapy with autophagy as the target may be a new direction for anti-tumor molecular targeted therapy in the future, aiming to provide multi-target collaborative therapy to benefit patients.

Objective To understand the genetic characteristics of Enterovirus 71 ( EVT1 ) circu-lating strains of Guangdong province in 2008. Methods We isolated an EV71 strain from the fatal case of the hand, foot and mouth disease during an epidemic of Guangdong in 2008. Its complete genome was se-quenced and analyzed comparatively. Results The results showed that the full length of EV71 GDFS-3 ge-nome( not including poly A tail ) is 7405 bp. No insertion or deletion is detected in the coding region. There are several insertions and deletions in 5'and 3'UTR. Phylogenetic analysis of GDFS-3 and reference strains showed GDFS-3 strain shares the highest nueleotide homology with TW984 strain(96.0% ) but low homology with SIN5865, MS and BrCr( about 81.0% ). GDFS-3 strain also shares the highest amino acid homology with TW984 strain(99.0% ). It clustered with reference strains of CA subgenotype in the phylogenetie tree. The nucleotide identity with CA reference strains is 91.0% -95.0%. Conclusion The phylogenetic analysis based on the entire genome demonstrates that GDFS-3 strain has the nearest genetic relationship with TW984 strains ( isolated in 2004). GDFS-3 may belong to the same subgenogroup ( CA ) with Taiwan predominant strains. Otherwise,Some mutations in 5'UTR of EV71 may play the very important role in heightened viru-lence.

This paper was aimed to study the quantitation method of bitterness intensity of bitter drug, and to ex-plore the mutual relations between the bitterness intensity and the concentration of bitter drugs solution. The mod-el drug of berberine hydrochloride, which was made into a series of solutions of different concentrations, was ap-plied. Twenty volunteers, who were screened, trained and qualified, tasted the different concentration of aqueous solution, with the purpose of detecting the rank bitterness intensity. After analyzing the features of the data and testing the logarithm model and Weibull curve model, as well as nonlinear fitting, we finally set up the appropri-ate relationship curve between the concentration and the bitterness intensity. There is a good curve positive corre-lation between the bitterness intensity and the concentration, which is consistent with the Weibull curve model (R2= 0.9973, RMSE = 0.0976, RMSECV = 0.1453). The fitting degree of the model established in this paper is high, which provides a reference for quantitation and forecast of the drug bitterness.

Objective To evaluate the efficacy and safety of autologous peripheral blood stem cell transplantation (APBSCT) in treatment of patients with decompensated hepatitis B cirrhosis.Methods Sixty two patients with decompensated hepatitis B cirrhosis admitted in Ningbo Second Hospital during January 2010 and December 2013 were enrolled in the study.Patients were randomly assigned in two groups: 50 patients in control group received comprehensive medical treatment only, and 12 patients in combination group received APBSCT on the basis of medical treatment.The levels of serum total bilirubin (TBil), albumin (Alb), alanine aminotransferase (ALT) and prothrombin time (PT) in two groups were mearsured at the 4th,12th,24th week.Overall survival (OS),progression-free survival (PFS) and complications were compared between two groups after 3 years follow-up.SPSS17.0 software was used to analyze the data.Results After APBSCT treatment, the level of Alb and PT at week 4,12 and 24 in combination group improved significantly(tAlb=-4.437,-5.210 and-6.915,tPT=12.083,11.251 and 10.640,all P<0.01),there were also significant differences between combination group and control group (tAlb=4.985, 5.565 and 6.260,tPT =-3.013、-3.727 and-3.983,all P<0.01).The 3-year OS and 3-year PFS of patients in combination group were higher than those of control group [(90.9±8.7)%vs.(60.7±7.4)%, (75.8±12.5)% vs.(47.9±7.3)%](χ2=6.887 and 5.565,P<0.05).Besides,APBSCT had more advantages than control group in reducing ascitic fluid and hepatic encephalopathy(χ2=7.992 and 4.681,P<0.05 or <0.01).Conclusion APBSCT combined with medical treatment can improve liver function and 3-year survival rate with mild adverse reaction in patients with decompensated hepatitis B cirrhosis.

Objective To investigate the aging-related changes in gap junction protein-connexin 43 (Cx 43) in rats and their effect on the high incidence rate of ventricular arrhythmia in aged rats. Methods The 64 healthy male Fischer 344 (F344) rats were randomly divided into four age groups (n=16,each): 3-6 months (juvenile), 9-12 months (young-adult), 18-21 months (middle-aged) and 24-26 months (aged). The incidence rate of ventricular arrhythmia was recorded by monitoring their limb-lead Electroa rdiogram(ECG). Morphological changes of ventricular myocardium were observed under optical microscope in Hematoxylin (HE) and Masson's stain. The distribution of connexins 43 (Cx43) and deophosphatase (NP) Cx43 was observed by confocal immunofluorescence microscopy and the Cx43 and NP-Cx43 protein expression was assessed by Western-Blot. Results The incidence rate of ventricular arrhythmia was much higher in aged group (75.0%) than in other three groups (0%,0%,12.5%), all P＜0.05, and the aged group showed that ventricular muscle cells were hypertrophy and arrayed sparsely and disorderly with hyperplasia of connective tissues. The distribution of Cx43 changed from end-to-end to disordered arrangement and the total expression amount of Cx43 decreased as age increased (P＜0.05). The expression amount of NP-Cx43 in middle-aged rats was notably decreased than in juvenile and aged rats (P＜0.05). Conclusions For aged rats, the high incidence rate of ventricular arrhythmia may be associated with ventricular myocardium reconstruction, disarrangement of ventricular muscle cells and gap junction proteins, decreased expression amount of Cx43 and relatively increased NP-Cx43.

Taste-masking effect of pharmaceutical formulation is important for the pharmacy worker to carry out study on taste-masking of pharmaceutical formulation. This study discussed the feasibility of electronic tongue in the evaluation of taste-masking effect. The berberine hydrochloride was used as model drug of bitterness. Sodium cycla-mate, 2,4-Dihydroxybenzoic acid and sodium cyclamate were used as bitterness inhibitors. Through detection of elec-tronic tongue, results from principal component analysis (PCA), and indexes such as distance of bitterness (D), dis-tance of bitterness reduction, inhibition rate (Ir), the determination was given on whether results from the bitterness inhibition of berberine hydrochloride and taste results from volunteers were the same. In addition, sodium cyclamate, which was the best bitterness inhibition, was made into different concentrations in order to optimize its using dosage. The data analysis results showed that in the berberine hydrochloride solution with the concentration of 0.005 mg/mL, the ranking order of the bitterness-masking efficiency was sodium cyclamate > 2,4-Dihydroxybenzoic acid > sodium acetate anhydrous. Along with the increasing concentration of sodium cyclamate, the taste-masking effect is better. However, after the concentration level of 0.2%, the change on taste-masking effect was relatively small. In the prac-tical work, the concentration of sodium cyclamate can be selected at the level of 0.2%. This experiment effect was the same as the human taste results. This study showed that the electronic tongue may be a useful tool in the evalua-tion of taste-masking efficiency to some extent.

To compare and evaluate the discriminatory ability and potential value of pulsed field gel electrophoresis (PF-GE) and multiple locus VNTRs analysis (MLVA) on the genotyping of Brucella ,a total of 60 strains of Brucella and three standards (16M ,544A ,1330S) were genotyped simultaneously by PFGE and MLVA .The result indicated that the similarity coefficient among the 63 isolates was from 72 .1-100 .0% by PFGE ,and could distinguish three species of B .melitensis ,B .su-is and B .abortus at the similarity level of 94 .4% .There were 14 clusters and 29 PFGE types identified by PFGE with discrim-inatory index (DI) of 0 .957 5 at the similarity level of 100% ;the similarity coefficient among the 63 isolates was from 16 .9-100 .0% by MLVA ,and could distinguish three species of Brucella at the similarity level of 52 .3% .There were 8 clusters and 47 MLVA types identified by MLVA with discriminatory index (DI) of 0 .985 2 at the similarity level of 100% .It's suggested that PFGE and MLVA could be used to distinguish three species of Brucella in the similarity coefficient of certain ,but could not effectively distinguish the type in the same species .Both of these two methods could be used for Brucella molecular typing , but MLVA is better than PFGE for its relatively higher discriminating ability .

Objective:To investigate the effect of exercise rehabilitation combined with psychotherapy and exercise rehabilitationn alone in elderly patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:A total of 150 elderly patients(≥65 years)admitted to our hospital with CHD after primary PCI were enrolled and randomly divided into the group A(conventional drug therapy), group B(conventional drug therapy+ exercise rehabilitation)and group C(conventional drug therapy + exercise rehabilitation+ psychotherapy), with 50 patients in each group.Patients in groups B and C were intervened at two weeks after PCI, once a week for 12 weeks.Changes of Hamilton anxiety scale(HAMD)scores, Hamilton depression scale(HAMA)score, 6 min walking test, left ventricular ejection fraction(LVEF)and metabolic equivalents(METs)were compared among the three groups.Results:Before treatment, the METs were significantly lower in the group B(3.58±0.14)compared with the groups A(3.69±0.18)and C(3.68±0.15), and were similar between groups A and C. After 12 weeks of treatment, compared with the indicators before treatment, the HAMA scores were similar in the group A(12.98±2.51 vs. 12.16±2.91, P>0.05), and were significantly decreased in groups B(12.90±2.12 vs.8.06±2.11, P<0.05)and C(13.03±2.52 vs.6.96±2.13, P<0.05); HAMD scores were all markedly decreased in all three groups(group A: 22.38±2.52 vs.20.87±2.12; group B: 22.58±2.57 vs.17.25±2.32; group C: 22.23±2.35 vs.13.39±2.25), and were decreased most in the group B, followed by groups A and B( P<0.05). Furthermore, the LVEF group A: (49.08±1.59)% vs.(52.15±1.91)%; group B: (48.99±2.11)% vs.(57.56±2.13)%; group C: (49.04±2.02)% vs.(59.92±1.93)%, 6 min walking distance test(m)(group A: 360.78±12.50 vs.370.16±12.41; group B: 359.21±10.54 vs.394.19±15.56; group C: 363.12±15.28 vs.413.29±18.15)and METs(group A: 3.69±0.18 vs.3.91±0.21; group B: 3.58±0.14 vs.4.89±0.09; group C: 3.68±0.15 vs.5.77±0.13)were significantly improved in all groups after the treatment.Among them, group C was improved most, followed by groups B and A(all P<0.05). Conclusions:Exercise rehabilitation combined with psychotherapy is of great significance to improve the physical condition of elderly patients with CHD after PCI, and it is better than the routine exercise rehabilitation alone.

OBJECTIVETo study long-term effect on renal function exposed to environmental cadmium.

METHODSStratified random sampling and cluster sampling method of epidemiological investigations were carried out in northern Guangdong province between April, 2011 and August, 2012. A total of 167 residents who lived in high cadmium exposure area for more than 15 years, aged above 40 were selected in exposed group. Moreover, A total of 145 residents who had similar living and economic conditions and lived in local for more than 15 years, aged above 40 were selected in control group. We used health questionnaires and medical examinations in order to acquire their health status. Home-harvested rice and vegetables were collected using quartering method for detection of cadmium level. Urine specimens of residents were collected for detection of cadmium level and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG), β2-microglobulin (β2-MG), and retinol binding protein(RBP), respectively. The analysis of spearman rank correlation and multiple regression were used to investigate the relationships between age, urinary cadmium levels and renal injury biomarkers.

RESULTSThe cadmium levels in rice and vegetables of exposed group were 0.75 and 0.10 mg/kg, both were significantly higher than 0.07 and 0.01 mg/kg in the control group (Z values were -6.32 and -7.84, all P values < 0.001). The urinary cadmium level of exposed group was 8.29 µg/g · cr, which was higher than that of the control group 2.03 µg/g · cr with significant difference (Z value was -11.39, P < 0.001). After stratified the total population by age, the urinary cadmium level in 40-49 years, 50-59 years and ≥ 60 years subgroups were 7.22, 8.71, and 13.10 µg/g · cr, which both were significantly higher than 1.80, 2.04, and 2.05 µg/g · cr in the control group (Z values were -5.22, -7.41, and -7.14, all P values < 0.001). After stratified the total population by gender, the urinary cadmium level of male and female were 5.12 and 12.36 µg/g · cr, which both were significantly higher than 1.79 and 2.16 µg/g · cr in the control group (Z values were -7.68 and -9.03, all P values < 0.001). Comparing the differences of renal dysfunction biomarkers (NAG, β2-MG, RBP) between two groups. The level of urinary β2-MG and RBP of exposed group were 0.21 and 0.04 µg/g · cr, which were higher than 0.05 and 0.00 µg/g · cr of the control group with significant difference (Z value was -7.08 and -9.65, all P values < 0.001). Pearson correlation analysis showed that NAG, β2-MG and RBP were positively correlated with urinary cadmium and age, the correlation coefficients were 0.57, 0.49, 0.21 and 0.22, 0.26, 0.23 respectively (all P values < 0.001). After adjusting the effect of age, it was appeared that urinary cadmium levels contributed most to the alteration of NAG, β2-MG and RBP, the standardized regression coefficients were 0.57, 0.49 and 0.20 (all P values < 0.001), and suggested that the cadmium body burden was one of the most important factors for renal dysfunction.

CONCLUSIONResidents, who had cadmium contaminated rice and vegetables for a long time, would take the risk of increasing body burden of cadmium and urinary early biomarkers of renal tubular injury that referred to occurrence of renal dysfunction.

Adult ; Aged ; Cadmium ; Creatinine ; Environmental Exposure ; Epidemiologic Studies ; Female ; Food Contamination ; Humans ; Kidney Diseases ; Male ; Middle Aged ; Multivariate Analysis ; Oryza ; Risk ; Time ; Vegetables

Objective: To study the alterations of mitochondrial biological characteristics during both cellular replicative and premature senescence induced by hydrogen peroxide in human embryonic lung fibroblasts (HEFs). Methods: The premature senescence was induced by 400 μmol/L H₂O₂ once a day at the same time and with 2 hours each time, after four consecutive days the premature senescence models were classified into premature senescence initiation group (PSi) and premature senescence persistence group (PSp). Based on the life span of HEFs, the cell replicative senescence was divided into five groups included young-age (22 PDL), middle-age (35 PDL), replicative senescence (49 PDL), PSi and PSp. The mitochondrial distribution, relative content, adenosine triphosphate (ATP) contents, 8-hydroxydeoxyguanosine (8-OHdG) levels, the relative mitochondrial transcription factor A (TFAM) as well as mitochondrial DNA methyltransferase 1 (mtDNMT1) mRNA levels, mtDNA copy number, the relative TFAM protein level and the total enzyme activity of mitochondrial DNA methyltransferases (mtDNMTs) were detected in five senescence groups. Results: The mtDNA copy number, 8-OHdG contents, level of mtDNMT1 mRNA and mtDNMTs activity in 49 PDL group were higher than those in 22 PDL group (all P values <0.05); The level of 8-OHdG in PSi was higher than that in 22 PDL group (P<0.05); The ATP contents, mtDNA copy number, the mRNA and protein expression levels of TFAM and mtDNMTs activity of PSp were higher than those in 22 PDL group (all P values<0.05). Conclusion During the cellular senescence of HEFs, the higher mtDNA copy number and mtDNMTs activity were common features regardless of replicative or premature senescence, with possibility that oxidative stress was involved in modifying the occurrence of premature senescence.