Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation

PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease.However,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration.Additionally,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit neurodegeneration.In our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent brains.To extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig tissues.In contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig tissues.Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain.Consistently,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD.These findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.

姜黄素改善小鼠功能性胃排空障碍的研究

目的探讨姜黄素灌胃是否通过影响乙酰胆碱途径改善小鼠胃排空障碍。方法利用一氧化氮NO前体盐酸左旋精氨酸(L-精氨酸)和乙酰胆碱受体阻断剂阿托品分别复制小鼠功能性胃排空障碍模型。选取健康昆明种雄性小鼠54只,分为对照组、姜黄素组、L-精氨酸组、阿托品组、姜黄素+(L-精氨酸)联合组、姜黄素+阿托品联合组,共6组,每组9只。实验方法 :姜黄素混悬液灌胃,共15 d;L-精氨酸混悬液于第11天起额外灌胃,共5 d;阿托品混合液于小鼠测量胃排空前40 min腹腔注射1次。其余组用溶媒溶液按照同样方式灌胃以及生理盐水腹腔注射作为对照。结果与对照组比较,L-精氨酸组和阿托品组小鼠胃排空率均降低,乙酰胆碱酯酶mRNA相对定量及蛋白表达均下降,乙酰胆碱酯酶活力降低,差异均有统计学意义(P <0.05);与L-精氨酸组比较,姜黄素+(L-精氨酸)联合组小鼠胃排空率升高,乙酰胆碱酯酶m RNA相对定量、蛋白表达及乙酰胆碱酯酶活力均改善,差异有统计学意义(P <0.05);与阿托品组比较,姜黄素+阿托品联合组小鼠胃排空率升高,乙酰胆碱酯酶m RNA相对定量、蛋白表达及乙酰胆碱酯酶活力也改善,差异有统计学意义(P <0.05);单用姜黄素组与对照组比较,上述指标差异无统计学意义(P>0.05)。结论姜黄素通过影响乙酰胆碱释放改善外源性NO和阿托品造成功能性胃排空障碍。

Experiment and numerical simulation of two-phase flow in oxygen enriched side-blown furnace

Taking an oxygen enriched side-blown furnace as the prototype,a hydraulic model was established according to the similarity principle.The influence of three factors on the gas-liquid two-phase flow was analyzed,i.e.the airflow speed,the submerged depth and the downward angle of the nozzle.A numerical simulation of the hydraulic model was carried out trying to find the suitable turbulence model which can describe the side-blown two-phase flow correctly by comparing the simulation results with the experimental data.The experiment shows that the airflow speed has a great influence on the flow of the water.The submerged depth of the nozzle has a relatively smaller influence on the penetration depth and the surface fluctuation height in the liquid phase.When the nozzle is at a downward angle of 15°,the penetration depth and the surface fluctuation height are reduced.It is concluded that the numerical results with the realizable k-εturbulence model are the closest to the experiment for the penetration depth,the surface fluctuation height and the bubble scale.

Polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 and esophageal cancer risk in Southeast Chinese males

AIM： To evaluate the impact of alcohol dehydrogenase-2 （ADH2） and aldehyde dehydrogenase-2 （ALDH2） polymorphisms on esophageal cancer susceptibility in Southeast Chinese males.METHODS： Two hundred and twenty-one esophageal cancer patients and 292 healthy controls from Taixing city in Jiangsu Province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase chain reaction and denaturing high-performance liquid chromatography. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （CI）.RESULTS： The ADH G allele carriers were more susceptible to esophageal cancer, but no association was found between ADH2 genotypes and risk of esophageal cancer when disregarding alcohol drinking status. Regardless of ADH2 genotype, ALDH2G/A or A/A carriers had significantly increased risk of developing esophageal cancer, with homozygous individuals showing higher esophageal cancer risk than those who were heterozygous. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk; the OR was 3.05 （95% CI： 2.49-6.25）. Compared with non-drinkers carrying both ALDH2 G/G and ADH2 A/A, drinkers carrying both ALDH2 A allele and ADH2 G allele showed a significantly higher risk of developing esophageal cancer （OR = 8.36, 95% CI： 2.98-23.46）.CONCLUSION： Both ADH2 G allele and ALDH2 A allele significantly increase the risk of esophageal cancer development in Southeast Chinese males. ALDH2 A allele significantly increases the risk of esophageal cancer development especially in alcohol drinkers. Alcohol drinkers carrying both ADH2 G allele and ALDH2 A allele have a higher risk of developing esophageal cancer.

CYP2E1 RsaⅠpolymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking

AIM： To investigate associations between the Rsa I polymorphism of CYP2E1 and risk of colorectal cancer. METHODS： A case-control study was conducted with 315 colorectal cancer cases （105 colon, 210 rectal） and 439 population-based controls in Jiangsu Province of China. Genomic DNA samples were assayed for restriction fragment length polymorphisms in CYP2E1 by PCR amplification followed by digestion with Rsa I. Information on smoking and alcohol drinking was collected using a questionnaire. Odds ratios （ORs） were estimated with an unconditional logistic model. RESULTS： The proportional distribution of the CYP2E1 Rsa I c1/c1, c1/c2 and c2/c2 genotypes were 61.4%, 35.6% and 3.0% in controls, 60.6%, 33.7% and 5.8% in colon cancer cases, and 58.4%, 34.0% and 7.7% in rectal cancer cases, respectively. A significant differencewas noted between controls and rectal cancer cases （P = 0.029）, the c2/c2 genotype being associated with elevated OR （adjusted age, sex and status of the smoking and alcohol drinking） for rectal cancer （1.64, 95% CI, 1.12-2.41, vs cl allele carriers）, but not for colon cancer. In interaction analysis between the CYP2E1 Rsa I genotype and smoking and drinking habits, we found a significant cooperative action between the c2/c2 genotype and alcohol drinking in the sex-, age-adjusted ORs for both colon （4.74, 95% CI, 1.10-20.40） and rectal （5.75, 95% CI, 1.65-20.05） cancers. Among nonsmokers, the CYP2E1 Rsa I c2/c2 genotype was also associated with elevated ORs in the two sites （1.95, 95% CI, 0.99-3.86 and 2.30, 95% CI, 1.32-3.99）. CONCLUSION： The results of the present study suggest that the CYP2E1 c2/c2 genotype increases susceptibility to rectal cancer and the gene-environmental interactions between the CYP2E1 polymorphism and smoking or alcohol drinking exist for colorectal neoplasia in general.

Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

AIM: To evaluate the relationship between drinking and polymorphisms of alcohol dehydrogenase 2 (ADH2) and/or aldehyde dehydrogenase 2 (ALDH2) for risk of colorectal cancer (CRC) in Chinese males. METHODS: A case-control study was conducted in 190 cases and 223 population-based controls. ADH2 Arg47His (G-A) and ALDH2 Glu487Lys (G-A)genotypes were identified by PCR and denaturing high-performance liquid chromatography (DHPLC). Information on smoking and drinking was collected and odds ratio (OR) was estimated. RESULTS: The ADH2 A/A and ALDH2 G/G genotypes showed moderately increased CRC risk. The age- and smoking-adjusted OR for ADH2 A/A relative to G/A and G/G was 1.60 (95% CI=1.08-2.36), and the adjusted OR for ALDH2 G/G relative to G/A and A/A was 1.79 (95% CI=1.19-2.69). Signif icant interactions between ADH2, ALDH2 and drinking were observed. As compared to the subjects with ADH2 G and ALDH2 A alleles, those with ADH2 A/A and ALDH2 G/G genotypes had a signif icantly increased OR (3.05, 95% CI= 1.67-5.57). The OR for CRC among drinkers with the ADH2 A/A genotype was increased to 3.44 (95% CI= 1.84-6.42) compared with non-drinkers with the ADH2 G allele. The OR for CRC among drinkers with the ALDH2 G/G genotype was also increased to 2.70 (95% CI= 1.57-4.66) compared with non-drinkers with the ALDH2 A allele. CONCLUSION: Polymorphisms of the ADH2 and ALDH2 genes are significantly associated with CRC risk. There are also signifi cant gene-gene and gene- environment interactions between drinking and ADH2 and ALDH2 polymorphisms regarding CRC risk in Chinese males.

磁性压迫融合技术在原位肝移植术后胆道吻合口重度狭窄再通畅中的应用与配合技巧

目的探讨磁性压迫融合技术(MCA)在原位肝移植(OLT)后胆道吻合口重度狭窄中的应用及配合技巧。方法回顾性分析1例OLT术后胆道吻合口重度狭窄的患者临床资料,该患者采用常规方法治疗失败后改用MCA治疗,在X线监视下通过经皮经肝穿刺胆道成像(PTC)和内镜下逆行胰胆管造影术(ERCP),分别在狭窄近端与远端各置入1枚磁铁,确认2枚磁铁位置及轴向与胆管长轴平行、磁铁近端及远端在同一条直线上后,缓慢释放磁铁。结果 7 d后2枚磁铁完全融合并移位,PTC证实胆管狭窄段已再通。再经ERCP去除磁铁,并置入胆道全覆膜金属支架。结论 MCA用于常规方法治疗失败的重度胆管狭窄和完全性胆道梗阻患者,可压迫狭窄部位组织,形成新通道,使胆管狭窄再通。

LKB1在鼻咽癌中的表达及与化疗敏感性的关系

目的研究鼻咽癌(NPC)组织中LKB1的表达,分析其与临床病理因素、化疗敏感性及预后的关系。方法采用免疫组织化学En Vision二步法检测74例NPC组织标本中LKB1的表达,根据其表达水平将标本分为LKB1低表达组和LKB1高表达组。采用ATP生物荧光肿瘤体外药敏检测技术体外检测NPC患者肿瘤细胞对8种常见化疗药物的敏感性。结合患者随访资料,分析LKB1表达与临床病理因素、化疗敏感性及预后的关系。结果在NPC组织中,LKB1蛋白在细胞核和细胞质均有表达,呈棕黄色;LKB1高、低表达组间患者年龄、病理组织学类型、TNM分期及临床分期比较,差异无统计学意义(P>0.05),仅性别比较差异有统计学意义(P <0.05)。NPC细胞对8种化疗药物敏感性不同(P <0.05)。在8种化疗药物中,仅LKB1低表达组的.环磷酰胺耐药率高于LKB1高表达组(P <0.05),其余差异无统计学意义(P>0.05)。LKB1低表达组患者的死亡率高于高表达组(P<0.05)。两组患者转移和复发率比较,差异无统计学意义(P>0.05)。LKB1低表达组患者的总生存率低于高表达组(P <0.05)。两组间无进展生存率比较,差异无统计学意义(P>0.05)。结论 LKB1表达水平与NPC患者的生存率有关,并且可能与环磷酰胺的耐药有关。