Histone methylation in pancreatic cancer and its clinical implications.

Pancreatic cancer (PC) is an aggressive human cancer. Appropriate methods for the diagnosis and treatment of PC have not been found at the genetic level, thus making epigenetics a promising research path in studies of PC. Histone methylation is one of the most complicated types of epigenetic modifications and has proved crucial in the development of PC. Histone methylation is a reversible process regulated by readers, writers, and erasers. Some writers and erasers can be recognized as potential biomarkers and candidate therapeutic targets in PC because of their unusual expression in PC cells compared with normal pancreatic cells. Based on the impact that writers have on the development of PC, some inhibitors of writers have been developed. However, few inhibitors of erasers have been developed and put to clinical use. Meanwhile, there is not enough research on the reader domains. Therefore, the study of erasers and readers is still a promising area. This review focuses on the regulatory mechanism of histone methylation, and the diagnosis and chemotherapy of PC based on it. The future of epigenetic modification in PC research is also discussed.

Investigation on Demodex infections among university students in Kunming City / 中国血吸虫病防治杂志

Objective To investigate the prevalence of Demodex infection among students in Kunming Medical University, and identify the factors affecting Demodex infections, so as to provide the evidence for the development of the strategy for the prevention of Demodex infections. Methods A total of 1 463 students from Grade 2014 who studied Medical Parasitology in Kunming Medical University were included in the survey. Demodex was examined in students’facial skin using the cellophane tape method, and the species was identified using microscopy. The students’gender, ethnicity, place of origin and skin type were captured using a questionnaire survey. Results The overall prevalence of Demodex infections was 19.07% (279/1 463) on the facial skin among the university students, and a higher prevalence was seen in girls (21.16%, 183/865) than in boys (16.05%, 96/598) (χ2 =5.965,P <0.05).TheprevalenceofDemodex infectionswas18.33%(66/360)amongminorethnicstudents,andnoethnicity-specific prevalence was seen (P > 0.05). Demodex folliculorum was the predominant species, with a prevalence of 50.54% (141/279), and mild infections were predominant among all infections (96.77%, 270/279), without severe infections seen. Multivariate nonconditional logistic regression analysis revealed that gender and roommates with Demodex infections were risk factors of Demodex infections, and the infection was not associated with ethnicity, place of origin or skin type. There were only 2.53% (37/1 463) of the subjects understanding the knowledge pertaining to the prevention and control of Demodex infection. Conclusions A relatively low prevalence of Demodex infection is detected in the facial skin of students from Kunming Medical University, and Demodex infection is associated with gender and roommates with Demodex infections. Health education pertaining to the prevention of Demodex infections is suggested to be intensified among university students.

Azithromycin inhibits muscarinic 2 receptor-activated and voltage-activated Ca2+ permeant ion channels and Ca2+ sensitization, relaxing airway smooth muscle contraction.

Azithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch-clamp techniques. AZM completely inhibited acetylcholine (ACH)-induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L-type voltage-dependent Ca2+ channels (LVDCCs)), Pyr3 (selective inhibitor of TRPC3 and/or STIM/Orai channels, which are nonselective cation channels (NSCCs)), and Y-27632 (selective inhibitor of Rho-associated kinase (ROCK)). Moreover, LVDCC- and NSCC-mediated currents were inhibited by AZM, and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca2+ permeant ion channels, M2 receptors, and TRPC3 and/or STIM/Orai, which decreased cytosolic Ca2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD.

The change of COX-2 expression in rats with stress urinary incontinence and its significance / 医学研究生学报

Objective　There are a few researches on the mechanism of stress urinary incontinence (SUI). The article aimed to examine the changes of COX-2 expression in the urethra, vagina and urethral smooth muscle of SUI rat mode to evaluate the effect of estrogen on COX-2 expression. Methods　Sixty unbearing healthy female SD rats and fifteen male SD rats were gathered for spontaneous delivery. SUI rat models were constructed using expanded vagina, expanded vagina + ovariectomy respectively after delivery, which were expanded vagina group and expanded vagina + ovariectomy group. Six successfully modeled rats were chosen for the follow-up experiment. SD rats modeled after normal pregnancy were the control group. Sneezing experiment and urodynamic examination were used to examine the maximum bladder capacity (MBC) and abdominal leak point pressure (ALPP). Fluorescent quantitative PCR and western blot were applied to detect the expressions of COX-2 mRNA and protein, and immunohistochemistry was used to detect the expressions of COX-2 in urethra, vagina and urethral smooth muscle. Results Compared with control group, ALPP in two experimental groups were significantly decreased, among which ALPP in expanded vagina + ovariectomy group was significantly decreased in comparison to expanded vagina group(P<0.05). Compared with control group, the expressions of COX-2 mRNA and protein in expanded vagina group and expanded vagina+ovariectomy group were significantly higher, among which the figures in expanded vagina+ovariectomy group were significantly higher than those in expanded vagina group(P<0.05). The result of immunohistochemistry showed staining intensity integral expression of COX-2 in vaginal tissues of control group, expanded vagina group and expanded vagina+ovariectomy group were 0.50±0.54, 5.55±0.54, 9.33±0.81, so differences between any two groups were of statistical significance(P<0.05); staining intensity integral expression of COX-2 in urethral smooth muscle of control group, expanded vagina group and expanded vagina+ovariectomy group were 0.66±0.51, 5.33±0.51, 8.50±0.54, so differences between any two groups were of statistical significance (P<0.05). Conclusion The expression of COX-2 was related to the mechanism of SUI. The decrease of estrogen may increase the expression of COX-2 in SUI rats, which supports the treatment of SUI.

Phenotype Analysis of 78 Cases of Abnormal Hemoglobin E Homozygotes / 中国实验血液学杂志

OBJECTIVE@#To analyze the hematological characteristics of HbE homozygotes.@*METHODS@#Complete blood cells count and hemoglobin electrophoresis were used for phenotypic analysis of 78 cases with HbE homozygotes from Yunnan province, China. The PCR-fluorescence hybridization was used to detect the common gene mutation of thalassemia. The hematological indexes, including MCV, MCH, Hb, HbA2, HbF and HbE were statistically analyzed between groups with different sex, ages and compound α thalassemia status.@*RESULTS@#In HbE homozygotes (HbEE), 89.5% (17/19) children presented mild to moderate microcytic hypochromic anemia, and 10.5% of them presented moderate anemia. 39.6% (19/48) of women with HbEE developed mild anemia ,while 11 cases of male with HbE homozygotes were asymptomatic. The levels of MCV and MCH in HbE homozygotes increased by co-inheritance of α thalassemia mutation.@*CONCLUSION@#The clinical phenotype of HbE homozygote shows highly heterogeneous, which is relates with age, sex and co-inheriting α-globin genotypes. In Hb EE women and children are more likely to develop mild to moderate anemia. The microcytic hypochromic anemia degree is relieved when HbEE combined with α- thalassemia.

Polygonum aviculare L. extract and quercetin attenuate contraction in airway smooth muscle.

Because of the serious side effects of the currently used bronchodilators, new compounds with similar functions must be developed. We screened several herbs and found that Polygonum aviculare L. contains ingredients that inhibit the precontraction of mouse and human airway smooth muscle (ASM). High K+-induced precontraction in ASM was completely inhibited by nifedipine, a selective blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). However, nifedipine only partially reduced the precontraction induced by acetylcholine chloride (ACH). Additionally, the ACH-induced precontraction was partly reduced by pyrazole-3 (Pyr3), a selective blocker of TRPC3 and stromal interaction molecule (STIM)/Orai channels. These channel-mediated currents were inhibited by the compounds present in P. aviculare extracts, suggesting that this inhibition was mediated by LVDCCs, TRPC3 and/or STIM/Orai channels. Moreover, these channel-mediated currents were inhibited by quercetin, which is present in P. aviculare extracts. Furthermore, quercetin inhibited ACH-induced precontraction in ASM. Overall, our data indicate that the ethyl acetate fraction of P. aviculare and quercetin can inhibit Ca2+-permeant LVDCCs, TRPC3 and STIM/Orai channels, which inhibits the precontraction of ASM. These findings suggest that P. aviculare could be used to develop new bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease.

Distinct Effects of Ca2+ Sparks on Cerebral Artery and Airway Smooth Muscle Cell Tone in Mice and Humans.

The effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone, as well as the underlying mechanisms, are not clear. In this investigation, we elucidated the underlying mechanisms of the distinct effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone. In CASMCs, owing to the functional loss of Ca2+-activated Cl- (Clca) channels, Ca2+ sparks activated large-conductance Ca2+-activated K+ channels (BKs), resulting in a decreases in tone against a spontaneous depolarization-caused high tone in the resting state. In ASMCs, Ca2+ sparks induced relaxation through BKs and contraction via Clca channels. However, the integrated result was contraction because Ca2+ sparks activated BKs prior to Clca channels and Clca channels-induced depolarization was larger than BKs-caused hyperpolarization. However, the effects of Ca2+ sparks on both cell types were determined by L-type voltage-dependent Ca2+ channels (LVDCCs). In addition, compared with ASMCs, CASMCs had great and higher amplitude Ca2+ sparks, a higher density of BKs, and higher Ca2+ and voltage sensitivity of BKs. These differences enhanced the ability of Ca2+ sparks to decrease CASMC and to increase ASMC tone. The higher Ca2+ and voltage sensitivity of BKs in CASMCs than ASMCs were determined by the ß1 subunits. Moreover, Ca2+ sparks showed the similar effects on human CASMC and ASMC tone. In conclusions, Ca2+ sparks decrease CASMC tone and increase ASMC tone, mediated by BKs and Clca channels, respectively, and finally determined by LVDCCs.

Association of polymorphisms of PTPN22 and PADI4 genes with rheumatoid arthritis in Yunnan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between genetic polymorphisms of 7 SNPs in PTPN22 and PADI4 genes and susceptibility to rheumatoid arthritis in Yunnan.</p><p><b>METHODS</b>A case-control study was carried out on 192 patients of rheumatoid arthritis and 288 healthy controls. Genotypes of rs33996649 and 1858 loci within PTPN22 gene, and rs11203366 and rs874881 loci within PADI4 gene were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotypes of rs1635579, rs2428736 and rs2240340 in PADI4 gene were determined with pyrosequencing.</p><p><b>RESULTS</b>The frequencies of alleles and genotypes of rs2240340 locus in PADI4 gene showed a significant difference between rheumatoid arthritis and controls in Yunnan population (P U+003C 0.05).</p><p><b>CONCLUSION</b>Our results suggested that rs2240340 in PADI4 gene is associated with susceptibility to rheumatoid arthritis in Yunnan.</p>

Association between polymorphisms of PSMB8, PSMB9 and TAP2 genes with rheumatoid arthritis in ethnic Han Chinese from Yunnan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between single nucleotide polymorphisms (SNPs) of PSMB8, PSMB9 and TAP2 genes and rheumatoid arthritis (RA) in ethnic Han Chinese from Yunnan.</p><p><b>METHODS</b>A case-control study was carried out using 177 RA patients and 288 healthy controls. Genotypes of rs2071543, rs55745125 and rs138635403 loci of PSMB8 gene, and rs17587 locus of PSMB9 gene were determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). And a polymerase chain reaction amplification refractory mutation system (ARMS-PCR) was used for typing rs2228396 locus of TAP2 gene. Genotypic and allelic frequencies were calculated. An Epi Info 7 software was used to calculate the Odds Ratio (OR) of above SNPs between the two groups.</p><p><b>RESULTS</b>Allelic and genotypic frequencies of rs138635403 and rs17587 loci have differed significantly between the two groups (P<0.05). The frequency of GG genotype for rs17587 locus was also higher in the RA group (0.672) compared with control group (0.524) (OR=1.862, 95%CI: 1.261-2.749).</p><p><b>CONCLUSION</b>Genetic polymorphisms of rs17587 appeared to be associated with RA in ethnic Han Chinese from Yunnan.</p>

Association between Alu insertion polymorphisms and HLA class I alleles in Chinese Lisu and Nu ethnic populations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the frequencies of HLA-Alu repeat polymorphisms (AluMICB, AluTF, AluHJ, AluHG and AluHF) in Chinese Lisu and Nu ethnic populations.</p><p><b>METHODS</b>The frequencies of HLA-Alu repeat polymorphisms in above populations were determined with polymerase chain reaction (PCR). The associations between HLA-Alu repeat polymorphisms and HLA-A, HLA-B and HLA-C alleles were also analyzed. Phylogenetic trees were constructed with genetic distance calculated from the frequencies of HLA-Alu repeat polymorphisms.</p><p><b>RESULTS</b>Frequencies of AluTF*2 and AluHF*2 were different between the two populations (P< 0.05), while those of other three insertions were similar. The strength of association between HLA-Alus and HLA alleles were different (P< 0.05) in the two populations. Although AluMICB*2 were associated with HLA-B*56:01 in both populations, the association was stronger in Lisu population (74.0%) but moderate in Nu population (30.7%). HLA-Alus were associated with particular HLA subtypes, e.g., AluHG*2 with certain HLA-A*02 subtypes. By phylogenetic analysis, Lisu and Nu were clustered together with southern Chinese and Thai populations.</p><p><b>CONCLUSION</b>The distribution of HLA-Alus and the strength of associations between HLA-Alus and HLA class I alleles have varied between the two populations. Study of this association may facilitate identification of origins, evolution, progenitor haplotypes and recombination within the HLA class I region.</p>

Association between gene polymorphisms and myocardial infarction in Han Chinese of Yunnan province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine frequencies of genetic polymorphisms of coagulation factor VII (FVII), coagulation factor FXII (FXII), fibrinogen (FBG) and 9p21 in ethnic Han Chinese from Yunnan province, and to assess the association between such polymorphisms and onset of myocardial infarction (MI).</p><p><b>METHODS</b>One hundred and forty-two patients with MI and 192 healthy controls were analyzed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and pyrosequencing were used to determine the genotypes of FVII, FXII, FBG and 9p21.</p><p><b>RESULTS</b>No significant difference was found in the frequencies of R353Q, 5'F7, C46T, -148C/T, rs1333049 and rs4977574 loci between the two groups (P> 0.05). However, the frequencies of AA of -455G/A, T and TT of rs1333040, T and TT of rs10116277 and G and GG of rs2383207 were significantly higher in MI group compared with the controls (P< 0.05), whilst the frequencies of CT of rs1333040 and GT of rs10116277 were significantly lower in MI group compared with the controls (P<0.05).</p><p><b>CONCLUSION</b>Polymorphisms of FVII, FXII, -148C/T of FBG and rs1333049 of 9p21 were not associated with myocardial infarction. Polymorphisms of -455G/A of FBG and rs1333040, rs10116277 and rs2383207 of 9p21 may be associated with MI in ethnic Han Chinese from Yunnan province.</p>

Detection and preliminary study of a family carrying a CCR5Δ32 deletional mutation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the frequencies of chemokine (C-C motif) receptor 5 gene (CCR5)Δ32 deletional mutation of in Han and Dai populations from Yunnan province. Immortalized cell lines were derived from a family carrying the CCR5Δ32 mutation.</p><p><b>METHODS</b>Blood samples of 346 Han and 355 Dai individuals were collected for genotyping. The coding regions of CCR5 gene were amplified with PCR followed by agarose gel electrophoresis. Suspected mutations were verified with DNA sequencing. Immortalized cell lines were constructed by using Epstain Barr virus and cyclosporine A. The difference between the cell lines and original blood samples was verified with PCR.</p><p><b>RESULTS</b>One ethnic Han individual was confirmed to be heterozygous for a deletional mutation by sequencing, which has led to discovery of a family with CCR5Δ32. Nine immortalized cell lines were established from this family, and no difference between the cell lines and original blood samples was detected by PCR.</p><p><b>CONCLUSION</b>Together with previous reports, this study has indicated a significant difference in CCR5Δ32 among different ethnic groups in China. Established immortalized cell lines can also provide material for future research.</p>

Association of EMILIN1 gene polymorphism with essential hypertension in Mongolian / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship between genetic polymorphisms of 3 single nucleotide polymorphisms (SNPs) in the elastin microfibril interfacer 1 (EMILIN1) gene and essential hypertension.</p><p><b>METHODS</b>A case-control study was conducted in which 201 hypertensive patients and 202 healthy controls in Mongolian population were enrolled, and the genotypes of rs3754734, rs2011616 and rs2304682 loci were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing techniques.</p><p><b>RESULTS</b>There were significant differences in the frequencies of alleles and genotypes for the rs2304682 between the hypertensives and normotensives in the population (P<0.05). The frequency of the G-G haplotype established by rs3754734 and rs2304682 was significantly higher in the hypertensive patients (P<0.05). The frequencies of alleles and genotypes for the rs2304682 also had significant differences between the group with high diastolic blood pressure and normal diasto lic blood pressure (P<0.05).There were no significant differences in the frequencies of alleles and genotypes for the 3 SNPs between the group with high systolic blood pressure and normal systolic blood pressure (P>0.05).</p><p><b>CONCLUSION</b>The rs2304682 locus in the EMILIN1 gene, as well as the haplotypes G-G constructed using rs3754734 and rs2304682, may associate with the susceptibility of essential hypertension in the Mongolian population. Also, rs2304682 may associate with the level of the diastolic blood pressure.</p>