Background As assessment of the peripapillary retinal nerve fiber layer (RNFL) has been an important approach for detecting structural damage in patients with glaucoma and myopia is a vital risk factor of primary open glaucoma,it is urgent to establish the correlation between RNFL thickness and myopia,not only for understanding the characteristics of RNFL with the change of the degree of myopia,but also for identifying those myopic patients with the early stage of glaucoma.Objective This study was to assess the influence of myopia for the thickness of RNFL measured by 3D optical coherence tomography (3D-OCT).Methods Two hundred and fifty-eight eyes of 258 myopic subjects from General Hospital of Ningxia Medical University were recruited.The myopic eyes were divided into low myopia group (42 eyes,-0.5 D ≤ SE ≤-3.0 D),middle myopia group (120 eyes,-3.0 D＜SE≤-6.0 D),high myopia group (58 eyes,-6.0 D＜SE≤-8.0 D) and extreme high myopia group (38 eyes,SE ＞-8.0 D).The peripapillary RNFL thickness profile including temporal,superior,nasal and inferior quadrants and each of the 12 clocks was measured by 3D-OCT.The measured values were compared among different degrees of myopia,and the correlations between spherical equivalent (SE) and axial length with RNFL thickness were analyzed using linear regression equation.Results The RNFL thickness was gradually declined with the increase of SE and elongation of axis,showing significant differences among the 4 groups in the superior,nasal and inferior quadrants and mean RNFL thickness (F=10.48,15.60,3.31,8.98,all at P＜0.05),but temporal RNFL thickness was increased with the SE rise,with markedly difference among the 4 groups (F =2.92,P =0.03) ; and RNFL thicknesses in the superior,nasal,inferior quadrants and mean RNFL thickness were evidently declined in the high and extreme high myopia group in comparison with low myopia group (all at P＜0.05).The overall RNFL parameters at 1:00,2:00,3:00,4:00,5:00,6:00,8:00,12:00 o'clock sectors were thinning as the increase of SE (all at P＜0.05) and unchanged at the 7:00,9:00,10:00,11:00 sectors in different SE groups (all at P＞ 0.05).Negative correlations were found between axial length or SE with the RNFL thicknesses at superior,nasal and inferior quadrants,average thickness as well as 1:00,2:00,3:00,4:00,5:00,6:00,11:00,12:00 o 'clock,and positive correlation was seen between the axial length or SE with the RNFL thicknesses at temporal quadrant.Conclusions The thickness of RNFL varys with the different degree of myopia and axial length.

Background Age-related macular degeneration (AMD) is the main cause of irreversible loss of central vision in old population.The incidence of AMD is increasing year by year,but the mechanism is not clearly understood.Objective This study was to investigate the association between genetic variants and the risk of AMD in Ningxia population.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and complied with the Helsinki Declaration.Written informed consent was obtained from each subject.One hundred and fifty patients with AMD and 145 ethnicity-and gender-matched controls were recruited in Ningxia Eye Hospital from January 2012 to March 2013.All individuals underwent comprehensive eye examinations and genomic DNA was prepared from peripheral blood.The single nucleotide polymorphisms (SNPs) of 8 susceptibility loci in four candidate genes,including complement factor H (CFH),complement factor B (CFB),age-related maculopathy susceptibility 2 (ARMS2) and high temperature required factor A1 (HTRA1),were genotyped with Mass Array and MALDI-TOF technique by Sequenom platform.The distribution of genotype was tested for Hardy-Weinberge equilibrium (HWE).The differences of genotype distribution of allele and haplotype frequencies were compared between patients and controls using chi-squared test and the P value was significant at ＜ 0.006 level after correction of age,and the relationship of genotype distribution with AMD was evaluated by Logistic regression analysis.Measures of linkage disequilibrium (LD) was carried out by Haploview.Results All the genetypes met HWE.Seven SNPs were found to be different in the genotypic distributions and allele frequencies between patients and normal controls (all at P＜ 0.05),however,after Bonferroni correction,the differences of only four SNPs were significant between the patients and controls in the genotype and allele distributions,including the SNPs of rs10737680 and rs1410996 in CFH gene,the SNP of rs10490924 in ARMS2 gene and SNP of rs11200638 in HTRA1 gene.The allele distributions of rs800292 (Pallele =0.006,OR =1.643,95 ％ CI:1.155-2.336) in CFH and rs641153 (Pallele =0.002,OR =0.273,95 ％ CI:0.120-0.620) in CFB were significantly associated with AMD.In addition,five SNPs in CFH gene were consisted of two blocks after analysis by Haploview.In addition,five SNPs in CFH were consisted of two blocks after analysis by Haploview.The first one SNPs (including rs551397 and rs800292) and another one SNPs (including rs12124794,rs10737680) and rs1410996 were in strong linkage disequilibrium (D'=1.00).After 50 000 permutations,the GC and AT haplotypes of the first block and the AAC,TCT and ACT haplotypes in the second block were significantly different between AMD patients and controls (P =0.010,0.010,0.001,0.041 and 0.033,respectively).The allel T of rs641153 was a protective factor of AMD (P=0.002,OR =0.273,95％ CI:0.120-0.620).Conclusions The SNPs rs10737680 and rs1410996 in CFH,rs10490924 of ARMS2 gene and rs11200638 of HTRA1 gene are associated with AMD in Ningxia population.

Background Age-related macular degeneration (AMD) is a heritable,progressive degenerative disorder that triggers central visual impairment.Research demonstrated that the single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor 1 (VEGFR1) gene is associated with AMD in different population.However,the results varied among diversified ethnic origin composition and distinct regions.Objective This study was to investigate the associations between the SNPs of VEGFR1 genetic variants along with smoking exposure and the risk of AMD in Hui and Han ethnics in the Ningxia population in China.Methods A case-control study was conducted.Four hundreds and thirty-two AMD patients including 325 Han ethnic patients and 107 Hui ethnic patients were recruited from March 2011 to June 2015,and 906 ethnicity-and gender-matched age-related cataract patients were contemporaneously recruited as control group,including 698 Han ethnic patients and 208 Hui ethnic patients.Periphery blood sample of 5 ml was collected from the subjects and genomic DNA was prepared.Eight tagging SNPs loci were acquired to cover rs2281827,rs3936415,rs7337610,rs7981680,rs9554320,rs9554322,rs9582036 and rs9943922,and the genotypes of SNPs were detected by using MassARRAYTM time-of-flight mass spectrometry system.Chi-square test and multi-factor Logistic regression analysis were utilized to estimate the discrepancy of allele frequency and genotype distribution in Hui and Han AMD patients.Moreover,the correlation of AMD with smoking and age statue were further analyzed.This study protocol complied with Helsinki Declaration and was approved by Ethic Committee of Ningxia Eye Hospital.Written informed consent was obtained before any relevant medical examination.Results There were significant differences in the age between AMD group and control group in both Han and Hui ethnicity (Han:P =0.000;Hui:P =0.009).The smoking exposure was significantly different between AMD group and control group in Han ethnicity (P =0.000),and smoking was the independent risk factor of AMD disease in Han ethnicity of N ingxia region (odds ratio [OR] =2.622,95％ confidence interval [CI]:1.899-3.619).The allele frequencies of SNPs were not significantly different in the AMD patients between Han and Hui ethnicity (all at P＞0.05).However,the allele frequencies and genotype distribution of rs7337610 and rs9554322 SNPs were significantly different between the AMD group and control group in both Han and Hui ethnicity (all at P=0.00).The genotype distribution of rs9582036 and rs9943922 SNPs was significantly different between the AMD group and control group in Han ethnicity (P=0.02,0.00).Allelic G of rs7337610 was the protective factor of AMD disease in Han and Hui ethnieity (OR=0.354,95％ CI:0.288-0.435;OR=0.446,95％ CI:0.315-0.632),while allelic C of rs9554322 was the risk factor of AMD disease in Han and Hui ethnicity (OR=1.671,95％ C1:1.234-2.262;OR=3.661,95％ CI:2.156-6.218).Allelic A of rs9582036 was the risk factor of AMD disease in Han ethnicity (OR =1.477,95％ CI:1.124-1.940).Conclusions Smoking is the independent risk component for Han population with AMD.Of the eight SNPs tagged,the genotypes and alleles of rs9554322 and rs7337610 seems to confer susceptibility to AMD in both Han and Hui ethnicity,the genotypes and alleles of rs9582036 and rs9943922 confer susceptibility to AMD in only Han ethnicity.

Background: Conjugated equine estrogen (CEE) treatment, a hormone replacement therapy, is restricted for use in perimenopausal and postmenopausal women because of security issues. Consequently, traditional Chinese herbal medicine has become an alternative choice for the patients with contraindications to hormone replacement therapy. Objective: To evaluate the efficacy and safety of Kuntai Capsule and CEE in treating cognitive function disorder and mental symptoms of early postmenopausal women. Design, setting, participants and interventions: A total of 57 cases of early postmenopausal women from Outpatient Department of West China Women and Children's Hospital were included. The subjects were randomly divided into two groups: Kuntai group with 28 cases and CEE group with 29 cases. The patients in Kuntai group received 6 g Kuntai capsules three times a day. The patients in CEE group received CEE 0.3 mg and 0.6 mg alternately once a day (average dose of 0.45 mg/d). The patients with intact uterus in CEE group were treated with 2 mg medroxyprogesterone acetate daily. Main outcome measures: In one-year treatment course, the recognition function and mental symptoms of each patient were investigated by questionnaires of Mini-Mental State Examination (MMSE), Kupperman, and quality of life (QOL) every three months. Both intention-to-treat (ITT) and per-protocol set (PPS) analyses were done. Results: The MMSE, Kupperman index and QOL scores at each time point were improved as compared with those before treatment (P<0.05), however there were no statistical differences between the two groups (P>0.05). The MMSE scores showed a tendency to escalate while mental symptoms investigated by Kupperman index and QOL scale showed a downtrend. No severe adverse effects occurred in the study phase and no statistical difference in incidence of side effects between the two groups was found except for vaginal bleeding. The incidence rates of vaginal bleeding in CEE and Kuntai groups were 39.3% and 11.1% respectively (P=0.029). Conclusion: Both Kuntai Capsule and CEE may contribute to maintain the cognitive function and ameliorate mental symptoms of early postmenopausal women.

Objective: To detect the alterations of telomerase activity and the expression for oxidative stress responsive genes related with senescence during cellular replicative senescence and hydrogen peroxide-induced premature senescence in human embryonic lung fibroblasts (HELFs) in vitro. Methods: The HELFs were divided into young cells (22 population doubling levels, 22PDL) , mid-aged cells (35PDL) and replicative senes-cent cells (49PDL) and premature senescent cells induced by H₂O₂(premature senescence, PS). The telomerase activity was detected by ELISA assay during cellular replicative and premature senescence. The mRNA level of oxidative stress responsive genes related with senescence for Foxo1, Foxo3, Pdx1, apoA-I and MMP1 was per-formed by RT-Q-PCR separately. Results: The mRNA level for Foxo1, Foxo3, apoA-I and Pdx1 was decreased separately during cellular replicative senescence compared to that in the young-stage cells with statistical signifi-cance (P<0.05). The expression of MMP1 was up-regulated 5.1-fold obviously (P<0.05). In premature senes-cence, the mRNA level was only decreased for Foxo1, Foxo3 and apoA-I, but up-regulated 2.3-fold and 6.2-fold for Pdx1 and MMP1 respcetively vs 22PDL significantly (P<0.05). The telomerase activity in young cells was not detected, and it increased in mid-aged cells and replicative senescence stages during cellular replicative se-nescence as compared to 22PDL with statistical significance (P<0.05). The telomerase activity in premature se-nescence was highly active. Conclusion The expression for genes related with senescence has differences be-tween replicative and premature senescence and hydrogen peroxide modifies their expression levels. The telomer-ase activity has been going up with increased PDLs.

Objective:To investigate the effects of disialyllacto-N-tetraose (DSLNT) on low molecular weight metabolic profile of intestinal contents in neonatal rats with necrotizing enterocolitis (NEC), in an attempt to explore the protective mechanism of DLSNT on intestinal tract of neonates.Methods:Immediately after birth, SD rats were randomly divided into the control group, the NEC group and the NEC+ DSLNT group according to random number tale method.All rats were hand-fed by special formula milk.Rats in the NEC group and NEC+ DSLNT group were exposed to hypoxia (950 mL/L nitrogen, 10 min, thrice per day) and cold stress (4 ℃, 10 min, thrice per day) for continuous 3 days to establish rodent NEC model.Rats in the NEC+ DSLNT group were hand-fed with special formula containing 300 μmol/L DSLNT.All rats were sacrificed after 72 h, and intestinal contents were collected from ileum and colon, followed by untargeted metabolomic determination with the ultrahigh-performance liquid chromatography Q extractive mass spectrometry (UHPLC-QE-MS) method.The terminal ileum was examined by hematoxylin-eosin staining.The metabolome data were analyzed with multivariable analysis using SIMCA 14.1.The metabolites that met both variable importance in the projection (VIP) >1 in the orthogonal partial least squares analysis (OPLS-DA) model and P<0.05 in the t-test were screened as differential metabolites between groups. Results:DSLNT reduced the incidence of NEC and pathological scores of ileum tissue from neonatal rats with NEC [3.0(2.0, 3.0) scores vs.1.0(1.0, 2.0) scores, P<0.01], and also significantly suppressed inflammatory infiltration.OPLS-DA model based on the metabolome data determined by UHPLC-QE-MS could perform effective discrimination between the NEC group and the control group, as well as the NEC+ DSLNT group and the NEC group.There were 64 differential metabolites between the NEC group and the control group (VIP value>1 and P<0.05 for the OPLS-DA model). These metabolites included docosahexaenoic acid (+ 288.0%, P=0.028), xanthine (+ 372.1%, P=0.007), L-arginine (+ 233.1%, P=0.027), L-leucine (+ 232.7%, P=0.015), N-acetylneuraminic acid (-41.6%, P=0.014), and so forth.These metabolites were associated with 34 metabolic pathways.Among them, such 6 pathways as arginine biosynthesis, arginine and proline metabolism were the most disturbed pathways affected by NEC.There were 15 diffe-rential metabolites in between NEC+ DSLNT group and NEC group, which included D-mannose (-73.5%, P=0.032), xanthine (-63.4%, P=0.008), linoleic acid (+ 137.9%, P=0.047), nicotinamide adenine dinucleotide (+ 278.2%, P=0.005), and so forth.These metabolites were mapped to 7 metabolic pathways, among them, linoleic acid metabolism pathway was the most relevant differential pathway affected by DSLNT.There were 8 overlapped meta-bolites in both comparison strategies, and the variation trend of these overlapped metabolites in the NEC group was significantly reversed by DSLNT supplementation. Conclusions:DSLNT could significantly attenuate the NEC pathological damage caused by hypoxia/cold stress in neonatal rats.This protective effect is associated with the improvement of the metabolic profile of intestinal contents caused by NEC and the modulation of the linoleic acid metabolic pathway.The early preventive supplementation of DSLNT is of great significance in maintaining neonatal intestinal homeostasis and preventing the process of NEC.

Objective:To discuss the change of ferritin ( Fn) and ferroportin expression quantity and time-related feature in the alveolar macrophages of mice , infected with different virulence of Mycobacterium Tuberculosis infected .Methods:The prepared bacte-ria of H37Rv or BCG were injected intravenously into the mice tails .On the day 1, 3, 5, 7, 9, 11, 13 and 15, the lavage fluids were collected and the alveolar macrophages were obtained from each group of mice .The expression of FPN and Fn were detected with ELISA and /or Western blot analysis .Results:The expression of Fn in the group of either H 37Rv or BCG infected mice was decreased on the day 7, 9 and 11, and was lowest on the day 7, which showed significantly statistical difference compared to that on the other days (P<0.05).The expression of FNP in the infected mouse macrophage was decreased gradually , which was obvious on the day 5. The expression levels reached to the lowest on the day 7 and 9.The expression was much lower than that in the negative control group (P<0.05).Conclusion:The expression of Fn and FPN in macrophages isolated from lungs of mice infected with Mycobacterium tu -berculosis H37Rv or BCG become decreased , and there is no difference between these two infected mouse groups .

Objective To explore the correlation between Mycobacterium tuberculosis ( MTB ) PhoPR two-component system and drug resistance of MTB clinical isolates widespread in Xinjiang region by analyzing the expression of PhoP gene and PhoR gene among different isolates .Methods Total RNA of MTB was extracted from drug-susceptible strains , the strains only resistant to a single first-line anti-TB drugs (INH, RFP, SM and EB) and multidrug-resistant (MDR) strains, respectively.The purity of total RNA was checked by agarose gel electrophoresis .The expressions of PhoP gene and PhoR gene were quantified by using SYBR Green I qRT-PCR and the differences of their gene expression in different isolates were ana-lyzed.Results Compared with the drug-susceptible strains of MTB, the expression of PhoP gene was up-regulated for about 1.48 times in MTB strains resistant to RFP (RFP-MTB) and 2.74 times in MDR strain (P<0.05).Compared with MDR strain, the expressions of PhoP gene in the isolates resistant to INH (IN-HMTB), RFP (RFP-MTB), SM (SM-MTB) and EB (EB-MTB) were down-regulated for 0.70, 0.50, 0.25 and 0.21 times respectively.The expressions of PhoR gene were down-regulated for 0.36, 0.54, 0.35 and 0.19 times, respectively (P<0.05).The expressions of PhoR gene in the isolates of INH-MTB, RFP-MTB, SM-MTB and EB-MTB were up-regulated for 6.33, 4.56, 2.34, 1.85 and 9.06 times, respectively as compared with the drug-susceptible strains (P<0.05).Conclusion Significant differences of PhoR gene and PhoP gene expressions were observed among drug-susceptible strains , INH-MTB, RFP-MTB, SM-MTB, EB-MTB and MDR strains.Therefore, the Mycobacterium tuberculosis PhoPR two-component system is asso-ciated with the drug resistance of MTB strains prevalent in Xinjiang region .

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species of Boraginaceae and Lamiaceae. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the H22-xenograft models by inhibiting the inflammatory cytokines and NF-κB p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given to H22 tumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of CD4⁺/CD8⁺ and the secretion of interleukin (IL)-2 and interferon-γ, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating Bax and Caspase-3 and down-regulating Bcl-2. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.
Animals ; Apoptosis ; Boraginaceae ; Carcinoma, Hepatocellular ; Caspase 3 ; Cytokines ; Interleukin-10 ; Interleukin-6 ; Interleukins ; Lamiaceae ; Mice ; STAT3 Transcription Factor ; Therapeutic Uses ; Tumor Microenvironment

Objective: To analysis the genotype and phenotype of hereditary retinal diseases (HRD) which are easily misdiagnosed as amblyopia. Methods: A case-control study was designed.The patients with HRD who were misdiagnosed as amblyopia in Ningxia Eye Hospital from January to December, 2017 were recruited in this study.The clinical medical history and ophthalmic examinations of patients and their family members were recorded, and family maps were drawed.Peripheral venous blood (5 ml) from each patient and their family members was collected, and genomic DNA was extract.The target sequence capture sequencing technology was used to detect the genetic testing in serum of the patient, and the pathogenic mutation site was determined by Sanger sequencing and co-segregation verification.Genetic testing results with related ophthalmic examination were considered together to analyze the relationship between genotype and phenotype.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject or the guardian prior to entering study cohort.This study protocol was approved by Ethic Committee of People's Hospital of Ningxia Hui Autonomous Region Hospital (No.2016018). Results: Twenty-two patients with HRD were enrolled in the study, including 10 Stargardt disease (STGD), 8 cases of cone dystrophy (COD) or cone and rod dystrophy (CRD), and 5 cases of familial exudative vitreoretinopathy(FEVER). Nine patients were detected to have pathogenic mutations, and the positive rate was 40.9%, of which 4 patients with STGD carried mutation gene, including ABCA4 and PROM1 genes; mutations in RPGR, PROM1 and GUCY2D genes were detected in 3 patients with COD or CRD; TSPAN12 gene mutation were detected in 2 patients with FEVER.Eleven mutation sites were detected, 4 of which were newly discovered mutation sites.All of the patients in 9 HRD families developed symptoms during adolescence.At the early stage of the disease, there was severe damage to the eyesight, but the fundus was normal or only slightly abnormal.As the disease progressed, the fundus changes were characteristic, and there were clinical phenotypic overlap between some diseases.All family genotypes and clinical phenotypes were co-separated. Conclusions The main pathogenic gene of STGD is ABCA4 gene, and PROM1 gene can also cause partial STGD; COD and CRD have similar clinical manifestations, and the pathogenic genes also cross each other, and the genetic pattern is diverse; FEVER caused by mutation of TSPAN12 gene is autosomal dominant, and the mutation type has missense mutation and frameshift mutation.HRDs lack typical early clinical signs, and genetic diagnosis can provide pre-symptomatic diagnosis.