Chronic infection with hepatitis B /C virus (HBV /HCV)is a widespread epidemic in China.The single nucleotide polymorphisms (SNPs)in interleukin 28B (IL28B)gene have been associated with chronic HBV /HCV infection and response to interferon therapy.The biological functions and characteristics of IL28B are elaborated on,the associations between HCV infection and IL28B SNPs are commented on,and current reports of associations between HBV infection and IL28B SNPs are reviewed.The results support the associations between IL28B SNPs and disease progression of HCV infection or the curative effect of interferon therapy.However,contradictive results have been obtained in studies of associations between IL28B SNPs and disease progression of HBV infection,the incidence of liver cirrhosis and primary liver cancer after HBV infection,or the curative effect of interferon therapy,so further investigation is needed.

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.

Objective To investigate the effect of statin on trabecular bone microstructure by using trabecular bone score (TBS), a new type of bone microstructure evaluation index. Methods A total of 253 middle and aged patients hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2014 and March 2016 were retrospectively analyzed. According to whether statin was used or not, patients were divided into two groups: 90 patients in the statin use group (statin was use for more than 1 year) and 163 in the control group (not taken any statin). Serum biochemical indicators, such as triacylglycerol, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, alkaline phosphatase, fasting blood glucose and 25 hydroxy vitamin D, were compared between the two groups. Dual energy X-ray absorptiometry (DXA) was used to measure the bone mineral density (BMD) of lumbar spine and femoral neck. TBS was calculated with TBS iNsight? software, and the DXA image of lumbar spine were analyzed. Results Values of total cholesterol and low density lipoprotein cholesterol were significantly lower in statin group compared with those of control group (P<0.001), while no significant differences in other biochemical indicators between two groups (P>0.05). There was higher lumbar spine BMD statin group compared to that of control group (g/cm2:1.04 ± 0.19 vs. 0.96 ± 0.14, P<0.01). There was higher lumbar spine BMD and higher TBS (1.31±0.09 vs. 1.26±0.09, P<0.01) in statin group than that of control group. There was no difference in the femoral neck BMD between the two groups (P>0.05). Conclusion Statin increases lumbar spine BMD and improves trabecular bone microstructure in middle and aged people.

OBJECTIVETo study mRNA expression of receptor activator nuclear factor kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG) in peri-implant tissue during unloading period.

METHODSAn animal model of dental implant was established in 6 male Beagle dogs of 1-2 years old. Bone remodeling was tested at 3, 7, 15, 30, 60 and 90 days since the placement of implants. RANKL and OPG mRNA expression were quantified by real-time polymerase chain reaction (PCR). Then mandibular bones were taken out and the morphological changes were observed by X-ray, bone tissue was tested by immunohistochemistry stain.

RESULTSThe most prominent period of bone remodeling occurred at 7th day after the placement of implants. The expression of RANKL and OPG increased in a time-dependent manner in both soft and hard tissue. After 7 days they gradually decreased.

CONCLUSIONRANKL and OPG can express in soft tissue, and the changing tendency is consistent with the change of bone remodeling, it indicates that RANKL and OPG play an important role in the bone remodeling.

Animals ; Bone Remodeling ; Bone and Bones ; Carrier Proteins ; Dogs ; Male ; NF-kappa B ; Osteoprotegerin ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B

Objective: To explore the relationship of sleep quality and emotional regulation difficulties in middle school students, and to analyze its mediating role of daytime dysfunction, social rejection and selfcontrol ability, so as to provide a scientific reference for improving middle school students mental health. Methods: From October to November, 2023, the Pittsburgh Sleep Quality Index, Adolescent Social Rejection Questionnaire, Brief Selfcontrol Scale and Difficulties in Emotion Regulation Scaleshort Form (DERS-16) were used to assess 806 students recruited from four middle schools in Bengbu City by a convenient cluster random sampling method. And model-6 of PROCESS and 5 000 Bootstraps were used to make a chainmediating model analysis. Results: Daytime dysfunction was positively correlated with sleep quality(r=0.57), social rejection(r=0.19), selfcontrol(r=0.29, P＜0.01). Selfcontrol was positively correlated with emotional regulation difficulties(r=0.54, P<0.01).Poor sleep quality showed a significant positive association with on daytime dysfunction, and daytime dysfunction further affected social rejection, selfcontrol ability and emotional regulation difficulties (β=0.86, 0.60, 1.27, 1.56, P<0.05). Meanwhile, daytime dysfunction, social rejection and selfcontrol played a serial mediating role in the relationship between sleep quality and emotional regulation difficulties (Estimate=0.11,95%CI=0.04-0.20,P<0.05). Conclusion The study reveals the complex relationship between sleep quality and emotional regulation difficulties in middle school students and provides a new theoretical basis for adolescent sleep improvement and mental health interventions.

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.

Objective To observe the gene mutation and clinical phenotype of patients with retinitis pigmentosa (RP) and cone rod dystrophy (CORD).Methods Thirty-seven patients with RP and 6 patients with CORD and 95 family members were enrolled in the study.The patient's medical history and family history were collected.All the patients and family members received complete ophthalmic examinations to determine the phenotype,including best corrected visual acuity,slit lamp microscope,indirect ophthalmoscopy,color fundus photography,optical coherence tomography,full-field electroretinogram,and fluorescein fundus angiography.DNA was abstracted from patients and family members.Using target region capture sequencing combined with next-generation sequencing to screen the 232 candidate pathogenic mutations.Polymerase chain reaction and direct sequencing were used to confirm the pathogenic pathogenic mutations and Co-segregation is performed among members in the family to determine pathogenic mutation sites.The relationship between genotype and clinical phenotype of RP and CORD was analyzed.Results Of the 37 patients with RP,13 were from 6 families,including 4 families with autosomal dominant inheritance,2 families with autosomal recessive inheritance,and 3 in 6 families were detected pathogenic gene mutations.24 cases were scattered RP.Six patients with CORD were from four families,all of which were autosomal recessive.Of the 43 patients,21 patients were detected the pathogenic gene mutation,and the positive rate was 48.8％.Among them,15 patients with RP were detected 10 pathogenic gene mutations including USH2A,RP1,MYO7A,C8orf37,RPGR,SNRNP200,CRX,PRPF31,C2orf71,IMPDH1,and the clinical phenotype included 10 typical RP,2 cases of RPSP,3 cases of Usher syndrome type 2 and 6 cases of CORD patients were all detected pathogenic gene mutations,including 2 cases of ABCA4,2 mutations of RIMS 1 gene,1 case of CLN3 gene mutation,and 1 case of CRB 1 and RPGR double gene mutation.Conclusions RP and CORD are clinically diverse in genotype and clinically phenotypically similar.For patients with early RP and CORD,clinical phenotype combined with genetic analysis is required to determine the diagnosis of RP and CORD.

Objective: To investigate the protective effect of carbon monoxide release molecule-2 (CORM-2) on sepsis-induced myocardial dysfunction in rats. Methods: 140 healthy male Sprague-Dawley (SD) rats were divided into sham operation (Sham) group, model group, CORM-2 pretreatment group, inactivated carbon monoxide release molecule-2 (iCORM) pretreatment group, and dimethyl sulfoxide (DMSO) control group by random number table, with 28 rats in each group. The rat sepsis model was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS). The rats in the Sham group were injected intraperitoneally with the same dose of normal saline (NS). The rats in the CORM-2 and iCORM-2 pretreatment groups were injected intraperitoneally with 8 mg/kg CORM-2 or iCORM-2 at 1 hour before LPS injection, respectively, and those in the DMSO group were injected intraperitoneally with the same dose of DMSO, but the rats in the Sham group and the model group were not treated after injection of NS or LPS. Twenty rats were randomly selected from each group to observe 10-day survival rate. Transthoracic echocardiography was performed on the remaining 8 rats at 12 hours after modeling, and the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were calculated to evaluate heart function. The blood of the inferior vena cava was harvested, then serum myocardial troponin I (cTnI) and brain natriuretic peptide (BNP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Then the rats were sacrificed, and the myocardial tissues were harvested, the pathological morphology and ultrastructure of myocardium were observed. Results: ① Survival rates: all rats in the Sham group survived; compared with the Sham group, the survival rates of the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased at 10 days [10% (2/20), 70% (14/20), 25% (5/20), 15% (3/20) vs. 100% (20/20), all P < 0.01]. However, the 10-day survival rate in the CORM-2 pretreatment group was significantly higher than those in the model group, iCORM-2 pretreatment group and DMSO control group (all P < 0.01). ② Cardiac function: compared with the Sham group, LVEF and LVFS in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased, and left ventricular dilatation was obvious, indicating myocardial dysfunction in rats. However, LVEF and LVFS in the CORM-2 pretreatment group were significantly higher than those in the model group, iCORM-2 pretreatment group, and DMSO control group [LVEF: 0.760±0.029 vs. 0.634±0.021, 0.629±0.066, 0.673±0.023; LVFS: (39.32±2.38)% vs. (29.75±1.52)%, (29.61±4.15)%, (32.43±1.66)%, all P < 0.05], and the left ventricular dilatation in the septic rats was attenuated. ③ Myocardial injury markers: compared with the Sham group, serum cTnI and BNP levels were significantly higher in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group. However, the levels of cTnI and BNP in the CORM-2 pretreatment group were significantly lower than those in the model group, iCORM-2 pretreatment group and DMSO control group [cTnI (ng/L): 3 283.54±803.50 vs. 6 449.18±1 105.10, 5 919.21±1 068.27, 6 349.80±1 153.08; BNP (ng/L): 3 456.62±905.85 vs. 6 070.18±1 287.62, 5 581.13±1 161.17, 5 974.89±988.89, all P < 0.05]. ④ Myocardial histopathological observation: optical microscope showed that the pathological changes in myocardial tissue of the model group, iCORM-2 pretreatment group and DMSO control group were severe. Transmission electron microscopy showed mitochondrial swelling, and some vacuoles changed. But the myocardial pathological morphology and mitochondrial ultrastructural integrity of the CORM-2 pretreatment group were significantly better than other groups of sepsis. Conclusion CORM-2 can attenuate myocardial dysfunction and improve survival rate of septic rats, especially to protect myocardial mitochondrial integrity in sepsis.

OBJECTIVE: To investigate the protective effect of carbon monoxide release molecule-2 (CORM-2) on sepsis-induced myocardial dysfunction in rats. METHODS: 140 healthy male Sprague-Dawley (SD) rats were divided into sham operation (Sham) group, model group, CORM-2 pretreatment group, inactivated carbon monoxide release molecule-2 (iCORM) pretreatment group, and dimethyl sulfoxide (DMSO) control group by random number table, with 28 rats in each group. The rat sepsis model was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS). The rats in the Sham group were injected intraperitoneally with the same dose of normal saline (NS). The rats in the CORM-2 and iCORM-2 pretreatment groups were injected intraperitoneally with 8 mg/kg CORM-2 or iCORM-2 at 1 hour before LPS injection, respectively, and those in the DMSO group were injected intraperitoneally with the same dose of DMSO, but the rats in the Sham group and the model group were not treated after injection of NS or LPS. Twenty rats were randomly selected from each group to observe 10-day survival rate. Transthoracic echocardiography was performed on the remaining 8 rats at 12 hours after modeling, and the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were calculated to evaluate heart function. The blood of the inferior vena cava was harvested, then serum myocardial troponin I (cTnI) and brain natriuretic peptide (BNP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Then the rats were sacrificed, and the myocardial tissues were harvested, the pathological morphology and ultrastructure of myocardium were observed. RESULTS: (1) Survival rates: all rats in the Sham group survived; compared with the Sham group, the survival rates of the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased at 10 days [10% (2/20), 70% (14/20), 25% (5/20), 15% (3/20) vs. 100% (20/20), all P < 0.01]. However, the 10-day survival rate in the CORM-2 pretreatment group was significantly higher than those in the model group, iCORM-2 pretreatment group and DMSO control group (all P < 0.01). (2) Cardiac function: compared with the Sham group, LVEF and LVFS in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased, and left ventricular dilatation was obvious, indicating myocardial dysfunction in rats. However, LVEF and LVFS in the CORM-2 pretreatment group were significantly higher than those in the model group, iCORM-2 pretreatment group, and DMSO control group [LVEF: 0.760±0.029 vs. 0.634±0.021, 0.629±0.066, 0.673±0.023; LVFS: (39.32±2.38)% vs. (29.75±1.52)%, (29.61±4.15)%, (32.43±1.66)%, all P < 0.05], and the left ventricular dilatation in the septic rats was attenuated. (3) Myocardial injury markers: compared with the Sham group, serum cTnI and BNP levels were significantly higher in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group. However, the levels of cTnI and BNP in the CORM-2 pretreatment group were significantly lower than those in the model group, iCORM-2 pretreatment group and DMSO control group [cTnI (ng/L): 3 283.54±803.50 vs. 6 449.18±1 105.10, 5 919.21±1 068.27, 6 349.80±1 153.08; BNP (ng/L): 3 456.62±905.85 vs. 6 070.18±1 287.62, 5 581.13±1 161.17, 5 974.89±988.89, all P < 0.05]. (4) Myocardial histopathological observation: optical microscope showed that the pathological changes in myocardial tissue of the model group, iCORM-2 pretreatment group and DMSO control group were severe. Transmission electron microscopy showed mitochondrial swelling, and some vacuoles changed. But the myocardial pathological morphology and mitochondrial ultrastructural integrity of the CORM-2 pretreatment group were significantly better than other groups of sepsis. CONCLUSIONS CORM-2 can attenuate myocardial dysfunction and improve survival rate of septic rats, especially to protect myocardial mitochondrial integrity in sepsis.
Animals ; Carbon Monoxide ; Lipopolysaccharides ; Male ; Myocardium/metabolism* ; Rats ; Rats, Sprague-Dawley ; Sepsis