Effects of wearing orthokeratology lens on ocular surface and meibomian gland in children and adolescents of different ages / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of orthokeratology lens on ocular surface and meibomian gland in children and adolescents of different ages.METHODS: A total of 120 cases(240 eyes)of myopic children and adolescents treated in the optometry clinic of our hospital from December 2020 to February 2021 were retrospectively selected, and they were divided into the orthokeratology group(60 cases, 120 eyes)and the frame glasses group(60 cases, 120 eyes)according to the myopia correction methods. The changes in ocular surface and meibomian gland after wearing glasses were analyzed, and those changes in patients of different ages were compared between the two groups.RESULTS: Corneal curvature decreased, non-invasive tear film break-up time(NIBUT)shortened and meibomian gland score increased at 3, 6, 9 and 12mo in the orthokeratology group after wearing lens, while lower tear meniscus height increased at 6, 9 and 12mo compared with that before wearing lens. In the frame glasses group, the lower tear meniscus height was higher at 6 and 9mo than that before wearing glasses(both P<0.05). At the same time point, the corneal curvature of the orthokeratology group was significantly lower than that of the frame glasses group at all time points, the NIBUT at 3, 9 and 12mo after wearing the lens was shorter than that of the frame glasses group and the meibomian gland scores were higher at 6, 9 and 12mo than those at the same time point in the glasses group(all P<0.05). After wearing lens for 12mo, the corneal curvature of the orthokeratology group at all ages was significantly lower than that of the frame glasses group, the NIBUT of the orthokeratology group at 8 to 12 years old and 13 to 15 years old was significantly lower than that of the frame glasses group, and the meibomian gland score was significantly higher than that of the frame glasses group(all P<0.05).CONCLUSION: Orthokeratology lens may affect the ocular surface and meibomian glands function, and the effects on ocular surface are more pronounced in children and adolescents under 12 years old. Therefore, younger children and adolescents could be prioritized for myopia correction with framed glasses, and then wearing orthokeratology lens when they get older.

Clinical analysis of elderly patients with anti-MDA5 antibody-positive dermatomyositis / 中华老年医学杂志

Objective:To retrospectively analyze the clinical characteristics of elderly patients with anti-MDA5 antibody-positive dermatomyositis.Methods:Data of 62 patients with anti-MDA5 antibody-positive dermatomyositis admitted to Second Xiangya Hospital from May 2016 to December 2019 were collected and patients were divided into an elderly group(≥60 years old, 17 cases)and a non-elderly group(<60 years old, 45 cases). The clinical manifestations, laboratory test resuls, treatment and prognosis of the patients in both groups were statistically analyzed.Results:A total of 62 patients with anti-MDA5 antibody-positive dermatomyositis were included in this study, including 17 elderly patients(27.4%)with an average age of(65.5±5.3)years and 45 non-elderly patients(72.6%)with an average age of(46.5±8.4)years.Compared with non-elderly patients, older patients had a shorter disease duration[(1.6±1.0)months vs.(3.7±3.3)months, t=3.883, P<0.001], a higher proportion of patients with exertional dyspnea(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024)and with combined positive anti-Ro-52 antibodies(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024), and a higher mortality rate[(12/17 or 70.6%) vs.(8/45 or 17.8%, χ2=15.748, P<0.001)]. In contrast, fewer elderly patients than non-elderly patients had the Heliotrope's sign(9/17 or 41.2% vs.38/45 or 57.8%), χ2=5.07, P=0.024). Conclusions:Elderly patients with anti-MDA5 antibody-positive dermatomyositis have a unique clinical phenotype with an acute onset, atypical rashes, severe pulmonary lesions, making treatment difficult, and have a poor prognosis.

Research Progress on Animal Model for Cancer-related Fatigue / 肿瘤防治研究

Cancer-related fatigue (CRF) is a common symptom which associated with cancer itself or cancer treatments. CRF will not only interrupt the patient's treatment, but also affect the patient's quality of life seriously. To date, the pathogenesis of CRF is still unclear, and recognized effective treatment is lacking. It is the precondition of establishing standardized animal models for CRF to find effective treatments. This paper summarizes the animal model of CRF in order to find suitable methods, and distinguish the effects of different interventions.

Correlations of Methylenetetrahydrofolate Reductase Gene Polymorphism and Genomic DNA Hypomethylation Level with Ankylosing Spondylitis / 中国医学科学院学报

To investigate the relationship of both DNA methylation level and methylenetrahydrofolate reductase(MTHFR)gene polymorphism with ankylosing spondylitis(AS). Totally 200 Chinese AS patients with HLA-B27(+)and 120 healthy controls were included from Hunan Province.All the cases were diagnosed according to the 1984 modified New York criteria for AS.The DNA methylation was examined by cytosine extension method,while the MTHFR gene C677T polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP).The plasma homocysteine(Hcy)level was examined by enzyme-linked immunosorbent assay(ELISA),while the red blood folate level was analyzed by the specific immunoassays. The ratio of the T/T genotype mutation in the AS group was significantly higher than in the control group(17.0% 5.0%;=9.874, =0.002).The plasma homocysteine concentration of AS group was(18.71 ± 2.42)μmol/L,which was significantly higher than that in normal control group [(10.97 ± 2.93)μmol/L](=24.402, <0.001).The plasma Hcy concentration of the T/T genotype [(21.70±1.80)μmol/L] was significantly higher than that of the C/C genotype[(18.31±1.94)μmol/L](=12.088, =0.01)and the C/T genotype [(17.80±2.18)μmol/L](=6.496, =0.01)in the AS group.The DNA methylation level of the T/T genotype in AS group was significantly lower than that in normal control group(=5.655, <0.001)and also significantly lower than those of the C/C genotype(=11.514, <0.001)and the C/T genotype in AS group(=10.287, <0.001). In the Han population in Hunan Province,the C677T polymorphism of the MTHFR gene is associated with the onset of AS.The T/T mutation at position 677 of the MTHFR gene is an important influencing factor for hyperhcyemia in the AS patients.The T/T mutation at position 677 of the MTHFR gene is associated with genomic DNA hypomethylation.Thus,hypomethylation of DNA may be one of the pathogenic mechanisms of AS.

Meta Analysis of Risks of Cardiocerebral Vascular Events in Patients with Primary Biliary Cholangitis / 中国医学科学院学报

To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events(=1.56,=0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups(=1.01,=0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients(=0.63,=0.03);however,there was no significant difference in the risk of stroke(=1.11,=0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.

High Expression of Multidrug Resistance Gene-1 Can Aggravate Resistance to Methotrexate in Rheumatoid Arthritis Patients / 中国医学科学院学报

Objective To explore the role of multidrug resistance gene-1(MDR1)gene in methotrexate(MTX)resistance in patients with rheumatoid arthritis(RA).Methods Fibroblast-like synoviocytes(FLS)from RA patients were infected with recombinant adenovirus Ad-EGFP-MDR1 to obtain MDR1 over-expressed RA FLS.The transcription level of MDR1 gene and the expression level of its coding product P-glycoprotein(P-gp) rotein were detected by real-time PCR and Western blot analysis.The efflux function was verified by rhodamine 123 efflux assay.The resistance to MTX was detected by MTT assay.Results RA FLS were infected with recombinant adenovirus Ad-EGFP-MDR1;72 hours later,the particles size in MDR1 over-expressed RA FLS increased,the cell volume became larger,and the growth rate decreased.The transcription level of MDR1(1.4325±0.3924 0.0650±0.0070;=6.035,=0.004),the expression level of P-gp protein(1.8667±0.2857 0.9367±0.0551;=5.536,=0.005),and the ability of extracellular rhodamine 123(979.43±196.81 1680.06±147.04;=-4.940,=0.008) in MDR1 over-expressed RA FLS were significantly higher than those of negative virus control RA-FLS,and the survival rate of MDR1 over-expressed RA FLS was significantly increased at each concentration of MTX(<0.05).Conclusion The high expression of MDR1 can affect the efflux ability to MTX by up-regulating the expression of P-gp,thus enhancing the drug resistance to MTX in RA FLS.

Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis / 中南大学学报(医学版)

Objective:To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).Methods:Twelve patients with severe refractory RA were treated with tocilizumab.The clinical and laboratory indices and the side effects were recorded after treatment.Results:The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients,which were significantly improved after TCZ therapy (P＜0.05),and no obvious adverse reactions were found.Conclusion:Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Expression of survivin in rheumatoid arthritis / 中南大学学报(医学版)

OBJECTIVE@#To detect the correlation between survivin and rheumatoid arthritis (RA) to determine the possible mechanism of RA and multidrug resistance in refractory rheumatoid arthritis (RRA).@*METHODS@#We collected 15 normal controls, 35 early untreated RA patients, 20 effectively treated RA patients and 25 RRA patients according to selection standard. The expression of survivin in the peripheral blood lymphocytes was detected by immunocytochemical method.@*RESULTS@#There was significant difference in the survivin expression in the peripheral blood lymphocytes between the early untreated and normal control group (χ(2)=29.59, P0.05). The survivin expression in the peripheral blood lymphocytes of the RRA group was significantly stronger than in the effectively treated RA group (χ(2)=24.35, P0.05).@*CONCLUSION@#Survivin has an influential role in the occurrence and development of rheumatism arthritis. Survivin might be involved in refractory multidrug resistance of RA and be one of the multidrug resistance mechanism of RRA.

Grey scale and power Doppler ultrasonographic assessment of bone erosion and disease activity in early rheumatoid arthritis / 中南大学学报(医学版)

objective:To evaluate the sensitivity and predictive value of grey scale and power Doppler ultrasound assessment of bone erosionin disease activity in patients with early rheumatoid arthritis (Ra). Methods:Fifty-six patients with early Ra underwent blinded sequential clinical, laboratory and ultrasound assessments, and at the same time 20 of these patients underwent X-ray and enhanced MRi. For each patient, 28-joint disease activity score (DaS28), erythrocyte sedimentation rate (eSR), C reactive protein (CRP) and health assessment questionnaire (haQ) were recorded. The presence of bone erosion and synovitis was investigated in 28 joints by gray-scale and power Doppler ultrasonography. The ultrasound joint count and index for active synovitis with power Doppler signal were calculated. Results:The number of bone erosions detected by ultrasonography was 5.7 times that of X-ray, while both MRi and ultrasonography were consistent (91.5%). The number of synovitis detected by ultrasonography was 1.6 times as much as by physical examination, and consistent MRi (95.7%). PDUS parameters demonstrated a highly significant correlation with DaS28, eSR and CRP, while a negative correlation with haQ. Conclusion:Grey scale and power Doppler ultrasonography is a sensitive and reliable method to assess bone erosion and inflammatory activity in early Ra. PDUS findings may have a predictive value in disease activity.

Meta analysis of infection risks of anti-TNF-αtreatment in rheumatoid arthritis / 中南大学学报(医学版)

Objective:To systematically evaluate the risks of anti-TNF-αtreatment-associated infection, severe infection and tuberculosis in rheumatoid arthritis (RA) patients, and to reduce the infection incidences associated with anti-TNF-αtherapy. Methods:We used Meta analysis to systematically review randomized controlled trials on anti-TNF-αtreatment associated risks of infecion, severe infection and tuberculosis in AR patients.Results:Although no statistically significant differences were detected in TB risk between anit-TNF-αtreatment and the control group (0.5%vs 0.07%;P=0.27, OR=1.85, 95%CI:0.62-5.52), there still existed a clinically obvious elevation of TB risk in monoclonal anti-TNF-αtreatment, which was illustrated by the results that no TB case was reported in the etanercept group, but 11 TBs in 2050 infliximab-treated cases, and 3 TBs in 722 adalimumab-treated cases. The total infection and severe infection risks were also signiifcantly higher in patients receiving anti-TNF-αtreatment (P0.05), while both kinds of monoclonal antibodies of TNF-αblockers showed a signiifcantly elevated infection or severe infection risks (P<0.05). High doses of anti-TNF-αtreatment were associated with statistically increased risks of severe infection (6.0%vs 2.8%, P=0.04, OR=1.68, 95%CI:1.02-2.78). Conclusion:The TB risk of anti-TNF-αtreatment deserves close attention, especially in places with high rate of BCG vaccination and MTb infection. Monoclonal anti-TNF-αtreatment brings higher risks of infection and severe infection than soluble TNF-αreceptor.

Clinical significance of antibody to proliferating cell nuclear antigen in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To study the clinical significance and diagnostic value of anti-proliferating cell nuclear antigen (PCNA) antibodies.Methods A retrospective analysis was conducted for the diagnoses and clinical features of 102 patients with anti-PCNA antibodies.Line immunoassay was used to detect anti-PCNA antibody of 536 systemic lupus erythematosus (SLE) patients.Possible relationship between anti-PCNA anti-body and clinical features and other antibodies in SLE were analyzed.Comparisons between groups were performed by t-test or x2 test.Results In the 102 patients with anti-PCNA antibodies,49 had SLE (48.0％).Other disorders associated with anti-PCNA antibodies included primary Sj(o)gren's syndrome(24.5％),systemic sclerosis (12.7％),primary biliary cirrhosis (3.9％),auto-immune thyroiditis (6.9％),polymyositis/dermatomyositis (2.0％) and hepatitis C virus infection (1.0％).9.1％ of SLE patients showed positive anti-PCNA antibody.Compared with those SLE patients with negative anti-PCNA antibody,the occurrences of rash,neuropsychiatric SLE,renal involvement was significantly higher in the anti-PCNA positive patients.In addition,the SLEDAI score was significantly higher in the latter.The positive rates of anti-Rib-P,anti-dsDNA,anti-Ro52,anti-RNP/Sm were higher in patients of SLE with positive anti-PCNA antibody.Conclusion Sera anti-PCNA antibody is not specific for SLE and it is associated with the occurrences of rash,Raynaud's phenomenon,neuropsychiatric SLE,renal involvement and positive rates of anti-Rib-P,anti-dsDNA,antiRo52,anti-RNP/Sm.In addition,anti-PCNA antibody is associa-ted with the disease activity of SLE.

Causative factor to cerebral inflammation in a transgenic mouse model of Alzheimer's disease / 中国综合临床

Objective To observe the changes of cerebral inflammation-related markers in brain of a transgenic mouse model of Alzheimer's disease (AD) ,and to determine the causative factor to the development of cerebral inflammation in AD. Methods 3- and 12-month-old β-amyloid protein precursor ( APP)/presenilin (PSI) transgenic mice and age-matched wild-type mice (WT) were used in the study. The changes of amyloid plaques, inflammatory factors ( interleukin 1β ( IL-1β ); interleukin 6( IL-6 ); tumor necrosis factor α (TNFα) ;prostaglandin E2 (PGE2)) in the brains among these mice were measured by immunohistochemistry and ELISA. Results Immunohistochemical analysis revealed that no amyloid plaques and activated astrocytes as well as microglia were observed in the 3-month-old APP/PS1 mice. There were no significant differences in the levels of inflammatory factors (IL-1β, IL-6 ,TNFα,and PGE2) between the 3-month-old APP/PS1 and WT mice ( Ps ＞ 0. 05 ). However, abundant amyloid plaques accompanied by a remarkable increase of activated astrocytes and microglia were found in the brain of the 12-month-old APP/PS1 mice. The levels of inflammatory factors (IL-1β,IL-6,TNFα, and PGE2 ) were significantly increased in the 12-month-old APP/PS1 mice ([56. 02 ±9. 04] ng/g, [8. 66 ±0.83] ng/g, [97.48 ±26.58] ng/g, [72. 18 ±21.01] ng/g) than in the WT mice ([29. 18 ± 6. 03] ng/g, [7. 73 ± 0. 74] ng/g, [61.98 ±11.11] ng/g, [37. 23 ± 10. 96] ng/g) and the 3-month-old APP/PS1 mice ( [30. 05 ± 3.53] ng/g, [7.43 ± 1.17] ng/g, [59.34 ± 10. 07] ng/g, [42. 56 ±5.93] ng/g) (P＜0.05,or P＜0.01,respectively). Conclusion This study demonstrates that the APP/PS1mice did not show cerebral inflammation before the appearance of amyloid plaques, and exhibited remarkable inflammation after amyloid plaque deposition. These findings suggest that the induction of cerebral inflammation is tightly associated with amyloid plaque formation, and deposition of amyloid-beta protein (Aβ) may be the direct causative factor to the development of cerebral inflammation in AD.

Relationship between early memory impairment and oxidative stress in transgenic mouse model of Alzheimer's disease / 中国综合临床

Objective To investigate the spatial learning and memory ability,the changes of indicators of oxidative stress,and their relationship in transgenic APP/PS1 mouse model of Alzheimer's disease(APP/PS1 mice). Methods The spatial learning and memory ability were assessed by Morris water maze test,and the activity or content of SOD, GSH-PX, MDA, and protein carbonyl in brain tissues were measured by ELISA in the APP/PS1 and wild type (WT) mice. Furthermore, the relationship between the learning and memory performances and the indicators of oxidative stress was examined. Results No significant difference in the spatial learning was observed between the APP/PS1 and WT mice (P ＜0. 05). The spatial memory which was measured as the percentage of time traveling in the targeted quadrant to the total traveling time was significantlydeclined in the APP/PS1 mice(29. 02 ± 4. 27) % as compared with the WT mice(47. 39 ± 6. 01) %(t =0. 000 ,P ＜0. 05). The percentage of length of traveling in the targeted quadrant to the total length traveled was significantly lower in the APP/PS1 mice(28. 85 ±3.77)% compared with the WT mice(46. 70 ±5.60)% (t =0. 000,P ＜0. 05). These findings indicated that the spatial learning and memory ability of APP/PS1 mice was significantly decreased compared to WT mice. There was no significant difference in activity or content of SOD,GSH-PX,and MDA in brain tissues between the APP/PS1 and WT mice (P ＜ 0. 05), while the content of protein carbonyl was significantly elevated in the APP/PS1 mice (2. 67 ±0. 19) than in the WT mice (2. 38 ±0. 15)(t = 0. 008, P ＜ 0. 05). Correlation analysis revealed that the elevated protein carbonyl was negatively correlated with the percentage of length traveled in the targeted quadrant(r = - 0. 639, P ＜ 0. 05) and the percentage of time traveled in the targeted quadrant(r = - 0. 636 ,P ＜ 0. 05). Conclusion The spatial memory impairment was negatively correlated with the elevated protein carbonyl in the APP/PS1 mice, suggesting that protein carbonylation caused by oxidative stress might play an important role in the development of memory impairment in the early stage of Alzheimer's disease.

Effects of resveratrol on proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of resveratrol (Res) on in vitro proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further to investigate the PI3 K/Akt/BAD signal mechanism.</p><p><b>METHOD</b>The inhibition rate of RA FLS was examined by MTT assay. Cell cycle and the amount of apoptotic cells was measured by flow cytometry. PI3K/Akt/BAD signal transduction proteins expression was measured by western blot.</p><p><b>RESULT</b>The living cells measured by MTT dose and time-dependently reduced in Res groups. In Res groups, the fraction of living cells in the S-phase and G2/M-phase decreased respectively, while that in G1-phase increased, the difference was statistically significant compared with the TNF-alpha group (P < 0.05). Flow cytometry demonstrated that the apoptosis rate increased with increased Res concentration. Res inhibited TNF-alpha induced phosphorylation of Akt and BAD in RA FLS.</p><p><b>CONCLUSION</b>Res can inhibit RA FLS proliferation and induce apoptosis through inhibition of PI3K/Akt/BAD signalling pathway. Res may provide a new therapeutic approach in treatment of RA.</p>

Effect of resveratrol on apoptosis and expression of bal-2 and bax protein in articular chondrocytes of experimental osteoarthritis model / 中华风湿病学杂志

Objective To observe the effect of resveratrol on the apoptosis and expressions of bal-2 and bax protein in articular chondrecytes of rabbits experimental osteoarthritis (OA) model,and further explore the mechanisms of resveratrol in the treatment of OA.Methods Thirty Newzealand rabbits were randomly divided into 5 groups：group A (normal control group),group B (model control group),group C (resveratrol intervention high dosage group),group D(resveratrol intervention middle dosage group),group E (resveratrel intervention low dosage group).The model of OA was established with Hulth's modeling method in group B,C,D,E.Four weeks later,groups A and B received intragastric administration of distilled water containing 0.1% DMSO daily and group C,D,E received intragastric administration of resveratrol solution daily (concentration was 60 mg/ml) in different dosages for 6 weeks.Daily dosages of group C,D,E were 120,60,30 mg·kg-1·d-1,respectively.Then the rabbits were sacrificed and the cartilage sections of right femoral medial condyle were analyzed by immunohistochemistry for bcl-2 and bax,TUNEL for apoptosis.Results ① The apoptosis rates of chondrocytes in group B,C,D,E were significantly higher than those in group A (P＜0.01).The apoptosis rates of chandrocytes in group C,D,E were decreased compared with those in group B (P＜0.05).②The positive rates of bcl-2 and bax expression in chondrocytes in group B were significantly higher than those in group A (P＜0.01),but the ratio of the positive rate of bcl-2 expression to that of bax in group B was lower than that in group A (P＜0.01).The positive rates of bcl-2 expression in chondrocytes in group C,D,E were much higher compared with those in group B (P＜0.01).The positive rotes of bax expression in chondrocytes in group C,D,E were lower compared with those in group B (P＜0.01).The ratio of the positive rate of bcl-2 expression to that of bax was increased in group C,D,E compared with group B (P＜0.01).Conclusion Resveratrol can suppress the excessive apoptosis of chondrocytes in experimental OA by up-regulating the expression of bcl-2 while down-regulating the expression of bax and improving the ratio of bcl-2 to bax .Suppressing the excessive apoptosis of chondrocytes in experimental OA may be one of the mechanisms for resveratroi's effect in the treatment of osteoarthritis.

The association analysis of plasma Hcy level and MTHFR gene polymorphism with ankylosing spondylitis / 中华风湿病学杂志

Objective To investigate the relationship between plasma homocysteine (Hey) level and ankylosing spondylitis (AS).To analyze the association between the NS,N10 methylenetetrahydrofolate reductase (MTFHR) gene polymorphism and AS.Methods One hundred patients with AS and 60 healthy controls were included in the study.The plasma Hey level was examined by enzyme-linked immunoadsorbent assay and MTHFR gene polymorphism was analyzed by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).Results Compared with heahhy controls,the plasma Hey level in AS patients was significantly higher than that of the controls (P＜0.01).There was no significant difference in the frequen-cies of MTHFR genotype and alleles between AS and the controls (P＞0.05),But the ratio of T/T genotype mutation was different between AS and the controls (P＜0.05).The plasma Hey level of T/T genotype was significantly higher than that of C/T or C/C genotype in AS and the controls (P＜0.01).Logisticalregression analysis indicated that Hey was an independent risk factor for AS (P＜0.01,0R=4.582,95%CI=1.984～10.585).Conclusion The plasma homocysteine level is significantly increased in AS patients.Hyperhomo-cysteinemia is an independent risk factor for AS.MTHFR T/T genotype mutation is an important mechanism of hyperhomocysteinemia and may be related with AS.