Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To observe the characteristics of macular telangiectasia (MacTel) in multi-color and multi-mode fundus images.Methods:An abservational case series study was conducted.Sixteen eyes of 12 patients diagnosed with MacTel by fluorescein fundus angiography (FFA) from January to November 2019 in Shandong Eye Hospital were analyzed.There were 8 cases (8 eyes) with MacTel type Ⅰ, among which 4 cases were male and 4 cases were female, with an average age of (62.3±12.5) years.The other 4 cases (8 eyes) had MacTel type Ⅱ, all of which were female, with an average age of (58.7±10.5) years.Best corrected visual acuity, slit lamp microscopy, color fundus photography, multicolor scanning laser imaging, FFA, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were carried out in all the patients.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shandong Eye Institute (No.2019S003).Results:In color fundus images of MacTel type Ⅰ eyes, annular macular exudation with macular edema occurred in 6 eyes, macular edema without hard exudates in 1 eye, and hard macular exudates without macular edema in 1 eye.However, the transparency of retina in temporal fovea in MacTel type Ⅱ eyes decreased, showing a gray color.In multi-color fundus images of MacTel type Ⅰ eyes, punctate granular yellow macular exudation and yellow-green macular edema were observed, which were clearer than those in color fundus images.Punctate exudation was seen in both the blue and green reflectance images, which was clearest in green reflectance image, followed by blue reflectance image and then the infrared reflectance image.In OCT images of MacTel type Ⅰ eyes, cystoid edema of inner retina or uneven reflection signal of outer plexiform retina were observed.Loss of inner and outer retinal structures and cavities were observable in MacTel type Ⅱ eyes, and outer retinal atrophy appeared in 2 eyes.In OCTA images, the destruction of superficial and deep capillary plexus in macular area were observed in both MacTel typeⅠand type Ⅱ eyes, and the destruction of deep capillary plexus was more obvious.In addition, more obviously increased vascular space, decreased vessel density, and increased foveal avascular zone were found in MacTel type Ⅱ eyes.In early stage of FFA, delayed capillary filling near fovea was seen in MacTel typeⅠeyes, and dilated temporal vessels in fovea, some of which showed tumor-like dilation, and the limited tumor-like dilation was enhanced in the later stage.Different degrees of dilated parafoveal blood vessels in the early stage, and the capillary in the temporal side of the macula showing diffuse strong fluorescence in the late stage of FFA was observed in MacTel type Ⅱ eyes.Conclusions:Multi-color scanning laser imaging can be used to observe the morphological characteristics of MacTel, and the imaging features of different types of MacTel are significantly different.

Objective:To understand the profile type of serum Epstein-Barr virus (EBV) antibodies in children with infectious mononucleosis (IM), and to analyze the significance of viral capsid antigen (VCA) IgG antibody affinity in the diagnosis of IM.Methods:Retrospective analysis was performed on the results of the serum anti-EBV antibody profile and plasma EBV nucleic acid test of 150 hospitalized children with IM diagnosed in Beijing Children′s Hospital, Capital Medical University, from May 2016 to May 2019.Anti-EBV antibody profiles, including anti-VCA-IgG, anti-VCA-IgM, anti-early antigen (EA) IgA, anti-EBV nuclear antigen (EBNA) IgG, and anti-VCA-IgG affinity, were detected by enzyme-linked immunosorbent assay (ELISA). Plasma EBV nucleic acids were detected by real-time quantitative PCR.Results:There were mainly two types of anti-EBV antibody profiles in 150 children with IM: (1)130 cases who were positive for anti-VCA-IgM/IgG, negative for anti-EBNA-IgG and positive for anti-VCA-IgG antibodies with low affinity, accounting for 86.7% (130/150 cases), of which 50 cases were positive for anti-early antigen IgA; (2)18 cases who were negative for anti-VCA-IgM, positive for anti-VCA-IgG, negative for anti-EBNA-IgG and positive for anti-VCA-IgG antibody with low affinity, accounting for 12.0% (18/150 cases), of which 5 cases were positive for anti-EA IgA.EBV DNA was measured in 132 children, with a posi-tive rate of 37.9% (50/132 cases).Conclusions:There were several types of serum EBV antibody profiles in children with IM, 12.0% of patients with IM in this study were negative for anti-VCA-IgM, and the diagnosis of IM was confirmed by the affinity of anti-VCA IgG.

Objective:To evaluate the performance of the Cepheid Xpert Xpress Flu/RSV assay (Xpert) in the detection of children infected with influenza virus (Flu) or respiratory syncytial virus (RSV).Methods:Nasopharyngeal specimens were collected from children who showed symptoms of respiratory infection and tested FluA, FluB and RSV by Xpert and sequencing assay respectively side by side. Discordant result were tested with a laboratory-developed real-time PCR for resolution.Results:A total of 388 nasopharyngeal swabs (NAPs) from children with acute respiratory tract infection were analyzed and the result showed 91.75-94.85% agreement between two tests. The sensitivity of FluA, FluB and RSV detected by Xpert and sequencing assay were 99.21% (125/126) vs. 92.86% (117/126), 100.00% (109/109) vs. 84.40% (92/109) and 100.00% (52/52) vs. 40.38% (21/52), respectively. The specificity of FluA, FluB and RSV detected by Xpert were all lower than that of the sequencing assay: 95.42% (250/262) vs 99.24% (260/262), 99.28% (277/279) vs 99.64% (278/279) and 99.70% (335/336) vs 100.00% (336/336). The positive predictive values (PPV) of FluA, FluB and RSV detected by Xpert were lower than those of the sequencing assay: 91.30% (126/138) vs. 98.33% (118/120), 98.18% (108/110) vs. 98.92% (92/93) and 98.11% (52/53) vs. 100.00% (21/21), respectively. The negative predictive values (NPV) of FluA, FluB and RSV detected by Xpert were higher than those of the sequencing assay: 99.60% (251/252) vs. 96.67% (261/270), 99.64% (279/280) vs. 94.27% (280/297) and 100.00% (337/337) vs. 91.60% (338/369).Conclusions:The Cepheid Xpert Xpress Flu/RSV assay is a sensitive, reliable and rapid assay for the detection of FluA, FluB and RSV in pediatrics.

Objective:To evaluate a multiplex fluorescent probe real-time PCR kit in the viral pathogen detection among children with acute lower respiratory tract infections.Methods:This study used multiplex fluorescent probe real-time PCR method to detect viral pathogens in 300 nasopharyngeal swabs from children with acute lower respiratory tract infection in Beijing Children′s Hospital (influenza A/B virus, respiratory syncytial virus, adenovirus, parainfluenza virus type I and parainfluenza virus type ⅡI), and liquid chip method was used for comparison. In addition, 136 positive-nasopharyngeal aspirates determined by immunofluorescence test were verified by the multiplex fluorescent probe real-time PCR method .Results:For the 300 nasopharyngeal swabs, 173 and 159 were determined positive by real-time PCR and liquid chip kit, respectively. In addition, real-time PCR method found 22 cases of mixed infection samples with two or more viral pathogens compared with the immunofluorescence method .Conclusions:The multiplex fluorescent probe real-time PCR method has high sensitivity and specificity, and has good application value for the detection of children′s acute lower respiratory tract viral pathogens.

Objective To investigate the effects and mechanisms of valproic acid on brain edema,neurobehavioral outcome and inflammatory response after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Fifty-four SD male rats,weighting 220-250 g,were randomly divided into 3 groups (n =18):sham operation group (group sham),traumatic brain injury group (group TBI) and valproic acid treatment group (group TBI + VPA).Experimental rats were treated with valproic acid (300 mg/kg,twice daily) by intraperitoneal injection.Rat behavioral outcomes were measured by modified neurologic severity score (mNSS) tests at day 1,3,and 7 after TBI.Brain water content was measured with wet-dry weight method.The blood cells infiltration into cerebral cortex were tested with immunohistochemistry staining against ED-1 for macrophage.Inflammatory cytokines (INF-γ,tumor necrosis factor-α,interleukin-6) were measured by Western blotting.The statistical analysis were performed by ANOVA and chi-square tests using the statistical software program SPSS 13.0.Results Compared with the Sham group,the levels of brain edema,mNSS and macrophage cell infiltration were significantly increased after TBI (all P =0.00).The expressions of inflammatory cytokines were also increased significantly (all P =0.00).Compared with the TBI group,TBI + VAP group had significantly lower brain water content[3day:(80.12 ±0.59)％ vs.(82.14 ±0.67)％,P=0.04;7day:(74.74 ±0.72)％ vs.(77.93 ±0.48)％,P=0.01],and mNSS scores [3 day:(10.53 ±0.32) vs.(11.74 ±0.48),P =0.02;7 day:(7.97 ± 0.32) vs.(10.73 ± 0.42),P =0.01].VPA suppressed macrophage cell infiltration into cerebral cortex [(36.44 ± 0.72) ％ vs.(25.93 ± 0.48) ％ P =0.00].Meanwhile,VPA inhibited the expressions of inflammatory cytokines (INF-γ,TNF-α,IL-6) (P ＜ 0.05).Conclusions Treatment with VPA markedly reduced brain edema and improved neurological outcomes after TBI,possibly mediated by inhibited TBI-induced cerebral inflammatory responses and macrophage cell infiltrating into cerebral cortex.

Aim To observe the effects of liver cirrho-sis on the expression of transforming growth factor-β1 ( TGF-β1 ) and ColⅠin rat myocardium and interven-tion of erythropoietin ( EPO ) . Methods Thirty-six male Sprague-Dasley rats were randomly divided into three groups:control group, liver cirrhosis group and EPO group, then the cardic hemodynamic parameters in vivo and levels of serum lactate dehydrogenase ( LDH ) as well as creatine kinase isoenzyme ( CK-MB) were measured. With Masson′s trichrome stain, changes of collagen formation of myocardial tissue in different groups were observed. Also the mRNA ex-pressions of TGF-β1 and ColⅠin myocardium were de-tected by RT-PCR. Results In contrast to control group, rats in liver cirrhosis group showed a decline in systolic and diastolic function of left ventricule, rising myocardial enzyme, a distinct increase of cardiac colla-gen deposition, as well as an elevation of TGF-β1 and ColⅠmRNA expressions. In contrast to liver cirrhosis group, rats in EPO group demonstrated an improve-ment in systolic and diastolic function of left ventricule as well as in cardiac collagen deposition, and a de-crease in both myocardial enzyme and TGF-β1 and ColⅠmRNA expressions. Conclusion Liver cirrhosis can lead to the changes of myocardial structure and function in rats,and it can accelerate myocardial inter-stitial fibrosis; EPO can protect the myocardial injury in liver cirrhosis rats.

OBJECTIVE: To explore the protective effects of hydrogen sulfide (H2S) on diaphragmatic muscle of Type 1 diabetic rats and its anti-apoptotic mechanism.
 METHODS: Thirty male Sprague Dawley rats were randomly divided into a control group, a diabetes group and a treatment group (n=10 per group). Streptozotocin (i.p.) was utilized to establish a rat model of Type 1 diabetes mellitus (DM). The DM rats were treated with NaHS solution (i.p.). After 8 weeks, the diaphragmatic muscle contractility was assessed by isolated diaphragmatic strips experiments. The peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT) and maximal rates of contraction/relaxation (±dT/dtmax) were measured. The alterations of diaphragmtic ultrastructure were observed by electron microscopy. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and caspase-3 were analyzed by spectrophotometric method. The expressions levels of Bcl-2 and Bax mRNA in diaphragmatic muscle were detected by RT-PCR.
 RESULTS: Compared with the control group, in the diabetic group, the Pt, Po and ±dT/dtmax were significantly reduced (all P<0.01), while CT and 1/2RT were significantly increased (both P<0.01); ultrastructure in the diaphragmatic muscle were obviously changed; the content of MDA and the activity of caspase-3 were increased (both P<0.01), while the activity of SOD was decreased (P<0.01); the ratio of Bcl-2/Bax at mRNA level was decreased (P<0.01). Compared with the diabetes group, in the treatment group, the diaphragm contractility and ultrastructural damage were improved; the content of MDA and the activity of caspase-3 were decreased (P<0.05, P<0.01 respectively), while the activity of SOD was increased (P<0.01), the ratio of Bcl-2/Bax at mRNA level was also increased (P<0.01). 
 CONCLUSION The exogenous H2S can protect diaphragmatic muscle of Type 1 diabetic rats, which is related to reducing oxidative damage and suppressing cell apoptosis.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; Diaphragm ; drug effects ; Hydrogen Sulfide ; pharmacology ; Male ; Malondialdehyde ; metabolism ; Muscle Contraction ; drug effects ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Sulfides ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the changes in diaphragmatic function and gene expressions of calcium regulatory proteins in diabetic rats and explore the mechanism of diaphragm dysfunction in diabetes mellitus.

METHODSSD rats were randomly divided into normal control group and diabetic (induced by intraperitoneal STZ injection) group. After 4 and 8 weeks, the body weight and diaphragm to body weight ratio were measured, and the activities of succinic dehydrogenase (SDH) in the diaphragm and blood glucose were assayed. The diaphragm contractility was assessed and the alterations of diaphragm ultrastructure were observed. RT-PCR was used to detect the changes in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) mRNA expressions in the diaphragm.

RESULTSThe diabetic rats showed a significant weight loss with a lowered diaphragm to body weight ratio (P<0.01) and SDH activity (P<0.01). The peak twitch tension and maximum tetanic tension of the diaphragm were significantly lowered and the time to peak contraction and half relaxation time significantly prolonged (P<0.01) in the diabetic rats, which also exhibited a lowered tetanic force in response to stimulus (P<0.01). Transmission electron microscopy revealed obvious ultrastructural changes of the diaphragm in diabetic rats. RT-PCR showed significantly decreased SERCA and increased PLB mRNA expressions in diabetic rat diaphragm (P<0.01), and these changes intensified with time (P<0.01).

CONCLUSIONDiabetes can cause impairment of diaphragmatic ultrastructure, mitochondrial injuries, and lowered SDH activity and ATP production. Decreased SERCA and increased PLB mRNA expressions in diabetes result in reduced Ca(2+) uptake by the diaphragm sarcoplasmic reticulum to induce diaphragm dysfunction.

Animals ; Body Weight ; Calcium ; metabolism ; Calcium-Binding Proteins ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; physiopathology ; Diaphragm ; metabolism ; physiopathology ; Glucose ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Succinate Dehydrogenase ; metabolism

Two-factor factorial design refers to the research involving two experimental factors and the number of the experimental groups equals to the product of the levels of the two experimental factors. In other words, it is the complete combination of the levels of the two experimental factors. The research subjects are randomly divided into the experimental groups. The two experimental factors are performed on the subjects at the same time, meaning that there is no order. The two experimental factors are equal during statistical analysis, that is to say, there is no primary or secondary distinction, nor nested relation. This article introduces estimation of sample size and testing power of quantitative data with two-factor factorial design.