Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

Objective: Children with autism spectrum disorder(ASD) who participated in the " Play-based Communication and Behavior Intervention(PCBI)" were studied in order to evaluate the impact of caregiver factors on the efficacy of the PCBI very early intervention model systematically. Methods: Seventy-six children with ASD aged 8-30 months were recruited in this study at Brain Hospital Affiliated to Nanjing Medical University form December 2017 to June 2018, and they were trained for PCBI very early intervention.The Autism Treatment Evaluation Checklist (ATEC) and the Gesell Developmental Schedules were used to evaluate the efficacy of the PCBI very early intervention.Parenting Stress Index Short Form, General Self-Efficacy Scale and the self-developed Caregiver Training Course Evaluation Scale and the Homework Completion Level Scale were used to assess the level of parental stress, self-efficacy, curriculum satisfaction and acceptance.A pair of sample t-test was used to analyze the ASD symptoms, developmental level and caregiver factors of ASD children before and after intervention.Multivariate regression analysis was used to analyze the caregiver factors and the effects of PCBI very early intervention. Results: (1) At the end of 12 weeks of PCBI very early intervention, the score of the ATEC (17.36±15.98) was lower than that before intervention (78.43±22.84), and the difference was statistically significant(P<0.05); the adaptive developmental quotient(5.90±15.45), the fine action developmental quotient(5.13±19.89), the language developmental quotient (12.43±20.60) and the personal social developmental quotient(4.79±16.02) scores of the Gesell Developmental Schedules were higher than those before intervention (73.08±20.54, 77.33±23.63, 52.24±19.12, 71.79±20.81), and the differences were statistically significant (all P<0.05). (2) At the end of PCBI very early intervention, there was a significant decrease in the scores of Parenting Stress Index Short Form, and the differences were statistically significant (4.84±14.69 vs.94.05±29.67, P<0.05). (3) Acceptance of the intervention model, and mastery of the skills in the caregiver factors had a positive predictive effect on the effect of PCBI very early intervention (t=3.068, 10.468, all P<0.05). Conclusions PCBI very early intervention can effectively reduce the parenting pressure of the caregivers, and in the PCBI very early intervention, the better the mastery of skills and the completion of homework, the better the efficacy of intervention.

Objective To explore the characteristics of social behaviors in toddlers with high-risk of autism spectrum disorder (HR-ASD),and the correlation to the severity of ASD symptoms.Method 32 high-risk ASD toddlers,aged from 12 months to 24 months,and 34 typical developmental (TD) infants/toddlers,aged from 6 months to 24 months,were recruited.Behavioral video of the Still-Face Paradigm (SFP) was used to measure the frequencies and duration of social behaviors,including non-social smiling,protest,eye contact,social smiling and social positive engagement,during the mother-infant interaction and the still face.Autism Diagnostic Observation Scale was used to evaluate severity of clinical symptoms in high-risk ASD toddler.Gesell Development Scale was used to assess the developmental level of the two groups.Independent-sample t test was used to compare the differences of social behaviors between two groups.Pearson correlation analysis was used to analyze the correlation between the social behaviors of high-risk ASD and the age,the developmental level and the severity of ASD symptoms.Binary logistic regression was used to analyze the power of discrimination of social behaviors between HR-ASD and TD.Results During mother-infant interaction,compared with TD group,HR-ASD had significantly shorter duration ((19.8±23.4) s vs.(61.5±34.0) s,t=-5.75,P＜0.01;(6.5±9.3) s vs.(29.0±25.2) s,t=-4.73,P＜0.01;(3.0±8.8) s vs.(13.2±23.1) s,t=-2.34,P=0.02) and lower frequencies (t=-6.62、-3.03、-2.74,all P＜0.01) of eye contact,social smiling and social positive engagement.During the still face,compared with TD group,HR-ASD had significantly shorter duration (t=-3.32,P＜0.01;t=-2.59,P=0.01) and lower frequencies (t=-6.13、-3.48,all P＜0.01) of eye contact and social positive engagement.According to Pearson correlation analysis,during the still face,in HR-ASD group,the duration of eye contact and social positive engagement had significantly negative influence on the score of the language and communication in ADOS (r=-0.49、-0.52,all P＜0.01);The duration and frequencies of eye contact and social positive engagement had significantly negative influence on the score of mutually social interaction in ADOS (r=-0.57,P＜0.01;r=-0.49,P＜0.01;r=-0.74,P＜0.01;r=-0.44,P=0.01);The duration of eye contact and social positive engagement had significantly negative influence on the score of the playing in ADOS (r=-0.43,P=0.01;r=-0.45,P=0.01).According to binary logistic regression,the duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction could distinguish between HR-ASD and TD (OR=1.36,95％CI:1.08-1.71,P=0.01;OR=5.99,95％CI:1.15-31.14,P=0.03).Conclusion HR-ASD hasthe lower levels of eye contact,social smiling and social positive engagement,which may suggestthe severity of ASD core symptoms.The duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction may possiblyfigure out theHR-ASD and could be further developed as a predictablebehavioral maker.

Objective To explore the characteristics of social behaviors in toddlers with high-risk of autism spectrum disorder (HR-ASD),and the correlation to the severity of ASD symptoms.Method 32 high-risk ASD toddlers,aged from 12 months to 24 months,and 34 typical developmental (TD) infants/toddlers,aged from 6 months to 24 months,were recruited.Behavioral video of the Still-Face Paradigm (SFP) was used to measure the frequencies and duration of social behaviors,including non-social smiling,protest,eye contact,social smiling and social positive engagement,during the mother-infant interaction and the still face.Autism Diagnostic Observation Scale was used to evaluate severity of clinical symptoms in high-risk ASD toddler.Gesell Development Scale was used to assess the developmental level of the two groups.Independent-sample t test was used to compare the differences of social behaviors between two groups.Pearson correlation analysis was used to analyze the correlation between the social behaviors of high-risk ASD and the age,the developmental level and the severity of ASD symptoms.Binary logistic regression was used to analyze the power of discrimination of social behaviors between HR-ASD and TD.Results During mother-infant interaction,compared with TD group,HR-ASD had significantly shorter duration ((19.8±23.4) s vs.(61.5±34.0) s,t=-5.75,P＜0.01;(6.5±9.3) s vs.(29.0±25.2) s,t=-4.73,P＜0.01;(3.0±8.8) s vs.(13.2±23.1) s,t=-2.34,P=0.02) and lower frequencies (t=-6.62、-3.03、-2.74,all P＜0.01) of eye contact,social smiling and social positive engagement.During the still face,compared with TD group,HR-ASD had significantly shorter duration (t=-3.32,P＜0.01;t=-2.59,P=0.01) and lower frequencies (t=-6.13、-3.48,all P＜0.01) of eye contact and social positive engagement.According to Pearson correlation analysis,during the still face,in HR-ASD group,the duration of eye contact and social positive engagement had significantly negative influence on the score of the language and communication in ADOS (r=-0.49、-0.52,all P＜0.01);The duration and frequencies of eye contact and social positive engagement had significantly negative influence on the score of mutually social interaction in ADOS (r=-0.57,P＜0.01;r=-0.49,P＜0.01;r=-0.74,P＜0.01;r=-0.44,P=0.01);The duration of eye contact and social positive engagement had significantly negative influence on the score of the playing in ADOS (r=-0.43,P=0.01;r=-0.45,P=0.01).According to binary logistic regression,the duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction could distinguish between HR-ASD and TD (OR=1.36,95％CI:1.08-1.71,P=0.01;OR=5.99,95％CI:1.15-31.14,P=0.03).Conclusion HR-ASD hasthe lower levels of eye contact,social smiling and social positive engagement,which may suggestthe severity of ASD core symptoms.The duration of social smiling during the still face and the frequencies of eye contact during mother-infant interaction may possiblyfigure out theHR-ASD and could be further developed as a predictablebehavioral maker.

Objective To explore the status of glucocorticoid application in patients with systemic lupus erythematosus (SLE) in China.Methods Epidemiological survey was used.The SLE patients who met the 1997 classification criteria of American College of Rheumatology were enrolled.The usage of glucocorticoid and related adverse reactions were recorded and analyzed.Results A total of 400 SLE patients were enrolled,including 35 men and 365 women.The average age was (37.4 ± 14.0) years old,and the average duration of disease was (6.7 ± 5.8) years.There were 310 patients using glucocorticoid as maintenance.Sixty-one percent (n =244) patients started using medium dose (prednisone 30-＜ 60 mg/d) as the initial treatment of glucocorticoid,which lasted for (37 ± 11) days.The time of drug duration in patients with low dose prednisone (7.5-＜30 mg/d)and high dose (60-100 mg/d) was(92 ± 20)and (17 ± 3) days respectively (P ＜ 0.05 between 3 groups).However,patients receiving different initial dosage were of no discrepancy in the maintenance therapy.During maintenance,even though 51.0％ (n =158) patients were on prednisone 2.5-5 mg/d,the duration of drug use in ＞ 5-10 mg/d groupwas longer [(29.9 ± 3.3) months].Patients with involvement of internal organs had a higher tendency to use 60-100 mg/d prednisone or pulse-dose therapy in the initial treatment,nevertheless these two groups had no difference of maintenance dosage.Among all 400 patients,62 patients withdrew glucocorticoid,including 17 patients with disease remission (4.3％),44 by self-withdrawal and one with adverse reaction.Conclusion In China,the medium dosage of glucocorticoid is the most common initial treatment in patients with SLE.Prednisone 2.5-5 mg/d was the most common choicefor maintenance therapy.Currently,the proportion of glucocorticoid withdrawal remains low in SLE patients achieving remission.

Objective:To establish an analytical method for the identification of donkey-hide gelatin in Fufang Ejiao Buxue gran-ule.Methods:The identification of donkey-hide gelatin in Fufang Ejiao Buxue granule was established by rapid resolution liquid chro -matography (UPLC) coupled with triple quadruple mass spectrometry (QQQ-MS).Results: The characteristic molecular peaks of donkey-hide gelatin were detected in ten batches of commercial samples .Conclusion:The present method is specific , precise and reli-able, and suitable for the identification of donkey-hide gelatin in Fufang Ejiao Buxue granule .The method provides scientific reference for the study of quality control method for gelatin ingredients in Chinese patent medicines .

OBJECTIVETo evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).

METHODSPatients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.

RESULTSA total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).

CONCLUSIONAnagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.

Humans ; Hydroxyurea ; administration & dosage ; therapeutic use ; Platelet Aggregation Inhibitors ; administration & dosage ; therapeutic use ; Platelet Count ; Quinazolines ; administration & dosage ; therapeutic use ; Thrombocythemia, Essential ; drug therapy ; Treatment Outcome

Objective:To establish a GC method for determining the content of amantadine hydrochloride in pediatric paracetamol and amanatadine hydrochloride granules. Methods:The ingredients were separated on an Agilent DB-5 quartz capillary column (30 m ×0.25 mm, 0.25 μm), the carrier gas was N2,and the flow rate was 1 ml·min-1. The column temperature was maintained at 130℃, the injection temperature was 250℃,the detection temperature was 280℃ with an FID as the detector , the injection volume was 2 μl, and the split ratio was 20∶1. Results:A good linear relationship was obtained between the peak area and the concentration of amantadine hydrochloride within the range from 0.103 2 to 6.456 0 mg·ml-1(r =0.999 9). The average recovery was 100.18%(RSD=0. 11%, n=6). Conclusion:The method is specific, accurate, reliable and reproducible, which can be used in the quality control of pediatric paracetamol and amanatadine hydrochloride granules.

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.