Objective To investigate the possible mechanism of endonuclease G (Endo G)-mediated non-Caspase-dependent apoptotic pathway in brain neuronal apoptosis in chronic fluorosis rats.Methods Sixty Sprague Dawley (SD) rats (half male and half female) were randomly divided into two groups:control group fed with tap water with fluoride content ＜ 0.5 mg/L and fluorine group in which sodium fluoride was added into drinking water with fluoride content of 50.0 mg/L.Both groups were fed with standard food with fluorine content ＜ 0.5 mg/kg.The experiment period was 10 months.At the end of the experiment,all the animals were sacrificed,and brain tissue was taken.Flow cytometry was used to examine apoptosis rate,immune-histochemistry was employed to detect the distribution of Endo G in brain tissue;Western blotting was used to test the protein expression of Endo G.Results Compared to the apoptosis rate of control group [(1.3 ± 0.6)％,(1.9 ± 0.3)％],the apoptosis rate in hippocampus and cortex of rats with chronic fluorosis [(2.6 ± 0.6)％,(3.1-± 0.7)％] was significantly increased (t =3.1,3.4,all P ＜ 0.05).The Endo G positive neurons and their degree of staining in CA1,CA2,CA3 and CA4 of hippocampus,frontal cortex as well as the upper layer of parietal cortex [(11.1 ± 2.2),(10.2 ± 1.9),(9.8 ± 3.1),(9.9 ± 1.6),(10.6 ± 2.9),(8.2 ± 2.4),(11.1 ± 2.8) scores] in rats with chronic fluorosis were significantly higher than those in the control group [(5.8 ± 1.8),(6.7 ± 2.6),(5.2 ± 2.4),(7.2 ± 2.1),(7.7 ± 2.6),(6.1 ± 1.9),(8.1 ± 2.6) scores,t =2.9,2.5,2.4,2.3,2.2,2.5,2.3,P ＜ 0.01 or ＜ 0.05].The protein level of Endo G in the mitochondria of rat brains with chronic fluorosis [(86.4 ± 7.2)％,(83.9 ± 6.8)％] was significantly lower than that of control group [(100.0 ± 6.1)％,(100.0 ± 5.5)％,t =2.6,2.3,all P ＜ 0.05].Meanwhile,the protein level of Endo G in the nucleus of neurons from chronic fluorosis rats [(117.5 ± 6.4)％,(115.2 ± 6.2)％] was significantly higher than that of the control [(100.0 ± 5.2)％,(100.0 ± 5.5)％,t =2.5,2.2,all P ＜ 0.05].Conclusion The high expression of Endo G and nuclear transfer are related to the neuron apoptosis in chronic fluorosis rat,which may be one of the mechanisms of brain injury of the disease.

Objective To investigate the clinical value of fetal echocardiography in prenatal diagnosis of partial and intermediate atrioventricular septal defect (AVSD). MethodsUltrasound images of11casesof partialandintermediateAVSDconfirmedbyautopsy orpostnatal echocardiography were retrospectively analyzed and the characteristics were summarized. Results Fetal echocardiography of seven cases of partial AVSD and four cases of intermediate AVSD at fourchamber view showed ostium primum atrial septal defect and the mitral and tricuspid valves attaching at the same level on the interventricular septum. Atrio-ventricular valves took on a straight, bar-liked appearance when closed and constituted a “T” shape with interventricular septum. One partial AVSD case showed left ventricle-right atrium canal. All intermediate AVSD cases showed upper ventricular septal defect. There were four cases associated with mitral reflux, one associated with mitral and tricuspid reflux and one with bilateral radius absence. Conclusions “T” shape image is of great clinical value in prenatal diagnosis of fetal partial and intermediate AVSD. The coronary sinus may lead to false positive diagnosis.

OBJECTIVE： To analyze chemical components as coumarin in Saposhnikovia divaricata， and to provide reference for comprehensive analysis of pharmacodynamic material base in S. divaricata. METHODS： UPLC-Q-TOF-MS method was adopted. Chromatographic condition： the determination was performed on ACQUITY UPLC BEH C18 column with mobile phase consisted of 0.1％ formic acid water-0.1％ formic acid acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 35 ℃， and sample size was 3 μL. MS condition： ESI， in positive and negative ion mode， ESI+/ESI－ 5 500 V/－4 500 V， declustering potential of 80-－80 V， auxiliary heating gas pressure of 55.00 psi， atomizing gas pressure of －55 psi， curtain gas pressure of －35.00 psi， desolvent temperature of 550 ℃， collision activation scanning energy of 15 eV， collision voltage of 35 psi. Component analysis was performed by comparing with the related literature data and the standard chromatogram control combined with accurate relative molecular mass of compounds provided by UPLC-Q-TOF-MS. RESULTS： Totally 135 chemical components were analyzed in ESI+ mode， and the 105 chemical components were analyzed in ESI－ mode. 11 chemical components as coumarin were identified in ESI+ mode， such as isoimperatorin， umbelliferone， scopolamine， xanthotoxin， psoralen， Ostenol， fraxidin， isoimperatorin， 5-hydroxyl-8-methoxypsoralen， phellopterin， decursin. CONCLUSIONS： The method is accurate and rapid， and can be used for the analysis of chemical components as coumarin in S. divaricata.

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 To prepar e and characterize danazol （DAZ）-sodium caseinate （SC）composite nanoparticles ，and to study the mechanism of preparing nanoparticles in “bottom-up”technology. METHODS SC was used as a stabilizer for regulating nanoparticles，so that DAZ-SC composite nanoparticles were prepared by anti-solvent precipitation method. The particle size ， Zeta-potential，micro-morphology，stability，encapsulation efficiency ，drug loading and in vitro dissolution rate were characterized. Fluorescence spectra ，IR spectra ，FBRM and other methods were used to analyze the interaction mechanism between DAZ and SC. RESULTS The particle size of DAZ-SC composite nanoparticles was （223.7±12.5）nm，and the polydispersity index was 0.274± 0.012. Zeta-potential was －（17.81±1.63）mV（n＝3）. The stability of nano-suspension was good ，the solid properties of DAZ were greatly improved ，and the dissolution rate was significantly increased. SC was statically quenched under the action of DAZ and the secondary structures of SC were changed. The crystallization process of DAZ was controlled under the action of SC ，and the interaction between DAZ and SC was mainly hydrogen bond and van der Waals force. CONCLUSIONS In this study ，DAZ-SC composite nanoparticles are successfully prepared. In the “bottom-up”technology，the interaction between SC and DAZ caused by hydrogen bond and van der Waals force inhibits the growth and agglomeration of drug crystals .

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome