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.

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration.Despite extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet.Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage.But to date,the absence of promising therapeutic biomaterials/scaffolds remains.The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds.To address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds.Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony edges.Especially,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered.This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

Antimicrobial peptides (AMPs) are a class of peptides widely existing in nature with broad-spectrum antimicrobial activity. It is considered as a new alternative to traditional antibiotics because of its unique mechanism of antimicrobial activity. The development and application of natural AMPs are limited due to their drawbacks such as low antimicrobial activity and unstable metabolism. Therefore, the design and optimization of derived peptides based on natural antimicrobial peptides have become recent research hotspots. In this paper, we focus on ribosomal AMPs and summarize the design and optimization strategies of some related derived peptides, which include reasonable primary structure modification, cyclization strategy and computer-aided strategy. We expect to provide ideas for the design and optimization of antimicrobial peptides and the development of anti-infective drugs through analysis and summary in this paper.
Antimicrobial Cationic Peptides/chemistry* ; Antimicrobial Peptides ; Drug Design ; Anti-Infective Agents/pharmacology* ; Anti-Bacterial Agents

Objective:To investigate the effect of celastrol (CEL) on autophagy and endoplasmic reticulum stress-mediated apoptosis in a mouse model of nonalcoholic fatty liver disease (NAFLD).Methods:Eighteen male C57BL/6J mice were randomly divided into normal control (NC, n=6), high-fat diet (HFD, n=6) and celastrol group (HFD+CEL, n=6). The normal control group was fed with regular diet, and the high-fat diet and celastrol group were fed with high-fat diet for 12 weeks. After successful modeling, celastrol group were injected with 100 μg?kg -1?d -1 celastrol intraperitoneally for 4 weeks, and NC and HFD group were injected intraperitoneally with the same doses of normal saline. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured in mouse after 4-weeks of intervention. HE and Oil Red O staining were used to observe the pathomorphological changes and lipid droplet deposition in mouse liver, and the findings were scored according to NAFLD activity score (NAS). Western blot was used to detect the expression levels of liver microtubule associated protein 1 light chain 3 (LC3), P62, glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), activated transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), cleaved Caspase-3(cleaved caspase-3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 related X protein (Bax).TUNEL staining was used to observe the apoptosis of hepatocytes. One-way analysis of variance was used for the intergroup comparison. Results:Serum levels of ALT (68.71±8.57) U/L, AST (209.63±28.64) U/L, TG (0.97±0.14) mmol/L, TC (4.12±0.64) mmol/L, and LDL -C (0.40±0.06) mmol/L were lower in celastrol group mouse than HFD group [(110.19±10.79) U/L, (399.72±73.47) U/L, (1.44±0.13) mmol/L, (5.65±0.54) mmol /L, (0.61±0.07) mmol/L] ( P<0.05); while the serum HDL-C level (1.29±0.17) mmol/L was higher in celastrol than HFD group (0.72±0.13) mmol/L ( P<0.05). HE and Oil Red O staining showed that lipid deposition and intralobular inflammation were apparent in the liver tissue of HFD group mouse, and the NAS score was significantly increased, while the hepatocyte steatosis and intralobular inflammation were alleviated after celastrol intervention, and the NAS score was decreased significantly ( P<0.05). Compared with HFD group, the ratio of LC3II/I was significantly increased in the liver of celastrol group mouse, and the P62 was significantly decreased ( P<0.05). Meanwhile, the expression level of GRP78, p-PERK/PERK , ATF4, and CHOP was significantly lower in celastrol than HFD group ( P<0.05). In addition, the expressions of cleaved caspase-3 and Bax were significantly lower in celastrol than HFD group, and the expression of Bcl-2 was significantly increased ( P<0.05). At the same time, the apoptosis rate of hepatocytes was also significantly lower in celastrol than HFD group ( P<0.05). Conclusion:Celastrol can effectively alleviate the lipid deposition, protect hepatocytes and delay the progression of non-alcoholic fatty liver disease in mouse liver with non-alcoholic fatty liver disease. In addition, its mechanism of action may be related to the induction of autophagy, inhibition of endoplasmic reticulum stress PERK/ATF4/CHOP pathway and its mediated apoptosis.

Objective To analyze the risk factors of multi-drug resistant organism (MDRO) infection after liver transplantation. Methods The clinical data of 77 recipients undergoing liver transplantation were retrospectively analyzed. According to the incidence of MDRO infection, all recipients were divided into the non-MDRO infection group (n=51) and MDRO infection group (n=26). The infection rate and strain distribution of MDRO in liver transplant recipients were summarized. The risk factors of MDRO infection in liver transplant recipients were identified. Clinical prognosis of all recipients was statistically compared between two groups. Results The infection rate of MDRO after liver transplantation was 34% (26/77), mainly carbapenem-resistant MDRO infection. The main sites of infection included lung, abdominal cavity and incision. Univariate analysis showed that postoperative tracheal intubation ≥48 h, length of intensive care unit (ICU) stay ≥72 h, length of hospital stay ≥30 d, re-operation, continuous renal replacement therapy (CRRT) and tacrolimus (Tac) blood concentration ≥15 ng/mL were the risk factors for MDRO infection after liver transplantation. Cox regression analysis indicated that postoperative tracheal intubation≥48 h, re-operation, CRRT and Tac blood concentration ≥15 ng/mL were the independent risk factors for MDRO infection after liver transplantation. The fatality in the MDRO infection group was significantly higher than that in the non-MDRO infection group [31%(8/26) vs. 10%(5/51), P=0.01]. Conclusions Postoperative tracheal intubation ≥48 h, re-operation, CRRT and Tac blood concentration ≥15 ng/mL may increase the risk of MDRO infection after liver transplantation and affect clinical prognosis of the recipients.

Objective: To compare the color stability of Biodentine and mineral trioxide aggregate (MTA) within the blood environment in vitro and to further investigate the underlying reasons for such color instability. Methods : We first generated Biodentine and MTA discs with a diameter of 5 mm and a height of 3 mm. 24 discs of each material were randomly divided into two groups: the deionized water group and the defibrinated sheep blood group. Discs of each group were immersed for 1 day or 7 days before assessments. First, all discs were photographed to directly compare the discoloration of Biodentine and MTA. The color degree of the two materials was tested by a spectrophotometer. Then, the high-resolution morphological characteristics were observed by scanning electron microscopy. Finally, the chemical contents of each element in the material were measured by energy-dispersive spectroscopy. Results : Compared to immediately after stripping, a change in the brightness of discs after immersion in defibrinated sheep blood for 1 day was observed only in MTA. On the 7th day after being immersed in blood, the colors of both the Biodentine and MTA discs darkened and turned deep red, but the darkness of the MTA discs increased significantly. The color change of MTA immersed in blood was measured on a spectrophotometer with a greater 7-day ∆E (21.257 ± 0.955) than the Biodentine 7-day ∆E (5.833 ± 0.501) (t=24.781, P < 0.001). MTA exhibits more discoloration as the immersion time goes on. A significant difference was noted between the 1-day ∆E(6.233 ± 0.888) and the 7-day ∆E(t=19.956, P < 0.001) of MTA immersed in blood. However, there was no statistically significant difference between the 1-day ∆E (6.790 ± 0.831) and the 7-day ∆E(t=1.707, P=0.163) of Biodentine immersed in blood. It was observed by scanning electron microscopy that after 7 days of immersion in the defibrinated sheep ablood, the surface porosity of MTA was larger than that of Biodentine, and the crystal edge of MTA became rounded and blunt. The analysis by energy-dispersive X-ray spectroscopy showed that the oxygen content decreased and the bismuth content increased in MTA after immersion in defibrinated sheep blood for 7 days. Zirconium was not detected in Biodentine due to its low radiodensity, but the contents of other elements were stable in Biodentine after immersion in defibrinated sheep blood for 7 days. Conclusion The color stability of Biodentine within the blood environment is better than that of MTA in vitro, which is mainly related to the low surface porosity and stable composition of the anti-radiation agent of Biodentine.

Objective To investigate the relationship between image quality of PET/CT in automatic tube current modulation and effective dose(ED) of patients and to determine the optimal acquisition scheme.Methods Scanning was performed on anthropomorphic phantom RS-550 using GE Discovery ST-16 or Discovery Elite PET/CT.The same CT acquisition conditions was used:tube voltage 120 kV,pitch 1.375,rotation speed 0.8 s,noise index ranged from 8 to 30,interval 2,automatic tube current low limit 30 mA,high limit ranged from 200 to 350 mA,interval 50 mA.The images were analyzed,and the noise,signal to noise ratio (SNR) and figure of merit (FOM) of main organs in the abdomen were calculated.The relationship between image quality and ED was analyzed.Two-sample t test was used for data analysis.Results The noise of each organ decreased significantly along with the increase of ED until the ED of ST-16 increased to 15 mSv or Elite increased to 12 mSv,then the image noise decreased gently.SNR of each organ image increased along with the increase of ED.The FOM of liver decreased along with the increase of ED,while the FOM of other organs did not change significantly with ED.All image indicators of Elite PET/CT were better than ST-16 PET/CT at the same ED (5-20 mSv),though there was no significant difference (t:0.133-4.701,all P＞0.05).When ED was 5 mSy,the noise of liver with ST-16 was 12.0％ (28.9 vs 25.8)higher than that with Elite,and the SNR and FOM of liver with Elite was 13.9％ (4.1 vs 3.6) and 66.7％ (0.50 vs 0.30) higher than that with ST-16,respectively.Conclusion When the ED caused by the 2 PET/CT systems was between 5-20 mSy,the image quality is improved along with the ED increasing in a certain range.

Objective To explore the altered expression of circular RNA (circRNA) and mRNA in the mouse cortex in the early phase of subarachnoid hemorrhage (SAH) and possible biological functions of the circRNA in early brain injury (EBI).Methods A total of 18 C57BL/6J male mice were randomly divided into a sham and a SAH group (n=9).SAH models were prepared by endovascular perforation.Total RNAs of brain samples were extracted to construct the cDNA library 24 h after operation.RNA-sequencing (RNA-seq) was carried out by HiSeqTM 2500 User Guide and followed by RT-qPCR for confirmation.Reads were aligned to the mouse transcriptome to obtain expression profiles ofcircRNA and mRNA.Bioinformatic study included GO analysis,KEGG pathway analysis and forecast of targeted miRNA of circRNA.Results A total of 26 circRNA (6 up-regulated and 20 down-regulated) and 804 mRNA (396 up-regulated and 408 down-regulated) were significantly changed.These altered mRNA were mainly related to regulation of neuronal synaptic plasticity,inflammatory and immune response.Bioinformatics showed that some significantly altered circRNA contained binding sites for many miRNA.The RT-qPCR analysis of 4 randomly selected circRNA (circFoxj3,circSetbp1,circArpp21 and circ2010111 I01Rik) confirmed the accuracy of RNA-seq.Conclusions SAH alters the expression of circRNA in mouse cortex and the differentially expressed circRNA may be involved in regulation of EBI following SAH,promising a potential therapeutic target for the diagnosis,treatment and prognosis of SAH.