ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

Objective:To analyze the frequency and characteristics of polymyositis (PM) in idiopathic inflammatory myopathy (IIM), and to investigate whether PM is over-diagnosed.Methods:Patients diagnosed as IIM according to the Bohan & Peter criteria of IIM hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2008 to 2019 were involved in the study. Definite PM (dPM) was defined as typical clinical and pathological features including elevated creatine kinase (CK) level, muscle weakness and muscle biopsy findings with endomysial CD8 + T cell infiltration and expression of MHC-1 on sarcolemma. Meanwhile, dermatomyositis (DM), anti-synthase syndrome(ASS), immune-mediated necrotic myopathy(IMNM), sporadic inclusion body myositis(sIBM) and other myopathies were excluded according to the new classification criteria of IIM subtypes respectively. Statistical analysis was performed using SPSS software 24.0. The Kruskal-Wallis test and χ2 test were used to compare the clinical characteristics between the dPM group and other IIM subtypes. Results:A total of 1 259 patients with IIM including 1 015 (80.6%) DM and 244(19.4%) PM were enrolled in this study. According to the strict definition of PM criteria, only 0.5% of patients (6/1 259) in IIM could be diagnosed as dPM. Most PM patients were IMNM and ASS according to the new IIM subtypes criteria, of which 48.0% (117/244) were IMNM and 32.0% (78/244) were ASS. 66.7%(4/6) of dPM patients were women. One complicated with RA, and one was dPM overlaped with systemic sclerosis. All of them had muscle weakness, mild elevation of CK level [611(391,1 451) U/L], and were myositis-specific autoantibodies negative. Except one dPM patients who did not receive immunoregulatory therapy due to chronic obstructive pulmonary disease, the others were administrated with low or medium dose prednisone combined with or without immunosuppressive agents. After a median follow-up of (38±26) months, the muscle strength of dPM patients were improved.Conclusion:dPM is a very rare clinical subtype of IIM. PM is an over-diagnosed entity in clinical practice. Patients with dPM have mild symptoms and good outcome.

Objective:To determine the serum levels of chemokine CCL27 and its clinical relevancein patients with dermatomyositis (DM).Methods:The serum CCL27 levels of 58 DM patients, 21 polymyositis (PM) patients, 20 systemic lupus erythematosus (SLE) patients and 31 healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The score of disease activity was measured by two physicians-based on the myositis disease activity assessment tool (MDAAT). Its correlation with serum levels of CCL27 was analyzed. The difference between multiple groups were compared using analysis of variance (ANOVA) and t test, and the relevance was analyzed using Spearman correlation analysis and generalized method of moments (GEE) model. Results:Theserum level of CCL27 in DM patients (178±49) pg/ml was significantly higher than PM (110±40) pg/ml, SLE (141±46) pg/ml and healthy controls (137±38) pg/ml ( F=14.192, P<0.01). Crosssectional analysis showed that the serum CCL27 levelwaspositively correlated with global disease activity ( r=0.301, P=0.022) andskin disease activity ( r=0.493, P<0.01). Patients with V sign had higher serum CCL27 levels (191±52) pg/ml than the patients without (153±33) pg/ml ( t=2.839, P<0.01). Patients with holster sign had higher serum CCL27 levels (196±58) pg/ml than the patients without (168±41) pg/ml ( t=2.176, P=0.034). Follow-up study also found that CCL27l evels were positively correlated with global disease activity ( β=0.031, P=0.042) and skin disease activity ( β=0.032, P<0.01). Conclusion:The serum CCL27 levels are increased in patients with DM and can reflect the skin disease activity. The results of this study suggest that CCL27 may be a marker for cutaneous damage and monitoring of therapeutic effect.

Objective: To evaluate the accuracy of endoscopic titanium clip localization combined with CT three-dimensional reconstruction for the control of incision margin in early gastric cancer under laparoscopy. Methods: A prospective analysis was made for gastric cancer whose lesions were located in the middle of the stomach and T stage was 1 to 2 from October 2017 to January 2019 at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital. Totally 25 patients were eventually enrolled in the study. There were 17 males and 8 females aging of (63.6±7.2) years (range: 48 to 77 years). All cases were treated with titanium clip localization under endoscope combined with CT three-dimensional(3D) reconstruction to construct a virtual panorama of gastric cavity and lesions, and to design surgical margins. Laparoscopic surgical resection was performed according to the surgical margins designed before operation. The distance from the gastric angle to the origin of the minor curvature of the incisional margin, the distance from the gastric angle to the the center of lesion and the distance of the upper incision margin were measured under three-dimensional CT reconstruction and under actual specimen. Paired t test was used to compare the three distances measured by two methods. Results: The measured distances from the gastric angle to the center of the lesion and the proximal incisional margin under 3D reconstruction CT were according to the measured values of actual specimens ((2.67±1.38) cm vs. (2.83±1.56) cm, t=1.51, P=0.14; (5.23±0.60) cm vs. 5 cm, t=1.93, P=0.07); the measured distances from the gastric angle to the origin of the minor curvature of the incisional margin under CT 3D reconstruction were different with the measured values of solid specimens ((5.94±0.94) cm vs. (6.37±0.90) cm, t=3.52, P=0.00). Conclusion The method of titanium clip localization combined with CT 3D reconstruction can provide a feasible laparoscopic localization method and incision edge solution for T1 to T2 gastric central cancer.

Objective To evaluate the accuracy of endoscopic titanium clip localization combined with CT three?dimensional reconstruction for the control of incision margin in early gastric cancer under laparoscopy. Methods A prospective analysis was made for gastric cancer whose lesions were located in the middle of the stomach and T stage was 1 to 2 from October 2017 to January 2019 at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital. Totally 25 patients were eventually enrolled in the study. There were 17 males and 8 females aging of (63.6± 7.2) years (range: 48 to 77 years). All cases were treated with titanium clip localization under endoscope combined with CT three?dimensional(3D) reconstruction to construct a virtual panorama of gastric cavity and lesions, and to design surgical margins. Laparoscopic surgical resection was performed according to the surgical margins designed before operation. The distance from the gastric angle to the origin of the minor curvature of the incisional margin, the distance from the gastric angle to the the center of lesion and the distance of the upper incision margin were measured under three?dimensional CT reconstruction and under actual specimen. Paired t test was used to compare the three distances measured by two methods. Results The measured distances from the gastric angle to the center of the lesion and the proximal incisional margin under 3D reconstruction CT were according to the measured values of actual specimens ((2.67±1.38) cm vs. (2.83±1.56) cm, t=1.51, P=0.14; (5.23±0.60) cm vs. 5 cm, t=1.93, P=0.07); the measured distances from the gastric angle to the origin of the minor curvature of the incisional margin under CT 3D reconstruction were different with the measured values of solid specimens ((5.94±0.94) cm vs. (6.37±0.90) cm, t=3.52, P=0.00). Conclusion The method of titanium clip localization combined with CT 3D reconstruction can provide a feasible laparoscopic localization method and incision edge solution for T1 to T2 gastric central cancer.

Objective To evaluate the accuracy of endoscopic titanium clip localization combined with CT three?dimensional reconstruction for the control of incision margin in early gastric cancer under laparoscopy. Methods A prospective analysis was made for gastric cancer whose lesions were located in the middle of the stomach and T stage was 1 to 2 from October 2017 to January 2019 at Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People′s Hospital. Totally 25 patients were eventually enrolled in the study. There were 17 males and 8 females aging of (63.6± 7.2) years (range: 48 to 77 years). All cases were treated with titanium clip localization under endoscope combined with CT three?dimensional(3D) reconstruction to construct a virtual panorama of gastric cavity and lesions, and to design surgical margins. Laparoscopic surgical resection was performed according to the surgical margins designed before operation. The distance from the gastric angle to the origin of the minor curvature of the incisional margin, the distance from the gastric angle to the the center of lesion and the distance of the upper incision margin were measured under three?dimensional CT reconstruction and under actual specimen. Paired t test was used to compare the three distances measured by two methods. Results The measured distances from the gastric angle to the center of the lesion and the proximal incisional margin under 3D reconstruction CT were according to the measured values of actual specimens ((2.67±1.38) cm vs. (2.83±1.56) cm, t=1.51, P=0.14; (5.23±0.60) cm vs. 5 cm, t=1.93, P=0.07); the measured distances from the gastric angle to the origin of the minor curvature of the incisional margin under CT 3D reconstruction were different with the measured values of solid specimens ((5.94±0.94) cm vs. (6.37±0.90) cm, t=3.52, P=0.00). Conclusion The method of titanium clip localization combined with CT 3D reconstruction can provide a feasible laparoscopic localization method and incision edge solution for T1 to T2 gastric central cancer.

Objective To investigate the association of distinct myositis specific autoantibodies (MSAs) with long-term survival of patients with polymyositis (PM) and dermatomyositis (DM).Methods We analyzed the clinical data and outcome of patients with PM and DM who were hospita-lized in the department of rheumatology of China-Japan Friendship hospital from 1994 to 2015,and evaluated the impact of MSAs on the prognosis of patients.Multivariate Cox regression analysis was used to identify the prognostic risk factors for PM/DM patients.Results A total of 383 PM/DM patients were followed up for 1-333 months.Cumulative survival and 10-year survival rate of all patients were 68.6％ and 76.2％,respectively.The survival rate of 80.4％ and 77.1％ at 3 and 5 years in patients with MSAs,which were lower than those of patients with-out MSAs,who had the survival rate of 90.1％ and 87.4％ at 3 and 5 years,respectively(x2=3.90 and 3.98,P＜0.05).There was significant difference for long-term survival in all MSAs positive groups (x2=40.654,P=0.000).Anti-MDA5 positive patients who had the 10-year survival rate of 28.7％ had the worst prognosis,while anti-HMGCR positive patients who had the l0-year survival rate of 100％ had the best outcome in all groups.Multivariate Cox regression analysis showed that independent risk factors associated with the long-term survival of patients were age of onset,complicated with malignancies,dysphagia,rapidly progress interstitial lung disease,antiMDA5 antibody positive,increased serum aspartate transferase and C reaction protein.Conclusion MSAs are strongly associated with the prognosis of patients with PM/DM.Patients with MSAs has worse 5-year overall survival than those without MSAs,which indicates that screening MSAs and aggressive treatment for PM/DM patients at very early stage of disease may improve the outcome.

Objective To identify clinical features and risk factors in adult dermatomyositis (DM) with calcinosis.Methods Four hundred and eighty patients' clinical data were collected.The correlation between calcinosis and no calcinosis in adult DM were calculated by t test,x2 test and Mann-whitney U test.Multifactor logistic regression model was established to analyze independent factors for adult DM with calcinosis.Results Calcinosis occurred in 22 cases among these 480 patients with DM.The incidence of adult DM with calcinosis was 4.6％.Calcinosis was most common in the extremities and trunks.Patients with calcinosis had a longer disease duration [48 (24,120) months vs 10 (3,24) months,U=1993,P=0.000)] and more myothenia (95.5％ vs 76.9％,x2=4.192,P=0.038),panniculitis (9.1％ vs 0.4％,P=0.011),periungual erythematosus (22.7％ vs 5.89％,x2=7.044,P=0.008),skin ulcer (50.0％ vs 5.2％,x2=55.767,P=0.000),Raynaud's phenomenon (27.5％ vs 8.1％,x2=3.956,P=0.047).The anti-NXP2 antibody (27.3％ vs 3.9％,x2=19.416,P=0.000) and antiMDA5 antibody (31.8％ vs 12.9％,x2=4.851,P=0.028) were more frequently found in patients with calcinosis.Multi-factor logistic regression showed that anti-NXP2 antibody [OR=10.899,95％CI (2.593,45.816),P=0.001],long diseases duration [OR=1.105,95％CI(1.008,1.021),P=0.000] and skin ulcer [OR=31.585,95％CI(10.683),93.387,P=0.000] were risk factors for adult DM with calcinosis.Conclusion The incidence of calcinosisis in adult DM is 4.5％ in our cohort.Patients with calcinosis are adistinct clinical subset of adult DM.Long disease duration,skin ulcer and anti-NXP2 positive are independent risk factors for adult DM with calcinosis.

Objective The aim of this study is to analyze the prevalence of myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese dermatomyositis (DM) patients. Methods Four hundreds and twenty-seven DM patients were enrolled in this retrospective study. Clinical features and sera were collected. Twelve subtypes of MSAs were detected by commercial test kits. The correlations between MSAs and clinical phenotypes in DM patients were calculated by t test, Mann-Whitney U test or χ2 test. In order to clarify whether MSAs subsets would be independent factors of certain clinical feature or not, separate models were established to test the correlation via the Logistic regression analysis. Results The positivity of MSAs was 69.8% in 427 patients with DM. Anti-ARS, anti-MDA5 and anti-TIF1-γ antibodies were the three most common MSAs in the DM patients with positivity of 19.9%, 17.6%and 17.1% respectively. Different kinds of rash associated with MSAs subtypes by χ2 test. Certain MSAs subtype might be an independent factor for clinical features via logistic regression analysis. Interstitial lung disease (ILD) was observed more frequently in patients carrying anti-MDA5 [OR=5.266, 95%CI (2.522, 10.996), P<0.01] and anti-Jo-1 [OR=6.232, 95%CI (1.674, 23.199), P=0.006]. On the contrary, anti-Mi2 [OR=0.208, 95%CI (0.074, 0.580, P=0.003] and anti-TIF1-γ [OR=0.189, 95%CI (0.096, 0.370), P<0.01] were protective factors against developing ILD. Anti-TIF1-γ was an independent risk factor for cancer-associated myositis [OR=5.907, 95%CI (2.868, 12.168), P<0.01]. Anti-TIF1-γ[OR=2.789, 95%CI (1.594, 4.880) P<0.01], anti-NXP2 [OR=2.983, 95%CI (1.274, 6.982), P=0.012] and anti-SAE1 [OR=4.815, 95%CI (1.082, 21.424), P=0.039] could worsen dysphagic tendencies. In contrast, anti-MDA5 [OR=0.349, 95%CI (0.169, 0.720), P=0.004] might decrease the prevalence of this manifestation. Conclusion Patients with DM have a high frequency of MSAs. Some subtypes of MSAs are correlated with and may be independent factors of different clinical phenotypes. These indicated that MSAs can be useful biomarkers in monitoring the extramuscular features in DM patients.

Objective To assess the mid-or long-term clinical outcomes of the structural bone graft of superolateral acetabulum in total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH).Methods Thirty-three patients with DDH (33 hips) were treated by THA with the structural bone graft of superolateral acetabulum technique between April 2002 and December 2011.There were 28 females and 5 males with the mean age at surgery 54.0±14.5 years (21-76 years).The degree of dislocation was graded preoperatively as Crowe Ⅱ in 12 patients,Crowe Ⅲ in 8 patients,and Crowe Ⅳ in 13 patients.The following outcomes were assessed,Harris hip score (HHS),the leg-length discrepancy,the height and horizontal distance of center of hip rotation,rate of cup coverage,the coverage ratio of bone graft,periprosthetic osteolysis,bone ingrowth,and cup loosening.Results The average follow-up was 9.3±3.3 years (5-15 years).The HHS improved from 40.9±13.7 preoperatively to 93.6±7.8 at the final follow-up (t=21.483,P=0.000).The leg-length discrepancy decreased from 24.2± 17.1 mm pre-operatively to 3.7±3.5 mm at postoperative 3 months (t=6.747,P=0.000).The height and horizontal distance of center of hip rotation decreased from preoperative 45.9±16.0 mm and 42.9±8.7 mm to postoperative 23.8±5.8 mm and 23.6±2.9 mm (t=7.460,P=0.000;t=12.090,P=0.000) at postoperative 3 days,respectively.The cup coverage and coverage ratio of bone graft was 100％ and 27.1％±6.9％,respectively.All grafts appeared to be incorporated without evidence of resorption and collapse.The mean time of incorporation was 7.6 ± 2.8 months.The coverage ratio of bone graft ＞25％ have a significantly long time of incorporation than that ＜25％ (9.4±2.3 months versus 6.3±2.4 months,t=5.357,P=0.000).At the final follow-up,all hips showed bone ingrowth fixation of the acetabular cup and stem.Five hips showed osteolysis,two hips in acetabular zone Ⅱ,three hips in femur zone Ⅰ and five hips in femur zone Ⅶ.The main complications were intraoperative femoral fractures (61％) without neurological damage,nonunion and dislocation.Conclusion The structural bone graft of superolateral acetabulum in THA for DDH can achieve satisfactory mid-or long-term outcomes.The superolateral acetabular deficiency can be reconstructed by bone graft.The bone graft coverage less than 25％ is conducive to fusion of bone graft and acetabular bone.However,intraoperative femoral fracture is common complication.