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 investigate the clinical characteristics, risk factors, and prognosis of invasive pulmonary aspergillosis (IPA) in patients with dermatomyositis associated with positive anti-melanoma differentiation-associated gene 5 (MDA5-DM).Methods:A total of 55 patients with MDA5-DM were analyzed. Patients were divided into IPA (+) group (14 cases) and IPA (-) group (41 cases) based on the presence of IPA. Microbiological examination and clinical data were analyzed. Risk factor analysis was performed using Binary Logistic regression, and survival analysis was carried out using Kaplan-Meier method.Results:Aspergillus flavus (5/14, 35.7%) and Aspergillus fumigatus (4/14, 28.6%) were the most common species in MDA5-DM patients with IPA. Compared to the IPA (-) group, IPA (+) group had higher serum level of α-hydroxybutyrate dehydrogenase (246 U/L vs. 191 U/L, Z=-2.02, P=0.043) and ferritin [1 306.7(518.7, 2 977.8)ng/ml vs. 472.6(269.0, 792.1)ng/ml, Z=-2.09, P=0.036], lower CD8 + T lymphocyte counts {[111.5 (68.3, 214.0)]×10 6/L vs. [188.0(141.0, 270.0)]×10 6/L, Z=-2.18, P=0.029}, and more positive BALF GM tests [70.0%(7/10) vs. 18.9%(7/37), χ2=9.82, P=0.004]. Elevated serum ferritin was found to be an independent risk factor for IPA occurrence [adjusted OR (95% CI)=1.001 (1.000, 1.002), P=0.031)]. In addition, the 6-month cumulative survival rate was significantly lower in the IPA (+) group than in the IPA (-) group (78.6% vs. 97.6%, P=0.021). Conclusion:The mortality of MDA5-DM patients is increased after IPA infection. Elevated serum ferritin is an independent risk factor for IPA occurrence, and active prevention and treatment of IPA are expected to improve the prognosis of patients.

The establishment of mother-infant bonding is closely related to maternal mental health and early growth and development of infants. This paper reviews the concept, evaluation tools, influencing factors and intervention measures of maternal-infant bonding, in order to provide a basis for promoting the normal establishment of postpartum maternal infant relationships and maternal infant health.

Objective:To investigate the effects of acetabular cup positions on the acetabular side stress in hip dysplasia after total hip arthroplasty (THA) using finite element analysis.Methods:Data were obtained from a 36-year-old female patient with developmental dysplasia of the hip. Three-dimensional finite element models were established for different acetabular cup positions using finite element analysis. Each model was categorized based on the center of rotation into four groups: anatomical rotation center, high rotation center, lateralized rotation center, superior-lateral rotation center. ANSYS software applied loads to the model to simulate the stress around the acetabulum in standing (588 N vertical stress) and walking conditions ( X=325 N, Y=-195 N, Z=1 462.5 N). Quantitative analyses of the relative displacement and stress at the acetabular-bone interface were conducted for each region under the two different loading conditions in all eight models. Results:In the standing position with a cup coverage of 90%, the relative displacement at the acetabular-bone interface was: 45.16 μm for the anatomical rotation center group, 47.57 μm for the high rotation center group, 77.27 μm for the lateralized rotation center group, and 96.13 μm for the superior-lateral rotation center group. Acetabular stress values were 9.07 MPa for the anatomical rotation center group, 11.23 MPa for the high rotation center group, 10.88 MPa for the lateralized rotation center group, and 17.75 MPa for the superior-lateral rotation center group. With a cup coverage of 70%, the relative displacements were 64.15, 65.71, 104.10, and 144.53 μm for the respective groups. The corresponding stresses were 9.30, 11.31, 13.98, and 21.45 MPa. In the walking state with a cup coverage of 90%, the relative displacements at the acetabular-bone interface were 189.67 μm for the anatomical rotation center group, 173.55 μm for the high rotation center group 311.03 μm for the lateralized rotation center group, and 572.93 μm for the superior-lateral rotation center group. The stresses were 39.92, 37.33, 47.92, and 71.94 MPa, respectively. With a cup coverage of 70%, the relative displacements were 239.09 μm for the anatomical rotation center group, 248.83 μm for the high rotation center group, 381.84 μm for the lateralized rotation center group, and 1105.90 μm for the superior-lateral rotation center group. The corresponding stresses were 40.62, 58.42, 56.26, and 3,606.30 MPa.Conclusion:With cup coverage at 70% and 90%, the high rotation center and anatomical rotation center exhibited lower and less frequent relative displacements at the acetabular-bone contact surface.

Purpose: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC).Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. Methods: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People’s Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. Results: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205–13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. Conclusion Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.

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 identify dermatopathological features of patients with dermatomyositis (DM) and analyze its correlation with cutaneous diseases activity.Methods:The clinical data and skin biopsies of 48 patients were collected. The relevance was analyzed using Spearman's correlation analysis. The two groups were compared using Chi-square test or Fisher's exact test. Multi-factors line regression model was established to analyze the relationship between cutaneous disease activity and dermatopathological features.Results:The most common dermatopathological feature was perivascular inflammation (37 cases, 88%), followed by epidermal atrophy (22 cases, 52%) and melanocyte loss (20 cases, 48%), basal vacuolization (15 cases, 36%). The incidence of basal vacuolization ( χ2=9.110, P=0.022), interface dermatitis ( χ2=11.672, P=0.005) and mucin deposition ( χ2=7.795, P=0.029) were significantly different in patients with myositis specific antibody (MSA) subgroup. The patients with positive tranional intermediary factor-1 (anti-TIF1-γ) antibody had higher incidence of interface dermatitis and basal vacuolization, and patients with melanoma differentiation-associated gene 5 (anti-MDA5) antibody had lower incidence of interface dermatitis. Interface dermatitis was positively associated with epidermal atrophy ( r=0.371, P=0.016) and parakeratosis ( r=0.316, P=0.041). Pigment inco-ntinence was positively associated with basal vacuolization ( r=0.384, P=0.012). Multi-factor line regression showed interface dermatitis was positively related to cutaneous disease area and severity index (CDASI). Conclusion:The dermatopathological features is different in subgroup of patients with DM ( β=10.295, P=0.004). Interface dermatitis is a marker of cutaneous disease activity, and its pathogenesis may be different from that of perivascular inflammation. Keratinocytes may be involved in the pathological process in interface dermatitis.

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 investigate the pathological characteristics of skeletal muscle and its association with anti-aminoacyl-tRNA synthetases(ARS) antibodies and clinical features in patients with anti-synthetase syndrome (ASS).Methods:Patients diagnosed as ASS at China-Japan Friendship Hospital from 2008 to 2018 were involved in this study. Immunohistochemistry staining of MHC-Ⅰ, CD3, CD4, CD8 and CD20 molecule were performed in all muscle specimen taken from these patients. According to the muscular pathological characteristics, all patients could be divided into six pathological subgroups: pathologic DM(pDM), pathologic PM (pPM), unspecified myositis(USM), necrotizing myopathies (NAM), only MHC-Ⅰexpression (MHC-Ⅰ) and normal pathology groups. Immunoblotting assay was used to detect anti-ARS antibodies. Statistical analysis was performed using Statistical Product and Service Solutions (SPSS) software. T-test, Mann-Whitney U test and Analysis of Variance (ANOVA) were used for the comparison of measurement data. Chi-square test or Fisher's test were used for categorical data. P<0.05 was considered statistically significant. Results:A total of 77 patients underwent muscle biopsy and anti-ARS antibodies test, with the average age of (50±12) years and disease course of 9(3-24) months. The prevalence of anti-Jo-1, anti-PL-7, anti-PL-12, anti-EJ and anti-OJ antibodies in these patients was 47%(36 cases), 29%(22 cases), 12%(9 cases), 13%(10 cases) and 0 respectively. Among all the ASS patients, the most common pathological type was USM(37/77, 48%), followed by pDM(14/77, 18%), the normal pathology(13/77, 17%), NAM(10/77, 13%) and MHC-Ⅰ (3/77, 4%) groups. There were no pPM subtypes in all groups. The frequency of pDM types was significantly different among the anti-ARS antibodies groups( χ2=9.075, P=0.028). The anti-EJ-positive patients had a higher frequency of pDM compared with anti-PL-7-group(40% vs 4%, χ2=6.555, P=0.024). Meanwhile, the CD20 expression in muscle tissue was observed in 30% of anti-EJ-positive patients and 4% of anti-Jo-1-positive ones. There was statistically significant difference in the positive rate of CD20 expression among anti-ARS antibodies groups ( χ2=12.837, P<0.01). Conclusion:The muscle pathological characteristics of ASS are polymorphic and relate to the anti-ARS antibodies. Performing muscle biopsy and distinguishing pathological types are helpful for the diagnosis and stratification of ASS.

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.