Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.

Objective:To know the clinical characteristics, seasonal pattern and influencing factors of atypical depression(AD) patients.Methods:A total of 203 depressed outpatients of Peking University Sixth Hospital from January 2021 to August 2021 were included.They were assessed with demographic questionnaire, inventory of depressive symptomatology self-report(IDS-SR30) and seasonal pattern assessment questionnaire(SPAQ). According the score of IDS-SR30, all patients were classified as atypical depression(AD) and non-atypical depression(non-AD). The data were analyzed by t-test, non-parametric test and Logistic regression using SPSS 26.0 software. Results:The prevalence of AD among depressed patients was 36.0% (95% CI=29.3%-42.6%). The IDS-30 score of the AD group was (41.59±10.59), and IDS-30 score of the non-AD group was (36.08±13.17), and the difference between the two groups was statistically significant ( t=3.062, P<0.05). The global seasonal score of the AD group was 6 (3, 9), and 17.8% of the AD group had seasonal pattren.The global seasonal score of the non-AD group was 5 (3, 8), and 14.6% of the non-AD group had seasonal pattern.There was no significant difference in the global seasonal score and the proportion of seasonal pattern between the two groups ( Z=0.389, χ2=0.359, P>0.05). Depression patients who were females ( β=1.08, OR=2.95, 95% CI=1.32-6.59, P<0.05), low self-evaluation ( β=0.82, OR=2.27, 95% CI=1.12-4.59, P<0.05)and psychomotor retardation ( β=0.93, OR=2.54, 95% CI=1.33-4.85, P<0.05) were more likely to be diagnosed as AD, and depression patients having mood variation ( β=-0.94, OR=0.39, 95% CI=0.19-0.81, P<0.05) were more likely to be diagnosed as non-AD. Conclusion:Women, low self-evaluation, psychomotor retardation and unobvious mood variation can predict and help to diagnose atypical depression in depressed patients.

Objective:To construct a quantitatively diagnostic nomogram model by analyzing the clinical information of patients and the features of multi-modality ultrasound images of thyroid lesions, so as to preoperatively predict the malignant probability of suspicious thyroid nodules and provide effective references for clinical decision-making.Methods:A total of 933 patients, 1 121 thyroid nodules of C-TIRADS 3-5 categories, who underwent surgery in the Second Affiliated Hospital of Harbin Medical University from September 1, 2020 to June 10, 2021 were collected. The nodules were randomly divided into training ( n=897) and test groups ( n=224) in 8∶2 ratio. Finally, the diagnostic performance was evaluated by area under the curve (AUC). Results:①After preliminary screening by univariate analysis, multivariate analysis showed that age, echogenicity, orientation, echogenic foci, margin, posterior features, and elastic score were significantly correlated with benign and malignant nodules (all P<0.001), and the difference of halo between benign and malignant nodules was also statistically significant ( P=0.012). ②The AUC of nomogram was up to 0.903(95% CI=0.862-0.944) in the test set, and 0.889(95% CI=0.832-0.946) and 0.960(95% CI=0.925-0.994) in nodules with maximum diameter of ≤10 mm and of >10 mm respectively, which showed high diagnostic performance. Conclusions:The nomogram model could accurately differentiate malignant from benign thyroid nodules preoperatively, with the highest diagnostic performance for the nodules with maximum diameter of >10 mm, and effectively avoid the unnecessary fine-needle biopsy and surgical operation.

Objective: To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD). Methods: Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV₁) in the predicted value, FEV₁/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve. Results: The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% (r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV₁/FVC, the percentage of FEV₁ in the predicted value, and sRAGE(r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% (r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95%CI(0.897-0.947)], 0.926[95%CI(0.899-0.952)]and 0.966 [95%CI(0.950-0.983)], respectively. Conclusion S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.

Objective To investigate the value of F-actin autoantibodies in the serum of patients with systemic lupus erythematosus (SLE),and to explore the relationships between F-actin autoantibodies and other clinical indicators.Methods ELISA was established to detect serum levels of F-actin autoantibodies in 93 inpatients with SLE from March 2017 to January 2018 (case group,n=93),72 patients with rheumatoid arthritis (RA) (disease control group) and 83 healthy subjects (healthy control group) were included during the same period.The positive rates of F-actin autoantibodies between the case group and the two control group were compared.Clinical data including SLE disease activity index (SLEDAI),immuno-globulin (lg)G,erythrocyte sedimentation rate (ESR),anti-dsDNA,and antinuclear antibody (ANA) of 93 patients with SLE were collected and the correlation analysis between F-actin autoantibodies units was applied respectively.The diagnostic performance of F-actin autoantibodies in SLE was analyzed by using the receiver operating characteristic curve (ROC).T test,Chi-square test and Spearman/Pearson correlation analysis were applied for statistical analysis.Results The serum levels of F-actin autoantibodies in the SLE case group,disease control group,and healthy control group were (18±13),(12±6),and (11±5) U,respectively,the differences between SLE case group and disease control group,and healthy control group were significant (t=3.163,P=0.001 9;t=4.436,P＜0.01).The positive rates of F-actin autoantibodies were 33％(31/93) in patients with SLE,10％(7/72) in disease control group,and 4％(3/83) in healthy control group.The F-actin autoanti-bodies units in SLE were correlated with SLEDAI,IgG,ESR,anti-dsDNA,and ANA (r=0.273 7,P=0.008 3;r=0.558 7,P＜0.01;r=0.419 9,P=0.000 1,r=0.351 4,P=0.001 1,r=0.460 9,P＜0.01),in which F-actin autoantibodies units showed significant correlation with IgG and ANA.In the ROC curve,the area under the curve(AUC) was 0.62 [95％CI(0.54,0.70)],P=0.001 3.which was statistically significant.When the cut-off value of the F-actin autoantibodies was 14.04 U,the Youden's index (YI) was the largest (YI=0.30),and the sen-sitivity for the diagnosis of SLE was 0.77,the specificity was 0.53.Conclusion The positive rate of F-actin autoantibodies in the serum of patients with SLE is higher than that of RA and healthy controls,so it has certain diagnostic value for SLE.The F-actin autoantibodies units is correlated with both SLEDAI,ESR,and anti-dsDNA,suggesting that F-actin autoantibodies units may be a new biomarker for disease activity assessment of SLE patients.