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 the expression of GJB4 gene in pancreatic cancer tissue and its correlation with clinicopathology.Methods The expression levels of GJB4 mRNA in pancreatic cancer and adjacent cancer tissues were analyzed using bioinformatics to analyze the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)RNA sequencing datasets.A total of 120 pancreatic cancer samples and 40 adjacent cancer samples from the Pathology Department of The Second Affiliated Hospital of Kunming Medical University from January 2019 to December 2023 were collected and sorted.Immunohistochemistry staining method was used to detect the expression difference of GJB4 protein between the two groups.RT-qPCR method was used to detect the expression levels of GJB4 in four pancreatic cancer cell lines.Univariate and multivariate Cox regression and Kaplan-Meier curves were used to analyze the clinical pathological data of GJB4 and pancreatic cancer patients.DAVID functional annotation bioinformatics and GSEA enrichment analysis were used to explore the relevant pathways of GJB4 in pancreatic cancer.Results The expression level of GJB4 mRNA in pancreatic cancer was higher than that in adjacent tissues,and the high expression of GJB4 was significantly associated with poor prognosis of patients(P<0.05).Immunohistochemical analysis showed that GJB4 protein was brown-yellow granular in pancreatic cancer tissues,mainly expressed in cytoplasm and cell membrane,and GJB4 protein expression was up-regulated in pancreatic cancer(P<0.05).The RT-qPCR test results showed that out of 4 pancreatic cancer cell lines,3 of them had upregulated expression(P<0.05).COX regression analysis showed that GJB4 gene was an independent risk factor in the prognosis of pancreatic cancer patients.The results of GO enrichment analysis showed that GJB4 was related to the transmembrane transport,ion channel,signal release and membrane potential regulation of pancreatic cancer.GSEA analysis showed that GJB4 was enriched in the Wnt/β-catenin signaling pathway.Conclusion In pancreatic cancer,the high expression level of GJB4 is closely related to the clinicopathological features of the patients,which may predict the poor prognosis of the patients.GJB4 may be involved in regulating the Wnt/β-catenin signaling pathway of pancreatic cancer,and is expected to be one of the potential biomarkers of pancreatic cancer prognosis.

AIM: To construct column-line plots to predict survival in elderly patients with early-stage HER2-positive breast cancer using the Surveillance, Epidemiology and End Results (SEER) database. METHODS: 5 220 (based on the era of single-targeted therapy) and 1 176 (based on the era of dual-targeted therapy) patients screened in the SEER database were randomized into a training group and an internal validation group. COX proportional risk regression was used to screen survival-related predictors and build a column-line graphical model, and the accuracy and utility of the model were tested using the consistency index (C-index), calibration curves, and time-dependent ROC curves. Patients receiving chemotherapy and non-chemotherapy were statistically paired using two-group propensity score matching, and subgroup analyses were performed on the screened variables. RESULTS: The single-targeted therapy era line graph was constructed from seven variables: age, marital status, T-stage, N-stage, surgery, chemotherapy, and radiotherapy. The dual-targeted therapy era line graph was constructed from five variables: age, AJCC staging, surgery, chemotherapy, and radiotherapy. The results of the subgroup analysis showed that older HER2-positive breast cancer patients who received chemotherapy had better OS. CONCLUSION: Based on the SEER database, an accurate column-line graph predicting survival in elderly patients with early-stage HER2-positive breast cancer was established and validated. This study suggests that chemotherapy increases survival benefit in elderly patients.

Objective To analyze the influencing factors of treatment compliance in patients undergoing intracranial aneurysm (IA) surgery based on based on latent growth mixture model (LGMM). Methods A total of 150 patients who underwent IA surgery were selected as the study objects. The general data of patients were collected and the compliance scale was used to evaluate the compliance of patients. LGMM was used to predict the change track of treatment compliance of patients with IA after surgery, and the influencing factors of treatment compliance of patients with IA were analyzed by multivariate Logistic regression analysis. Results A total of 138 valid questionnaires were collected in this study, and the effective questionnaire recovery rate was 92.00%. The treatment compliance score of patients with IA was (5.18±1.59) points. After LGMM fitting, 3 potential profiles were selected. There were 37 patients with good compliance (26.81%), 42 patients with moderate compliance (30.43%), and 59 patients with poor compliance (42.75%). The potential profile category attribution probability matrix was 97.29% for patients with good compliance, 95.24% for patients with moderate compliance, and 98.31% for patients with poor compliance. The proportion of poor compliance patients with age of 30 to 50 years old, junior high school education level or below, combined with two or more diseases, out-of-pocket (medical expenses) and Hunt-Hess grade Ⅲ was significantly higher than those with good compliance and moderate compliance (P < 0.05). Age of 30 to 50 years old, Hunt-Hess grade Ⅲ, combined with two or more diseases, education level as junior high school or below and self-expense (medical expenses) were the influential factors of treatment compliance (P < 0.05). Conclusion Treatment compliance of patients undergoing IA surgery is low and heterogeneous. Age of 30 to 50 years old, junior high school education level or below, combination of more than two diseases, medical insurance payment method of self-payment and Hunt-Hess grade Ⅲ are all influencing factors for compliance of IA surgery patients.

Objective To investigate the construction and application of a risk prediction model for deep vein thrombosis (DVT) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods A total of 250 patients with aSAH were enrolled in this study and divided into DVT (n=45) and non-DVT groups (n=205) based on the occurrence of DVT. General information and routinelaboratory indicators were collected and compared between the two groups. Multivariate Logistic regression analysis was performed to identify risk factors for DVT in aSAH patients. A nomogram prediction model for DVT after aSAH was established and its discriminative ability was evaluated using the receiver operating characteristic (ROC) curve. The clinical utility of the nomogram was assessed by decision curve analysis. Results Statistically significant differences were observed in age, history of hypertension, Glasgow Coma Scale (GCS) score, Hunt-Hess grade and length of hospital stay between the DVT and non-DVT groups (P < 0.05). The plasma fibrinogen level was significantly higher in the DVT group compared to the non-DVT group (P < 0.05), while no significant differences were found for other indicators (P>0.05). Multivariate Logistic regression analysis revealed that age, Hunt-Hess grade, length of hospital stay, and plasma fibrinogen level were influencing factors of the occurrence of DVT in aSAH patients(P < 0.05). ROC analysis showed that the nomogram exhibited good predictive performance in both the modeling and validation groups, with areas under the curve (AUCs) of 0.875 (95%CI, 0.802 to 0.948) and 0.872 (95%CI, 0.757 to 0.987), respectively. Decision curve analysis indicated that the nomogram provided a high net benefit for predicting DVT in aSAH patients across a wide range of threshold probabilities. Conclusion Age, Hunt-Hess grade, length of hospital stay, and plasma fibrinogen level are influential factors for DVT in aSAH patients. The nomogram in predicting DVT after aSAH demonstrates good discriminative ability, calibration degree, and clinical application value. This model can better identify high-risk patients and provide individualized prevention and treatment strategies.

Amino-containing compounds,including amino acids,aliphatic amines,aromatic amines,small peptides and catecholamines,are involved in various biological processes and play vital roles in multiple meta-bolic pathways.Previous studies indicated that some amino-containing metabolites are significant diagnostic and prognostic biomarkers of gastric cancer.However,the discovery of precise biomarkers for the preoperative diagnosis of gastric cancer is still in an urgent need.Herein,we established a polarity-regulated derivatization method coupled with liquid chromatography-mass spectrometry(LC-MS)for amino-containing metabolites profiling in the serum samples of patients with gastric cancer and healthy controls,based on our newly designed and synthesized derivatization reagent(S)-3-(1-(diisopropox-yphosphoryl)pyrrolidine-2-carboxamido)-N-hydroxysuccinimidyl ester(3-DP-NHS).Enhanced separa-tion efficiency and detection sensitivity for amino-containing metabolites were achieved after derivatization.This method exhibited good linearity,recovery,intra-and inter-day precision and accu-racy.Only 5 μL serum is needed for untargeted analysis,enabling 202 amino-containing metabolites to be detected.Statistical analysis revealed altered amino acid metabolisms in patients with gastric cancer.Furthermore,ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS)analysis quantification revealed increased serum levels of tryptamine and decreased concen-trations of arginine and tryptophan in patients with gastric cancer.Receiver operating characteristic(ROC)curves indicated that an increased tryptamine/tryptophan ratio could serve as a potential biomarker for gastric cancer diagnosis.This study demostrated the possibility of using serum amino acid biomarkers for gastric cancer diagnosis,providing new avenues for the treatment of gastric cancer.

Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

BACKGROUND: Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells (CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells. METHODS: BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells. Tumor growth and pulmonary metastasis were assessed. ALDEFLOUR™ assays were performed to identify aldehyde dehydrogenasebright (ALDHbr) tumor cells. ALDHbr cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry. The effects of CD8+ T cells on ALDHbr tumor cells were assessed in vitro and in vivo. The expression profiles of ALDHbr and ALDHdim 4T1 tumor cells were determined. The levels of plasma IFN-γ were measured by enzyme-linked immunosorbent assay, and their associations with the percentages of ALDHbr tumor cells were evaluated. The effects of IFN-γ on ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro. RESULTS: There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice (25.40 vs. 54.67, P < 0.050). CD8+ T cells decreased the percentages of ALDHbr 4T1 tumor cells in vitro (control vs. effector to target ratio of 1:1, 10.15% vs. 5.76%, P < 0.050) and in vivo (control vs. CD8+ T cell depletion, 10.15% vs. 21.75%, P < 0.001). The functions of upregulated genes in ALDHbr 4T1 tumor cells were enriched in the pathway of response to IFN-γ. The levels of plasma IFN-γ decreased gradually in tumor-bearing BALB/c mice, while the percentages of ALDHbr tumor cells in primary tumors increased. IFN-γ at a concentration of 26.68 ng/mL decreased the percentages of ALDHbr 4T1 tumor cells (22.88% vs. 9.88%, P < 0.050) and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells (0.86 vs. 0.49, P < 0.050) and inhibited the abilities of sphere formation (sphere diameter <200 μm, 159.50 vs. 72.0; ≥200 μm, 127.0 vs. 59.0; both P < 0.050) and invasion (89.67 vs. 67.67, P < 0.001) of 4T1 tumor cells. CONCLUSION CD8+ T cells and IFN-γ decreased CSC numbers in a 4T1 mouse model of breast cancer. The application of IFN-γ may be a potential strategy for reducing CSCs in breast cancer.
Aldehydes ; Animals ; Breast Neoplasms ; Cell Line, Tumor ; Female ; Humans ; Interferon-gamma ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplastic Stem Cells

Molecular biology is a biology course containing multiple core concepts and complex biological processes, which are organized in a strong logic. In order to help the medical students in college of traditional Chinese medicine (TCM) understand the content of this professional foundation course, we integrated the mind mapping model into the three sessions of teaching this course. First, putting forward teaching questions through a "nine grids analysis" model before the class teaching; second, transforming class teaching through a "six thinking hats" model; third, reviewing teaching content through a "pyramid principle" model, which helps students develop closed-loop thinking skills. The students' understandings to the course content were enhanced by connecting, merging and diverging the relevant knowledge through thinking visualization. According to the questionnaire, 91% of the students believe that the application of mind mapping model is an effective teaching method, which improves the teaching efficiency and effect. Furthermore, 76% of the students deem this method helps them improve their thinking ability and they also try to apply this method to the study process of other courses. Therefore, the application of mind mapping model in teaching plays an important role in fostering students' high-order thinking skills and provides a new approach for college curriculum teaching.
Curriculum ; Humans ; Molecular Biology ; Students ; Thinking