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.

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 disclose phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B virus (Victoria) (BV) in the 2023-2024 influenza surveillance season in Beijing, and understand the matching with influenza vaccine component strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) in the 2023-2024 influenza surveillance season were collected from surveillance network labs in Beijing and BV strains were isolated through MDCK or chicken embryo culture. After extracting nucleic acid, HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity were conducted and the maximum likelihood method in Mega 5.0 software was used to construct the phylogenetic tree of HA gene. N-glycosylation sites of HA were performed online. Furthermore, three-dimensional structure of HA was available from SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) tests were performed to analyze antigenic characteristics of HA of BV strains.Results:Fifty-four BV strains were randomly selected to be analyzed further. Compared with the HA gene of this influenza season vaccine strain (B/Austria/1359417/2021), there are three amino acid mutations among all BV strains, two of which are located in two different antigenic determinants. Furthermore, the phylogenetic tree analysis revealed that only one subgroup of 1A.3a.2 was circulating simultaneously. All BV strains are located in Clade 1A.3a.2 subgroup, and in the same subgroup with that of the vaccine component BV strain in 2023-2024. All BV strains have the same glycosylation sites as that of the vaccine component BV strain in 2023-2024. Antigenic analysis showed that all BV strains were antigenically similar with its vaccine strain.Conclusions:In the 2023-2024 influenza surveillance season, the prevalent BV strains in the population in Beijing city are located in Clade 1A. 3a. 2 subgroup. The antigen matching between BV epidemic strains and vaccine BV components is relatively high during this surveillance season.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective:To characterize the epidemic of influenza in Beijing from 2022 to 2023 and the variation of gene and antigenicity of hemagglutinin (HA) of influenza A H3N2 virus, so as to provide scientific basis for influenza prevention and control in Beijing.Methods:Statistical analysis was carried out on the result of influenza pathogenic monitoring in Beijing from week 14, 2022 to week 20, 2023, and 79 strains of influenza A H3N2 virus were selected at different time and population sources, and their genetic variation and evolution characteristics were analyzed through HA gene amplification sequencing and antigenicity analysis.Results:From week 14, 2022 to week 20, 2023, 24 244 throat swabs of influenza like cases were collected in Beijing, and 4 987 influenza virus nucleic acid positive cases were detected, including 2 749 influenza A H3N2 positive cases, with a detection rate of 11.34%. Among the 79 strains, 50 strains (63.29%) showed low response, 94.44% of the strains from August to November 2022 had low response, and 54.10% of the strains from February to March 2023 had low response, with a statistically significant difference ( χ2=8.079, P=0.004). Compared with the vaccine strain A/Darwin/9/2021, the HA gene sequence of 79 strains of influenza A H3N2 showed nucleotide similarity of 97.47% to 98.47% and amino acid similarity of 97.05% to 98.17%. Genetic evolution analysis showed that the 18 strains isolated from August to November 2022 were all distributed in the 3C.2a1b.2a.1a.1 branch, while the 61 strains isolated from February to March 2023 all belonged to the 3C.2a1b.2a.3a.1 branch. Compared with the vaccine strain, there were multiple site mutations distributed at multiple antigenic determinants and receptor binding sites in A, B, C, D, and E. All strains had potential glycosylation sites of 8NST, 22NGT, 38NAT, 45NSS, 63NCT, 126NWT, 133NGT, 246NST, 285NGS, 483NET, while one strain missed 165NVT glycosylation sites; 55 strains between February and March 2023 missed 122NES glycosylation sites. Conclusions:The HA gene locus of influenza A H3N2 virus detected in Beijing from week 14, 2022 to week 20, 2023 showed multiple mutations, continuous monitoring of this subtype variation is crucial.

Objective:To explore the features the gait of elderly persons with type 2 diabetes and peri-pheral neuropathy.Methods:Twenty patients no less than 60 years old with type 2 diabetes and peripheral neuropathy (DPN) formed a DPN group, while 20 counterparts with type 2 diabetes but without peripheral neuropathy composed the DM group, and another 20 healthy counterparts served as a control group. The three groups were tested using the Swedish Qualisys motion capture system and their walking speed, step length, step width, stride frequency and stride length, bipedal foot support phase time, single foot support phase time, peak plantar pressure, and regional-holding time were collected and compared.Results:The average walking speed, stride length and stepping frequency of the DPN group were all significantly lower than the other 2 groups′ averages. Their bipedal support phase was significantly longer, but their single foot support phase time was significantly shorter. And in the DPN group the average first and second peak plantar pressures and the second peak pressure time were significantly greater than the other groups′ averages.Conclusions:Elderly patients with type 2 diabetes and peripheral neuropathy have significant gait abnormalities, decreased walking stability, as well as increased plantar pressure and plantar compression time.

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

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.

Objective:To explore the inducing factors of symptom onset in patients with symptomatic carotid artery stenosis, and to provide basis for preventive care.Methods:Totally 104 patients with symptomatic carotid artery stenosis hospitalized in Stroke Ward from September 2014 to December 2017 were selected by convenience sampling method. The clinical data of patients were analyzed retrospectively, and the possible inducing factors were analyzed.Results:there were 104 patients with symptomatic carotid artery stenosis, and 35 patients (33.7%) had obvious inducing factors before onset, but 69 patients (66.3%) had not. The inducing factors were classified into ten categories: posture, activity and fatigue, mood, blood pressure reduction, eating, drinking, noisy environment, hot bath, sweating and cold stimulation. There was no significant difference in gender, age, single and bilateral stenosis, comorbidities (hypertension, diabetes, coronary artery disease, hyperlipidemia) and smoking between the induced group and the non-induced group ( P>0.05). Among the 31 patients with a history of alcohol consumption, 15 had an inducement, accounting for 48.4%; among the 73 patients without a history of alcohol consumption, 20 had an inducement, accounting for 27.4%. The difference between the two groups was statistically significant ( χ 2=4.294, P<0.05).Three cases (8.6%) were directly caused by drinking alcohol. Conclusion:There are many inducing factors for symptomatic carotid artery stenosis, especially for drinking patients, health education should be given, and corresponding preventive measures should be taken to reduce the occurrence of symptoms.