Objective To determine the time point when porcine pancreatic elastase(PPE)induced abdominal aortic aneurysm(AAA)reaches the regression phase in mice and observe the histological characteristics of AAA in regression phase.Methods AAAs were induced by transient intraluminal infusion of PPE in C57BL/6J mice.The diameters of the mouse abdominal aortas were measured before PPE infusion and sacrifice time,day 14 for AAA progression phase or day 56 for regression phase after PPE infusion,respectively.The histological characteristics of the aneurysm lesion site on day 14 and day 56 after surgery were compared and analyzed.Results The diameters of the abdominal aortas were significantly increased in both day 14 and day 56 after PPE infusion groups(diameter growth rate 147％and 155％,respectively)as compared to the baseline diameters.In the day 14 group,the infused aortas showed typical AAA characteristics,such as elastin break/degradation,medial smooth muscle cells depletion,and inflammatory cell diffused infiltration.In the day 56 group after PPE infusion,although the artery diameter did not change significantly as compared to the day 14 group,histology showed that elastin was partially repaired,new smooth muscle cells were added to the damaged aorta media,the infiltrated inflammatory cells were significantly subsided,and the adventitia neovascularization was reduced,showing a significant feature of the disease regression phase.Conclusion In the PPE-induced mouse AAA model,day 56 after surgery is an appropriate time point for observing aneurysm regression,and the histological characteristics of the regression are obvious.

The oral microbiota has been dynamically changing in the process of formation, development and prognosis of oral squamous cell carcinoma (OSCC), and the two promote and complement each other inseparably. Oral microbiota is different in healthy people, patients with precancerous lesions of OSCC, and patients with OSCC, which means it can be used as a biomarker for the diagnosis of precancerous lesions of OSCC or OSCC. In addition, there are differences in the levels of oral microbiota both at baseline and after treatment among different OSCC patients, which can be used as a prognostic biomarker for OSCC. Furthermore, the modulation of oral microbiota can be used as a microbial therapy to improve the prognosis of OSCC patients by being added to the existing standard therapies.

Objective: Investigate osteogenic differentiation of canine periodontal ligament stem cells ( cPDLSCs) via over-expression ephrinB2 in cPDLSCs． Methods : cPDLSCs were isolated from the premolars and molars of Beagle．After transfected with EfnB2-GFP-Bsd and GFP-Bsd empty Vector，cPDLSCs were induced to osteogenic differentiation．Western blot was used to invest the expression of ephrinB2 protein．The effect of osteogenic differentiation of EfnB2-cPDLSCs and Vector-cPDLSCs were analyzed by RT-PCR , CCK-8，Alizarin-red S staining and ALP. Results: There was no significant difference in cell proliferation between EfnB2-cPDLSCs and Vector-cPDLSCs．While EfnB2-cPDLSCs displayed an enhanced ALP activity and more prominent mineralized nodules compared with Vector-cPDLSCs．The odonto-/ osteogenic genes in EfnB2-cPDLSCs were also highly enhanced． Conclusion The results of our study indicated that ephrinB2 gene-transfected cPDLSCs showed enhanced osteogenic differentiation.

Asymptomatic spleen-stomach diseases refer to diseases without related symptoms and signs of abdo-minal pain， bloating， diarrhea an others in patients， but showing lesions or pathological changes discovered by modern medical techniques such as endoscopy， CT， MRI. The four examination techniques of traditional Chinese medicine （TCM） are based on symptoms and signs of patients， which are the advantage of TCM but also have certain limitations. In the context of the increasingly modernized diagnosis and treatment in TCM， it is proposed to expand the application of the four examination techniques from three aspects including microcosmic syndrome differentiation， data sharing， and artificial intelligence in asymptomatic spleen-stomach diseases， in order to achieve the goals of dynamically observing the disease process， collecting disease data in multiple dimensions， and intelligently processing disease data. This will strengthen the modern requirements of early diagnosis and treatment in TCM， and highlight the advantages of TCM in “treating disease before it arises and treating the symptoms beforehand”.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

OBJECTIVE To study the immunotherapeutic effect of chimeric virus-like particles(VLPs) based on hepatitis E virus(HEV) against human papillomavirus type 16(HPV 16) tumor. METHODS HPV16 E7 was inserted into the p239 protein of HEV to form the recombinant chimeric protein p239-HPV16 E7. The constructed recombinant protein was expressed by Escherichia coli, purified, and then refolded, and the protein was detected by electron microscopy and dynamic light scattering to confirm size and shape. Then, the C57B/L mice were immunized with the protein grain, and the lymphocyte differentiation of mouse spleen was detected by flow cytometry and enzyme-linked immune spot immunoassay; in addition, TC-1 tumor cells were used to construct tumor models in C57B/L mice to evaluate the anti-tumor immune effect of protein particles in mice. RESULTS After refold in vitro, the structure of chimeric protein was observed under electron microscopy, and the size of particle was 22.80 nm. The obtained protein particles induced favorable specific cellular immune response in C57B/L mice. Compared with the control group, the proportions of CD3+/CD4+ and CD3+/CD8+ in spleen lymphocytes of experimental groups were significantly different(P＜0.05), and effector T cells secreting IFN-γ interferon were also increased remarkably. At the same time, the obtained protein particles could effectively inhibit the growth of tumor cells in TC-1 tumor-bearing mice, and the mice did not die during the experimental period, while the tumors in the control mice grew rapidly and all died after 6 weeks. CONCLUSION Chimeric protein p239-HPV16E7 which was expressed in prokaryotes can form virus-like particles and effectively induce anti-tumor immunity against HPV16.

Objective:To analyze the clinical effects of the pre-expanded internal mammary artery perforator flap in large chest keloids surgical treatment.Methods:Patients with large chest keloid were treated with the pre-expanded internal mammary artery perforator flap between January 2017 and September 2021. The surgical treatment was divided into two different phases. In the first phase, a tissue expander was implanted beneath the skin within the angiosome of the internal mammary artery perforator. The expander was injected with normal saline once a week. In the second phase, the expander and the keloid tissue were removed, and a pre-expanded internal mammary artery perforator flap was designed to cover the wound. Radiotherapy and hyperbaric oxygen therapy were performed in the postoperative period. The treatment effect was followed up. The postoperative complications were analyzed, and the recurrence and patient satisfaction rates were recorded.Results:A total of 41 patients were enrolled, including 20 male and 21 female patients. The patients’ age ranged from 24 to 64, with a mean disease history of 11.9 years. The mean size of the keloid was 9 cm × 8 cm. Some patients were treated with one expander, but four expanders were needed in some extensive cases. The volume of the expander ranged from 80 to 600 ml. The mean volume was 300 ml, with a mean expansion time of 3 months. The mean flap size was 9 cm × 8 cm. Two cases with distal necrosis were observed. Five cases suffered from partial incision scar hyperplasia. No recurrence occurred during the followed-up period. Thirty-six patients (87.8%) were satisfied with the operation effect, and five (12.2%) thought the effect was acceptable.Conclusions:The pre-expanded internal mammary artery perforator flap is an effective treatment for the large chest keloid. It can provide sufficient skin tissue for wound repair, with a stable blood supply and an excellent curative effect.

Objective:To analyze the clinical effects of the pre-expanded internal mammary artery perforator flap in large chest keloids surgical treatment.Methods:Patients with large chest keloid were treated with the pre-expanded internal mammary artery perforator flap between January 2017 and September 2021. The surgical treatment was divided into two different phases. In the first phase, a tissue expander was implanted beneath the skin within the angiosome of the internal mammary artery perforator. The expander was injected with normal saline once a week. In the second phase, the expander and the keloid tissue were removed, and a pre-expanded internal mammary artery perforator flap was designed to cover the wound. Radiotherapy and hyperbaric oxygen therapy were performed in the postoperative period. The treatment effect was followed up. The postoperative complications were analyzed, and the recurrence and patient satisfaction rates were recorded.Results:A total of 41 patients were enrolled, including 20 male and 21 female patients. The patients’ age ranged from 24 to 64, with a mean disease history of 11.9 years. The mean size of the keloid was 9 cm × 8 cm. Some patients were treated with one expander, but four expanders were needed in some extensive cases. The volume of the expander ranged from 80 to 600 ml. The mean volume was 300 ml, with a mean expansion time of 3 months. The mean flap size was 9 cm × 8 cm. Two cases with distal necrosis were observed. Five cases suffered from partial incision scar hyperplasia. No recurrence occurred during the followed-up period. Thirty-six patients (87.8%) were satisfied with the operation effect, and five (12.2%) thought the effect was acceptable.Conclusions:The pre-expanded internal mammary artery perforator flap is an effective treatment for the large chest keloid. It can provide sufficient skin tissue for wound repair, with a stable blood supply and an excellent curative effect.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

In clinic, it is very common that a variety of drugs are used in the treatment of diseases. However, the combination of drugs can easily lead to the occurrence of drug-drug interaction (DDI), which can lead to the reduction or loss of drug efficacy, the increase of adverse reactions, and even lead to serious adverse reactions. Drug transporters play an important role in the occurrence and development of DDI by influencing the disposal process of combined drugs in vivo. In this paper, the relationship between DDI and transporter was summarized. The effects of transporter-mediated DDI on the drug disposal process in vivo, and the relations of DDI and disease or multidrug resistance were reviewed. The current guiding principles of DDI research in China were briefly introduced. The purpose was to remind clinical medical workers to pay attention to transporter-mediated DDI and improve the safety of drug combination, further to provide a new vision and ideas for disease treatment and avoiding multidrug resistance.