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1.
J Nanobiotechnology ; 22(1): 333, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877492

ABSTRACT

In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of microRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin flap survival. These effects are attributed to their influence on specific miRNAs.


Subject(s)
Adipose Tissue , Apoptosis , Ischemia , MicroRNAs , Animals , Mice , Adipose Tissue/cytology , MicroRNAs/metabolism , Stem Cells/cytology , Stem Cells/metabolism , Oxidative Stress , Surgical Flaps , Cells, Cultured , Mice, Inbred C57BL , Male , Cell Survival , Neovascularization, Physiologic , Cell Culture Techniques, Three Dimensional/methods
2.
Front Surg ; 11: 1363827, 2024.
Article in English | MEDLINE | ID: mdl-38596165

ABSTRACT

Background: Replantation represents a treatment option for patients with severed finger pulps. However, in some cases, replantation is a challenging task. Case presentation: We report a successful case of finger pulp reconstruction of the ring finger using free flaps from a nonreplantable index finger in a spare-parts procedure. A 43-year-old worker accidentally injured the index, middle and ring fingers of his left hand on a machine turntable. The severed index and middle fingers and the distal pulp of the ring finger could not be replanted in situ due to extensive contusion of blood vessels and soft tissues. After vascular and nerve anastomosis, a free skin flap isolated from the nonreplantable index finger was transplanted to the wound of the distal pulpal defect of the ring finger. The flap survived completely postoperatively. Six months after the operation, only a slight deformity of the ring finger was observed. Moreover, sensation of the digit recovered well. Conclusions: Spare-part surgery is a surgical approach that effectively saves and utilizes tissue that would otherwise be discarded in cases of severe limb trauma. This idea may be applied to treatment of severe injuries to multiple fingers. Additionally, in the process of tissue transplantation and repair, attention should be given to protecting the tissue in the recipient area to avoid damage to the original undamaged tissue structure, which can adversely affect healing and recovery of the tissue.

3.
Sci Rep ; 14(1): 8669, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622251

ABSTRACT

The factors influencing geogrid-soil interface characteristics are critical design parameters in some geotechnical designs. This study describes pull-out tests performed on gravelly soils commonly encountered in the Xinjiang region and reinforced with two types of geogrids. The factors affecting the geogrid-gravelly soil interface properties are investigated with different experimental loading methods (pull-out velocity, normal stress), geogrid types, and soil particle size distributions and water contents. The ultimate pull-out force increases with the normal stress and pull-out velocity. Furthermore, with increasing coarse particle content and water content, the ultimate pull-out force increases and then decreases sharply. Based on these research results, this paper provides reasonable parameters and recommendations for the design and pull-out testing of reinforced soil in engineering structures. In reinforced soil structure design, the grid depth should be increased appropriately, and the coarse particle content of the overlying soil should be between 30 and 40%. During construction, the gravelly soil should be compacted to the maximum compaction at the optimal water content, and the structure should have a reasonable waterproofing system. According to the calculation results of the interface strength parameters, the uniaxial geogrid-gravelly soil interface has a high cohesive force csg, which should not be ignored in reinforced soil structure design.

4.
BMC Cancer ; 23(1): 925, 2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37784054

ABSTRACT

BACKGROUND: The interferon-induced protein known as guanylate-binding protein 2 (GBP2) has been linked to multiple different cancer types as an oncogenic gene. Although the role of GBP2 in cancer has been preliminarily explored, it is unclear how this protein interacts with tumor immunity in gastric cancer. METHODS: The expression, prognostic value, immune-correlations of GBP2 in gastric cancer was explored in multiple public and in-house cohorts. In addition, the pan-cancer analysis was performed to investigate the immunological role of GBP2 based on The Cancer Genome Atlas (TCGA) dataset, and the predictive value of GBP2 for immunotherapy was also examined in multiple public cohorts. RESULTS: GBP2 was highly expressed in tumor tissues and associated with poor prognosis in gastric cancer. In addition, GBP2 was associated with the immune-hot phenotype. To be more specific, GBP2 was positively related to immuno-modulators, tumor-infiltrating immune cells (TIICs), immunotherapy biomarkers, and even well immunotherapeutic response. In addition to gastric cancer, GBP2 was expected to be an indicator of high immunogenicity in most cancer types. Importantly, GBP2 could predict the immunotherapeutic responses in at least four different cancer types, including melanoma, urothelial carcinoma, non-small cell lung cancer, and breast cancer. CONCLUSIONS: To sum up, GBP2 expression is a promising pan-cancer biomarker for estimating the immunological characteristics of tumors and may be utilized to detect immuno-hot tumors in gastric cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Transitional Cell , Lung Neoplasms , Stomach Neoplasms , Urinary Bladder Neoplasms , Humans , Stomach Neoplasms/therapy , Prognosis , Immunotherapy , GTP-Binding Proteins/genetics
5.
Ann Plast Surg ; 91(4): 468-472, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37556581

ABSTRACT

BACKGROUND: Complex injuries involving the nerves and other soft tissues in the forearm and hand lead to functional and aesthetic defects. In such situations, multiple types of nerve autografts and flap donor sites are available. However, multiple donor sites cause donor morbidity in different locations and may lead to awkward operational positions. Therefore, based on the anatomical characterization, we aimed to modify the utilization of the lateral arm donor site for reconstruction, which restricts donor morbidity in the affected upper extremity. METHODS: We report a case series (N = 6) using a lateral arm flap (LAF) to reconstruct complex soft tissue defects in the forearm, palm, and finger. The posterior antebrachial cutaneous nerve (PACN) is the primary option for nerve bridging, whereas the LAF can carry the lower lateral brachial cutaneous nerve (LBCN) as a sensory flap. Once the PACN was insufficient, the LBCN was harvested simultaneously. All the cases included in this study were performed between January 2012 and August 2021. Demographic information, flap and nerve characteristics, complications, and hand function were analyzed. RESULTS: The LAF plus PACN or plus LBCN as nerve autograft, both successfully repaired 6 complex injuries: 2 cases in the forearm side, 1 in the hand palm, and 3 in the finger defects. Posterior antebrachial cutaneous nerve was the most used (8-15 cm), and LBCN plus PACN was used to bridge nerve defects when necessary (in total, 20 and 21 cm). The average follow-up time was 19.7 months. The disabilities of the arm, shoulder and hand score ranged between 6 and 12, and the mean 2-point discrimination values ranged between 6 and 12. The Semmes-Weinstein monofilament test result was under 5.46. In addition, 2 patients underwent a secondary debulking surgery. The average length of hospital stay was 10.4 days. Hematoma occurred in 2 cases, and all patients reported numbness in the donor nerve innervated areas. CONCLUSIONS: This surgical refinement can reconstruct complex injuries in the forearm and hand. In addition, this approach restricts donor morbidity in the affected limb, comforts the operational position, and is achieved under brachial plexus anesthesia.


Subject(s)
Hand Injuries , Plastic Surgery Procedures , Soft Tissue Injuries , Humans , Forearm/surgery , Arm/surgery , Treatment Outcome , Upper Extremity/surgery , Skin Transplantation , Hand Injuries/surgery , Soft Tissue Injuries/surgery
6.
J Hand Surg Am ; 2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36732128

ABSTRACT

PURPOSE: Data objectively comparing outcomes following pollicization versus toe-to-thumb transfer for reconstruction after traumatic thumb amputation in adults remains sparse. Given that this decision is reliant on personal preference, it is important to understand the subjective nature of these preferences, particularly in the context of culture. The purpose of this study was to compare Eastern and Western societal and hand surgeon preferences for pollicization versus toe-to-thumb transfer for traumatic thumb reconstruction. METHODS: Investigators from 6 international locations recruited local hand surgeons and members of the general population. Austria, Germany, the United States, and Spain were grouped as "Western" nations. China and India separately represented "Eastern" nations. Participants completed a questionnaire evaluating their personal preferences for pollicization and toe-to-thumb transfer. The questions posed to the general population and hand surgeons were identical. Demographic data were also collected. RESULTS: When comparing the Western nations, China, and India, there was no difference in personal preferences within the general population for pollicization versus toe-to-thumb transfer. In contrast, most Indian hand surgeons favored toe-to-thumb transfer and most Western surgeons were uncertain about which procedure they would favor. Surgeons had more optimistic expectations regarding postoperative hand function, new thumb sensation, and hand appearance following pollicization than the general population. Similarly, for toe-to-thumb transfer, a greater proportion of surgeons predicted good-to-excellent function, sensation, and appearance. CONCLUSIONS: There was no clear, observed "East" versus "West" difference in the general population's personal preferences for pollicization versus toe-to-thumb transfer among study participants. The members of the general population and hand surgeons had different outcome expectations. CLINICAL RELEVANCE: Understanding how culture influences patient and hand surgeon preferences for pollicization versus toe-to-thumb transfer may help guide future decision-making for traumatic thumb reconstruction.

7.
Clin Immunol ; 246: 109204, 2023 01.
Article in English | MEDLINE | ID: mdl-36503156

ABSTRACT

Formins are evolutionarily conserved genes and profoundly affect cancer progression. This study aims to explore the expressions, prognostic values, and immunological correlations of Formins in cancer. Specific Formins were dysregulated and immuno-biologically correlated in breast cancer (BRCA). Formins showed different expression patterns, namely some were enriched in immune cells while some were enriched in tumor cells. Among all Formins, DIAPH1 was enriched in tumor cells and associated with an inflamed tumor microenvironment (TME). DIAPH1 functioned as an oncogene in BRCA and mediated TGF-ß1-induced epithelial-mesenchymal transformation (EMT) and PD-L1 expression. Moreover, DIAPH1 was overexpressed in most cancers and functioned as a novel pan-cancer immuno-marker, which could predict the response to anti-PD-1/PD-L1 immunotherapy. Overall, DIAPH1 functions as an oncogene and is immunologically correlated, which could be utilized as an alternative biomarker for predicting the immunotherapeutic response.


Subject(s)
B7-H1 Antigen , Neoplasms , Humans , Formins , Neoplasms/drug therapy , Prognosis , Immunotherapy , Tumor Microenvironment
8.
Int J Gen Med ; 15: 8285-8298, 2022.
Article in English | MEDLINE | ID: mdl-36444244

ABSTRACT

Background: FMNL3 (Formin-like protein 3) is involved in the tumorigenesis of multiple cancers. The critical role of FMNL3 in malignancies has been preliminarily explored, but its immunological correlation is not clear. Methods: A pan-cancer analysis was performed to investigate the expressions, prognostic values, and immunological roles of FMNL3 across cancer types in The Cancer Genome Atlas (TCGA) database. Next, the correlations between FMNL3 and immunological features in the tumor microenvironment (TME) of pancreatic cancer (PAAD) were assessed. Besides, the role of FMNL3 in predicting the clinical characteristics and the responses to various therapies in PAAD was evaluated as well. Besides, the correlations between FMNL3 and the emerging immune-related biomarkers were also evaluated. Results: The pan-cancer analysis uncovered inconsistent expression status and prognostic values in several cancers. Besides, FMNL3 exhibited positive correlations with a majority of immunomodulators and tumor-infiltrating immune cells (TIICs) in several cancer types, including PAAD. In addition, FMNL3 was associated with an inflamed phenotype in the TME and predicted significantly higher responses to multiple anti-cancer therapies. In addition, FMNL3 was notably correlated with immune-related microbiota and N6-methyladenosine (m6A) genes. Conclusion: In summary, FMNL3 predicts an immuno-hot phenotype, which could be a promising indicator for identifying high immunogenicity in PAAD.

9.
Front Pharmacol ; 13: 1025921, 2022.
Article in English | MEDLINE | ID: mdl-36313290

ABSTRACT

It has been well-defined that tumor-infiltrating lymphocytes (TILs) play critical roles in pancreatic cancer (PaCa) progression. This research aimed to comprehensively explore the composition of TILs in PaCa and their potential clinical significance. A total of 178 samples from the TCGA and 63 samples from the GSE57495 dataset were enrolled in our study. ImmuCellAI was applied to calculate the infiltrating abundance of 24 immune cell types in PaCa and further survival analysis revealed the prognostic values of TILs in PaCa. Moreover, the Hallmark enticement analysis of differentially expressed genes (DEGs) between low- and high-risk groups was performed as well. Immunohistochemistry staining was used to evaluate NEUROD1 expression. As result, different kinds of TILs had distinct infiltrating features. In addition, Specific TILs subsets had notable prognostic values in PaCa. We further established a 6-TILs signature to assess the prognosis of PaCa patients. Kaplan-Meier and Cox regression analyses both suggested the significant prognostic value of the signature in PaCa. Based on the prognostic signature, we screened a great deal of potential prognostic biomarkers and successfully validated NEUROD1 as a novel prognostic biomarker in PaCa. Overall, the current study illuminated the immune cells infiltrating the landscape in PaCa and identified a TILs-dependent signature and NEUROD1 for prognostic prediction in PaCa patients.

10.
Ann Plast Surg ; 89(4): 451-458, 2022 10 01.
Article in English | MEDLINE | ID: mdl-36149984

ABSTRACT

BACKGROUND: Although the angiosome concept is a well-accepted theory, unexpected necrosis suggests that other factors can influence the flap survival. Our study uses the rat model to explore the flow capacity of the choke vessels across 2 angiosomes. METHODS: The medioventral line of Sprague-Dawley rats' abdominal flap was equally divided into 4 sections, which were preserved in 7 different groups (n = 6/group): A, no dissection; B to D, preserve the inferior 1/4, 2/4, and 3/4 sections; E to G, preserve the superior 1/4, 2/4, and 3/4 sections. The ratio (%) of the survival area of the distal/proximal territory was calculated. Indocyanine green, lead-oxide gel imaging, hematoxylin and eosin, and CD31 histology tests were performed. RESULTS: Compared with 96.0 ± 1.4% flap survival in group A, groups B, C, and D had distal territory flap loss (34.8% ± 4.1%, 65.0% ± 3.7%, and 94.3% ± 3.1% respectively). Group E lost the majority of the distal territory (3.5% ± 2.4%), whereas groups F and G (15.5% ± 3.8% and 79.2% ± 3.3%, respectively) had larger flap survival. Except for groups A and D, each of the other 2 groups showed statistically significant results ( P < 0.001). Indocyanine green indicated no blood flow at the superior 1/4 part. Lead-oxide gel and histology showed that the choke vessels residing along the medioventral line had no significant difference. CONCLUSIONS: Choke vessels do not carry blood flow equally. Two categories of choke vessels-"resting" and "active"-are proposed. The "active" form has variable flow carrying capabilities when the flap is harvested in different designs.


Subject(s)
Graft Survival , Indocyanine Green , Animals , Eosine Yellowish-(YS) , Graft Survival/physiology , Hematoxylin , Oxides , Rats , Rats, Sprague-Dawley
11.
J Oncol ; 2022: 3224373, 2022.
Article in English | MEDLINE | ID: mdl-35242187

ABSTRACT

OBJECTIVE: To investigate the regulatory effect of ZEB1 on PD-L1 expression and the pharmacodynamic effects of Biochanin A on the malignant biological behaviors of colorectal cancer (CRC). METHODS: The correlation between epithelial-mesenchymal transition (EMT) score and features of the tumor microenvironment (TME) was investigated using the Cancer Genome Atlas (TCGA) dataset. The correlation between ZEB1 and PD-L1 expression was validated using immunohistochemistry (IHC) staining, and the regulatory effect of ZEB1 on PD-L1 expression was explored by in vitro assays. Moreover, the pharmacodynamic effects of Biochanin A on ZEB1 and PD-L1 expression, as well as malignant biological behaviors of CRC cells, were evaluated by in vitro and in vivo assays. RESULTS: EMT score was positively correlated with a majority of immunostimulators, immune checkpoints, activities of antitumor immunity cycles, and infiltration levels of most immune cells in the TCGA dataset. In addition, ZEB1 was correlated with and positively regulated PD-L1 expression in CRC. Besides, Biochanin A, an inhibitor for the ZEB1/PD-L1 axis, notably inhibited ZEB1-mediated aggressiveness and PD-L1 expression of CRC cells. Moreover, Biochanin A also exerted a tumor-inhibitory role in vivo in the CRC mouse model. CONCLUSION: Overall, we found that ZEB1 is a main regulator of PD-L1 expression in CRC. In addition, we also identified Biochanin A as a novel inhibitor for the ZEB1/PD-L1 axis, which could inhibit tumor progression and immune escape.

12.
Front Mol Biosci ; 9: 750083, 2022.
Article in English | MEDLINE | ID: mdl-35281277

ABSTRACT

Background: DAAM2 participates in the oncogenesis and progression of human cancers. Although the role of DAAM2 in cancers has been preliminarily investigated, its correlations with antitumor immunity are unclear. Methods: A pancancer analysis was conducted to explore the immunological role of DAAM2 based on RNA sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). Next, correlations between DAAM2 and immunological characteristics in the tumor microenvironment (TME) of pancreatic adenocarcinoma (PAAD) were evaluated. In addition, the role of DAAM2 in predicting the clinical characteristics and the response to various therapies in PAAD were also assessed. In addition, the correlations between DAAM2 and the emerging immunobiomarker N6-methyladenosine (m6A) genes were also evaluated. Results: Pancancer analysis revealed that DAAM2 exhibited positive correlations with a majority of immunomodulators, tumor-infiltrating immune cells (TIICs) and inhibitory immune checkpoints in several cancer types, including PAAD. In addition, DAAM2 was associated with an inflamed phenotype in the tumor microenvironment (TME). DAAM2 also predicted significantly higher responses to chemotherapy, anti-EGFR therapy and immunotherapy but lower responses to anti-ERBB2 and antiangiogenic therapy. In addition, DAAM2 was correlated with immune-related microbiota. Conclusion: In PAAD, DAAM2 is associated with an immuno-hot phenotype and can help predict the outcome of various therapeutic options. Overall, DAAM2 is a promising indicator for assessing high immunogenicity in PAAD.

13.
Tohoku J Exp Med ; 255(3): 257-265, 2021 11.
Article in English | MEDLINE | ID: mdl-34853247

ABSTRACT

Acute radiation enteritis is a common complication occurring in patients with pelvic and abdominal tumors who receive radiotherapy. Acute radiation enteritis seriously reduces the life quality, even threatens the lives of patients. Untargeted metabolomics is an emerging strategy to explore the novel biomarkers and uncover potential pathogenesis of acute radiation enteritis. Acute radiation enteritis rat model was established by single abdominal irradiation with a gamma-ray dose of 10 Gy. Serum from 15 acute radiation enteritis rats and 10 controls was extracted for metabolomics analysis by UHPLC-Q-TOF/MS. Clinical manifestations and morphological alterations of intestine confirmed the successful establishment of acute radiation enteritis. According to the metabolomics data, 6,044 positive peaks and 4,241 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory discriminatory power between acute radiation enteritis rats and controls. Subsequent analysis extracted 66 significantly differentially expressed metabolites, which might be potential biomarkers for acute radiation enteritis diagnosis. Moreover, Kyoto Encyclopedia of Genes and Genomes enrichment analyses uncovered the potential mechanisms through which differentially expressed metabolites participated in acute radiation enteritis pathogenesis. To sum up, we summarized several differentially expressed serum metabolites as potential biomarkers for diagnosis of acute radiation enteritis and provide latent clues for elucidating acute radiation enteritis pathology.


Subject(s)
Enteritis , Metabolomics , Animals , Biomarkers , Enteritis/etiology , Humans , Rats
14.
Am J Transl Res ; 13(10): 11771-11785, 2021.
Article in English | MEDLINE | ID: mdl-34786106

ABSTRACT

A comprehensive study focusing on immune-related long non-coding RNAs (lncRNAs) in cervical cancer (CC) was performed. Through the integration of TCGA data, a total of 266 immune-related lncRNAs were obtained. We defined all samples as an entire set, and randomly divided them into train set and test set at a ratio of 1:1. Univariate, LASSO and multivariate Cox regression analyses were carried out based on train set for key lncRNAs (UBL7-AS1, AC083809.1, LIPE-AS1, PCED1B-AS1, ELFN1-AS1 and NCK1-DT) to construct a prognostic model, while the others were used for validation. The overall survival (OS) suggested that we may have longer survival expectations for patients classified into the low-risk group. The P values of risk score in univariate analysis and multivariate analysis were all less than 0.05, indicating the ability of risk score to independently assess the prognosis of patients. For clinical application, a nomogram with a high degree of agreement between the predicted curve and the actual curve was constructed. Subsequently, immune status and chemotherapy response were investigated in two prognostic subtypes. The associations between risk score and immune cell were estimated, in which CD8+ T cells showed the highest positive correlation and activated mast cell showed the highest negative correlation. In addition, checkpoint proteins (CTLA4, LAG3, PD-1, and TIGIT) showing negative correlation with risk score were found to be upregulated in low-risk group. A total of 3 chemotherapy drugs including paclitaxel, vinorelbine and methotrexate were considered effective in patients of high-risk group. Using 6 key immune-related lncRNAs, we identified two prognostic subtypes and provided new insights for CC immunotherapy.

15.
Bioengineered ; 12(1): 8147-8156, 2021 12.
Article in English | MEDLINE | ID: mdl-34615436

ABSTRACT

Solute carrier family 39, member 1 (SLC39A1) is a member of the zinc-iron permease family and located to the cell membrane, acting as a zinc uptake transporter. However, the clinical impacts of SLC39A1 in early-stage hepatocellular carcinoma (EHCC) have not been defined. In this research, we compared the differential expression of SLC39A1 in EHCC and normal tissues based on tissue microarray, and the clinical significance of SLC39A1 in EHCC was evaluated as well. Compared with adjacent tissues, SLC39A1 was remarkably decreased in paired EHCC tissues. Besides, decreased SLC39A1 expression was significantly associated with several clinic-pathological features and serum biochemical indicators. Furthermore, Kaplan-Meier analysis exhibited that both overall survival (OS) and relapse-free survival (RFS) of patients with low expression of SLC39A1 were notably poorer than that of patients with high expression. Moreover, Cox regression analyses revealed that low expression of SLC39A1 was an independent prognostic factor for OS in patients with EHCC. Subgroup analysis also revealed beneficiary populations benefiting from the prognostic evaluation using SLC39A1 expression. Collectively, we summarized that downregulated expression of SLC39A1 is a worse prognostic factor for patients with EHCC, which can be used as a promising diagnostic and prognostic biomarker for EHCC.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/pathology , Cation Transport Proteins/metabolism , Down-Regulation , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/metabolism , Case-Control Studies , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Liver Neoplasms/metabolism , Male , Neoplasm Staging , Prognosis , Survival Analysis
16.
Front Immunol ; 12: 704965, 2021.
Article in English | MEDLINE | ID: mdl-34456915

ABSTRACT

Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-induced membrane protein, which has been identified as a functional gene in multiple human cancers. The role of IFITM3 in cancer has been preliminarily summarized, but its relationship to antitumor immunity is still unclear. A pancancer analysis was conducted to investigate the expression pattern and immunological role of IFITM3 based on transcriptomic data downloaded from The Cancer Genome Atlas (TCGA) database. Next, correlations between IFITM3 and immunological features in the bladder cancer (BLCA) tumor microenvironment (TME) were assessed. In addition, the role of IFITM3 in estimating the clinical characteristics and the response to various therapies in BLCA was also evaluated. These results were next confirmed in the IMvigor210 cohort and a recruited cohort. In addition, correlations between IFITM3 and emerging immunobiomarkers, such as microbiota and N6-methyladenosine (m6A) genes, were assessed. IFITM3 was enhanced in most tumor tissues in comparison with adjacent tissues. IFITM3 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, and inhibitory immune checkpoints. In addition, IFITM3 was associated with an inflamed phenotype and several established molecular subtypes. IFITM3 expression also predicted a notably higher response to chemotherapy, anti-EGFR therapy, and immunotherapy but a low response to anti-ERBB2, anti-ERBB4, and antiangiogenic therapy. In addition, IFITM3 was correlated with immune-related microbiota and m6A genes. In addition to BLCA, IFITM3 is expected to be a marker of high immunogenicity in most human cancers. In conclusion, IFITM3 expression can be used to identify immuno-hot tumors in most cancers, and IFITM3 may be a promising pancancer biomarker to estimate the immunological features of tumors.


Subject(s)
Biomarkers, Tumor/immunology , Databases, Nucleic Acid , Gene Expression Regulation, Neoplastic/immunology , Transcriptome/immunology , Tumor Microenvironment/immunology , Urinary Bladder Neoplasms/immunology , Humans , Inflammation/immunology , Membrane Proteins , RNA-Binding Proteins
17.
Int J Biol Sci ; 17(2): 448-459, 2021.
Article in English | MEDLINE | ID: mdl-33613104

ABSTRACT

Endometrial carcinoma (EnCa) is one of the deadliest gynecological malignancies. The purpose of the current study was to develop an immune-related lncRNA prognostic signature for EnCa. In the current research, a series of systematic bioinformatics analyses were conducted to develop a novel immune-related lncRNA prognostic signature to predict disease-free survival (DFS) and response to immunotherapy and chemotherapy in EnCa. Based on the newly developed signature, immune status and mutational loading between high­ and low­risk groups were also compared. A novel 13-lncRNA signature associated with DFS of EnCa patients was ultimately developed using systematic bioinformatics analyses. The prognostic signature allowed us to distinguish samples with different risks with relatively high accuracy. In addition, univariate and multivariate Cox regression analyses confirmed that the signature was an independent factor for predicting DFS in EnCa. Moreover, a predictive nomogram combined with the risk signature and clinical stage was constructed to accurately predict 1-, 2-, 3-, and 5-year DFS of EnCa patients. Additionally, EnCa patients with different levels of risk had markedly different immune statuses and mutational loadings. Our findings indicate that the immune-related 13-lncRNA signature is a promising classifier for prognosis and response to immunotherapy and chemotherapy for EnCa.


Subject(s)
Endometrial Neoplasms/immunology , RNA, Long Noncoding/immunology , Biomarkers, Tumor/genetics , Disease-Free Survival , Female , Gene Expression Profiling , Humans , Prognosis
18.
Ann Plast Surg ; 87(4): 451-456, 2021 10 01.
Article in English | MEDLINE | ID: mdl-33587459

ABSTRACT

BACKGROUND: Dynamic infrared thermography provides a new imaging method of perforator detection. This study introduces an augmented technique to improve its accuracy by tourniquet-reperfusion and reports its preliminary use in the distal lower leg reconstruction. METHODS: A tourniquet (450 mm Hg) was applied for 3 minutes on proximal thighs. After the tourniquet release, the rewarming rate and pattern of hotspots were observed by thermography to delineate the location and quality of perforators. The results were compared with those detected by computed tomographic angiography. Clinically, the local transferred posterior tibial artery or peroneal artery propeller perforator flap was performed in 9 patients for the distal lower leg reconstruction. RESULTS: There was a 20- to 140-second "perforator observing window" after the tourniquet release. Tourniquet-reperfusion augmented thermal imaging method (TRATIM) had a sensitivity of 90.3% and a positive predictive value of 93.3%. The TRATIM and computed tomographic angiography had an excellent concordance with a kappa index value of 0.839 (P < 0.001). Based on the TRATIM, 9 propeller perforator flaps were successfully designed and raised for the distal lower leg resurfacing. All flaps survived entirely, except one with size of 1.0 cm × 2.0 cm that had terminal necrosis. CONCLUSIONS: The TRATIM is a quick, easy, cheap, and reliable approach for perforator detection in the lower leg. With the aid of TRATIM, a customized propeller perforator flap could be raised efficiently for the distal lower leg reconstruction.


Subject(s)
Perforator Flap , Plastic Surgery Procedures , Humans , Leg/surgery , Reperfusion , Thermography , Tourniquets
19.
Microsurgery ; 40(8): 874-880, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33068317

ABSTRACT

BACKGROUND: Arterial supercharging and venous superdrainage have been the commonly used vascular augmentation techniques for resolving partial loss of flaps in reconstructive surgery. It remains controversial which one of them is more effective in improving flap survival. The purpose of this study was to compare the effect of distal venous superdrainage and arterial supercharging on the survival of an extended dorsal perforator flap in rats. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were randomly divided into three groups (n = 20 in each group). An extended dorsal perforator flap with the size of 3 × 12 cm based on the deep circumflex iliac artery and vein was elevated in each rat. In arterial supercharging group, the thoracodorsal artery was retained as the distal supercharging vessel; In venous superdrainage group, the thoracodorsal vein was retained as the distal superdrainage vessel. In control group, no other arteries and veins were retained except the main vascular pedicle. On the seventh day after operation, the survival area of flap was calculated as a percentage of viable area to the total flap. Vascular changes in the choke zones were assessed by angiography. Microvascular density and diameter were assessed via immunohistochemistry staining of CD31 on the fifth day after operation. RESULTS: The flap survival area in arterial supercharging group was significantly higher than that in venous superdrainage group (98.9 ± 0.8% vs. 81.5 ± 3.5%, p < .001). By gross observation, the extent of dilation of choke zone vessels in venous superdrainage group was smaller compared with that in arterial supercharging group. The density of CD31-positive vessels and the diameter of choke zone vessels in arterial supercharging group were significantly larger than that in venous superdrainage group (23.4 ± 4.6 mm-2 vs. 13.1 ± 4.2 mm-2 , p < .05; and 37.5 ± 5.8 µm vs. 27.8 ± 4.9 µm, p < .05). CONCLUSION: Compared with venous superdrainage, distal arterial supercharging in the potential territory resulted in better survival of an extended dorsal perforator flap in a rat model.


Subject(s)
Perforator Flap , Angiography , Animals , Arteries/surgery , Graft Survival , Rats , Rats, Sprague-Dawley , Veins/surgery
20.
Int Immunopharmacol ; 88: 106882, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32799114

ABSTRACT

Cervical cancer (CeCa) is becoming an intractable public health issue worldwide. Emerging evidence uncovers that the tumor progression and prognosis of patients with CeCa are tightly associated with the abundance of tumor-infiltrating immune cells. In the current study, the abundance of tumor-infiltrating immune cells in CeCa samples was assessed by using the ssGSEA, thereby generating two immune-related groups according to the immune status. A 4-gene prognostic signature (RIPOR2, DAAM2, SORBS1, and CXCL8) was next established based on the grouping and its predictive capability was validated by multiple analyses. The TIMER database was used to evaluate the association between 4 hub gene expression and immune cell infiltration. Immunophenoscore (IPS) was used to assess response to immune checkpoint inhibitors in CeCa samples. As the results, a novel grouping strategy based on immune cell infiltration was developed and validated. Based on the grouping, a 4-gene signature was identified to be an independent prognostic indicator for overall survival (OS) in CeCa patients. Among the 4 hub genes, RIPOR2 and CXCL8 expression were significantly correlated with immune cell infiltration. Besides, higher immune checkpoints expression and IPS scores were found in the 4-gene signature low-risk group, suggesting a more immunoactive status that tended to respond to immune checkpoint inhibitors. To sum up, a novel immune-related signature is established to predict CeCa patients' prognosis and also associated with response to immune checkpoint inhibitors, which might be a promising prognostic stratification strategy and innovate therapeutic management.


Subject(s)
Biomarkers, Tumor/immunology , Genes/immunology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/immunology , Computational Biology/methods , Correlation of Data , Databases, Genetic , Female , Gene Expression Regulation, Neoplastic/immunology , Humans , Immune Checkpoint Inhibitors/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Proteins/genetics , Immune Checkpoint Proteins/metabolism , Immunophenotyping , Immunotherapy , Kaplan-Meier Estimate , Lymphocytes, Tumor-Infiltrating/metabolism , Nomograms , Prognosis , Regression Analysis , Risk Factors , Transcriptome/immunology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/drug therapy
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