BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

OBJECTIVE: To evaluate the effectiveness of the innervated medial plantar flap for reconstructing soft tissue defects, particularly in the weight-bearing zone, after resection of foot tumors. METHODS: A retrospective analysis was conducted on 12 patients with malignant skin and soft tissue tumors of the foot treated between October 2023 and December 2024. The cohort included 8 males and 4 females, aged 42-67 years (mean, 57.5 years). Tumor types comprised malignant melanoma (5 cases), squamous cell carcinoma (4 cases), arsenical keratosis (2 cases), and tumor-induced osteomalacia (1 case). Soft tissue defects located in the heel weight-bearing region in 10 cases and non-weight-bearing ankle region in 2 cases, with defect sizes ranging from 4.0 cm×3.0 cm to 6.0 cm×4.0 cm. Preoperative photon-counting CT angiography (PC-CTA) was performed to assess the medial plantar artery and its perforators. All patients underwent radical tumor resection with confirmed negative margins. The resulting defects were reconstructed using a innervated medial plantar flap incorporating sensory branches of the medial plantar nerve. The flap donor site was covered with a split-thickness skin graft harvested from the ipsilateral inguinal region. RESULTS: The operation was successfully completed in all 12 patients. All flaps survived completely without vascular compromise, partial necrosis, or total loss. Incisions healed primarily without dehiscence or infection. Minor skin graft necrosis occurred at the donor site in 3 patients, which healed within 2-3 weeks with routine dressing changes. No donor site complication (e.g., tendon or nerve injury) occurred. Patients were followed up 2-16 months (mean, 10.3 months). At last follow-up, there was no tumor recurrence. Flaps exhibited good color and texture match with surrounding tissue, restored sensation, and all feet achieved normal weight-bearing activity. CONCLUSION The innervated medial plantar flap, precisely designed based on PC-CTA localization, provides reliable blood supply and effective sensory restoration. It is an ideal method for reconstructing soft tissue defects after foot tumor resection, especially in the heel weight-bearing region.
Humans ; Male ; Middle Aged ; Female ; Plastic Surgery Procedures/methods* ; Adult ; Aged ; Retrospective Studies ; Soft Tissue Neoplasms/surgery* ; Surgical Flaps/blood supply* ; Foot/surgery* ; Skin Neoplasms/surgery* ; Soft Tissue Injuries/surgery* ; Carcinoma, Squamous Cell/surgery* ; Treatment Outcome ; Skin Transplantation/methods* ; Melanoma/surgery*

OBJECTIVE: To explore the technical key points and effectiveness of the facial artery perforator myomucosal flap (FAPMF) in repairing oral and perioral tissue defects. METHODS: Between June 2023 and December 2024, 8 patients with oral and perioral tissue defects were repaired with the FAPMF. There were 4 males and 4 females, with an average age of 57.6 years (range, 45-72 years). Among them, 4 cases had floor-of-mouth defects and 3 cases had buccal mucosa defects remaining after squamous cell carcinoma resection, and 1 case had lower lip defect caused by trauma. The size of tissue defects ranged from 4.5 cm×3.0 cm to 6.0 cm×5.0 cm. The preoperative mouth opening was (39.55±1.88) mm, and the preoperative swallowing score of the University of Washington Quality of Life Questionnaire (UW-QOL) was 64.64±8.47. Preoperatively, CT angiography and Doppler ultrasound were used to locate the perforator vessels. A myomucosal flap pedicled with the perioral perforators of the facial artery was designed, with the harvesting size ranging from 4.0 cm×2.5 cm to 6.5 cm×4.0 cm. The length of the vascular pedicle was 4.2-6.8 cm (mean, 5.2 cm). Postoperatively, FAPMF survival, complications, and functional recovery were observed. RESULTS: All 8 surgeries were successfully completed without conversion to other repair methods or complications such as facial nerve injury. The total operation time ranged from 110 to 180 minutes, with an average of 142.5 minutes; among this, the harvesting time of the FAPMF ranged from 35 to 65 minutes, with an average of 48.7 minutes. The intraoperative blood loss was 50-150 mL, with an average of 85.6 mL. All FAPMFs survived completely. One patient developed venous reflux disorder at 24 hours after operation, which relieved after conservative treatment. All patients were followed up 7-16 months (mean, 12.4 months). All FAPMFs achieved complete epithelialization at 3 months after operation, showing a similar soft texture to the surrounding mucosa. At 7 months after operation, the mouth opening was (39.11±1.79) mm, slightly lower than preoperative level, but the difference was not significant (P>0.05). The swallowing score of the UW-QOL was 63.78±8.31, which was significantly lower than preoperative score (P<0.05). The visual analogue scale (VAS) score for patient satisfaction was 7-10, with an average of 8.9. CONCLUSION The FAPMF has advantages such as reliable blood supply, high mucosal matching degree, and concealed donor site, making it an ideal option for repairing small and medium-sized oral and perioral tissue defects.
Humans ; Male ; Middle Aged ; Female ; Perforator Flap/blood supply* ; Aged ; Plastic Surgery Procedures/methods* ; Mouth Neoplasms/surgery* ; Mouth Mucosa/surgery* ; Mouth/surgery* ; Quality of Life ; Face/surgery* ; Treatment Outcome ; Carcinoma, Squamous Cell/surgery* ; Arteries/surgery*

Objective To explore the mechanism of TPT1-AS1 targeting miR-324/TWIST1 axis to regulate the proliferation, invasion, migration and angiogenesis of epithelial ovarian cancer (EOC) cells, thereby affecting ovarian cancer (OC) progression. Methods RT-qPCR was used to detect the expression of TPT1-AS1 and miR-324 in 29 OC lesions and adjacent tissue samples. The two OC cell models of TPT1-AS1 overexpression and miRNA324 knockdown were constructed, and the cell proliferation, invasion and migration abilities were detected by CCK-8, Transwell^TM and scratch test. Western blot analysis was used to detect the protein expression levels of TWIST1, epithelial cadherin (E-cadherin), Vimentin, and vascular endothelial growth factor A (VEGF-A) in OC cells. Fluorescence in situ hybridization (FISH) and RNA pull-down experiments were used to verify the interaction between TPT1-AS1 and miR-324. Immunohistochemistry and Targetscan bioinformatics analysis were used to verify the negative regulatory role of miR-324 in the epithelial-mesenchymal transition (EMT) process. Results The TPT1-AS1 expression was significantly higher in OC tissues than that in para-cancerous tissues, while the miR-324 expression was significantly lower. In SKOV3 cells with TPT1-AS1 overexpression, the miR-324 expression decreased significantly, and TPT1-AS1 was negatively correlated with miR-324. It was also found that TPT1-AS1 and miR-324 were co-expressed in OC cells, and there was a direct binding relationship between them. Down-regulation of miR-324 significantly promoted the proliferation, invasion and migration of SKOV3 cells. Further studies revealed that miR-324 had a binding site at the 3'-UTR end of the TWIST1, a key transcription factor for EMT. Inhibiting miR-324 expression increased the transcription level of TWIST1, leading to a decrease in E-cadherin protein expression and an increase in Vimentin protein expression. Additionally, the downregulation of miR-324 resulted in an increased expression level of VEGF-A protein, which in turn enhanced angiogenesis of OC. Conclusion TPT1-AS1 promotes EOC cell proliferation, invasion, migration and angiogenesis by negatively regulating the miR-324/TWIST1 axis, thus promoting the development of OC. These findings provide new potential targets for the diagnosis and treatment of OC.
Humans ; MicroRNAs/metabolism* ; Female ; Cell Movement/genetics* ; Ovarian Neoplasms/blood supply* ; Twist-Related Protein 1/metabolism* ; Cell Line, Tumor ; Neovascularization, Pathologic/genetics* ; Neoplasm Invasiveness ; Carcinoma, Ovarian Epithelial/metabolism* ; Nuclear Proteins/metabolism* ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic ; RNA, Long Noncoding/metabolism* ; Cadherins/genetics* ; Vascular Endothelial Growth Factor A/genetics* ; Vimentin/genetics* ; Angiogenesis

BACKGROUND: In the real world, the plasma drug concentration range of Icotinib treated with epidermal growth factor receptor (EGFR) gene mutant non-small cell lung cancer (NSCLC) is not yet clear, and there may be a correlation between drug concentration and its efficacy, as well as adverse reactions. This study conducted therapeutic drug monitoring (TDM) of Icotinib. The aim of this study was to analyze the drug exposure of Icotinib in targeted therapy for NSCLC, and to investigate the relationship between Icotinib drug concentration and its efficacy and safety. METHODS: Prospective blood samples were collected from NSCLC patients with EGFR-sensitive mutations who received treatment with Icotinib in Peking University Cancer Hospital from April 2022 to July 2024. The drug trough concentration of Icotinib in plasma was detected, and the correlation between drug concentration and efficacy, as well as the toxic side effects, were further analyzed based on the patient's clinical medical records. RESULTS: 22 patients who were treated with Icotinib underwent TDM, but one of them did not acquire the data due to prolonged discontinuation. The remaining 21 patients, each with 1-7 blood draws, obtained a total of 32 plasma drug concentration data. The drug concentration of icotinib is a range of 126.9-2317.1 ng/mL. Among the 21 patients, 18 cases were female (85.7%), and 3 cases were male (14.3%), with an age range of 44-85 years old. The pathological types are all lung adenocarcinoma. Except for 5 patients receiving postoperative adjuvant therapy, 16 patients had assessable tumors. The objective response rate was 43.8% (7/16), and the disease control rate reached 100.0% (16/16). The median value of drug concentration is 805.5 ng/mL among those 21 patients. Compared with the patients who achieved stable disease, the median value of drug concentrations of Icotinib in patients who achieved partial response were 497.2 and 1195.5 ng/mL, respectively (P=0.017). The median value of drug concentrations for patients who did not experience adverse reactions during treatment and those who experienced adverse reactions were 997.0 and 828.6 ng/mL, respectively (P=0.538). CONCLUSIONS Icotinib demonstrates good therapeutic effect and tolerable toxicity on the EGFR gene mutant NSCLC. There is a certain negative correlation between the plasma drug concentration of Icotinib and its efficacy, while there seems no significant correlation with safety.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/metabolism* ; Lung Neoplasms/genetics* ; Male ; Female ; Crown Ethers/blood* ; Middle Aged ; Drug Monitoring ; Aged ; Quinazolines/blood* ; Mutation ; Adult ; Aged, 80 and over ; Antineoplastic Agents/blood* ; Prospective Studies

Objective:Retrospective analysis of the correlation between clinicopathologic features and related indexes and prognosis in patients with recurrent nasopharyngeal carcinoma. Methods:One hundred and eight nasopharyngeal cancer（NPC） patients with post-treatment recurrence in Yunnan Cancer Hospital from January 2013 to January 2018 were collected, and the survival time was estimated by Kaplan-Meier method, and clinicopathological characteristics were analyzed by log-rank test; risk factors and prognosis were analyzed by Cox proportional risk model for single-factor and multifactorial analysis. A P-value <0.05 was considered statistically significant. Results:The median survival of all patients was 54 months, with a 3-year survival rate of 80.2% and a 5-year survival rate of 39.8%. The 5-year overall survival rate was 50.2% for patients >46 years old and 27.9% for patients ≤46 years old（P<0.05）, a statistically significant difference. Univariate analysis showed that overall survival was associated with age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, γ-interferon, α-tumor necrosis factor, IL-10, and IL-4（P<0.05）. Multifactorial analysis revealed that age, chemotherapy regimen, EBV early antigen IgA, plasma D-dimer, glycan antigen-125, and interleukin 10 were independent influences on the prognosis of recurrent nasopharyngeal carcinoma（P<0.05）. Conclusion:Differences in chemotherapy regimens affect the prognosis of recurrent nasopharyngeal carcinoma. Elevated plasma D-dimer, glycan antigen 125, and interleukin 10 levels affect the overall survival of recurrent nasopharyngeal carcinoma, which may be a valid independent prognostic factor, and are expected to provide new biomarkers for nasopharyngeal carcinoma in the clinic.
Humans ; Prognosis ; Nasopharyngeal Neoplasms/mortality* ; Nasopharyngeal Carcinoma ; Retrospective Studies ; Neoplasm Recurrence, Local ; Male ; Middle Aged ; Female ; Survival Rate ; Adult ; Risk Factors ; Interleukin-10/blood* ; Aged ; Proportional Hazards Models

Objective:To explore the predictive value of preoperative peripheral hematological parameters combined with clinicopathological features for cervical lymph node metastasis（CLNM） in patients with laryngeal squamous cell carcinoma（LSCC）, and to construct and validate a nomogram model for CLNM. Methods:A retrospective analysis was conducted on the clinical data of 264 LSCC patients who underwent surgical treatment and were pathologically confirmed, collected from the Second Affiliated Hospital of Shandong First Medical University and Taian 88 Hospital. Specifically, 161 patients from one hospital were allocated to the training cohort, while 103 patients from another hospital constituted the validation cohort. Based on postoperative pathological results, patients were categorized into CLNM-positive and CLNM-negative groups. The general clinical data, clinicopathological features, and hematological parameters of the two groups were analyzed and compared. A preoperative predictive model for CLNM was developed using logistic regression analysis, followed by validation and sensitivity analysis to evaluate the robustness of the model's predictive performance. Results:The results showed that there were significant differences in tumor location, tumor size, tumor differentiation, neutrophil percentage, lymphocyte count, lymphocyte percentage, c-reactive protein（CRP）, fibrinogen, neutrophil-to-lymphocyte ratio（NLR）, platelet-to-lymphocyte ratio（PLR）, systemic immune-inflammation index（SII）, systemic inflammation response index（SIRI）, and prognostic inflammatory index（PIV） between the CLNM-positive and CLNM-negative groups（P<0.05）. Lasso regression identified tumor location, clinical T stage, tumor size, tumor differentiation degree, red blood cell distribution width（RDW） -coefficient of variation（RDW-CV）, CRP, FIB, D-dimer, NLR, and lymphocyte-to-monocyte ratio（LMR） were the most predictive parameters. Multivariate logistic regression revealed that tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients（P<0.05）. A nomogram was constructed based on these five factors. The model demonstrated excellent discrimination, with a C-index of 0.837（95%CI 0.766-0.908） in the training cohort and 0.809（95%CI 0.698-0.920） in the validation cohort. Calibration curves and DCA curves in both cohorts confirmed the clinical utility of the model. Sensitivity analysis further supported the robustness of the results, showing good discrimination and calibration across different age and BMI subgroups. Conclusion:Tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients. The nomogram based on these variables exhibits strong discrimination, calibration, and clinical applicability, and may serve as a valuable tool for preoperative risk assessment and individualized treatment planning.
Humans ; Nomograms ; Laryngeal Neoplasms/blood* ; Retrospective Studies ; Lymphatic Metastasis ; Carcinoma, Squamous Cell/blood* ; Lymph Nodes/pathology* ; Male ; Female ; Middle Aged ; Neck ; C-Reactive Protein ; Aged ; Logistic Models ; Neutrophils ; Prognosis

Objective:This study aims to investigate the influence of microvessel density（MVD） and microlymphatic vessel density（MLVD） on the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to develop a nomogram prediction model for prognosis based on pathological characteristics. Methods:A retrospective analysis was conducted on clinicopathological and follow-up data from HPSCC patients who underwent surgical treatment at our institution between June 2010 and June 2020. Immunohistochemical staining was performed on tumor tissues and adjacent normal margin tissues to evaluate MVD and MLVD. The associations among MVD, MLVD, and clinicopathological features were analyzed. Univariate and multivariate Cox regression analyses were conducted to identify independent risk factors affecting overall survival（OS）. Based on these findings, a nomogram model was constructed and its predictive accuracy was assessed using C-index, receiver operating characteristic（ROC） curve, and calibration curve. Results:Both MVD and MLVD were significantly higher in HPSCC tumor tissues compared to normal tissues. Patients in the high MVD and high MLVD groups exhibited significantly lower OS rates than those in the low MVD and low MLVD groups. Multivariate Cox regression analysis revealed that N stage, recurrence, nerve invasion, lymph node capsule invasion, MVD, and MLVD were independent prognostic factors of OS. Based on these factors, a nomogram prognosis model was successfully constructed. The nomograms demonstrated superior performance in terms of C-index, area under the ROC curve, and calibration, outperforming the AJCC TNM staging system. Conclusion:Elevated MVD and MLVD levels are associated with poorer prognosis in HPSCC patients. The nomogram model based on pathological features provides valuable insights for clinical assessment and decision-making.
Humans ; Hypopharyngeal Neoplasms/blood supply* ; Prognosis ; Retrospective Studies ; Microvascular Density ; Nomograms ; Lymphatic Vessels/pathology* ; Male ; Female ; Middle Aged ; Carcinoma, Squamous Cell/blood supply* ; Microvessels/pathology* ; Lymphatic Metastasis ; Survival Rate

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

OBJECTIVE: To analyze the influence of type 2 diabetes mellitus (DM) on the prognosis of oral squamous cell carcinoma (OSCC) patients with surgical treatment. METHODS: The clinical data of 309 patients, who were diagnosed with OSCC and admitted to the same ward of Peking University Hospital of Stomatology from January 2014 to December 2017 were retrospectively reviewed, of whom, 104 were classified into DM group and 205 into non-DM group. The basic clinical data and follow-up results of the patients were analyzed and compared. Propensity score matching (PSM) was used to reduce confounding bias between the DM group and the non-DM group. Kaplan-Meier was used to calculate the survival rate of the two groups. Proportional hazards model was used to analyze the independent prognostic factors. The effect of glucose level on survival was analyzed. RESULTS: After PSM, 77 patients in each group were matched and the variables were balanced. There were statistically significant differences in postoperative oral dysplasia and local recurrence between the two groups (P < 0.05). There was no significant difference in survival analysis between the two groups, but the survival rate of the DM group had the tendency to be lower than that of the non-DM group after matching. Univariate analysis and multiva-riate analysis both revealed that the tumor stage was an independent factor influencing the overall survival rate and tumor-specific survival rate of the OSCC patients (P < 0.05), while diabetes had no significant influence on the survival of the OSCC patients (P>0.05). Multivariate analysis showed that tumor stage, triglyceride level, preoperative mean capillary fasting blood glucose, postoperative mean postprandial blood glucose were indepen-dent prognostic factors for overall survival in the DM group. Tumor stage and mean postoperative postprandial blood glucose were independent prognostic factors for tumor-specific survival in the DM group. The risk of postoperative complications and distant metastasis in the DM group with poor glycemic control was higher than that in the good glycemic controls. CONCLUSION There is no significant difference in overall survival and tumor-specific survival of the patients with or without DM. However, the possibility of mucosal dysplasia or local recurrence in the DM group is higher than that in the non-DM group. The tumor stage, triglyceride level and glycemic control of the patients with DM may affect their prognosis.
Humans ; Diabetes Mellitus, Type 2/complications* ; Mouth Neoplasms/mortality* ; Retrospective Studies ; Prognosis ; Carcinoma, Squamous Cell/mortality* ; Male ; Female ; Survival Rate ; Neoplasm Recurrence, Local ; Propensity Score ; Proportional Hazards Models ; Blood Glucose/analysis* ; Middle Aged ; Kaplan-Meier Estimate