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Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.
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OBJECTIVE: Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. METHODS: Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. RESULTS: In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). CONCLUSION: Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.
Subject(s)
Arthroscopy , Chitosan , Osteoarthritis, Knee , Humans , Chitosan/administration & dosage , Osteoarthritis, Knee/surgery , Arthroscopy/methods , Male , Female , Middle Aged , Injections, Intra-Articular , Aged , Pain Measurement , Body Mass Index , Combined Modality TherapyABSTRACT
BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: 60 patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), VAS, WOMAC scoring, and AKS scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the pre-surgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced a slightly more pronounced decline in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.
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Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitinâproteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.
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OBJECTIVES: To investigate the epidemiological trend for nasopharyngeal carcinoma among children and young adults and the disease burden they caused. MATERIALS AND METHODS: Data were collected from the Global Burden of Disease (GBD) study 2019. A comprehensive analysis was performed, with age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), disability-adjusted life-years (DALYs) and estimated annual percentage changes (EAPC). And decomposition and frontier analyses were done. Future trends were predicted using Bayesian age-period-cohort model. RESULTS: Globally, there were decreases in the ASIR (EAPC -0.175, 95 % confidence interval [CI]: -0.352 to 0.002), ASMR (EAPC -2.681, 95 % CI: -2.937 to -2.424), and age-standardized DALYs rates (EAPC -2.643, 95 % CI: -2.895 to -2.391). However, the ASIR for males in global (EAPC 0.454, 95 % CI: 0.302 to 0.606), Asia (EAPC 0.782, 95 % CI: 0.610 to 0.954) and America (EAPC 0.448, 95 % CI: 0.379 to 0.517), as well as females in European (EAPC 0.595, 95 % CI: 0.479 to 0.712) and American (EAPC 0.369, 95 % CI: 0.324 to 0.415), showed an increasing trend. The future ASIR per 100,000 will likely show a slight upward trend in 2020 to 2040 (increased from 0.254 to 0.284), particularly among females (increased from 0.177 to 0.206), and a continued decline in ASMR for both sexes (decreased from 0.070 to 0.061). CONCLUSIONS: Globally, NPC in children and young adults remains a major public health issue, with the global distribution and magnitude of the burden varies markedly, highlighting the need to formulate regional and population-based policies for primary prevention.
Subject(s)
Global Burden of Disease , Nasopharyngeal Carcinoma , Humans , Male , Female , Nasopharyngeal Carcinoma/epidemiology , Nasopharyngeal Carcinoma/mortality , Child , Adolescent , Young Adult , Global Burden of Disease/trends , Adult , Nasopharyngeal Neoplasms/epidemiology , Nasopharyngeal Neoplasms/mortality , Incidence , Child, Preschool , Global Health/statistics & numerical data , Bayes Theorem , Infant , Disability-Adjusted Life Years/trendsABSTRACT
Reduced adipogenesis is a prominent characteristic of aging adipose tissue and is closely tied to the development of metabolic disorders associated with aging. Epigenetic modification plays a crucial role in the aging process, yet the role of N6-methyladenosine (m6A), the most prevalent RNA modification, in regulating adipose tissue aging remains uncertain. Our study found that levels of m6A and its recognition protein, heterogeneous nuclear ribonucleoprotein C (HNRNPC), decrease in adipose tissue as individuals age. Lower levels of HNRNPC were also linked to reduced adipogenesis during aging. Through loss and gain of function experiments with HNRNPC, we established a positive correlation between HNRNPC and adipogenesis in vitro. Hnrnpc-APKO mice displayed decreased adipogenesis, increased insulin resistance, elevated expression of aging-related and inflammation-related genes, decreased lipogenesis-related genes, and other metabolic disorders compared to their littermates. Additionally, we discovered that HNRNPC facilitated the stability of lymphocyte cytosolic protein 1 (Lcp1) mRNA by binding to the m6A motif of LCP1. Overexpression of LCP1 mitigated the inhibition of adipogenesis caused by decreased HNRNPC through modulation of cytoskeletal remodeling. Finally, our findings demonstrate that anti-aging treatments could enhance HNRNPC levels. In conclusion, HNRNPC is positively associated with reduced adipogenesis during aging, and increacing HNRNPC levels through anti-aging treatments highlights its potential as a therapeutic target for addressing metabolic imbalances in adipose tissue related to aging.
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OBJECTIVES: Thoracoscopic sympathectomy is an effective treatment for palmar hyperhidrosis. However, compensatory hyperhidrosis occurs frequently as a postoperative complication of the procedure. The goal of this study was to elucidate the clinical significance of thoracoscopic sympathectomy using our surgical procedure. METHODS: Consecutive 151 patients who underwent thoracoscopic sympathectomy for palmar hyperhidrosis were studied. In addition, to investigate patients' satisfaction and long-term quality of life, 111 patients were asked to complete a mailing questionnaire survey, and 84 responded (response rate of 75.7%). RESULTS: All of the 151 patients reported a reduction in palmar sweating during the immediate postoperative period. None of the patients had pneumothorax, hemothorax, Horner's syndrome, or worsening of bradycardia. Based on the questionnaire, the surgical success rate was 98.8%. None of the patients had a recurrence of palmar hyperhidrosis during the long-term postoperative period. However, compensatory hyperhidrosis was reported in 82 patients (97.6%). In total, 94.0% of patients had high levels of postoperative satisfaction. CONCLUSIONS: Thoracoscopic sympathectomy is an effective surgical treatment for palmar hyperhidrosis. By contrast, the careful preoperative explanation of compensatory hyperhidrosis is considered to be very important.
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In the realm of obstetric care, discerning the subtle signs of primary hyperparathyroidism (PHPT) amidst common pregnancy symptoms remains a formidable challenge. Our exploration into a case of gestational hypercalcemia peels back the layers of this complexity, revealing the clinical conundrum posed by overlapping gastrointestinal manifestations. The journey from diagnosis through surgical intervention to the resolution of symptoms underscores the importance of vigilance for PHPT in pregnant patients. This case further prompts consideration of gamma-aminobutyric acid (GABA) as a potential piece in the puzzle of persistent symptoms post-calcium normalization, inviting a broader dialogue on the intricacies of parathyroid pathology in pregnancy.
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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported comparable 3-year regional relapse-free survival (RRFS) using elective upper-neck irradiation (UNI) in N0-1 nasopharyngeal carcinoma (NPC) compared with standard whole-neck irradiation (WNI). Here, we present the prespecified 5-year overall survival (OS), RRFS, late toxicity, and additional analyses. In this randomized trial, patients received UNI (n = 224) or WNI (n = 222) for an uninvolved neck. After a median follow-up of 74 months, the UNI and WNI groups had similar 5-year OS (95.9% v 93.1%, hazard ratio [HR], 0.63 [95% CI, 0.30 to 1.35]; P = .24) and RRFS (95.0% v 94.9%, HR, 0.96 [95% CI, 0.43 to 2.13]; P = .91) rates. The 5-year disease-free survivors in the UNI group had a lower frequency of hypothyroidism (34% v 48%; P = .004), neck tissue damage (29% v 46%; P < .001), dysphagia (14% v 27%; P = .002), and lower-neck common carotid artery stenosis (15% v 26%; P = .043). The UNI group had higher postradiotherapy circulating lymphocyte counts than the WNI group (median: 400 cells/µL v 335 cells/µL, P = .007). In conclusion, these updated data confirmed that UNI of the uninvolved neck is a standard of care in N0-1 NPC, providing outstanding efficacy and reduced long-term toxicity, and might retain more immune function.
Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Female , Male , Middle Aged , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/mortality , Adult , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/mortality , Aged , NeckABSTRACT
BACKGROUND AND PURPOSE: Whether concurrent chemoradiotherapy would provide survival benefits in patients with stage II and T3N0 NPC with adverse factors remains unclear in IMRT era. We aimed to assess the value of concurrent chemotherapy compared to IMRT alone in stage II and T3N0 NPC with adverse features. MATERIALS AND METHODS: 287 patients with stage II and T3N0 NPC with adverse factors were retrospectively analyzed, including 98 patients who received IMRT alone (IMRT alone group) and 189 patients who received cisplatin-based concurrent chemotherapy (CCRT group). The possible prognostic factors were balanced using propensity score matching (PSM). Kaplan-Meier analysis was used to evaluate the survival rates, and log-rank tests were employed to compare differences between groups. RESULTS: The median follow-up duration was 90.8 months (interquartile range = 75.6-114.7 months). The IMRT alone and the CCRT group were well matched; however, for all survival-related endpoints, there were no significant differences between them (5-year failure-free survival: 84.3% vs. 82.7%, P value = 0.68; 5-year overall survival: 87.3% vs. 90.6%, P value = 0.11; 5-year distant metastasis-free survival: 92.8% vs. 92.5%, P value = 0.97; 5-year locoregional relapse-free survival: 93.4% vs. 89.9%, P value = 0.30). The incidence of acute toxicities in the IMRT alone group was significantly lower than that in the CCRT group. CONCLUSION: For patients with stage II and T3N0 NPC with adverse features treated using IMRT, no improvement in survival was gained by adding concurrent chemotherapy; however, the occurrence of acute toxicities increased significantly. For those combined with non-single adverse factors, the comprehensive treatment strategy needs further exploration.
Subject(s)
Chemoradiotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Staging , Propensity Score , Radiotherapy, Intensity-Modulated , Humans , Male , Female , Chemoradiotherapy/adverse effects , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Retrospective Studies , Adult , Radiotherapy, Intensity-Modulated/adverse effects , Cisplatin/therapeutic use , Cisplatin/administration & dosage , Cohort Studies , Survival Rate , Carcinoma/therapy , Carcinoma/pathology , Carcinoma/mortality , AgedABSTRACT
Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
Subject(s)
Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/pathology , Docetaxel/therapeutic use , Nasopharyngeal Neoplasms/pathology , Transcription Factors/therapeutic use , Drug Resistance, Neoplasm , Fluorouracil/therapeutic use , Chemoradiotherapy/methods , Cisplatin/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ubiquitin ThiolesteraseABSTRACT
BACKGROUND: Treating nasopharyngeal carcinoma (NPC) with radiotherapy frequently causes hearing impairment (HI). HI risk data haven't been evaluated quantitatively. This study aimed to analyze the probability of HI and sever HI (SHI), develop a nomogram to quantify individual prediction, and provide dose limitation suggestions. METHODS AND MATERIALS: This single-center, retrospective study was conducted based on 588 adolescents and young adults with non-metastatic NPC treated using intensity modulated radiation therapy (IMRT) at Sun Yat-sen University Cancer Center between 2010 and 2016. A least absolute shrinkage and selection operator (LASSO) logistic regression model and univariate analysis were used to screen potential risk factors. The concordance index and a calibration curve evaluated the nomogram models' predictive ability, with bootstrap resampling validation. RESULTS: We analyzed 588 patients with NPC, with a median follow-up of 103.4 months. HI occurred in 39.5 % of patients, with 29.7 % experiencing SHI. Two factors were classified as precursors for HI (volume 45 Gy of the inner ear (IEV45) and volume 50 Gy of the internal auditory canal (IACV50)), and IACmin and IACV60 for SHI, respectively. Prognostic nomograms were developed to predict HI and SHI probabilities, showing excellent discriminative abilities (c-index values = 0.806 and 0.793, respectively). We also suggested IEV45 < 50 % and/or IACV50 < 40 % as rational dose limitations for HI, and IACmin < 44 Gy and/or the IACV60 < 40 % for SHI. CONCLUSION: Comprehensive analysis could predict the risk of HI and SHI in NPC after IMRT, proposing rational dose limitations and improving long-term quality of life.
Subject(s)
Hearing Loss , Nasopharyngeal Neoplasms , Radiotherapy, Intensity-Modulated , Adolescent , Young Adult , Humans , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/pathology , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Retrospective Studies , Nasopharyngeal Neoplasms/pathology , Quality of Life , Nomograms , Hearing Loss/etiology , Risk FactorsABSTRACT
AIM: Despite the high risk of tumor recurrence, patients with nasopharyngeal carcinoma (NPC) with persistently (at least twice) detected circulating cell-free Epstein-Barr virus (EBV) DNA levels during follow-up are routinely recommended to keep observation. For these patients, whether administering more aggressive treatment could improve survival outcomes remains unknown. MATERIALS AND METHODS: We retrospectively included 431 patients with nonmetastatic NPC with persistently detected EBV DNA during follow-up, who do not have clinical or imaging evidence of recurrence. Among these patients, 79 were administered oral chemotherapy, and the remaining 352 underwent observation alone. Baseline characteristics were balanced with propensity score matching (PSM) analysis. The primary endpoint was modified disease-free survival (mDFS), defined as time from detectable EBV DNA result to tumor recurrence or death. The secondary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: One-to-three PSM resulted in 251 eligible patients (oral chemotherapy group, 73; observation group, 178). In the matched cohort, the oral chemotherapy group had higher median mDFS (12.9 months [95 % confidence interval [CI] 9.6-16.3] vs. 6.8 months [95 % CI 5.8-7.8], p = 0.009) and DFS (24.1 months [95 % CI 18.5-29.7] vs. 16.7 months [95 % CI 14.4-19.1], p = 0.035) than the observation group. The median OS was numerically higher in the oral chemotherapy group than in the observation group (57.9 months [95 % CI 42.5-73.3] vs. 50.8 months [95 % CI 39.7-61.9], p = 0.71). A consistent benefit favoring oral chemotherapy was observed for mDFS in all subgroups analyses for male, <45 years, stage III-IVa disease, pretreatment EBV DNA load ≥ 4,000 copies/mL, no induction chemotherapy, or a detectable EBV DNA load ≥ 1,200 copies/mL. After adjusting for other confounders in the multivariate analysis, oral chemotherapy remained a significantly favorable factor for both mDFS (hazard ratio [HR] 0.67, 95 % CI 0.50-0.89; p = 0.006) and DFS (HR 0.68, 95 % CI 0.51-0.91; p = 0.01), but not a significant factor for OS (HR 0.89, 95 % CI 0.62-1.27; p = 0.52). CONCLUSIONS: In patients with NPC having persistently detected EBV DNA levels but without clinical or imaging evidence of recurrence during follow-up, oral chemotherapy significantly prolongs mDFS and DFS. Employing oral chemotherapy as a more aggressive treatment option, as opposed to mere observation, could potentially benefit these patients, although further prospective validation is necessitated.
Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Humans , Male , Nasopharyngeal Carcinoma/drug therapy , Herpesvirus 4, Human/genetics , Epstein-Barr Virus Infections/complications , Retrospective Studies , Follow-Up Studies , Neoplasm Recurrence, Local , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , PrognosisABSTRACT
Epithelial-mesenchymal transition (EMT) promotes primary tumor progression toward a metastatic state. The role of tumor-associated macrophages (TAMs) in inducing EMT in lung squamous cell carcinoma (LUSC) remains unclear. We aimed to clarify the significance of TAMs in relation to EMT in LUSC. We collected 221 LUSC specimens from patients who had undergone surgery. Immunohistochemistry was performed to evaluate M1-like and M2-like TAM distribution and EMT by E-cadherin and vimentin staining. Human LUSC cell lines (H226 and EBC-1) and a human monocyte cell line (THP-1) were used for in vitro experiments. M2-like polarization of TAMs and EMT marker expression in LUSC cells were evaluated by western blotting. The biological behavior of LUSC cells was evaluated by migration, invasion, and cell proliferation assays. Immunohistochemical analysis showed that 166 (75.1%) tumors were E-cadherin-positive and 44 (19.9%) were vimentin-positive. M2-like TAM density in the tumor stroma was significantly associated with vimentin positivity and worse overall survival. Western blotting demonstrated higher levels of CD163, CD206, vascular endothelial growth factor, and transforming growth factor beta 1 (TGF-ß1) in TAMs versus unstimulated macrophages. Furthermore, increased TGF-ß1 secretion from TAMs was confirmed by ELISA. TAM-co-cultured H226 and EBC-1 cells exhibited EMT (decreased E-cadherin, increased vimentin). Regarding EMT-activating transcriptional factors, phosphorylated Smad3 and ZEB-family proteins were higher in TAM-co-cultured LUSC cells than in parental cells. TAM-co-cultured H226 and EBC-1 cells demonstrated enhanced migration and invasion capabilities and improved proliferation. Overall, the present study suggests that TAMs can induce EMT with increased metastatic potential and tumor cell proliferation in LUSC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Humans , Transforming Growth Factor beta1 , Vimentin/metabolism , Transforming Growth Factor beta , Genes, Homeobox , Tumor-Associated Macrophages/metabolism , Vascular Endothelial Growth Factor A , Cell Line, Tumor , Carcinoma, Squamous Cell/pathology , Cell Proliferation , Epithelial-Mesenchymal Transition , Cadherins/metabolism , Lung Neoplasms/metabolism , Zinc Fingers , Lung/pathology , Cell MovementABSTRACT
OBJECTIVES: To investigate the value of integrating primary gross tumor volume (GTVp) and gross tumor volume of nodes (GTVn) after induction chemotherapy (IC) and dynamic changes in plasma cell-free Epstein-Barr virus DNA (cfEBV DNA) during sequential chemoradiotherapy (CRT) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). MATERIALS AND METHODS: We retrospectively reviewed 988 patients with LA-NPC undergoing IC plus concurrent chemoradiotherapy (CCRT) between 2014 and 2018. The entire cohort was divided into four subgroups according to tumor volume and the cfEBV DNA load. Using a supervised statistical clustering approach, we stratified the subgroups into three clusters. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were calculated using Kaplan-Meier analysis and inter-group differences were compared using the log-rank test. RESULTS: We observed that GTVp & GTVn and cfEBV DNApostIC & cfEBV DNApostCRT were powerful prognostic factors for OS (p = 0.004, p < 0.001, p < 0.001, and p < 0.001, respectively). The survival curves of the three clusters were significantly different. The 5-year OS for the low-risk, intermediate-risk and high-risk clusters were 97.0%, 86.2% and 77.1% (all P values < 0.001), respectively. The risk stratification system showed better predictive performance than the current tumor-node-metastasis (TNM) classification for OS (area under curve [AUC]: 0.653 versus 0.560, p < 0.001), DFS (AUC: 0.639 versus 0.540, p < 0.001), DMFS (AUC: 0.628 versus 0.535, p < 0.001) and LRRFS (AUC: 0.616 versus 0.513, p < 0.001). CONCLUSION: Both tumor volume and the cfEBV DNA level during sequential CRT are effective prognostic indicators for patients with high-risk LA-NPC. The developed risk stratification system incorporating above factors improved survival prediction and demonstrated potential value in decision-making.
Subject(s)
Epstein-Barr Virus Infections , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/pathology , Prognosis , Herpesvirus 4, Human/genetics , Nasopharyngeal Neoplasms/drug therapy , Retrospective Studies , Tumor Burden , Neoplasm Recurrence, Local/etiology , DNA , Chemoradiotherapy/adverse effects , Induction ChemotherapyABSTRACT
Objective: Traditional Chinese medicine (TCM) has been used as a complementary treatment for cancer patients, but there has been no quantitative comprehensive analysis of TCM's efficacy. The purpose of this paper is to explore the current status and hotspots of TCM in cancer research from 2002 to 2022 and to provide a reference for future research. Methods: We retrieved articles published between 2002 and 2022 from the Web of Science database and analyzed them using R software, VOSviewer, and CiteSpace software. Results: A total of 7,129 articles were included in this study. The publication rate of TCM cancer research increased steadily from 2002 to 2022, with a rapid increase from 2010 to 2021. China was the country with the most published articles, followed by the United States, Republic of Korea, Germany, and Japan. China was also the country with the most international collaborations, and China Medical University and Shanghai University of Traditional Chinese Medicine were the most representative cooperation centers. The Journal of Ethnopharmacology was the most published and cited journal. Apoptosis, expression, in vitro, activation, and other related keywords were commonly used in these articles. Breast cancer, colorectal cancer, gastric cancer, liver cancer, and lung cancer were the most studied cancer types in TCM research. Pathway-related apoptosis, anti-inflammation, and oxidative stress were the hotspots and trends of TCM's anti-cancer mechanism. Metabolomics combined with network pharmacology was the main research method. Conclusion: Traditional Chinese medicine as an anti-cancer drug has received increasing attention from researchers worldwide, and it is expected to be a hotspot for developing new anti-cancer drugs in the future. Our study provides a comprehensive analysis of the current status and hotspots of TCM cancer research, which could serve as a valuable reference for future studies.
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China is the largest producer and consumer of rice, and the classification of filled/unfilled rice grains is of great significance for rice breeding and genetic analysis. The traditional method for filled/unfilled rice grain identification was generally manual, which had the disadvantages of low efficiency, poor repeatability, and low precision. In this study, we have proposed a novel method for filled/unfilled grain classification based on structured light imaging and Improved PointNet++. Firstly, the 3D point cloud data of rice grains were obtained by structured light imaging. And then the specified processing algorithms were developed for the single grain segmentation, and data enhancement with normal vector. Finally, the PointNet++ network was improved by adding an additional Set Abstraction layer and combining the maximum pooling of normal vectors to realize filled/unfilled rice grain point cloud classification. To verify the model performance, the Improved PointNet++ was compared with six machine learning methods, PointNet and PointConv. The results showed that the optimal machine learning model is XGboost, with a classification accuracy of 91.99%, while the classification accuracy of Improved PointNet++ was 98.50% outperforming the PointNet 93.75% and PointConv 92.25%. In conclusion, this study has demonstrated a novel and effective method for filled/unfilled grain recognition.
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BACKGROUND: Verticillium wilt is the major disease of cotton, which would cause serious yield reduction and economic losses, and the identification of cotton verticillium wilt is of great significance to cotton research. However, the traditional method is still manual, which is subjective, inefficient, and labor-intensive, and therefore, this study has proposed a novel method for cotton verticillium wilt identification based on spectral and image feature fusion. The cotton hyper-spectral images have been collected, while the regions of interest (ROI) have been extracted as samples including 499 healthy leaves and 498 diseased leaves, and the average spectral information and RGB image of each sample were obtained. In spectral feature processing, the preprocessing methods including Savitzky-Golay smoothing (SG), multiplicative scatter correction (MSC), de-trending (DT) and mean normalization (MN) algorithms have been adopted, while the feature band extraction methods have adopted principal component analysis (PCA) and successive projections algorithm (SPA). In RGB image feature processing, the EfficientNet was applied to build classification model and 16 image features have been extracted from the last convolutional layer. And then, the obtained spectral and image features were fused, while the classification model was established by support vector machine (SVM) and back propagation neural network (BPNN). Additionally, the spectral full bands and feature bands were used as comparison for SVM and BPNN classification respectively. RESULT: The results showed that the average accuracy of EfficientNet for cotton verticillium wilt identification was 93.00%. By spectral full bands, SG-MSC-BPNN model obtained the better performance with classification accuracy of 93.78%. By feature bands, SG-MN-SPA-BPNN model obtained the better performance with classification accuracy of 93.78%. By spectral and image fused features, SG-MN-SPA-FF-BPNN model obtained the best performance with classification accuracy of 98.99%. CONCLUSIONS: The study demonstrated that it was feasible and effective to use fused spectral and image features based on hyper-spectral imaging to improve identification accuracy of cotton verticillium wilt. The study provided theoretical basis and methods for non-destructive and accurate identification of cotton verticillium wilt.
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This study aims to analyse the pathological features of skeletal muscle injury repair by using rats to model responses to different exercise intensities. Eighty-four rats were randomly divided into five groups for treadmill exercise. The short-term control, low-intensity, medium-intensity and high-intensity groups underwent gastrocnemius muscle sampling after 6, 8 and 12 weeks of exercise. The long-term high-intensity group underwent optical coherence tomography angiography and sampling after 18 weeks of exercise. RNA sequencing was performed on the muscle samples, followed by the corresponding histological staining. Differentially expressed genes were generally elevated at 6 weeks in the early exercise stage, followed by a decreasing trend. Meanwhile, the study demonstrated a negative correlation between time and the gene modules involved in vascular regulation. The modules associated with muscle remodelling were positively correlated with exercise intensity. Although the expression of many genes associated with common angiogenesis was downregulated at 8, 12 and 18 weeks, we found that muscle tissue microvessels were still increased, which may be closely associated with elevated sFRP2 and YAP1. During muscle injury-remodelling, angiogenesis is characterized by significant exercise time and exercise intensity dependence. We find significant differences in the spatial distribution of angiogenesis during muscle injury-remodelling, which be helpful for the future achievement of spatially targeted treatments for exercise-induced muscle injuries.