Individualized radiology screening for newly diagnosed nasopharyngeal carcinoma.

OBJECTIVES: Current guidelines recommend universal PET/CT screening for metastases staging in newly diagnosed nasopharyngeal carcinoma (NPC) despite the low rate of synchronous distant metastasis (SDM). The study aims to achieve individualized screening recommendations of NPC based on the risk of SDM. METHODS AND MATERIALS: 18 pre-treatment peripheral blood indicators was retrospectively collected from 2271 primary NPC patients. A peripheral blood risk score (PBRS) was constructed by indicators associated with SDM on least absolute shrinkage and selection operator (LASSO) regression. The PBRS-based distant metastases (PBDM) model was developed from features selected by logistic regression analyses in the training cohort and then validated in the validation cohort. Receiver operator characteristic curve analysis, calibration curves, and decision curve analysis were applied to evaluate PBDM model performance. RESULTS: Pre-treatment Epstein-Barr viral DNA copy number, percentage of total lymphocytes, serum lactate dehydrogenase level, and monocyte-to-lymphocyte ratio were most strongly associated with SDM in NPC and used to construct the PBRS. Sex (male), T stage (T3-4), N stage (N2-3), and PBRS (≥1.076) were identified as independent risk factors for SDM and applied in the PBDM model, which showed good performance. Through the model, patients in the training cohort were stratified into low-, medium-, and high-risk groups. Individualized screening recommendations were then developed for patients with differing risk levels. CONCLUSION: The PBDM model offers individualized recommendations for applying PET/CT for metastases staging in NPC, allowing more targeted screening of patients with greater risk of SDM compared with current recommendations.

Significance of saline nasalirrigation for COVID-19 infection: observations and reflections from nursing care of nasopharyngeal carcinoma.

Background: Coronavirus disease 2019 (COVID-19) has placed a tremendous burden on the world's healthcare systems, prompting medical professionals worldwide to diligently research and experiment with treatment methods to prevent infection and alleviate symptoms. Previous studies have shown the potential of nasal irrigation in reducing viral clearance time and alleviating local symptoms of COVID-19. However, views differ regarding its efficacy in improving systemic symptoms. Thus, we sought to examine whether saline nasal irrigation might play a role in treatment and self-care after COVID-19 infection, but further validation is still necessary. Methods: We conducted a retrospective analysis of 468 patients and 51 healthcare personnel concurrently. The participants were grouped based on whether they received saline nasal irrigation. We used χ2 tests and Fisher's exact tests to assess the differences in the rates of COVID-19 infection and the rates of developing a fever after COVID-19 infection among different groups. Additionally, we used independent samples t-tests and Mann-Whitney U tests to evaluate differences in the maximum fever temperature and fever duration among participants with fever in different groups. Results: The rate of developing a fever after COVID-19 infection was lower (37.7%) in the patients who underwent saline nasal irrigation. Among all febrile patients, there was no difference in the highest fever temperature, but patients who underwent saline nasal irrigation had a shorter fever duration (1.72±1.05 days). Additionally, the rate of COVID-19 infection and the rate of developing a fever were higher, and fever symptoms were more severe in the healthcare worker group than in the patient group. Conclusions: Saline nasal irrigation can alleviate symptoms caused by COVID-19 infection.

Developing and validating the model of tumor-infiltrating immune cell to predict survival in patients receiving radiation therapy for head and neck squamous cell carcinoma.

Background: Radiotherapy (RT) is a mainstay of head and neck squamous cell carcinoma (HNSCC) treatment. Due to the influence of RT on tumor cells and immune/stromal cells in microenvironment, some studies suggest that immunologic landscape could shape treatment response. To better predict the survival based on genomic data, we developed a prognostic model using tumor-infiltrating immune cell (TIIC) signature to predict survival in patients undergoing RT for HNSCC. Methods: Gene expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Data from HNSCC patients undergoing RT were extracted for analysis. TIICs prevalence in HNSCC patients was quantified by gene set variation analysis (GSVA) algorithm. TIICs and post-RT survival were analyzed using univariate Cox regression analysis and used to construct and validate a tumor-infiltrating cells score (TICS). Results: Five of 26 immune cells were significantly associated with HNSCC prognosis in the training cohort (all P<0.05). Kaplan-Meier (KM) survival curves showed that patients in the high TICS group had better survival outcomes (log-rank test, P<0.05). Univariate analyses demonstrated that the TICS had independent prognostic predictive ability for RT outcomes (P<0.05). Patients with high TICS scores showed significantly higher expression of immune-related genes. Functional pathway analyses further showed that the TICS was significantly related to immune-related biological process. Stratified analyses supported integrating TICS and tumor mutation burden (TMB) into individualized treatment planning, as an adjunct to classification by clinical stage and human papillomavirus (HPV) infection. Conclusions: The TICS model supports a personalized medicine approach to RT for HNSCC. Increased prevalence of TIIC within the tumor microenvironment (TME) confers a better prognosis for patients undergoing treatment for HNSCC.

Serine Protease 27, a Prognostic Biomarker in Pan-cancer and Associated with the Aggressive Progression of Breast Cancer.

BACKGROUND: To create effective medicines, researchers must first identify the common or unique genes that drive oncogenic processes in human cancers. Serine protease 27 (PRSS27) has been recently defined as a possible driver gene in esophageal squamous cell carcinoma. However, no thorough pan-cancer study has been performed to date, including breast cancer. METHODS: Using the TCGA (The Cancer Genome Atlas), the GEO (Gene Expression Omnibus) dataset, and multiple bioinformatic tools, we investigated the function of PRSS27 in 33 tumor types. In addition, prognosis analysis of PRSS27 in breast cancer was carried out, as well as in vitro experiments to verify its role as an oncogene. We first explored the expression of PRSS27 in over 10 tumors and then we looked into PRSS27 genomic mutations. RESULTS: We discovered that PRSS27 has prognostic significance in breast cancer and other cancers' survival, and we developed a breast cancer prognostic prediction model by combining a defined set of clinical factors. Besides, we confirmed PRSS27 as an oncogene in breast cancer using some primary in vitro experiments. CONCLUSION: Our pan-cancer survey has comprehensively reviewed the oncogenic function of PRSS27 in various human malignancies, suggesting that it may be a promising prognostic biomarker and tumor therapeutic target in breast cancer.

Prognostic value analysis of cholesterol and cholesterol homeostasis related genes in breast cancer by Mendelian randomization and multi-omics machine learning.

Introduction: The high incidence of breast cancer (BC) prompted us to explore more factors that might affect its occurrence, development, treatment, and also recurrence. Dysregulation of cholesterol metabolism has been widely observed in BC; however, the detailed role of how cholesterol metabolism affects chemo-sensitivity, and immune response, as well as the clinical outcome of BC is unknown. Methods: With Mendelian randomization (MR) analysis, the potential causal relationship between genetic variants of cholesterol and BC risk was assessed first. Then we analyzed 73 cholesterol homeostasis-related genes (CHGs) in BC samples and their expression patterns in the TCGA cohort with consensus clustering analysis, aiming to figure out the relationship between cholesterol homeostasis and BC prognosis. Based on the CHG analysis, we established a CAG_score used for predicting therapeutic response and overall survival (OS) of BC patients. Furthermore, a machine learning method was adopted to accurately predict the prognosis of BC patients by comparing multi-omics differences of different risk groups. Results: We observed that the alterations in plasma cholesterol appear to be correlative with the venture of BC (MR Egger, OR: 0.54, 95% CI: 0.35-0.84, p<0.006). The expression patterns of CHGs were classified into two distinct groups(C1 and C2). Notably, the C1 group exhibited a favorable prognosis characterized by a suppressed immune response and enhanced cholesterol metabolism in comparison to the C2 group. In addition, high CHG score were accompanied by high performance of tumor angiogenesis genes. Interestingly, the expression of vascular genes (CDH5, CLDN5, TIE1, JAM2, TEK) is lower in patients with high expression of CHGs, which means that these patients have poorer vascular stability. The CAG_score exhibits robust predictive capability for the immune microenvironment characteristics and prognosis of patients(AUC=0.79). It can also optimize the administration of various first-line drugs, including AKT inhibitors VIII Imatinib, Crizotinib, Saracatinib, Erlotinib, Dasatinib, Rapamycin, Roscovitine and Shikonin in BC patients. Finally, we employed machine learning techniques to construct a multi-omics prediction model(Risklight),with an area under the feature curve (AUC) of up to 0.89. Conclusion: With the help of CAG_score and Risklight, we reveal the signature of cholesterol homeostasis-related genes for angiogenesis, immune responses, and the therapeutic response in breast cancer, which contributes to precision medicine and improved prognosis of BC.

Significance of chemotherapy for older patients with nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A propensity score matching analysis.

INTRODUCTION: This study aimed to evaluate the survival and prognosis of older patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy using propensity score matching (PSM). MATERIALS AND METHODS: We enrolled 841 older patients with NPC aged 60 years and above without metastasis receiving IMRT alone or chemoradiotherapy from 2012 to 2019. The comorbidity was assessed by adult comorbidity evaluation (ACE-27). PSM (1:3 ratio) was conducted between the two treatment groups based on four clinical factors including age, T-stage, N-stage, and ACE-27. Differences in overall survival (OS) and cancer-specific survival (CSS) were analyzed by the Kaplan-Meier method and Cox proportional hazard model. RESULTS: A total of 841 patients with NPC were included in the study, there were 94 patients in the IMRT alone group and 747 patients in the chemoradiotherapy (CRT) group. After a 1:3 ratio PSM, 89 patients underwent IMRT alone and 223 patients underwent CRT. The baseline analysis showed an insignificant difference after PSM (P > 0.05). In multivariate analysis, we found that ACE-27 (≥2) was associated with worse five-year OS and CSS (HR = 1.994, 95%CI: 1.276-3.116, P = 0.002; HR = 1.849, 95%CI: 1164-2.935, P = 0.009, respectively). Chemotherapy was an independent prognosticator of better five-year OS and CSS (HR = 0.333, 95%CI: 0.213-0.552, P < 0.001; HR = 0.327, 95%CI: 0.204-0.524, P < 0.001, respectively). In terms of subgroup analysis, chemotherapy was a statistically beneficial predictor for stage III-IV patients (P < 0.05), but no significant difference in stage II patients (P > 0.05). About the adverse events, the incidence of hepatotoxicity (P = 0.002), neutropenia (P < 0.001), anemia (P < 0.001), and thrombocytopenia (P < 0.001) were significantly higher in the CRT group. DISCUSSION: Combined modality therapy was associated with improved five-year OS and CSS in older adults with stage III-IV NPC, but was not associated with improved survival over IMRT alone in patients with stage II disease. Risk factors including T3-4 disease, positive lymph nodes, ACE-27 score ≥ 2, and IMRT alone were were associated with worse OS and CSS. There was a significantly higher incidence of hepatotoxicity and blood toxicity in the CRT group.

Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.

BACKGROUND: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity. METHODS: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis. RESULTS: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro. In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth. CONCLUSIONS: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.

LINC00891 promotes tumorigenesis and metastasis of thyroid cancer by regulating SMAD2/3 via EZH2.

BACKGROUND: Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays. METHODS: To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion apoptosis, and of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting. RESULTS: Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown. CONCLUSION: In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.

Do all patients at the initial stage of nasopharyngeal carcinoma need bone metastasis screening? A retrospective study.

BACKGROUND: To identify patients at low risk of synchronous bone metastasis who should not receive bone scans when initially diagnosed with nasopharyngeal carcinoma (NPC). METHODS: In total, 6652 patients were enrolled in the training cohort and 1919 patients in the multicenter external validation cohort. Logistic regression analyses were performed to assess independent predictors of synchronous bone metastasis for the nomogram model. RESULTS: After risk stratification, 46.3% (3081/6652) patients were separated into the low-risk group with an incidence of 0.71% for synchronous bone metastasis. The odds ratio of the intermediate and high-risk groups was 5.61 and 23.82 times that of the low-risk group, respectively. For patients with high EBV DNA, we recommend routine screening for N2-3 female patients, but that all male subgroups are screened. CONCLUSIONS: Bone scans should not be routine. Patients in the low-risk group should not be screened, which would avoid excessive radiation and economize iatrical resource.

Analysis of risk characteristics for metachronous metastasis in different period of nasopharyngeal carcinoma.

OBJECTIVE: To identify the main risk factors for metachronous metastatic nasopharyngeal carcinoma (NPC) in different periods after radiotherapy and estimate the weight of various factors in the early or late metachronous metastasis (EMM/LMM) groups. METHODS: This retrospective registry consists of 4434 patients with newly diagnosed NPC. Cox regression analysis was used to assess the independent significance of various risk factors. The Interactive Risk Attributable Program (IRAP) was used to calculate the attributable risks (ARs) for metastatic patients during different periods. RESULTS: Among 514 metastatic patients, 346 (67.32%) patients diagnosed with metastasis within 2 years after treatment were classified into the EMM group, while other 168 patients were classified into the LMM group. The ARs of T-stage, N-stage, pre-Epstein-Barr virus (EBV) DNA, post-EBV DNA, age, sex, pre-neutrophil-to-lymphocyte ratio, pre-platelet-to-lymphocyte ratio, pre-hemoglobin (HB), and post-HB were 20.19, 67.25, 2.81, 14.28, 18.50, - 11.17%, 14.54, 9.60, 3.74% and - 9.79%, respectively, in the EMM group. In the LMM group, the corresponding ARs were 3.68, 49.11, - 18.04%, 2.19, 6.11, 0.36, 4.62, 19.77, 9.57 and 7.76%, respectively. After multivariable adjustment, the total AR for tumor-related factors was 78.19%, and that for patient-related factors was 26.07% in the EMM group. In the LMM group, the total AR of tumor-related factors was 43.85%, while the weights of patient-related factors was 39.97%. In addition, except for these identified tumor- and patient-related factors, other unevaluated factors played a more important role in patients with late metastasis, with the weight increasing by 15.77%, from 17.76% in the EMM group to 33.53% in the LMM group. CONCLUSION: Most metachronous metastatic NPC cases occurred in the first 2 years after treatment. Early metastasis was mainly affected by tumor-related factors, which accounted for a declining percentage in the LMM group.

The pan-cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target.

In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.

Detection of fungicide resistance to fludioxonil and tebuconazole in Fusarium pseudograminearum, the causal agent of Fusarium crown rot in wheat.

Fusarium crown rot (FCR) on wheat is a soil-borne disease that affects the yield and quality of the produce. In 2020, 297 Fusarium pseudograminearum isolates were isolated from diseased FCR wheat samples from eight regional areas across Hebei Province in China. Baseline sensitivity of F. pseudograminearum to fludioxonil (0.0613 ± 0.0347 µg/mL) and tebuconazole (0.2328 ± 0.0840 µg/mL) were constructed based on the in vitro tests of 71 and 83 isolates, respectively. The resistance index analysis showed no resistance isolate to fludioxonil but two low-resistance isolates to tebuconazole in 2020. There was an increased frequency of resistant isolates from 2021 to 2022 based on the baseline sensitivity for tebuconazole. There was no cross-resistance between fludioxonil and tebuconazole. This study provides a significant theoretical and practical basis for monitoring the resistance of F. pseudograminearum to fungicides, especially the control of FCR.

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma.

OBJECTIVE: This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC. METHODS: This retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan-Meier. RESULTS: The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS. CONCLUSION: The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy.

Biological target volume based on fluorine-18-fluorode-oxyglucose positron emission tomography/computed tomography imaging: a spurious proposition?

PURPOSE: To assess whether the high metabolic region of fluorine-18-fluorode-oxyglucose (18F-FDG) in the primary lesion is the crux for recurrence in patients with nasopharyngeal carcinoma (NPC), to assess the feasibility and rationale for use of biological target volume (BTV) based on 18F-FDG positron emission tomography/computed tomography (18F-FDG-PET/CT). METHODS: The retrospective study included 33 patients with NPC who underwent 18F-FDG-PET/CT at the time of initial diagnosis as well as the time of diagnosis of local recurrence. Paired 18F-FDG-PET/CT images for primary and recurrent lesion were matched by deformation coregistration method to determine the cross-failure rate between two lesions. RESULTS: The median volume of the Vpri (primary tumor volume using the SUV thresholds of 2.5), the Vhigh (the volume of high FDG uptake using the SUV50%max isocontour), and the Vrecur (the recurrent tumor volume using the SUV thresholds of 2.5) were 22.85, 5.57, and 9.98 cm3, respectively. The cross-failure rate of Vrecur∩high showed that 82.82% (27/33) of local recurrent lesions had < 50% overlap volume with the region of high FDG uptake. The cross-failure rate of Vrecur∩pri showed that 96.97% (32/33) of local recurrent lesions had > 20% overlap volume with the primary tumor lesions and the median cross rate was up to 71.74%. CONCLUSION: 18F-FDG-PET/CT may be a powerful tool for automatic target volume delineation, but it may not be the optimal imaging modality for dose escalation radiotherapy based on applicable isocontour. The combination of other functional imaging could delineate the BTV more accurately.

Recommendation for imaging follow-up strategy based on time-specific disease failure for nasopharyngeal carcinoma.

BACKGROUND: To develop a common follow-up strategy for appropriate imaging examination at an appropriate time for nasopharyngeal carcinoma (NPC). METHODS: Independent prognostic factors were identified by Cox regression analysis, and a nomogram model was developed. Random survival forest (RSF) model was constructed to depict probability of disease failure during a 5-year follow-up and establish a reasonable risk-based follow-up strategy. RESULTS: The nomogram model finally categorized the patients into three risk groups. RSF model demonstrated distribution trends for local and regional recurrences, bone metastasis, liver metastasis, and lung metastasis of NPC. Adequate imaging at follow-up should be considered between 10 and 21 months for patients at moderate-risk of recurrence or metastasis and 7-36 months for those at high-risk. CONCLUSIONS: The temporal distribution of incidence rates of recurrence or metastasis varied among different risk groups. We recommend implementing a focused and targeted imaging surveillance intervention at appropriate times to improve its efficiency and reduce costs.

First Report of Anthracnose on Chili Pepper Caused by Colletotrichum sojae in Hebei Province, China.

China is the largest chili pepper producing country, and Hebei Province stands out as the forth with planting area at about 1500 km2 in China. Pepper (Capsicum annuum L.) is susceptible to Colletotrichum spp. infection during its growth, which seriously affects production yield and quality. In September 2020, widespread anthracnose was observed on pepper in Hebei (115.48° N, 38.77° E), China. Necrotic lesions on pepper fruits were suborbcular, sunken, with acervuli arranged in the middle of lesion (e-Xtra 1A). To perform fungal isolation, small tissue with 0.3 cm2 in size at the symptomatic tissue margin was surface disinfested with 75% ethanol for 10 s, and 0.1% HgCl2 for 40 s, then washed three times with sterile ddH2O. Fragments were placed on potato dextrose agar (PDA) amended with 100 mg·L-1 chloramphenicol and incubated at 28 ºC under darkness for 4 days. One of the strains of Colletotrichum spp., named HQY157, was purified by single-spore isolation, then used for morphological characterization, phylogenetic analysis, and pathogenicity tests. Colonies presented light grey aerial mycelium, occasionally mixed with gray-black strips, and the reverse was similar to the surface on PDA (e-Xtra 1B). Conidia were smooth-walled, aseptate, straight with obtuse to slightly rounded ends, 17.3-28.5 × 3.1-7.4 µm (n=50) (e-Xtra 1C). For molecular identification, the internal transcribed spacer (ITS) region, partial sequences of actin (ACT), ß-tublin (TUB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and chitin synthase (CHS) were sequenced using the specific primers (Weir et al. 2012). Sequences were deposited in GenBank with the following accession numbers OM317600-OM317604. A Maximum-Likelihood phylogenetic tree was constructed, based on the concatenated sequences (ACT, CHS, GAPDH, TUB, and ITS) of HQY157 and other closely matching Colletotrichum species obtained from GenBank, by using MEGA-X. It showed that HQY157 was grouped with the C. sojae with bootstrap values of 100% (e-Xtra 2). To confirm the pathogenicity, surface-sterilized healthy pepper fruits and healthy fruits with wounds (deal with a sterile toothpick after surface-sterilized) were then inoculated with 2 µL of conidial suspension (106 conidia/mL). The fruits inoculated with 2 µL sterile distilled water were taken as negative controls. After inoculation, the fruits were kept in a plastic box with sterilized filter paper moistened with sterilized water, and maintained at 25°C in the dark. The experiment was repeated three times. Anthracnose symptoms were observed 7 days after inoculation on the wounded pepper fruits, whereas the unwounded and negative control fruits remained symptomless (e-Xtra 1D). Colletotrichum sojae was re-isolated from the infected pepper fruits and identified by morphological and molecular analysis, fulfilling Koch's postulates. Colletotrichum sojae occurs mainly on Fabaceae plants such as Glycine max, Medicago sativa, Phaseolus vulgaris, and Vigna unguiculata (Damm et al. 2019, Talhinhas and Baroncelli, 2021), and Panax quinquefolium (Guan et al. 2021). To our knowledge, this is the first report of C. sojae causing anthracnose on pepper in China. This study provided crucial information for epidemiologic studies and appropriate control strategies for this chili pepper disease.

ErbB inhibitors as neoadjuvant therapy for triple-positive breast cancer: a network meta-analysis.

BACKGROUND: Evidence on the effectiveness of ErbB inhibitor interventions for women with triple-positive breast cancer (TPBC) is scarce. Exposure to hormone receptors was reported to eclipse targeted intervention effectiveness. Here, we aimed to explore the optimum targeted regimen for TPBC. METHODS: We conducted a thorough search of the literature focusing on neoadjuvant targeted therapy with both hormone receptor-positive and HER2 (ErbB2)-positive patients and performed a network meta-analysis comparing the regimens using a random-effects model. The rate of pathological complete response (pCR) (ypT0/is) was the primary outcome. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association among twelve regimens. RESULTS: Thirteen studies meeting the inclusion criteria were included. Significantly more TPBC patients receiving ado-trastuzumab emtansine plus lapatinib experienced pCR events than other patients. In the high-performance ranking of the twelve regimens, ado-trastuzumab emtansine plus lapatinib (TDM-1+L) ranked top, followed by ado-trastuzumab emtansine (TDM-1), trastuzumab plus carboplatin, taxanes and pertuzumab (TCHP), trastuzumab plus docetaxel and lapatinib (THL), trastuzumab, taxanes and pertuzumab (THP), ado-trastuzumab emtansine plus pertuzumab (TDM1+P), trastuzumab plus taxanes (TH), trastuzumab plus taxanes and neratinib, taxanes plus pertuzumab (HP), taxanes and neratinib (HN), trastuzumab plus lapatinib (TL), trastuzumab plus pertuzumab (TP) in sequence. CONCLUSION: Double-targeted therapy in chemotherapy-based regimens was associated with better pCR than single-targeted therapy, and TDM-1+L stood out. For either single-targeted or double-targeted therapies, regimens free of chemotherapy were always worse than those with targeted therapy. Our data support guidelines that recommend combinations of chemotherapies plus targeted therapies in the neoadjuvant setting for early TPBC.

Construction and Analysis of a Colorectal Cancer Prognostic Model Based on N6-Methyladenosine-Related lncRNAs.

Given the relatively poor understanding of the expression and functional effects of the N6-methyladenosine (m6A) RNA methylation on colorectal cancer (CRC), we attempted to measure its prognostic value and clinical significance. We comprehensively screened 37 m6A-related prognostic long non-coding RNAs (lncRNAs) with significant differences in expression based on 21 acknowledged regulators of m6A modification and data on 473 colorectal cancer tissues and 41 para-cancer tissues obtained from the TCGA database. Accordingly, we classified 473 CRC patients into two clusters by consensus clustering on the basis of significantly different survival outcomes. We also found a potential correlation between m6A-related prognostic lncRNAs and BRAF-KRAS expression, as well as immune cell infiltration. Then, we established a prognostic model by selecting 16 m6A-related prognostic lncRNAs via LASSO Cox analysis and grouped the CRC patients into low- and high-risk groups to calculate risk scores. Then, we performed stratified sampling to validate and confirm our model by categorising the 473 samples into a training group (N = 208) and a testing group (N = 205) in a 1:1 ratio. The survival curve showed a distinct clinical outcome in the low- and high-risk subgroups. We reconfirmed the reliability and independence of the prognostic model through various measures: risk curve, heat map and univariate and multivariate Cox analyses. To ensure that the outcomes were applicable to clinical settings, we performed stratified analyses on different clinical features, such as age, lymph node status and clinical stage. CRC patients with downregulated m6A-related gene expression, lower immune score, distant metastasis, lymph node metastasis or more advanced clinical staging had higher risk scores, indicating less-desirable outcomes. Moreover, we explored the immunology of colorectal cancer cells. The risk score showed positive correlations with eosinophils, M2 macrophages and neutrophils. In summary, our effort revealed the significance of m6A RNA methylation regulators in colorectal cancer, and the prognostic model we constructed may be used as an essential reference for predicting the outcome of CRC patients.

Serum TSH levels are associated with postoperative recurrence and lymph node metastasis of papillary thyroid carcinoma.

OBJECTIVE: To explore the relationship between thyroid-stimulating hormone (TSH) levels in the serum and postoperative recurrence and lymph node metastasis (LNM) in papillary thyroid cancer (PTC) patients after surgery. METHODS: We selected 272 patients diagnosed with PTC from June 2011 to July 2014. The clinical and pathological data of 272 PTC patients were collected at the First Affiliated Hospital of Wenzhou Medical University and analysed retrospectively. All PTC patients were tested for the BRAFV600E gene mutation before surgery by fine-needle aspiration (FNA) cytology, and TSH levels in the serum were determined one month after surgery. The optimal cut-off value of thyroid-stimulating hormone (TSH) for predicting the recurrence or metastasis of PTC after surgery was determined by the establishment of a receiver operating characteristic (ROC) curve. Kaplan-Meier and Cox regression analyses were used to evaluate the correlation between the optimal cut-off value of TSH and disease-free survival rate and prognosis. RESULTS: Of 272 patients, only 182 (73 BRAFV600E+, 109 BRAFV600E-) met the final study criteria. Among them, 60 cases had recurrence or metastasis, and 122 cases were controls. The optimal cut-off value of TSH for the prediction of recurrence or metastasis of PTC after surgery was 2.615 mlU/L. In our study, a high TSH level (> 2.615 mlU/L) was correlated with the BRAFV600E mutation, multifocality, lymph node metastasis, recurrence, and metastasis. In all 182 patients, those with high TSH levels had worse disease-free survival. This result was more obvious in the 73 BRAFV600E+ patients. The univariate analysis showed that lymph node metastasis, multifocality, lymph node dissection, tumour size, sex, BRAFV600E mutation, and a high postoperative TSH level were all significantly correlated with recurrence or metastasis in PTC patients (all P < 0.05). In addition, the Cox multivariate analysis showed that lymph node metastasis, BRAFV600E mutation, and high postoperative TSH levels were independent risk factors for PTC recurrence or metastasis (all P < 0.05). CONCLUSION: PTC patients with high TSH levels (> 2.615 mlU/L) have worse disease-free survival, which is more obvious in the BRAFV600E+ population.