Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

PANoptosis induced by inflammatory cytokines promotes salivary glands radiation injury.

OBJECTIVE: Salivary glands are frequently damaged in patients undergoing radiotherapy for head and neck cancer. Whether PANoptosis, which is characterized by pyroptosis, apoptosis, and necroptosis, occurs during radiation injury to the salivary glands and its role remain unclear. MATERIALS AND METHODS: Radiation-induced injury models of mouse submandibular gland, as well as primary acinar cells and HSG cell lines were established to determine the presence of radiation-induced PANoptosis. Several programmed cell death inhibitors, PFTα, disulfiram, Nec-1 and zVAD, were used to compare the effects of different cell death pathway on radiation injury. The LEGENDplex™ Human Inflammation Panel was used to characterize the inflammatory landscape secreted by salivary gland cells after radiotherapy. RESULTS: Single 15Gy or 8Gy radiotherapy triggered PANoptosis in mouse submandibular gland or salivary gland cells. Compared to the suppression of pyroptosis, apoptosis, or necroptosis alone, the inhibition of PANoptosis is more effective in preventing radiation injury to the salivary glands (p < 0.0001). The levels of multiple inflammatory cytokines were significantly up-regulated in the supernatants of HSG cells within 48 h after IR. Neutralizing inflammatory cytokines are capable of inhibiting salivary glands PANoptosis. CONCLUSIONS: Inhibition of PANoptosis induced by inflammatory cytokines can effectively prevent radiation injury of salivary glands.

Stair-stepped mandibulotomy: Clinical indication, surgery program design, and operation points.

For radical treatment of malignancies in the posterior region of the oral cavity and oropharynx, surgical exposure of the tumor by mandibulotomy is often required. Midline or paramedian vertical mandibulotomies are commonly performed in clinical practice, but these can damage the suprahyoid musculature and genioglossus, and weaken the swallowing and speech function of patients. Stair-stepped mandibulotomy is a new procedure, developed on the principles of functional surgery, that preserves the structure and function of the mandible whilst providing a clear field and avoiding damage to critical muscle attachments. Stair-stepped mandibulotomy is suitable for patients whose primary tumor is located in the middle and posterior part of the tongue or oropharynx, especially if the lesion involves extrinsic tongue muscles. In this case report, we draw on 2 cases of typical patients in our center to elaborate the surgery program design, operation points, advantages and disadvantages of stair-stepped mandibulotomy.

Prognosis influence of additional chromosome abnormalities in newly diagnosed acute promyelocytic leukemia with t(15;17)(q24;q21).

OBJECTIVES: In patients with acute promyelocytic leukemia (APL), additional chromosomal abnormalities (ACAs) are prognostic indicators. However, the clinical features of ACAs were not systematically reported in Chinese patients. Therefore, we enrolled a large cohort of APLs to demonstrate the clinical characteristics and prognostic value of ACAs. METHODS: 268 patients with newly diagnosed APL with t(15;17)(q24;q21) were retrospectively enrolled, and their clinical characteristics and the predictive value of ACAs were assessed between patients with the presence and absence of ACAs. RESULTS: APL patients with and without ACAs did not differ significantly in their clinical features or treatment response and clinical outcomes like overall survival (OS) and disease-free survival (DFS). It appeared to be substantially associated with worse OS in APL patients with trisomy 8, which was the most common ACA, although DFS was unaffected. Interestingly, the presence of ACAs or trisomy 8 affected OS and DFS in the subgroup of patients aged ≥60 years; by contrast, ACAs had no effect on OS or DFS in any treatment subgroup (ATRA + ATO/RIF or ATRA + ATO/RIF + CH or ATRA + CH), except for the ATRA + ATO/RIF + CH treatment subgroup, where their impact on DFS was less favorable. CONCLUSIONS: Our results suggested that OS and DFS were unaffected by ACAs. Nonetheless, in the subgroup of patients older than 60, the existence of ACAs or trisomy 8 appeared to impact OS and DFS negatively. Individuals with t(15;17) alone had a higher DFS and were more susceptible to ATRA + ATO/RIF + CH than individuals with t(15;17) ACAs.

[Research progress on the treatment improvement of HPV-associated oropharyngeal cancer].

The number of new cases of oropharyngeal cancer is increasing year by year among the world, and HPV infection is one of the risk factors for this malignant tumor. Compared with HPV-negative oropharyngeal cancer, HPV-positive patients are more sensitive to radiotherapy and have a better prognosis, but there is no accepted treatment for HPV-positive patients. Reducing treatment intensity moderately and exploring the best option to minimize side effects of treatment are urgent issues to be addressed. This article reviews the research progress on the treatment improvement of HPV-associated oropharyngeal cancer in recent years.

Correlation between ABO blood group and prognosis of hepatectomy for hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: The relationship between ABO blood group and prognosis of patients with hepatocellular carcinoma (HCC) remains unclear. We investigated the relationship between prognosis and ABO blood group in patients with hepatitis B-associated HCC after radical hepatectomy. METHODS: The medical records of 874 patients with hepatitis B-associated HCC who underwent radical liver tumor resection were retrospectively collected. Cox proportional risk models were constructed for analysis, and the patient data were further balanced using propensity score matching (PSM) analysis to assess the impact of ABO blood group on the prognosis of patients with hepatitis B-associated HCC. RESULTS: In univariate Cox regression analysis, the overall survival (OS) of non-A blood type group vs. A blood type group [hazard ratio (HR) (95% confidence interval [CI]) = 1.504 (1.003-2.255), P = 0.048], in multivariate Cox regression analysis the OS of non-A blood type group versus A blood type group [HR (95% CI) = 1.596 (1.054-2.417), P = 0.027]. After PSM, the baseline information was more balanced between the two groups, yielding the same results as above [HR (95% CI) = 1.550 (1.012-2.373), P = 0.044]. CONCLUSION: The difference in OS after radical hepatectomy in patients with hepatitis B-associated HCC was statistically significant in terms of ABO blood group, OS was lower in patients with non-A blood group than in patients with A blood group.

AMLnet, A deep-learning pipeline for the differential diagnosis of acute myeloid leukemia from bone marrow smears.

Acute myeloid leukemia (AML) is a deadly hematological malignancy. Cellular morphology detection of bone marrow smears based on the French-American-British (FAB) classification system remains an essential criterion in the diagnosis of hematological malignancies. However, the diagnosis and discrimination of distinct FAB subtypes of AML obtained from bone marrow smear images are tedious and time-consuming. In addition, there is considerable variation within and among pathologists, particularly in rural areas, where pathologists may not have relevant expertise. Here, we established a comprehensive database encompassing 8245 bone marrow smear images from 651 patients based on a retrospective dual-center study between 2010 and 2021 for the purpose of training and testing. Furthermore, we developed AMLnet, a deep-learning pipeline based on bone marrow smear images, that can discriminate not only between AML patients and healthy individuals but also accurately identify various AML subtypes. AMLnet achieved an AUC of 0.885 at the image level and 0.921 at the patient level in distinguishing nine AML subtypes on the test dataset. Furthermore, AMLnet outperformed junior human experts and was comparable to senior experts on the test dataset at the patient level. Finally, we provided an interactive demo website to visualize the saliency maps and the results of AMLnet for aiding pathologists' diagnosis. Collectively, AMLnet has the potential to serve as a fast prescreening and decision support tool for cytomorphological pathologists, especially in areas where pathologists are overburdened by medical demands as well as in rural areas where medical resources are scarce.

Biomimetic cytomembrane-coated ZIF-8-loaded DMDD nanoparticle and sonodynamic co-therapy for cancer.

Background: Breast cancer (BC) is the most common type of cancer affecting females. It is also a leading cause of cancer-related death in women worldwide. Methods: Sonodynamic therapy (SDT) is an emerging therapeutic strategy for cancer treatment. SDT ensures non-invasive penetration of deep tumors and results in activation of non-toxic sonosensitizers administered in deep tumor sites to become cytotoxic. It has been reported that 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has a significant anti-tumor effect against various cancer types including BC. However, DMDD is hydrophobic. Therefore, a one-step encapsulation method was used in the current study to construct zeolitic imidazole frameworks-8 (ZIF-8) loaded with DMDD and sonosensitizer chlorin e6 (Ce6). ZIF-8 was further modified by coating it with a biomimetic cell membrane to improve targeted delivery. Results: In vitro and in vivo results indicated that the nanomedicines had great biocompatibility properties and targeting ability. The nanocomposite exhibited a higher release rate under an acidic tumor microenvironment. The tumor killing effect of reactive oxygen species (ROS) generated from Ce6 and inhibition of tumor growth was enhanced after ultrasound (US) treatment, which might be caused by the increase in apoptosis rate. Conclusions: These findings show that the combination of nanomedicine and SDT provides a potential therapeutic method for BC.

Optimal Parameters of Gas Drainage and Carbon Dioxide Inerting Technology and Its Application in a High Gassy and Spontaneous Combustion Mine.

In the process of coupling disaster prevention and control of gas and coal spontaneous combustion in goaf, there is a great contradiction between the gas drainage and carbon dioxide inerting technology. The key performance indexes are put forward to solve the coupling disaster, such as the air quantity of the intake airway (A), the gas drainage rate (B), the carbon dioxide injection rate (C), and the injection depth (D). Using the numerical simulation method and the orthogonal test of four factors and three levels, we establish the coupling disaster model of the no. 7436 working face in the Kongzhuang coal mine. Using a combination of the relative membership degree method and range analysis, the optimal level of each factor is determined, which is AIIBIIICIIDII. Furthermore, the distribution law of the airflow field is obtained under the conditions of different gas drainage rates and carbon dioxide injection rates. The results show that the gas concentration decreases with an increase in gas drainage in the upper corner, but it has little impact on the width of the oxidation zone. The gas concentration can be reduced to 1%, while the gas drainage rate is higher than 35 m3/min. With an increase in gas injection rate, the carbon dioxide emission rate increases in the upper corner, but the width of the oxidation zone decreases. Also, the gas injection rate should be less than 800 m3/h. Moreover, with an increase in injection time in the upper corner during the injection process, the carbon dioxide and gas concentrations increase, and the maximum carbon dioxide concentration is 1.3%, and the maximum gas concentration is 0.42%, which is consistent with the results of numerical simulations.

Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione on autophagy and the PI3K/AKT/mTOR signaling pathway in human cholangiocarcinoma QBC939 cells.

Background: 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has been reported to have good antitumor effects. The aim of this study was to investigate whether DMDD induces apoptosis and autophagy in human cholangiocarcinoma (CCA) QBC939 cells and determine its effect on the PI3K/AKT/mTOR signaling pathway. Methods: QBC939 cells were cultured in vitro and changes in cell viability were detected by the Cell Counting Kit (CCK8) assay after treatment with different concentrations of DMDD for 24, 48, and 72 h. The cells were divided into control and DMDD-treated groups (treated concentrations were 10, 15, and 20 µM/L), and the cell cycle, apoptosis, and autophagic vesicles were assessed. The expression levels of PI3K, AKT, mTOR, microtubule-associated protein 1 light chain 3 beta (LC3-II)/I, Beclin-1, and P62 were detected by Western blot. A xenograft mouse model was constructed to detect the effect of DMDD on CCA. Results: The experimental results showed that DMDD was able to inhibit proliferation, migration, and invasion and induce cell cycle arrest and autophagy of QBC939 cells. In addition, DMDD decreased the protein expression of PI3K, AKT, and mTOR and increased the expression of LC3-II/I, Beclin-1, and P62. In mice, DMDD was able to inhibit the growth of tumors. Conclusions: DMDD inhibits CCA cell viability and induces cell cycle arrest and autophagy by a mechanism that may be related to the downregulation of the PI3K/AKT/mTOR signaling pathway.

Platelet to white blood cell ratio was an independent prognostic predictor in acute myeloid leukemia.

BACKGROUND: Recently, platelet to white blood cell ratio (PWR) was reported as an independent prognostic predictor in acute promyelocytic leukemia. Acute myeloid leukemia (AML) often presents with abnormal platelet counts and white blood cell counts (WBC) at disease diagnosis. However, the clinical impact of PWR on cytogenetically normal AML (CN-AML) is still unclear. Therefore, we evaluate its prognostic impact on CN-AML patients. METHODS: We recorded the clinical information at the time of disease diagnosis, and calculated the ratio of platelet counts to WBC in 338 patients with CN-AML. To assess the prognostic value of PWR, we divided patients into low, intermediate and high group based on the values of PWR. The independent prognostic value of PWR was investigated in the context of the well-established predictors including white blood cell counts, age, and genes of NPM1, FLT3-ITD, CEBPA, and DNMT3A mutations. Receiver operating characteristic (ROC) curve was used to assess the performance of its prognostic prediction. RESULTS: Higher PWR have the higher levels of platelet counts, but lower levels of white blood cell counts, percentage of bone marrow blasts, FLT3-ITD and NPM1 mutations. The performance of survival prediction was comparable between PWR alone and combined molecular biomarkers. Moreover, PWR had the additional prognostic information to the molecular biomarkers. Finally, PWR was associated with favorable overall survival and event free survival in CN-AML patients independent of genetic subtypes and clinical parameters. CONCLUSION: We found PWR was an independent prognostic predictor in CN-AML.

Down regulated oncogene KIF2C inhibits growth, invasion, and metastasis of hepatocellular carcinoma through the Ras/MAPK signaling pathway and epithelial-to-mesenchymal transition.

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer death. Kinesin family member 2C (KIF2C) has been shown as oncogene in a variety of tumors. However, its role in HCC remains unclear. Methods: In this study, the expression level of KIF2C in HCC was detected by immunohistochemical staining and RT-PCR, and verified by Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine database. A curve was established to evaluate the diagnostic efficiency of KIF2C. The effect of KIF2C on HCC was investigated by flow cytometry, Cell Counting Kit-8, Transwell, and the wound-healing assay. We explored the underlying mechanism through epithelial-to-mesenchymal transition (EMT) and transcriptome sequences analysis. Results: KIF2C was overexpression in HCC tissue and related to neoplasm histologic grade (P<0.001), pathology stage (P=0.001), and a dismal prognosis (overall, recurrence-free, and disease-free survival). The diagnostic efficacy of KIF2C was >90% in diagnosing HCC. The HCC cell function experiments showed that KIF2C promoted HCC cell proliferation, migration, invasion, and an accelerated cell cycle, and inhibited apoptosis. Based on western blot analysis and RT-PCR, we found that KIF2C promoted HCC invasion and metastasis through activation of the EMT. Based on transcriptome sequences, we showed that KIF2C promoted HCC through the Ras/MAPK and PI3K/Akt signaling pathway. Conclusions: KIF2C was found to promote the progression of HCC and is anticipated to serve as a biomarker for HCC diagnosis, prognosis, and targeted therapy.

Gender disparity in hepatocellular carcinoma recurrence after curative hepatectomy.

INTRODUCTION AND OBJECTIVES: Whether there is gender disparity in the recurrence of hepatocellular carcinoma (HCC) has been not fully addressed. This study aimed to investigate the impact of gender on HCC recurrence following curative hepatectomy. PATIENTS AND METHODS: This retrospective cohort study included 1087 patients with HCC (917 males, 170 females) who underwent curative hepatectomy. Cox regression models were constructed to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the risk parameters associated with HCC recurrence. In the sensitivity analysis, subgroup analysis, and propensity score matching (PSM) analysis were used. Logistic regression models were used to assess the odds ratio (OR) and 95% CI of the risk parameters related to early and late recurrence. RESULTS: Male patients showed significantly higher risk for HCC recurrence than females, in both multivariate Cox regression analysis (HR [95% CI] = 1.480 [1.084-2.020], P = 0.014) and PSM analysis (HR [95% CI] = 1.589 [1.093-2.312], P = 0.015). Higher risk of HCC recurrence was again found in males in the subgroup analysis, but the effect of male versus female gender on HCC recurrence did not depend on any selected subgroups (all P for interaction > 0.05). Gender was an independent risk factor for early recurrence (OR [95% CI] = 1.864 [1.215-2.936], P = 0.006), but not for late recurrence. CONCLUSIONS: There is gender disparity in the recurrence of patients with HCC after curative hepatectomy: males had a higher risk for HCC recurrence than females.

Biased gene expression reveals the contribution of subgenome to altitude adaptation in allopolyploid Isoetes sinensis.

Allopolyploids are believed to inherit the genetic characteristics of its progenitors and exhibit stronger adaptability and vigor. The allotetraploid Isoetes sinensis was formed by the natural hybridization and polyploidization of two diploid progenitors, Isoetes taiwanensis and Isoetes yunguiensis, and was believed to have the potential to adapt to plateau environments. To explore the expression pattern of homoeologous genes and their contributions to altitude adaptation, we transplanted natural allotetraploid I. sinensis (TnTnYnYn) along the altitude gradient for a long-term, and harvested them in summer and winter, respectively. One year after transplanting, it still lived well, even in the extreme environment of the Qinghai-Tibet Plateau. Then, we performed high-throughput RNA sequencing to measure their gene expression level. A total of 7801 homoeologous genes were expressed, among which 5786 were identified as shared expression in different altitudes and seasons. We further found that altitude variations could change the subgenome bias trend of I. sinensis, but season could not. Moreover, the functions of uniquely expressed genes indicated that temperature might be an important restrictive factor during the adaptation process. Through the analysis of DEGs and uniquely expressed genes, we found that Y subgenome provided more contributions to high altitude adaptation than T subgenome. These adaptive traits to high altitude may be inherited from its plateau progenitor I. yunguiensis. Through weighted gene co-expression network analysis, pentatricopeptide repeats gene family and glycerophospholipid metabolism pathway were considered to play important roles in high-altitude adaptation. Totally, this study will enrich our understanding of allopolyploid in environmental adaptation.

Atractylodin may induce ferroptosis of human hepatocellular carcinoma cells.

BACKGROUND: It has been reported that atractylodin has a potential antitumor effect. This study aimed to investigate the effects of atractylodin on Huh7 and Hccm hepatocellular carcinoma (HCC) cells and its molecular mechanism. METHODS: Huh7 and Hccm cells were cultured in vitro, and their viability was detected by CCK-8 assay and the half inhibitory concentration (IC50) was calculated. The cells were treated with different concentrations of atractylodin, and the migration and invasion ability of cells was detected by scratch assay and Transwell assay. The cell cycle change and apoptosis rate were detected by flow cytometry. IlluminaHiSeq4000 platform was used for transcriptome sequencing, and the results were analyzed for gene differential expression, gene function, and signal pathway enrichment. Morphological changes of cells were detected by transmission electron microscopy, reactive oxygen species (ROS) levels were detected by DCFH-DA probe, and the expressions of ferroptosis related proteins GPX4, ACSL4, FTL, and TFR1 were detected by Western blot. RESULTS: The results showed that atractylodin could inhibit the proliferation, migration, and invasion of Huh7 and Hccm cells, regulate the cell cycle, and induce cell apoptosis and G1 phase cell cycle arrest. In addition, it could significantly induce the increase of intracellular ROS levels, decrease the expression of GPX4 and FTL proteins, and up-regulate the expression of ACSL4 and TFR1 proteins. CONCLUSIONS: Atractylodin can inhibit the proliferation, migration, and invasion of Huh7 and Hccm liver cancer cells, and induce cell apoptosis and cell cycle arrest. In addition, our results suggest that atractylodin may induce ferroptosis in HCC cells by inhibiting the expression of GPX4 and FTL proteins, and up-regulating the expression of ACSL4 and TFR1 proteins.

Effect of timing of surgical resection of primary hepatocellular carcinoma on survival outcomes in elderly patients and prediction of clinical models.

BACKGROUND: The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients. METHODS: A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed. RESULTS: A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival. CONCLUSIONS: We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy.