WNK1 Interaction with KEAP1 Promotes NRF2 Stabilization to Enhance the Oxidative Stress Response in Hepatocellular Carcinoma.

Cellular oxidative stress plays a key role in the development and progression of hepatocellular carcinoma (HCC). A better understanding of the processes that regulate reactive oxygen species (ROS) homeostasis could uncover improved strategies for treating HCC. Here, we identified WNK1 as an antioxidative factor and therapeutic target in HCC. In human HCC, WNK1 expression was increased and correlated with poor patient prognosis. WNK1 knockdown significantly inhibited cell proliferation and xenograft tumor growth. Mechanistically, WNK1 competed with NRF2 for binding to the partial Kelch domain of KEAP1, reducing NRF2 ubiquitination and promoting NRF2 accumulation and nuclear translocation to increase antioxidant response. WNK1 silencing increased H2O2-induced apoptosis and inhibited cell growth by elevating reactive oxygen species (ROS) levels, which could be rescued by treatment with the antioxidant N-acetylcysteine (NAC) and NRF2 activator tert-butylhydroquinone (tBHQ). Liver-specific WNK1 knockout mouse models of HCC substantiated that WNK1 promoted HCC development by regulating ROS levels. WNK463, an inhibitor of the WNK kinase family, suppressed HCC progression and altered the redox status. These findings suggest that WNK1 plays a critical role in HCC development and progression and that the WNK1-oxidative stress axis may be a promising therapeutic target for HCC.

Protective effect of naringin against radiation-induced heart disease in rats via Sirt1/NF-κB signaling pathway and endoplasmic reticulum stress.

This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation-induced heart disease (RIHD) in rats. Rats were divided into four x-ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin-eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis-related proteins, endoplasmic reticulum stress-related proteins, and Sirt1 (silent information regulator 1)/NF-κB (nuclear factor kappa-B) signaling pathway-related proteins in cardiac tissues. Additionally, enzyme-linked immunosorbent assay was utilized to detect the activities of pro-inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR-induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis-related proteins (Col I, collagen type I; α-SMA, α-smooth muscle actin; and TGF-ß1, transforming growth factor-beta 1) and endoplasmic reticulum stress-related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro-inflammatory cytokines [interleukin-6, interleukin-1ß, and monocyte chemoattractant protein-1 (MCP-1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose-dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF-κB signaling pathway.

Tailoring the Use of Central Pancreatectomy Through Prediction Models for Major Morbidity and Postoperative Diabetes: International Retrospective Multicenter Study.

OBJECTIVE: To develop a prediction model for major morbidity and endocrine dysfunction after CP which could help in tailoring the use of this procedure. SUMMARY BACKGROUND DATA: Central pancreatectomy (CP) is a parenchyma-sparing alternative to distal pancreatectomy for symptomatic benign and pre-malignant tumors in body and neck of the pancreas CP lowers the risk of new-onset diabetes and exocrine pancreatic insufficiency compared to distal pancreatectomy but it is thought to increase the risk of short-term complications including postoperative pancreatic fistula (POPF). METHODS: International multicenter retrospective cohort study including patients from 51 centers in 19 countries (2010-2021). Primary endpoint was major morbidity. Secondary endpoints included POPF grade B/C, endocrine dysfunction, and the use of pancreatic enzymes. Two risk model were designed for major morbidity and endocrine dysfunction utilizing multivariable logistic regression and internal and external validation. RESULTS: 838 patients after CP were included (301 (36%) minimally invasive) and major morbidity occurred in 248 (30%) patients, POPF B/C in 365 (44%), and 30-day mortality in 4 (1%). Endocrine dysfunction in 91 patients (11%) and use of pancreatic enzymes in 108 (12%). The risk model for major morbidity included male sex, age, BMI, and ASA score≥3. The model performed acceptable with an area under curve (AUC) of 0.72(CI:0.68-0.76). The risk model for endocrine dysfunction included higher BMI and male sex and performed well (AUC:0.83 (CI:0.77-0.89)). CONCLUSIONS: The proposed risk models help in tailoring the use of CP in patients with symptomatic benign and premalignant lesions in the body and neck of the pancreas and are readily available via www.pancreascalculator.com.

EphA2 is a functional entry receptor for HCMV infection of glioblastoma cells.

Human cytomegalovirus (HCMV) infection is associated with human glioblastoma, the most common and aggressive primary brain tumor, but the underlying infection mechanism has not been fully demonstrated. Here, we show that EphA2 was upregulated in glioblastoma and correlated with the poor prognosis of the patients. EphA2 silencing inhibits, whereas overexpression promotes HCMV infection, establishing EphA2 as a crucial cell factor for HCMV infection of glioblastoma cells. Mechanistically, EphA2 binds to HCMV gH/gL complex to mediate membrane fusion. Importantly, the HCMV infection was inhibited by the treatment of inhibitor or antibody targeting EphA2 in glioblastoma cells. Furthermore, HCMV infection was also impaired in optimal glioblastoma organoids by EphA2 inhibitor. Taken together, we propose EphA2 as a crucial cell factor for HCMV infection in glioblastoma cells and a potential target for intervention.

Prenatal DEHP Exposure Induces Premature Testicular Aging by Promoting Leydig Cell Senescence through the MAPK Signaling Pathways.

Previous studies show that prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure induces premature testicular aging. However, the evidence is weak, and the underlying mechanisms remain unclear. p38/extracellular signal-regulated kinase (ERK)/c-Jun NH(2)-terminal kinase (JNK) MAPK pathways participate in aging. Leydig cell (LC) senescence results in testicular aging. Whether prenatal DEHP exposure induces premature testicular aging by promoting LC senescence warrants further study. Here, male mice undergo prenatal exposure to 500 mg per kg per day DEHP, and TM3 LCs are treated with 200 µm mono (2-ethylhexyl) phthalate (MEHP). MAPK pathways, testicular toxicity, and senescent phenotypes (ß-gal activity, p21, p16, and cell cycle) of male mice and LCs are explored. Prenatal DEHP exposure induces premature testicular aging in middle-aged mice (poor genital development, reduced testosterone synthesis, poor semen quality, increased ß-gal activity, and upregulated expression of p21 and p16). MEHP induces LCs senescence (cell cycle arrest, increased ß-gal activity, and upregulated expression of p21). p38 and JNK pathways are activated, and the ERK pathway is inactivated. In conclusion, prenatal DEHP exposure induces premature testicular aging by promoting LC senescence through MAPK signaling pathways.

Prediction of myometrial invasion of bladder cancer based on texture analysis of the bladder wall at tumor base / 中华超声影像学杂志

Objective:To identify the value of ultrasound radiomic features extracted from the bladder wall at tumor base in predicting myometrial invasion of bladder cancer.Methods:A total of 175 cases with bladder cancer confirmed by pathology from January 2017 to February 2022 in the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. They were divided into training set and testing set in a ratio of 7∶3. The MaZda texture analysis software was used to draw the region of interest (ROI) of the bladder wall and the tumor region for extracting texture features. The minimum absolute reduction and variable selection operator (LASSO) regression and 10-fold cross-validation were used to screen the features of training set for establishing the models. And the ROC curve was used to evaluate the efficiency of the models.Results:A total of 279 texture features were extracted from the ROI of the bladder wall and the tumor region, and 5 texture features were screened out for constructing omics scoring models by LASSO regression and 10-fold cross-test. The area under ROC curve (AUC)s used in training set and testing set of the bladder wall were 0.921 and 0.856, while the AUCs applied in training set and testing set of the tumor region were 0.849 and 0.704. Both in the training set and test set, the AUCs of the model of the bladder wall were higher than those of the model of the tumor region (all P<0.05). Conclusions:The omics scoring model based on the texture features of the bladder wall at tumor base can effectively identify muscle-invasive bladder cancer(MIBC) and non-muscle-invasive bladder cancer(NMIBC), and has better performance than the model based on the texture feature of the tumor region.

Predicting glioblastoma molecular subtypes and prognosis with a multimodal model integrating convolutional neural network, radiomics, and semantics.

OBJECTIVE: The aim of this study was to build a convolutional neural network (CNN)-based prediction model of glioblastoma (GBM) molecular subtype diagnosis and prognosis with multimodal features. METHODS: In total, 222 GBM patients were included in the training set from Sun Yat-sen University Cancer Center (SYSUCC) and 107 GBM patients were included in the validation set from SYSUCC, Xuanwu Hospital Capital Medical University, and the First Hospital of Jilin University. The multimodal model was trained with MR images (pre- and postcontrast T1-weighted images and T2-weighted images), corresponding MRI impression, and clinical patient information. First, the original images were segmented using the Multimodal Brain Tumor Image Segmentation Benchmark toolkit. Convolutional features were extracted using 3D residual deep neural network (ResNet50) and convolutional 3D (C3D). Radiomic features were extracted using pyradiomics. Report texts were converted to word embedding using word2vec. These three types of features were then integrated to train neural networks. Accuracy, precision, recall, and F1-score were used to evaluate the model performance. RESULTS: The C3D-based model yielded the highest accuracy of 91.11% in the prediction of IDH1 mutation status. Importantly, the addition of semantics improved precision by 11.21% and recall in MGMT promoter methylation status prediction by 14.28%. The areas under the receiver operating characteristic curves of the C3D-based model in the IDH1, ATRX, MGMT, and 1-year prognosis groups were 0.976, 0.953, 0.955, and 0.976, respectively. In external validation, the C3D-based model showed significant improvement in accuracy in the IDH1, ATRX, MGMT, and 1-year prognosis groups, which were 88.30%, 76.67%, 85.71%, and 85.71%, respectively (compared with 3D ResNet50: 83.51%, 66.67%, 82.14%, and 70.79%, respectively). CONCLUSIONS: The authors propose a novel multimodal model integrating C3D, radiomics, and semantics, which had a great performance in predicting IDH1, ATRX, and MGMT molecular subtypes and the 1-year prognosis of GBM.

Impact of acute pancreatitis during pregnancy in Chinese women: a meta-analysis.

A random-effects meta-analysis was performed in English and Chinese databases since its inception to August 2020 to assess the incidence, causes and severity of acute pancreatitis (AP) at various stages of pregnancy, maternal and foetal mortality. A total of 154 articles representing 4034 patients with AP during pregnancy in China were included for the analysis. The incidence of AP during pregnancy was 0.0469 (95% confidence interval [CI], 0.0349; 0.0627) in the first trimester, whereas it was 0.2518 (95% CI, 0.2210; 0.2854) and 0.6323 (95% CI, 0.5870; 0.6753) in the second and third trimester, respectively. The major causes of AP were hypertriglyceridaemia (0.351 [95% CI, 0.3202; 0.3834]) and biliary pancreatitis (0.424 [95% CI, 0.4094; 0.5002]). The severity of AP was mild in majority of the patients. The incidence of AP at maternal mortality was 0.0184 (95% CI, 0.0126; 0.0269) and foetal mortality was 0.1018 (95% CI, 0.0867; 0.1192). Our meta-analysis revealed that hypertriglyceridaemia and biliary pancreatitis remain the major causes of AP during pregnancy. Foetal mortality requires further investigation. IMPACT STATEMENTWhat is already known on this subject? Acute pancreatitis (AP) in pregnant women is characterised by acute onset and delay in understanding the interaction of the metabolic changes with pancreatic pathophysiology, and thus becomes difficult to diagnose the disease and provide timely treatment to the patients. This poses a greater health risk among women and their foetus by increasing their chances of mortality.What the results of this study add? We performed an exhaustive, random-effects meta-analysis involving 154 articles representing 4034 patients to assess the incidence of AP at various stages of pregnancy, the causes of AP and the severity of AP during pregnancy, maternal and foetal mortality.What are the implications of these findings for clinical practice and/or further research? Our meta-analysis revealed that hypertriglyceridaemia and biliary pancreatitis remain the major causes of AP during pregnancy. Although the rates of maternal mortality have decreased in the recent years, foetal mortality still remains high and requires further investigation.

The application of fluorescein sodium for the resection of medulloblastoma.

INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.

Survival Benefit from Surgical Resection in Lung Cancer Patients with Brain Metastases: a Single-Center, Propensity-Matched Analysis Cohort Study.

BACKGROUND: Brain metastases (BMs) are the most serious complication of lung cancer, affecting the prognosis of lung cancer patients, and pose distinct clinical challenges. This study was designed to explore the prognostic factors related to lung cancer BM and the value of surgical resection in BMs from lung cancer. METHODS: A retrospective analysis was performed on 714 patients with lung cancer BMs screened between January 2010 and January 2018 at the Sun Yat-sen University Cancer Center. A 1:1 propensity score matching analysis was performed to reduce the potential bias between the surgery and the nonsurgery group. In both the raw and the propensity-score matched dataset, univariate and multivariate Cox proportional hazards regression analyses were used to evaluate risk factors for survival. RESULTS: After matching, 258 patients (129 surgery, 129 no surgery) were analyzed. Multivariate analyses after propensity score matching demonstrated that surgical resection was an independent protective factor for overall survival (OS), and older age, lower Karnofsky Performance Scale (KPS) score, and extracranial metastases were independent risk factors for worse OS. Patients without extracranial metastases, without synchronous BM and with a single BM had a better prognosis. CONCLUSIONS: The findings showed that surgical resection, age, KPS score, and extracranial metastases are independent prognostic factors for predicting the OS of patients with lung cancer BMs, and surgical resection for brain metastatic lesions could significantly improve the OS. However, only certain groups of patients with BMs can benefit from intracranial lesion resection, such as no extracranial metastases and metachronous metastases.

Cross lagged analysis of boredom proneness and smoking, drinking behavior among adolescents / 中国学校卫生

Objective@#To explore the development and interactive correlations between boredom proneness, smoking and drinking behavior.@*Methods@#A total of 416 adolescents from one senior high school and one college in the Inner Monggol Autonomous Region were recruited to complete the short version boredom proneness scale, as well as smoking and drinking behavior scale at baseline and in the 12 month follow up.@*Results@#There were significant and positive correlation between boredom proneness and smoking and drinking behavior at both cross sectional levels (T1 r =0.30, 0.34, T2 r =0.24, 0.45, P ＜0.01). Significant autoregressive coefficients were observed for boredom proneness, smoking and drinking behavior in adolescents ( β=0.53, 0.61, 0.45, P ＜ 0.01). Moreover, the cross lagged analyses revealed that the relationship between bordom proneness and smoking behavior was unilaterally influencing ( β=0.12, P＜0.01; β=0.03, P ＞0.05), the relationship between bordom proneness and drinking behavior was bidirectional over the 12 months ( β=0.21, 0.09, P ＜0.05).@*Conclusion@#Boredom proneness of adolescents is closely related to smoking and drinking behavior, boredom proneness can positively predict smoking and drinking behavior, and drinking behavior can positively predict boredom proneness.

Progress of poly (adenosine diphosphate-ribose) polymerase inhibitors in treatment of colorectal cancer / 肿瘤研究与临床

Colorectal cancer is one of the most common malignant tumors, and its morbidity and mortality increase year by year. In recent years, some patients with colorectal cancer have benefited from precision targeted therapies, but the overall prognosis is still unsatisfactory. Treatment of homologous recombination deficiency represented by BRCA1/2 has become a hot research direction at present. With the wide application and exact curative effect of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in ovarian cancer, breast cancer, pancreatic cancer and other malignant tumors, PARP inhibitors are also gradually being used in colorectal cancer. This review summarizes the current research progress of PARP inhibitors in treatment of colorectal cancer.

Application of two RT-PCR methods for detection of norovirus in market-sold oysters and norovirus genetic characteristic analysis, a survey conducted in Beijing / 中华流行病学杂志

Objective: To evaluate the application of real-time RT-PCR and semi-nested RT-PCR in the detection of norovirus in oysters and analyzing the genetic characteristics of the isolates. Methods: Real-time fluorescent RT-PCR and semi-nested RT-PCR were used to detect norovirus GⅠ/GⅡ in fresh oysters collected from the markets in Beijing from November 2014 to October 2015. The detection rate of the parallel test was also analyzed. In addition, the reliability of semi-nested RT-PCR was evaluated by agreement rate and consistency test (Kappa value). The positive products of norovirus GⅠ/GⅡ capsid protein region gene by semi-nested RT-PCR were sequenced. Software BioEdit 7.0.9.0 was used for sequence alignment, and software Mega 6.0 was used to construct the evolutionary tree. Results: In 72 samples, the detection rate of norovirus was 31.94% (23/72) by real-time RT-PCR, 38.89% (28/72) by semi-nested RT-PCR and 48.61% (35/72) by parallel test. The coincidence rate of the two methods was 73.61%, a moderate degree (Kappa value =0.43). A total of 13 norovirus strains were successfully sequenced, and 11 strains (7 GⅡ.17 strains, 2 GⅡ. 4 Sydney_ 2012 strains, 1 GⅡ. 1 strain and 1 GⅡ. 21 strain) were obtained from norovirus positive samples by two RT-PCR methods, two strains (1 GⅡ. 17 strain and 1 GⅡ. 3 strain) were obtained from real-time RT-PCR negative samples which were positive for norovirus by semi-nested RT-PCR. The similarity between these strains and reference strains from diarrhea patients, environmental sewage, and shellfish products were 84.4% - 100.0%. Conclusions: The parallel test of norovirus in oysters by two RT-PCR methods can improve the detection rate and detect more genotypes. Norovirus strains in oysters were highly homologous with reference strains from diarrheal patients, environmental sewage, and shellfish products. Therefore, surveillance, prevention and control for norovirus should be carried out in people who have frequent contacts with oysters and related environments.

lncRNA CDK5RAP3 regulates the proliferation and invasion of gastric cancer cells via miR-223-3p / 国际外科学杂志

Objective:To explore the expression of long non-coding RNA (lncRNA) CDK5RAP3 in gastric cancer tissue and its regulatory effect on gastric cancer cell proliferation and invasion.Methods:The expression differences of CDK5RAP3 in gastric cancer tissues and adjacent tissues were analyzed by TCGA database. By transfecting the pcDNA3.1-CDK5RAP3 plasmid into Hs-746T cells, a gastric cancer cell line overexpressing CDK5RAP3 (CDK5RAP3 group) was constructed, and the pcDNA3.1 plasmid was transfected into Hs-746T cells as a control group. The changes of CDK5RAP3 expression in the two groups of cells were detected by real-time quantitative PCR (qRT-PCR). The effects of overexpression of CDK5RAP3 on the proliferation and invasion of Hs-746T cells were detected by CCK-8 assay and Transwell assay, respectively. The binding sites of CDK5RAP3 and miR-223-3p were predicted by the starBase v2.0 database. The direct binding of CDK5RAP3 and miR-223-3p was verified by dual-luciferase reporter gene experiment. The expression levels of miR-223-3p in Hs-746T cells in each group were detected by qRT-PCR. Western blot was used to detect the expression levels of proliferation proteins and invasion proteins in Hs-746T cells in each group. The experimental data were analyzed by SPSS 17.0 software, and the measurement data conforming to the normal distribution were expressed as Mean±SD. The t-test was used to compare between two groups, and the one-way analysis of variance was used to compare the means of multiple groups. Results:Compared with adjacent tissues, the expression level of CDK5RAP3 in gastric cancer tissues was significantly lower ( P<0.01). The expressions of CDK5RAP3 in Hs-746T cells in the control group and CDK5RAP3 group were (1.08±0.77) and (10.63±2.14), respectively, and the difference was statistically significant ( P<0.01). Up-regulation of CDK5RAP3 significantly decreased the proliferation activity of Hs-746T cells ( P<0.05). The number of invasive cells in the control group and CDK5RAP3 group were (137.80±28.72) and (57.76±24.95), respectively, and the difference was statistically significant ( P<0.01). CDK5RAP3 could directly bind miR-223-3p ( P<0.01). The expression of miR-223-3p in Hs-746T cells in control group and CDK5RAP3 group were (6.22±1.20) and (1.01±0.98), respectively, and the difference was statistically significant ( P<0.01). Compared with the control group, up-regulation of CDK5RAP3 significantly reduced the expression levels of proliferation and invasive proteins. Conclusion:The expression of CDK5RAP3 is low in gastric cancer tissue, and CDK5RAP3 inhibits the proliferation and invasion of gastric cancer Hs-746T cells by targeting miR-223-3p.

Immunogenomic Profiling Demonstrate AC003092.1 as an Immune-Related eRNA in Glioblastoma Multiforme.

Enhancer RNAs, a type of long non-coding RNAs (lncRNAs), play a critical role in the occurrence and development of glioma. RNA-seq data from 161 glioblastoma multiforme (GBM) samples were acquired from The Cancer Genome Atlas database. Then, 70 eRNAs were identified as prognosis-related genes, which had significant relations with overall survival (log-rank test, p < 0.05). AC003092.1 was demonstrated as an immune-related eRNA by functional enrichment analysis. We divided samples into two groups based on AC003092.1 expression: AC003092.1 High (AC003092.1_H) and AC003092.1 Low (AC003092.1_L) and systematically analyzed the influence of AC003092.1 on the immune microenvironment by single-sample gene-set enrichment analysis and CIBERSORTx. We quantified AC003092.1 and TFPI2 levels in 11 high-grade gliomas, 5 low-grade gliomas, and 7 GBM cell lines. Our study indicates that AC003092.1 is related to glioma-immunosuppressive microenvironment, and these results offer innovative sights into GBM immune therapy.

A novel Foxp3-related immune prognostic signature for glioblastoma multiforme based on immunogenomic profiling.

Foxp3+ regulatory T cells (Treg) play an important part in the glioma immunosuppressive microenvironment. This study analyzed the effect of Foxsp3 on the immune microenvironment and constructed a Foxp3-related immune prognostic signature (IPS)for predicting prognosis in glioblastoma multiforme (GBM). Immunohistochemistry (IHC) staining for Foxp3 was performed in 72 high-grade glioma specimens. RNA-seq data from 152 GBM samples were obtained from The Cancer Genome Atlas database (TCGA) and divided into two groups, Foxp3 High (Foxp3_H) and Foxp3 Low (Foxp3_L), based on Foxp3 expression. We systematically analyzed the influence of Foxp3 on the immune microenvironment. Least Absolute Shrinkage and Selection Operator (LASSO) Cox analysis was conducted for immune-related genes that were differentially expressed between Foxp3_H and Foxp3_L GBM patients. We found a differential expression of Foxp3 in high-grade glioma tissues. The presence of Foxp3 was significantly associated with poor OS. From the four-gene IPS developed, GBM patients were stratified into low-risk and high-risk groups in both the training set and validation sets. Furthermore, we developed a novel nomogram to evaluate the overall survival in GBM patients. This study offers innovative insights into the GBM immune microenvironment and these findings contribute to individualized treatment and improvement in the prognosis for GBM patients.

Th9, Th17, Treg Cells and their related cytokines in primary diagnosis of multiple myeloma / 中国输血杂志

【Objective】 To detect the abnormal expression of Th9, Thl7, Treg cells, interleukin-9 (IL-9), interleukin-17 (IL-17) and transforming growth factor-β(TGF-β) in patients with multiple myeloma (MM), and to explore their roles in primary diagnosis of MM. 【Methods】 The level of Th9, Th17 and Treg cells in peripheral blood of 54 MM patients with(patient) and 45 healthy volunteers (control) were measured by flow cytometry, and the levels of IL-9, IL-17 and TGF-β were detected by ELISA. 【Results】 The percentages(%) of Th9, Thl7 in MM patients increased significantly in comparison to controls [1.37±0.39 vs 0.79±0.26; 2.02±0.41 vs 1.18±0.32] (P<0.05). The proportion(%) of CCD4+ CD25+ FoxP3+ Treg cells in patients was significantly lower than those in controls (4.92±0.83 vs 7.04±1.85, P<0.05). The expression levels (%) of IL-9 and IL-17 in the peripheral blood of patients were significantly higher than those in controls (25.74 1±7.33 vs 16.82±5.58; 11.01±3.71 vs 7.68 ± 2.57, P<0.05). The levels of TGF-β in patients and controls were (3.73±1.44)% vs (6.95±2.12)%, showing a significant decrease (P<0.05). 【Conclusion】 The abnormal percentage of Th9, Thl7, Treg cells and the abnormal expression levels of IL-9, IL-17, TGF-β in MM patients may play an important role in the initial diagnosis of MM.

Characteristics and influencing factors of esophageal stenosis after endoscopic submucosal dissection for early esophageal carcinoma / 中华消化内镜杂志

Objective:To investigate the characteristics and influencing factors of esophageal stenosis after endoscopic submucosal dissection (ESD) for early esophageal carcinoma.Methods:Patients who underwent ESD in the Digestive Endoscopy Center of the Second Affiliated Hospital of Army Medical University from January 2011 to December 2018 were included. The data were obtained from medical records and follow-up. The influencing factors of stenosis were determined by single factor and Cox regression analysis.Results:A total of 654 patients underwent ESD and 79 (12.1%) of them developed postoperative esophageal stenosis. The median time of stenosis development was 27 (17, 43) days. The morphology and lesion circumferential proportion were independent factors for the occurrence of stenosis after ESD. The stenosis incidence of type Ⅱa was 6.601 times (95% CI: 1.518-28.709, P=0.012) compared with that of type Ⅱc. The incidence of stenosis in lesions with 75%-<100% and 100% circumference was 17.408 times (95% CI: 8.009-37.839, P<0.001)and 52.439 times (95% CI: 23.905-115.029, P<0.001) respectively compared with that of patients <75%. Among the 79 patients, 27 had severe stenosis, and the lesion circumferential proportion was an independent factor for stenosis. Compared with the group of lesion circumferential proportion of less than 75%, the incidences of stenosis of lesion circumferential proportion of 75%-<100% and 100% were 7.775 (95% CI: 1.977-30.577, P=0.003) and 70.062 (95% CI: 19.879-246.926, P<0.001) times respectively. Conclusion:The morphology and lesion circumferential proportion are two independent factors for the occurrence of esophageal stenosis after ESD. Additionally, lesion circumferential proportion is an independent factor for the occurrence of severe esophageal stenosis after ESD.

Bone marrow mesenchymal stem cell-derived exosomes improve hippocampal neuron injury in rats with depression via microRNA-1297/CTGF axis / 中华微生物学和免疫学杂志

Objective:To investigate the effect and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomal microRNA-1297 (miR-1297) on hippocampal neuron damage in depressed rats.Methods:BMSCs and BMSCs-derived exosomes were prepared and identified. Rats were first injected with corticosterone to establish the model of depression, and then injected with BMSCs-derived exosomes. Superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), TNF-α and IL-1β in rat serum samples, hippocampal tissues and neurons were detected. Expression of miR-1297 in hippocampal tissues and neurons was detected by RT-qPCR. A rat hippocampal neuron injury model was established to investigate the role of BMSC-derived exosomes and miR-1297 in neuronal apoptosis and proliferation. The targeting relationship between miR-1297 and connective tissue growth factor (CTGF) was analyzed using dual luciferase reporter genes.Results:In the hippocampus of depressed rats, the expression of miR-1297 was low, while the expression of CTGF was elevated. Exosomes derived from BMSCs can inhibit the expression of CTGF by up-regulating the level of miR-1297, thereby inhibiting neuronal cell apoptosis in the hippocampus of depressed rats, while increasing the level of SOD, and reducing inflammatory damage, and ultimately improving the behavioral function of depressed rats.Conclusions:Depressed rats showed decreased expression of miR-1297 and increased expression of CTGF. BMSC-derived exosomes inhibited CTGF expression through up-regulating miR-1297, thereby improving hippocampal neuron damage in rats with depression.