An information-motivation-behavioral skills model-based intervention for patients with epilepsy.

PURPOSE: Self-management is crucial for patients with epilepsy (PWE) as it can effectively control the condition, improve treatment outcomes, and reduce the risk of seizures. The objective of this study was to evaluate the effectiveness of health education based on the Information-Motivation-Behavioral Skills (IMB) model in improving self-management, quality of life, and medication adherence among PWE. METHOD: This study was conducted in a district in Shanghai, China, from September 2022 to March 2023. A total of 90 PWE were randomly assigned to an intervention group or a control group. Patients in the intervention group received health education based on the IMB model, whereas those in the control group received routine medical treatment only. The effectiveness of the intervention was evaluated by measuring self-management ability, quality of life, and medication adherence at three months and six months after the intervention. RESULTS: The study included a total of 90 PWE; among them, 55 patients (61.11%) were male, divided into two groups: 45 participants in the control group and 45 participants in the intervention group. After 3 and 6 months of intervention, the self-management scores of the intervention group were significantly higher than those of the control group (t = 14.274, 12.448; P < 0.05). After 6 months of the intervention, the quality-of-life scores of the intervention group were significantly higher than those of the control group (t = 2.025, P < 0.05), and the medication adherence in the intervention group was significantly higher than that in the control group (X2 = 9.003, P < 0.05). CONCLUSION: Health education based on the IMB model is a promising approach to improving self-management, quality of life, and medication adherence among PWE. It provides personalized, patient-centered interventions that consider patients' knowledge, motivation, and behavior skills, and could be a useful tool for healthcare providers in developing comprehensive care plans for individuals with epilepsy.

Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3).

Gastric cancer remains a significant health burden worldwide. In continuation of our previous study and development of effective small molecules against gastric cancer, a series of benzochalcone analogues involving heterocyclic molecules were synthesised and biologically evaluated in vitro and in vivo. Among them, the quinolin-6-yl substituted derivative KL-6 inhibited the growth of gastric cancer cells (HGC27, MKN28, AZ521, AGS, and MKN1) with a submicromolar to micromolar range of IC50, being the most potent one in this series. Additionally, KL-6 significantly inhibited the colony formation, migration and invasion, and effectively induced apoptosis of MKN1 cells in a concentration-dependent manner. The mechanistic study revealed that KL-6 could concentration-dependently suppress STAT3 phosphorylation, which may partly contribute to its anticancer activity. Furthermore, in vivo antitumour study on the MKN1 orthotopic tumour model showed that KL-6 effectively inhibited tumour growth (TGI of 78%) and metastasis without obvious toxicity. Collectively, compound KL-6 may support the further development of candidates for gastric cancer treatment.

Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism.

Gastric cancer (GC) is among the most lethal malignancies due to its poor early diagnosis and high metastasis rate, and new therapeutic targets are urgently needed to develop effective anti-GC drugs. Glutathione peroxidase-2 (GPx2) plays various roles in tumor progression and patient survival. Herein, we found that GPx2 was overexpressed and negatively correlated with poor prognosis by using clinical GC samples for validation. GPx2 knockdown suppressed GC proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in vitro and in vivo. In addition, proteomic analysis revealed that GPx2 expression regulated kynureninase (KYNU)-mediated metabolism. As one of the key proteins involved in tryptophan catabolism, KYNU can degrade the tryptophan metabolite kynurenine (kyn), which is an endogenous ligand for AhR. Next, we revealed that the activation of the reactive oxygen species (ROS)-mediated KYNU-kyn-AhR signaling pathway caused by GPx2 knockdown was involved in GC progression and metastasis. In conclusion, our results showed that GPx2 acted as an oncogene in GC and that GPx2 knockdown suppressed GC progression and metastasis by suppressing the KYNU-kyn-AhR signaling pathway, which was caused by the accumulation of ROS.

Deep learning radio-clinical signatures for predicting neoadjuvant chemotherapy response and prognosis from pretreatment CT images of locally advanced gastric cancer patients.

BACKGROUND: Early noninvasive screening of patients who would benefit from neoadjuvant chemotherapy (NCT) is essential for personalized treatment of locally advanced gastric cancer (LAGC). The aim of this study was to identify radio-clinical signatures from pretreatment oversampled computed tomography (CT) images to predict the response to NCT and prognosis of LAGC patients. METHODS: LAGC patients were retrospectively recruited from six hospitals from January 2008 to December 2021. An SE-ResNet50-based chemotherapy response prediction system was developed from pretreatment CT images preprocessed with an imaging oversampling method (i.e. DeepSMOTE). Then, the deep learning (DL) signature and clinic-based features were fed into the deep learning radio-clinical signature (DLCS). The predictive performance of the model was evaluated based on discrimination, calibration, and clinical usefulness. An additional model was built to predict overall survival (OS) and explore the survival benefit of the proposed DL signature and clinicopathological characteristics. RESULTS: A total of 1060 LAGC patients were recruited from six hospitals; the training cohort (TC) and internal validation cohort (IVC) patients were randomly selected from center I. An external validation cohort (EVC) of 265 patients from five other centers was also included. The DLCS exhibited excellent performance in predicting the response to NCT in the IVC [area under the curve (AUC), 0.86] and EVC (AUC, 0.82), with good calibration in all cohorts ( P >0.05). Moreover, the DLCS model outperformed the clinical model ( P <0.05). Additionally, we found that the DL signature could serve as an independent factor for prognosis [hazard ratio (HR), 0.828, P =0.004]. The concordance index (C-index), integrated area under the time-dependent ROC curve (iAUC), and integrated Brier score (IBS) for the OS model were 0.64, 1.24, and 0.71 in the test set. CONCLUSION: The authors proposed a DLCS model that combined imaging features with clinical risk factors to accurately predict tumor response and identify the risk of OS in LAGC patients prior to NCT, which can then be used to guide personalized treatment plans with the help of computerized tumor-level characterization.

Integrative proteomic characterization of adenocarcinoma of esophagogastric junction.

The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct proteomics and phosphoproteomics profiling of 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing of 94 tumor-NAT pairs, and RNA sequencing in 83 tumor-NAT pairs. Our analysis reveals an extensively altered proteome and 252 potential druggable proteins in AEG tumors. We identify three proteomic subtypes with significant clinical and molecular differences. The S-II subtype signature protein, FBXO44, is demonstrated to promote tumor progression and metastasis in vitro and in vivo. Our comparative analyses reveal distinct genomic features in AEG subtypes. We find a specific decrease of fibroblasts in the S-III subtype. Further phosphoproteomic comparisons reveal different kinase-phosphosubstrate regulatory networks among AEG subtypes. Our proteogenomics dataset provides valuable resources for understanding molecular mechanisms and developing precision treatment strategies of AEG.

Development of a tongue image-based machine learning tool for the diagnosis of gastric cancer: a prospective multicentre clinical cohort study.

Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88-0.92 in the internal verification and 0.83-0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

Huaier Inhibits Gastric Cancer Growth and Hepatic Metastasis by Reducing Syntenin Expression and STAT3 Phosphorylation.

Gastric cancer (GC) is a common malignant tumor worldwide and poses a serious threat to human health. As a traditional Chinese medicine, Huaier (Trametes robiniophila Murr.) has been used in the clinical treatment of GC. However, the mechanism underlying the anticancer effect of Huaier remains poorly understood. In this study, we used in vivo imaging technology to determine the anticancer effect of the Huaier n-butanol extract (HBE) on orthotopic and hepatic metastasis of GC mouse models. We found that HBE suppressed tumor growth and metastasis without causing apparent host toxicity. Proteomic analysis of GC cells before and after HBE intervention revealed syntenin to be one of the most significantly downregulated proteins after HBE intervention. We further demonstrated that HBE suppressed the growth and metastasis of GC by reducing the expression of syntenin and the phosphorylation of STAT3 at Y705 and reversing the epithelial-mesenchymal transition (EMT). In addition, we confirmed that syntenin was highly expressed in GC tissue and correlated with metastasis and poor prognosis. In conclusion, our results suggest that Huaier, a clinically used anticancer drug, may inhibit the growth and liver metastasis of GC by inhibiting the syntenin/STAT3 signaling pathway and reversing EMT.

Trametes robiniophila Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment.

Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo. Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-ß and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8+ T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8+ T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8+ T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.

Prognostic value and clinicopathological correlation of the tumor regression grade in neoadjuvant chemotherapy for gastric adenocarcinoma: a retrospective cohort study.

Background: Neoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC. Methods: In total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients. Results: Among the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients. Conclusions: TRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response.

GPR30 Activation Promotes the Progression of Gastric Cancer and Plays a Significant Role in the Anti-GC Effect of Huaier.

Gastric cancer (GC) is one of the most common types of cancer. The n-butanol extract of Huaier (NEH) is the alcohol-soluble part extracted by the systematic solvent method, which is effective against gastric cancer (GC). However, the mechanism of action of NEH remains unclear. In this study, we aim to evaluate the clinical relevance of GPR30 expression in GC patients and the role of the GPR30/PI3K/AKT signalling pathway in the anti-GC effect of NEH. The expression of GPR30 was examined using immunohistochemistry. Cell counting kit 8 (CCK-8) assay, wound healing, and transwell experiments were used to investigate the viability, migration, and invasion of gastric cancer cells. Western blotting was used to detect the expression of GPR30 and its downstream signalling molecules of the PI3K/AKT signalling pathway. Gastric cancer patient-derived xenografts (PDX) mouse model was used to evaluate the antitumor effect of NEH in vivo. In addition, the graded doses and the maximum tolerated dose of NEH were administered intraperitoneally into the mice for acute toxicity test. We demonstrate that GPR30 expression in GC tissues was significantly higher than that in corresponding adjacent noncancerous tissues and the expression of GPR30 was correlated with a poor prognosis in GC patients. Moreover, GPR30 expression was involved in the migration and invasion of GC cells in vitro. Additionally, we found that NEH can suppress the growth of GC in patient-derived xenograft tumors in vivo. Furthermore, NEH inhibited the proliferation, migration, and invasion in GC cells in a concentration-dependent manner through inhibiting the GPR30-mediated PI3K/AKT signalling pathway in vitro. Acute toxicity test showed that NEH caused no toxic reaction or death and the maximum tolerated dose of NEH in mice was greater than 1600 mg/kg. Our results demonstrate that the high expression of GPR30 is an independent factor of poor prognosis in patients with GC and NEH could be a new agent for the treatment of gastric cancer.

Control of the gyrotron filament power supplies for the experimental advanced superconducting tokamak.

The electron cyclotron heating system including four gyrotrons is being developed in the Institute of Plasma Physics, Chinese Academy of Sciences. The filament is an important part of the gyrotron, which is used to heat the cathode. The gyrotron output power can be controlled by adjusting the filament power. We have developed the filament power control and measurement system using Labview. The filament characteristics were tested using this power control system. The test results show that the filament current can be fitted with the e-exponential function of the filament voltage. It can be seen that as the voltage increases, the filament resistance gradually increases. We have developed a new "burst" function to prevent the beam current from dropping too fast, which is conducive to long pulse stable operation of the gyrotrons.

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

Gastric cancer is the third most common cause of cancer-related death worldwide. Drug resistance is the main inevitable and vital factor leading to a low 5-year survival rate for patients with gastric cancer. Autophagy, as a highly conserved homeostatic pathway, is mainly regulated by different proteins and non-coding RNAs (ncRNAs) and plays dual roles in drug resistance of gastric cancer. Thus, targeting key regulatory nodes in the process of autophagy by small molecule inhibitors or activators has become one of the most promising strategies for the treatment of gastric cancer in recent years. In this review, we provide a systematic summary focusing on the relationship between autophagy and chemotherapy resistance in gastric cancer. We comprehensively discuss the roles and molecular mechanisms of multiple proteins and the emerging ncRNAs including miRNAs and lncRNAs in the regulation of autophagy pathways and gastric cancer chemoresistance. We also summarize the regulatory effects of autophagy inhibitor and activators on gastric cancer chemoresistance. Understanding the vital roles of autophagy in gastric cancer chemoresistance will provide novel opportunities to develop promising therapeutic strategies for gastric cancer.

Torsional friction behavior of the contact interface between the materials of an artificial knee joint replacement.

The torsional friction behavior of the materials (CoCrMo alloy and ultra-high-molecular-weight polyethylene (UHMWPE)) that are used in artificial knee joint replacement (AKJR) were investigated under dynamic loading. The torsional friction torque, wear loss and scars and stress distribution were analyzed and compared. The results show the following: (1) the friction torque declines rapidly at the beginning of the experiments, and meanwhile, the maximum normal load and the torsional angle amplitude show very little effect on the steady value; (2) the wear loss decreases with the increased torsional angle amplitude but increases with the increased maximum normal load; additionally, as the cycle times increase, the wear rate decreases, and the wear is minimal; (3) unloading and secondary loading significantly reduce the friction and wear of the materials, and thus, patients should rest after prolonged exercise to reduce wear; (4) the margins of UHMWPE and CoCrMo are worn, and the wear mechanism is abrasive wear; (5) around the center of the UHMWPE, the surface is peeled off, and the wear mechanism is fatigue wear; and (6) in terms of the compressive stress and shear stress, the calculated results from a finite element model match the experimental results well.

High power continuous wave microwave test bench at 4.6 GHz for experimental advanced superconducting tokamak.

The lower hybrid current drive (LHCD) is an effective approach for auxiliary heating and non-inductive current drive in the experimental advanced superconducting tokamak. The 6 MW/4.6 GHz LHCD system is being designed and installed with twenty-four 250 KW/4.6 GHz high power klystron amplifiers. The test bench operating at 250 KW/4.6 GHz in continuous wave mode has been set up, which can test and train microwave components for the 6 MW/4.6 GHz LHCD system. In this paper, the system architecture and software of the microwave test bench are presented. Moreover, the test results of these klystrons and microwave units are described here in detail. The long term operation of the test bench and improved performance of all microwave component samples indicated that the related technologies on test bench can be applied in the large scale LHCD systems.