Purpose To explore the value of CT-based radiomics in the preoperative prediction of lymphatic invasion of node-negative gastric cancer,and to construct a nomogram combined with clinical variables.Materials and Methods The clinical and CT imaging data of 173 gastric cancer patients with lymph node negative and pathologically confirmed gastric cancer in the Sir Run Run Shaw Hospital from January 2019 to June 2021 were retrospectively analyzed.A total of 60 cases with lymphovascular invasion(LVI)positive patients and 113 cases with LVI negative patients were included,and randomly divided into train cohort(n=121)and test cohort(n=52)at 7∶3.Based on the train cohort,the clinical model,the radiomics model,the fusion model were constructed and verified in the test cohort.Clinical data and conventional CT features included age,gender,tumor marker,tumor location,tumor morphology,enhancement range,etc.The clinical significant variables were selected through univariate and multivariate analysis to establish the clinical model.The tumor regions of interest were segmented and radiomics features were extracted by using the 3D-Slicer software.Key features were screened through least absolute shrinkage and selection operator regression analysis,and then the radiomics model was constructed with random forest algorithm,and converted to random forest score(RF score).The fusion model was constructed via combining clinical significant variables and RF score,and visualized as a nomogram.The receiver operator characteristic curve and area under curve(AUC)were used to evaluate the prediction performance of the models.Decision curve analysis was used to calculate the clinical practicability.Results The radiomics model was superior to the clinical model.The radiomics model AUC of the train cohort and the test cohort were 0.872(0.810 to 0.935)and 0.827(0.707 to 0.947),the clinical model AUC were 0.767(0.682 to 0.852)and 0.761(0.610 to 0.913).The nomogram further improved the predictive efficiency,the AUC in train cohort and test cohort reached 0.898(0.842 to 0.953)and 0.844(0.717 to 0.971),respectively.Decision curve analysis demonstrated clinical benefits of nomogram.Conclusion The radiomics model can be used to preoperatively predict LVI of node-negative gastric cancer.The nomogram can further improve the prediction efficiency.

Objective:To explored the role and mechanism of antisense RNA of long non-coding RNA(LncRNA)GA binding protein transcrip-tion factor β subunit 1(GABPB1-AS1)in regulating the proliferation,invasion,migration,and apoptosis of acute myeloid leukemia(AML)cells by targeting the microRNA-497-5p/heat shock protein 8(miR-497-5p/HSPA8)axis.Methods:HL-60 cells were divided into the normal con-trol,si-NC,si-GABPB1-AS1,si-GABPB1-AS1+NC,and si-GABPB1-AS1+miR-497-5p inhibitor groups.Quantitative real time polymerase chain re-action(RT-qPCR)was used to detect the expression levels of LncRNA GABPB1-AS1,miR-497-5p,and HSPA8.Double luciferase reporter gene assay was used to verify the targeting relationship between LncRNA GABPB1-AS1,miR-497-5p,and HSPA8;MTT was used to detect cell viab-ility;while 5-ethynyl-2'-deoxyuridine(EdU)was used to detect proliferation.Transwell chamber experiments were used to detect invasion and migration while flow cytometry was used to detect apoptosis.Western blot was used to detect the levels of proliferating cell nuclear an-tigen(PCNA),HSPA8,metastasis-associated proteins(MTA2),homolog of yeast Atg6(Beclin-1),and Caspase-3 proteins.A mouse trans-planted tumor model was established to verify the effect of LncRNA GABPB1-AS1 on the growth of AML transplanted tumors.Results:Com-pared to human bone marrow monocytes,LncRNA GABPB1-AS1 was highly expressed[(1.29±0.10),(1.58±0.12),(2.02±0.17),(3.17±0.24)vs.(1.02±0.07)]while miR-497-5p was lowly expressed[(0.94±0.07),(0.75±0.03),(0.57±0.03),(0.25±0.01)vs.(1.05±0.09)]in different AML cells(THP-1,NB4,U-937,and HL-60,respectively).The HL-60 cell line was selected for functional verification experiments since LncRNA GABPB1-AS1 expression was highest in the HL-60 cells.Knockdown of LncRNA GABPB1-AS1 reduced HL-60 cell viability,the EdU positive rate,cell in-vasion and migration,the expression of HSPA8 mRNA,and HSPA8,PCNA,and MTA2 protein contents.It increased the apoptosis rate,and the expression of miR-497-5p,Caspase-3 and Beclin-1 protein(P<0.05).miR-497-5p had a targeting relationship with LncRNA GABPB1-AS1 and HSPA8;inhibiting the expression of miR-497-5p reversed the inhibitory effect of LncRNA GABPB1-AS1 knockdown on the malignant bio-logical behavior of HL-60 cells.Meanwhile,inhibiting the expression of LncRNA GABPB1-AS1 constrained the growth of transplanted tumors.Conclusions:Knockdown of LncRNA GABPB1-AS1 inhibits the progression of AML cells,which may be related to the upregulation of miR-497-5p expression and downregulation of HSPA8 expression.

Objective: To investigate the changes of ambient dose equivalent rate in 99mTcO4- single photon emission computed tomography (SPECT) of the thyroid among patients with hyperthyroidism, so as to provide insights into radiation protection guidance. Methods: Patients with hyperthyroidism who underwent 99mTcO4- SPECT of the thyroid in a tertiary hospital were enrolled. The ambient dose equivalent rate was measured at different time points following 99mTcO4- infection and at sites with different distances from patients' neck, and the effects of time post-injection, distance from patients' neck, 24-hour thyroidal radioiodine uptake and thyroid weight on the ambient dose equivalent rate were examined using a generalized linear mixed model. Results: Totally 100 patients with hyperthyroidism were enrolled, including 24 men and 76 women and with a mean age of (38.5±14.0) years. The generalized linear mixed model was statistically significant (F=6 610.165, P<0.001), and patients' thyroid weight, time post-injection and distance from patients' neck significantly affected the ambient dose equivalent rate (F=57.967, 15 988.574, 11 200.645, all P<0.001), and the ambient dose equivalent rate positively correlated with patients' thyroid weight and negatively correlated with time post-injection and distance from patients' neck. Conclusions The ambient dose equivalent rate is affected by patients' thyroid weight, time post-injection and distance from patients' neck among patients with hyperthyroidism undergoing 99mTcO4- SPECT of the thyroid. Delay in contact with patients or keeping distance from patients may be effective for radiation protection.

Background Gastrointestinal microbiota plays an important role in the development of Parkinson's disease (PD), and dietary factors have a great impact on intestinal micro ecology. At present, few studies focus on red meat and PD, especially prodromal PD (pPD). Objective To understand the relationships of the intake of red meat and processed meat products with pPD and the number of risk/prodromal markers, and to explore the association of dietary factors with pPD. Methods Based on the data of Community-based Cohort Study on Nervous System Disease in 2018 and 2020, adults aged 55 years and older with complete demographic information, dietary survey information, and information on risk factors related to PD were selected from four provinces of China. After excluding those reporting abnormal total energy intake or those reporting alcohol drinking or abused drugs for a long period of time, and confirmed mental diseases with prescribed drugs, a total of 10003 subjects were included. Food frequency questionnaire was used to calculate the intake of red meat and processed meat products. The pPD-related risk/prodromal markers were selected following the International Parkinson and Movement Disorder Society criteria for pPD, and the risk level and the number of markers of pPD were then calculated. The relationship between the intake of red meat and processed meat and the risk level of pPD was analyzed by multiple linear regression. The relationship between the intake of red meat and processed meat and the pPD marker number groups was analyzed by multinomial logit regression model. Results In 2018, the intake of red meat and processed meat was 28.57 g·d⁻¹ in the target population. In 2020, the median of the number of risk/prodromal markers was 3, and the median M (P₂₅, P₇₅) of the posterior probability of pPD was 0.74% (0.42%, 1.49%). The multiple linear regression analysis showed that the higher the intake of red meat and processed meat, the higher the risk level of pPD in follow-up (b=0.021, P<0.05). The multiple logit regression model showed that compared with the lowest quartile (Q1), the highest quartile (Q4) group of red meat and processed meat intake were more likely reporting 3−5 risk/prodromal markers than ≤ 2 risk/prodromal markers (OR=1.185, 95%CI: 1.015−1.382). Conclusion The intake level of red meat and processed meat is related to the risk level of pPD, and a higher intake of red meat and processed meat may be a potential risk factor of pPD.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

BACKGROUND: In recent years, immunotherapy represented by programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunosuppressants has greatly changed the status of non-small cell lung cancer (NSCLC) treatment. PD-L1 has become an important biomarker for screening NSCLC immunotherapy beneficiaries, but how to easily and accurately detect whether PD-L1 is expressed in NSCLC patients is a difficult problem for clinicians. The aim of this study was to construct a Nomogram prediction model of PD-L1 expression in NSCLC patients based on 18F-fluorodeoxy glucose (18F-FDG) positron emission tomography/conputed tomography (PET/CT) metabolic parameters and to evaluate its predictive value. METHODS: Retrospective collection of 18F-FDG PET/CT metabolic parameters, clinicopathological information and PD-L1 test results of 155 NSCLC patients from Inner Mongolia People's Hospital between September 2016 and July 2021. The patients were divided into the training group (n=117) and the internal validation group (n=38), and another 51 cases of NSCLC patients in our hospital between August 2021 and July 2022 were collected as the external validation group according to the same criteria. Then all of them were categorized according to the results of PD-L1 assay into PD-L1+ group and PD-L1- group. The metabolic parameters and clinicopathological information of patients in the training group were analyzed by univariate and binary Logistic regression, and a Nomogram prediction model was constructed based on the screened independent influencing factors. The effect of the model was evaluated by receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) in both the training group and the internal and external validation groups. RESULTS: Binary Logistic regression analysis showed that metabolic tumor volume (MTV), gender and tumor diameter were independent influences on PD-L1 expression. Then a Nomogram prediction model was constructed based on the above independent influences. The ROC curve for the model in the training group shows an area under the curve (AUC) of 0.769 (95%CI: 0.683-0.856) with an optimal cutoff value of 0.538. The AUC was 0.775 (95%CI: 0.614-0.936) in the internal validation group and 0.752 (95%CI: 0.612-0.893) in the external validation group. The calibration curves were tested by the Hosmer-Lemeshow test and showed that the training group (χ2=0.040, P=0.979), the internal validation group (χ2=2.605, P=0.271), and the external validation group (χ2=0.396, P=0.820) were well calibrated. The DCA curves show that the model provides clinical benefit to patients over a wide range of thresholds (training group: 0.00-0.72, internal validation group: 0.00-0.87, external validation group: 0.00-0.66). CONCLUSIONS The Nomogram prediction model constructed on the basis of 18F-FDG PET/CT metabolic parameters has greater application value in predicting PD-L1 expression in NSCLC patients.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Positron Emission Tomography Computed Tomography ; Lung Neoplasms/drug therapy* ; Fluorodeoxyglucose F18/therapeutic use* ; Nomograms ; Retrospective Studies ; B7-H1 Antigen/metabolism* ; Glucose/therapeutic use* ; Positron-Emission Tomography/methods*

SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.

Objective To observe the impact of readout-segmented echo-planar imaging(RS-EPI)based on small field of view(FOV)and saturation band on image quality of orbital diffusion weighted imaging(DWI).Methods Orbital MR scanning were prospectively performed in 33 healthy subjects.T1W,RS-RPI and optimized RS-EPI(based on small FOV and saturation band)images were acquired.Imaging quality of RS-EPI and optimized RS-EPI on displaying intraorbital structures(eyeballs,optic nerve and intraconal compartment)and periorbital structures(nasal cavity,orbital gyrus,optic chiasma,pituitary and temporal lobe)were evaluated subjectively using 5-point method.The geometric parameters of eyeball,signal-to-noise ratio(SNR)and apparent diffusion coefficient(ADC)were compared between images of RS-EPI and optimized RS-EPI.Results The display of eyeball,nasal cavity,orbital gyrus,optic chiasm,pituitary and temporal lobe on optimized RS-EPI were all better than those on RS-EPI(all P＜0.01),whereas no significant difference of optic nerve nor intraconal compartment was found between optimized RS-EPI and RS-EPI images(P＞0.05).Deformations of eyeball volume,sphericity,surface area,3D maximum diameter,axial maximum diameter and sagittal maximum diameter of bilateral eyes on optimized RS-EPI images were all slighter than those on RS-EPI(all P＜0.01),whereas no significant difference of deformations of coronal maximum diameters was found between optimized RS-EPI and RS-EPI images(P＞0.05).SNR of left temporal lobe white matter and ADC of vitreous body on optimized RS-EPI images were both lower than those on RS-EPI(both P＜0.01),whereas no significant difference of ADC of left temporal lobe white matter nor that of pons was found between optimized RS-EPI and RS-EPI images(P＞0.05).Conclusion Optimized RS-EPI with small FOV and saturation band could be used to improve imaging quality of orbital DWI.

Objective:To evaluate and summarize the best evidence of exercise management of cancer-related fatigue in cancer patients.Methods:Evidence-based questions were identified using the PIPOST model to determine retrieval strategies and inclusion and exclusion criteria. According to the "6S" evidence model, the clinical decision-making, best clinical practice, guidelines, systematic review and expert consensus on the exercise management of cancer-related fatigue in cancer patients were searched in UpToDate, British Medical Journal Best Practice, Joanna Briggs Institute Evidence-based Health Care Center Database, Cochrane Library, National Institute for Health and Clinical Excellence, National Comprehensive Cancer Network, Guidelines International Network, Canadian Medical Association: Clinical Practice Guidelines, PubMed, Web of Science, Embase, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, China Biology Medicine disc and professional association platform. The retrieval time limit was from the establishment of the database to January 31, 2022. Three researchers evaluated the quality of the literature and collated, evaluated and integrated the evidence.Results:A total of 20 articles were included, including 1 clinical decision-making, 4 guidelines, 2 evidence summaries, 10 systematic reviews, and 3 expert consensus. A total of 25 best evidences were summarized from 8 aspects, namely, safety and effectiveness of exercise, exercise timing, exercise evaluation, exercise principle, exercise mode, exercise intensity and duration, exercise compliance and exercise risk management.Conclusions:The best evidence on the exercise management of cancer-related fatigue in cancer patients provides evidence-based evidence support and reference opinions for clinical standardized exercise. It is suggested that medical and nursing staff should select the best evidence according to the specific clinical situation and individual differences of patients in the process of evidence transformation, and formulate a personalized exercise management plan to alleviate the cancer-related fatigue of patients.