3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

ObjectiveTo explore the association between triglyceride-glucose （TyG） index and major adverse cardiovascular events （MACEs） risk in coronary heart disease （CHD） patients with blood stasis syndrome after percutaneous coronary intervention （PCI）. MethodsA total of 857 CHD patients with blood stasis syndrome after PCI were enrolled and divided into four groups according to the baseline TyG index quartiles， Q1 （TyG ＜ 8.51）， Q2 （8.51 ≤ TyG ＜ 8.88）， Q3 （8.88 ≤ TyG ＜ 9.22）， and Q4 （TyG ≥ 9.22）. The clinical outcome was defined as a compound endpoint of cardiovascular events including cardiac death， non-fatal myocardial infarction， unplanned revascularization， in-stent restenosis and stroke. The machine learning Boruta algorithm was used for feature selection related to MACEs risk. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to compare the differences in MACEs risk among the four groups. Restricted cubic spline （RCS） and subgroup analysis were performed to determine the relationship between the TyG index and MACEs risk. The area under the receiver operating characteristic （ROC） curve （AUC）， calibration curve and Hosmer-Lemeshow test， and decision curve analysis （DCA） were plotted to evaluate the predictive value of the TyG index for MACEs risk. ResultsThe median follow-up time of the included patients was 2.45 years. During the follow-up period， 313 cases （36.52%） of new MACEs occurred. The incidence of MACEs in Q1， Q2， Q3， Q4 group was 28.17% （60/213）， 29.05% （61/210）， 39.45% （86/218） and 49.07% （106/216）， respectively. Kaplan-Meier survival analysis suggested statistically significant differences in MACEs risk among the four groups （P＜0.001）. Cox proportional hazards regression model analysis found that the risk of MACEs in patients with high TyG index increased by 60.1% （P＜0.01）. Using Q1 as the reference， the MACEs risk in Q2， Q3 and Q4 groups gradually increased， and the trend was statistically significant （P＜0.05）. RCS model suggested that the TyG index was nonlinearly associated with the MACEs risk （P＜0.001）. The TyG index had a good predictive performance for MACEs risk according to ROC analysis （AUC=0.758， 0.724-0.792） and Hosmer-Lemeshow test （χ² = 4.319， P = 0.827）. Additionally， DCA analysis also suggested a good clinical efficacy of the TyG index for predicting MACEs. Subgroup analysis showed that different baseline TyG index was positively correlated with the MACEs risk in the stratification of age， male， BMI， history of diabetes and hypertension， and low-density lipoprotein cholesterol （LDL-C）≥1.8 mmol·L^-1（P＜0.05）. ConclusionThe elevated TyG index is closely corrected with an increased risk of MACEs in CHD patients with blood stasis syndrome after PCI， indicating a guiding significance for early risk stratification and clinical decisions.

Objective To investigate the changes in microglia phenotype after cerebral ischemia reperfusion(1R)injury and the effects of adenosine on nerve injury of cerebral IR injured rats.Methods Thirty-six healthy male Sprague Dawley rats were randomly divided into the sham operation(Sham)group,IR group,and adenosine pretreatment(AP)group,with 12 rats in each group.Before modeling,rats in the AP group were intraperitoneally injected with 2 mL of adenosine injection daily for 3 consecutive days,and rats in the Sham group and IR group were intraperitoneally injected with 2 mL of normal saline daily for 3 consecutive days.The middle cerebral artery occlusion models of rats in the IR group and AP group were constructed by using the suture-occluded method,and only the carotid artery of rats was isolated in the Sham group without ligation of blood vessels.At 2 hours after modeling,the neuroethology of rats in each group were evaluated according to a 5-point neurobehavioral scale.At 24 hours after restoring the blood perfusion in the middle cerebral artery,the rats in each group were executed,and their brain tissues were removed.The morphological changes of the brain tissues in the ischemic penumbra region were observed after hematoxylin-eosin(HE)staining.The co-expression of M1-type microglia markers and M2-type microglia markers was detected by immunofluorescence staining.The relative expression levels of pro-inflammatory factors inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α)and interleukin(IL)-1β released by M1-type microglia,and anti-inflammatory factors IL-4,IL-10 and transforming growth factor-β(TGF-β)released by M2-type microglia were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Results The neurobehavioral scores of rats in the IR group and AP group were significantly higher than those in the Sham group,and the neurobehavioral score of rats in the IR group was significantly higher than that in the AP group(P＜0.05).HE staining results showed that the brain cells of rats in the Sham group were structurally complete and tightly arranged,with visible nuclei and no interstitial edema;the brain cells of rats in the IR group were structurally damaged and irregularly arranged,with loose cytoplasm and vacuoles in the cytosome;the structure of brain cells of rat in the AP group was better than that in the IR group,and there were many regularly-arranged normal cells,with complete nuclei.Immunofluorescence staining results showed that the number of M1-type and M2-type microglia in the ischemic penumbra region of rats in the IR group and AP group was significantly higher than that in the Sham group;the number of M1-type microglia in the IR group was significantly higher than that in the AP group,and the number of M2-type microglia was significantly lower than that in the AP group(P＜0.05).qRT-PCR results showed that the relative expression levels of pro-inflammatory cytokines TNF-α,IL-1β,iNOS and anti-inflammatory cytokines IL-4,IL-10,TGF-β in the IR group and AP group were significantly higher than those in the Sham group(P＜0.05);the relative expression levels of pro-inflammatory factors TNF-α,IL-1β and iNOS in the AP group were significantly lower than those in the IR group(P＜0.05),while the relative expression levels of anti-inflammatory factors IL-4,IL-10 and TGF-β were significantly higher than those in the IR group(P＜0.05).Conclusion AP can promote the polarization of microglia from M1 type to M2 type,inhibit the release of pro-inflammatory factors,increases the expression of anti-inflammatory factors,and thus has a neuroprotective effect on rats after cerebral IR injury.

Objective To propose an attention mechanism-based YOLOv5 algorithm to relieve the wrong or missed diagnosis due to the complexity and variability of trauma conditions.Methods A YOLOv5-attention algorithm was constructed with YOLOv5 algorithm as the basic framework,which introduced the convolutional attention mechanism module into the feature fusion network and embedded the self-attention module at the end of the feature extraction network and the feature fusion network,respectively.The YOLOv5-attention algorithm was trained and validated on the Kaggle platform and compared with Fast-RCNN and YOLOv5 algorithms for determining fracture sites.Results The YOLOv5-attention algorithm achieved an average presicion of 0.859 8 for fracture site determination,which behaved better than Fast-RCNN algorithm with an average presicion of 0.697 5 and YOLOv5 algorithm with an average presicion of 0.847 1.Conclusion The YOLOv5-attention algorithm with high accuracy and robustness can identify and locate trauma conditions effectively and accurately.[Chinese Medical Equipment Journal,2024,45(9):1-6]

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.
Humans ; Carcinoma, Renal Cell/pathology* ; Cell Proliferation ; Hypoxia ; Kidney Neoplasms ; MicroRNAs/genetics* ; Neoplasm Invasiveness/genetics* ; RNA, Circular/metabolism* ; RNA, Small Interfering ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics*

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Atypical polypoid adenomyoma (APA) is an uncommon type of polypoid characterized by fibroid stroma and endometrial glands. It occurs mostly in premenopausal women and rarely in postmenopausal women with irregular vaginal bleeding. In our current case, a 76-year-old woman presented with irregular vaginal bleeding. The final pathological diagnosis of the mass was APA. APA is not easy to diagnose before surgery. On the one hand, there was no obvious particularity in imaging features and clinical features, especially for uncomfortably identifying endometrial cancer. On the other hand, APA has a pedicle, attaching to any part of the uterine cavity, which can cause pseudocoel between the mass with the uterine cavity wall. So, when it comes to getting the pathological tissue in the absence of hysteroscopy, it is easy to access to the pseudocoel and obtain endometrial tissue rather than the pathological tissue of the mass. Therefore, preoperative imaging examination is of great significance diagnosis way of thinking to clinicians for APA. In the meantime, pathological tissue of APA can be obtained by hysteroscopy in visual conditions.
Adenomyoma/pathology* ; Aged ; Female ; Humans ; Hysteroscopy ; Magnetic Resonance Imaging ; Pregnancy ; Uterine Hemorrhage ; Uterine Neoplasms/diagnostic imaging*

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.
Biomarkers, Tumor ; Carcinoembryonic Antigen ; Humans ; Inflammation/classification* ; Lymphocytes ; Neutrophils ; Nomograms ; Preoperative Period ; Prognosis ; Rectal Neoplasms/surgery* ; Retrospective Studies

Objective: To investigate the possible pathophysiological mechanism of laryngopharyngeal reflux (LPR) in the development of lingual tonsil hypertrophy (LTH). Methods: The lingual tonsil tissues were collected from 73 patients [48 males and 25 females, aged from 24 to 76 (52.86±12.04) years] who underwent surgery for laryngopharyngeal diseases at the Department of Otolaryngology and Head and Neck Surgery, Southern Hospital of Southern Medical University from October 2019 to December 2020, and the lingual tonsil grade (LTG), reflux symptom index (RSI) and reflux finding score (RFS) were assessed. The expression of pepsin in LTH was detected by immunohistochemistry. The coexpression of pepsin and macrophages were detected by immunohistofluorescence. In vitro, cytological experiments and pathway assays were performed on macrophages stimulated by pepsin. Pathway alterations of macrophages in pepsin-positive high-grade LTH were detected by double-fluorescence immunohistochemistry. Data were analyzed by SPSS 20.0 software. Results: There were 44 clinically significant LPRD patients with LTG 3 and 4, and the pepsin positive rate was 88.6% (39/44). While, the pepsin positive rate of LTG 1 and 2 was 48.3% (14/29). LTG was significantly positively correlated with RFS/RSI positive rate(χ²=23.01/19.62, P<0.001/0.001; r=0.54/0.51, P<0.001/0.001) and pepsin tissue staining intensity (H=21.58, P<0.001; r=0.53, P<0.001), respectively. Pepsin and macrophages were clearly colocalized in high grade LTH. In vitro, pepsin promoted macrophage proliferation (P<0.05) and production of IL-6/IL-8 (P<0.05). Pepsin significantly up-regulated the p38/JNK MAPK pathway in macrophages (P<0.05). Pepsin up-regulated the expression of IL-6 and IL-8 of macrophages by activating the p38 MAPK pathway (P<0.05), and up-regulated the expression of IL-8 by activating the JNK pathway (P<0.05). The p38/JNK MAPK pathways were highly expressed in macrophages of pepsin-positive LTH (P<0.05). Conclusions: LPR is an important pathogenic factor in LTH. Macrophages may mediate pepsin-induced inflammation and the pathogenesis of LTH.
Female ; Male ; Humans ; Palatine Tonsil ; Pepsin A ; Interleukin-6 ; Interleukin-8 ; Hypertrophy ; Macrophages ; Laryngopharyngeal Reflux