Copper-Catalyzed [3 + 2] Annulation of O-Acyl Oximes with 4-Sulfonamidophenols for the Synthesis of 5-Sulfonamidoindoles and 2-Amido-5-sulfonamidobenzofuran-3(2H)-ones.

A copper-catalyzed [3 + 2] annulation of O-acyl oximes with 4-sulfonamidophenols is developed. The advantage of this method lies in the concurrent double activation of two substrates to form nucleophilic enamines and electrophilic quinone monoimines. The substituent on the α-carbon of O-acyl oxime determines two different reaction pathways, thereby leading to the selective generation of 5-sulfonamidoindoles and 2-amido-5-sulfonamidobenzofuran-3(2H)-ones.

Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

Integrated analysis of bulk RNA-seq and single-cell RNA-seq reveals the function of pyrocytosis in the pathogenesis of abdominal aortic aneurysm.

Pyrocytosis is involved in the development of abdominal aortic aneurysm (AAA), we explored the pyrocytosis-related hub genes in AAA and conducted a diagnostic model based on the pyrocytosis-related genes score (PRGs). A total of 2 bulk RNA-seq (GSE57691 and GSE47472) datasets and pyrocytosis-related genes were integrated to obtain 24 pyrocytosis-related different expression genes (DEGs). The LASSO Cox regression analysis was conducted to filter out 7 genes and further establish the nomogram signature based on the PRGs that exhibited a good diagnosis value. Weighted gene co-expression network analysis (WGCNA) established 14 gene modules and further identified 6 hub genes which were involved in the regulatory process of pyrocytosis in AAA. At the single cell level, we further identified 3 immune cells were highly associated with the pyrocytosis process in AAA. Finally, the cell-cell communication demonstrated that fibroblasts and endothelial cells and myeloid cells maintained close communications. Here, we identified the dysfunctional expressed pyrocytosis-related genes and immune cells in AAA, which provide a comprehensive understanding of the pathogenesis of AAA.

Development and validation of an online calculator to predict the pathological nature of colorectal tumors.

BACKGROUND: No single endoscopic feature can reliably predict the pathological nature of colorectal tumors (CRTs). AIM: To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy. METHODS: This was a single-center study. During the identification stage, 530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group. Logistic regression analysis was performed. A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally. During the validation stage, two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists [five highly experienced endoscopists and five less experienced endoscopists (LEEs)] for external validation before and after systematic training. RESULTS: A total of 750 patients were included, with an average age of 63.6 ± 10.4 years. Early colorectal cancer (ECRC) was detected in 351 (46.8%) patients. Tumor size, left semicolon site, rectal site, acanthosis, depression and an uneven surface were independent risk factors for ECRC. The C-index of the ECRC calculator prediction model was 0.906 (P = 0.225, Hosmer-Lemeshow test). For the LEEs, significant improvement was made in the sensitivity, specificity and accuracy (57.6% vs 75.5%; 72.3% vs 82.4%; 64.2% vs 80.2%; P < 0.05), respectively, after training with the ECRC online calculator prediction model. CONCLUSION: A novel online calculator including tumor size, location, acanthosis, depression, and uneven surface can accurately predict the pathological nature of ECRC.

Highly Site-Selective Oxidative Cyclization of Ene-ynamides via Non-Noble-Metal Catalysis: Access to Functionalized Lactams.

Herein, an unprecedented non-noble-metal-catalyzed oxidation/cyclization of ene-ynamides is developed, allowing the synthesis of diversely functionalized lactams in moderate to good yields with excellent diastereoselectivities without the observation of typical cyclopropanation products. In combination with Ellman's tert-butylsulfinimine chemistry, chiral γ-lactams containing three contiguous stereocenters are obtained with high diastereo- and enantioselectivity. Moreover, density functional theory (DFT) calculations indicate that this protocol probably undergoes a carbon cation or proton transfer process.

Endoscopic classification and pathological features of primary intestinal lymphangiectasia.

BACKGROUND: The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL). AIM: To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes. METHODS: We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type. RESULTS: According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers. CONCLUSION: Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.

Effects of dihydroartemisinin, a metabolite of artemisinin, on colon cancer chemoprevention and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) is an anti-malaria natural compound with a moderate anticancer action. As a metabolite of ART, dihydroartemisinin (DHA) may have stronger anti-colorectal cancer (CRC) bioactivities. However, the effects of DHA and ART on CRC chemoprevention, including adaptive immune regulation, have not been systematically evaluated and compared. METHODS: Coupled with a newly-established HPLC analytical method, enteric microbiome biotransformation was conducted to identify if the DHA is a gut microbial metabolite of ART. The anti-CRC potential of these compounds was compared using two different human CRC cell lines for cell cycle arrest, apoptotic induction, and anti-inflammation activities. Naive CD4+ T cells were also obtained for testing the compounds on the differentiation of Treg, Th1 and Th17. RESULTS: Using compound extraction and analytical methods, we observed for the first time that ART completely converted into its metabolites by gut microbiome within 24 h, but no DHA was detected. Although ART did not obviously influence cancer cell growth in the concentration tested, DHA very significantly inhibited the cancer cell growth at relatively low concentrations. DHA included G2/M cell cycle arrest via upregulation of cyclin A and apoptosis. Both ART and DHA downregulated the pro-inflammatory cytokine expression. The DHA significantly promoted Treg cell proliferation, while both ART and DHA inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: As a metabolite of ART, DHA possessed stronger anti-CRC activities. The DHA significantly inhibited cell growth via cell cycle arrest, apoptosis induction and anti-inflammation actions. The adaptive immune regulation is a related mechanism of actions for the observed effects.

Resistance of C57BL/6 Mice to Different Artemisinin-sensitive Strains of PbK173 / 中国实验方剂学杂志

ObjectiveThe tolerance of C57BL/6 mice to artemisinin-sensitive and -resistant strains of Plasmodium berghei （Pb） K173 and the differences in blood parameters， spleen coefficient and spleen structure during infection were compared to explore whether the artemisinin resistance of Pb would aggravate malaria infection. MethodPbK173 artemisinin-sensitive and -resistant strains were tested in parallel. C57BL/6 mice were randomly divided into 1 control group， 4 artemisinin-sensitive strain groups and 4 artemisinin-resistant strain groups by body weight. Each infection group was simultaneously inoculated （ip） with 1×107 infected red blood cells （iRBCs） of sensitive/resistant strain. For the mice in the survival test group， the body weight was recorded every day post infection， and the tail vein blood smear was collected to calculate the Pb infection rate. In the other infection groups， peripheral blood and spleen were collected on 2， 5 and 9 d after infection. Peripheral blood parameters， spleen coefficient， pathological section of spleen and spleen cells were detected in each group. ResultOn 1-3 d after infection， the infection rate of the resistant strain （0.4±0.0， 0.8±0.1， 1.9±0.4）% was always higher than that of the sensitive strain （0.2±0.1， 0.4±0.1， 1.1±0.3）% （P<0.01）. From the 4th d of infection， the infection rate of the two groups gradually approached. The survival period of the sensitive strain group （20.5±1.2） d was shorter than that of the resistant strain group （23.3±1.4） d （P<0.01）. On the 9th d， the white blood cell count of the sensitive strain group （16.2±1.1）×109 cells/L was higher than that of the resistant strain group （10.6±1.8）×109 cells/L （P<0.01）. Flow cytometry analysis of spleen cells showed that the sensitive strain group （3.6±0.4） demonstrated a higher CD4+/CD8+ value than the resistant strain group （2.3±0.2） on the 9th d （P<0.01）. The spleen of C57BL/6 infected mice was gradually enlarged during infection， and on the 9th d， the resistant strain group （3.1±0.1）% showed a higher spleen coefficient than the sensitive strain group （2.7±0.2）% （P<0.01）. In the early stage of C57BL/6 infected mice， the red pulp of spleen was hyperemic and swollen. On the 9th d， the marginal area of the spleen disappeared and the structure of the red and white pulp was destroyed. ConclusionWithout drug treatment， the protective immune responses of peripheral blood and spleen of C57BL/6 mice were more sensitive to PbK173 artemisinin-sensitive strain. The artemisinin-resistant strain of PbK173 bred with mouse-to-mouse blood transmission and increased artemisinin dose exhibited shortened growth period and reduced toxicity.

[Reasearch on lipid metabolism of Plasmodium and antimalarial mechanism of artemisinin].

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.

Efficacy and safety of different ticagrelor regimens versus clopidogrel in patients with coronary artery disease: a retrospective multicenter study (SUPERIOR).

Current guidelines favor dual anti-platelet therapy with ticagrelor 90 mg BID (T90BID) over clopidogrel 75 mg QD (C75QD) in addition to aspirin for acute coronary syndrome. However, an increased risk of ticagrelor-related adverse events prompted the evaluation of low-dose regimens. This study (NCT03381742) retrospectively analyzed the data from 11 hospitals on 3,043 patients with coronary artery disease, who received C75QD, T90BID, ticagrelor 45 mg BID (T45BID), or ticagrelor 90 mg QD (T90QD). Compared with C75QD, both T45BID and T90QD showed significantly higher inhibition of platelet aggregation (P < .0001) and lower platelet-fibrin clot strength (P < .0001) induced by adenosine diphosphate. Furthermore, compared with T90BID, two low-dose regimens had a much lower minor bleeding rate and a significantly higher proportion of patients within the therapeutic window for P2Y12 receptor reactivity. There were no significant differences between T45BID and T90QD in the trough plasma concentrations of ticagrelor and its active metabolite. Similar efficacy and safety outcomes were observed in the propensity score-matched analysis. In conclusion, the low-dose ticagrelor regimen, either T45BID or T90QD, may provide a more attractive benefit-risk profile than C75QD or T90BID.

LncRNA NORAD promotes proliferation, migration and angiogenesis of hepatocellular carcinoma cells through targeting miR-211-5p/FOXD1/VEGF-A axis.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death around the world. Despite improvement in the prevention and treatment of HCC, the clinical prognosis is still poor with increasing mortality. Non-coding RNAs play pivotal roles in HCC oncogenesis, but the detailed mechanism is poorly known. Therefore, the functions and interaction of lncRNA NORAD and miR-211-5p in HCC was investigated in this study. METHODS: Quantitative real-time PCR method was used to analyze the expression of NORAD and miR-211-5p in clinical HCC tissues and cultured cell lines. Knockdown of NORAD and overexpression of miR-211-5p were then carried in HCC cells. Moreover, bioinformatics analysis and luciferase report assays were further employed to analyze the interaction between miR-211-5p and NORAD or FOXD1. RESULTS: Increased lncRNA NORAD and decreased miR-211-5p expression were first detected in HCC compared with the peritumorial area. Further studies showed that knockdown of NORAD or overexpression of miR-211-5p impaired the proliferation, migration and angiogenesis of HCC cells. Mechanistically, we found that NORAD functions as a sponge for miR-211-5p. Moreover, it was revealed that decreased miR-211-5p induced the expression of FOXD1 as well as its downstream target VEGF-A, thereby contributes to enhanced angiogenesis of HCC. CONCLUSION: Elevated NORAD works as a sponge for miR-211-5p in HCC, thus release the inhibition effect of the latter on its downstream target FOXD1 and VEGF-A, which finally promotes angiogenesis. These results provide new insights into the interaction between NORAD and miR-211-5p in HCC and their potential usage as targets for the development of novel therapeutics against HCC.

Effect of Dihydroartemisinin on Oxidative Damage and Energy Metabolism of HepG2 Cells and Its Synergistic Effect with Sorafenib / 中国实验方剂学杂志

Objective:To explore the inhibitory effect of dihydroartemisinin （DHA） on the proliferation of HepG2 cells， elucidate the mechanism from the perspectives of oxidative damage and energy metabolism， and discuss the possibility of combined use of DHA with sorafenib （Sora）. Method:Cell counting kit-8 （CCK-8） assay was used to obtain the 50% inhibitory concentration （IC₅₀） of DHA and Sora on HepG2 and SW480 cells and Chou-Talalay method was used to obtain the combination index （CI） of DHA and Sora. HepG2 cells were classified into the control group， DHA group （10 µmol·L^-1）， Sora group （5 µmol·L^-1）， and DHA + Sora group （DHA 10 µmol·L^-1， Sora 5 µmol·L^-1） and then incubated with corresponding drugs for 8-12 h. Seahorse XF glycolytic rate assay kit and cell mito stress test kit were employed to respectively detect the glycolysis function of cells and oxidative phosphorylation function of mitochondria. DCFH-DA and lipid peroxidation MDA assay kit were separately used to analyze the intracellular levels of reactive oxygen species （ROS） and malondialdehyde （MDA）. Western blot was applied to determine the intracellular levels of heme oxygenase-1 （HO-1） and glutamate-cysteine ligase catalytic subunit （GCLC）. Result:Compared with the control group， DHA alone inhibited the ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， increased the levels of intracellular ROS and MDA （<italic>P<</italic>0.05）， and decreased the levels of HO-1 and GCLC （<italic>P<</italic>0.05） in HepG2 cells. DHA and Sora had synergistic inhibitory effect on proliferation of HepG2 and SW480 cells， with CI < 0.90. The DHA + Sora group showed stronger suppression of ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， higher levels of intracellular ROS and MDA （<italic>P<</italic>0.01）， and lower levels of intracellular antioxidation-related proteins HO-1 and GCLC in HepG2 cells （<italic>P<</italic>0.01） than the DHA group. Conclusion:DHA may increase the level of MDA by reducing HO-1 and GCLC and increasing ROS in HepG2 cells， which results in mitochondria oxidative damage， restricts cell glycolysis and mitochondrial oxidative phosphorylation， and thus finally inhibits the proliferation of HepG2 cells. DHA and Sora have synergistic inhibitory effect on the proliferation of HepG2 and SW480 cells， and the mechanism may be related to the synergistic oxidative damage that affects the mitochondrial electron transport chain and suppresses cell energy metabolism.

Reasearch on lipid metabolism of Plasmodium and antimalarial mechanism of artemisinin / 中国中药杂志

As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type Ⅱ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.

The research progress on artemisinin resistance and mechanism of spleen clearing Plasmodium / 中国药理学通报

The resistance to artemisinin generated by plasmodium is defined as follows: After being treated with ACTs for three days, the time to clear plasmodium from the blood of patients with malaria becomes prolonged. The elimination rate of plasmodium in vivo is not only related to the parasiticidal efficacy of antimalarial drugs, but also affected by biological factors such as the mutation of plasmodium themselves, the regulation of human immune function(such as the recognition and processing of phagocytes) , and the efflux of foreign l>odies from immune organs. This article primarily reviews the mutation of plasmodium themselves , the physical and biochemical process of the spleen eliminating plasmodium, including K13 changes, the two blood circulation pathways of the spleen. Since the endothelial cell gap of the splenic venous sinus is elastic, plasmodium or red blood cell debris can be trapped by physical and mechanical sensing methods. The red pulp is the main venue to filter blood, where the immune cells are responsible for the removal of the residues of plasmodium. The physical process of the splenic venous sinus trapping plasmodium is called pitting, and its incidence is influenced by the growth cycle of plasmodium and therapeutic drugs. In this paper, the function of the spleen to eliminate plasmodium will be explained, in an attempt to provide a reference for the biological nature of the artemisinin resistance generated by plasmo-dium.

[Research progress on energy metabolism of Plasmodium at erythrocytic stage].

As a single-cell organism, Plasmodium has a large and complex metabolic network system. There is a close relationship between various metabolic pathways to maintain the transformation of Plasmodium's own energy and substances. Plasmodium energy metabolism pathways mainly include glycolysis and oxidative phosphorylation. Among them, Plasmodium at the erythrocytic stage takes glycolysis as the main energy supply method, and less energy is generated by oxidative phosphorylation. In addition, the two carbon metabolism pathways closely relating to energy metabolism are the tricarboxylic acid(TCA) cycle pathway and glutamate metabolism pathway. As the core of metabolism, the TCA cycle connects glycolysis and glutamate metabolism; glutamate metabolism, as the main carbon metabolism pathway, also participates in various metabolic pathways, such as pyrimidine metabolism, porphyrin metabolism, and protein biosynthesis. This article reviews the energy metabolism pathways of Plasmodium and carbon metabolism pathways that are closely related to energy metabolism, in order to deepen the understanding of the energy metabolism of Plasmodium at the erythrocytic stage, and then provide the theoretical basis and references for studying the mechanisms of action and the drug resistance of antimalarial drugs.

Expression of HSPA8 in Nucleus Pulposus of Lumbar Intervertebral Disc and Its Effect on Degree of Degeneration.

INTRODUCTION: This study aimed to investigate the expression of a 70-kDa heat shock protein [heat shock 70-kDa protein 8 (HSPA8)/heat shock protein 70 (Hsc70)] in human degenerative lumbar intervertebral discs and its relationship with the degree of degeneration of human intervertebral discs. METHODS: A total of 72 cases of lumbar intervertebral disc nucleus pulposus tissues were collected. Among these, 18 cases of nucleus pulposus tissue were assigned to the control group, while 54 cases of nucleus pulposus tissues were assigned to the experimental group. According to the preoperative MRI, cases in the experimental group were further divided into three groups: protrusion group (n = 18), extrusion group (n = 18), and sequestration group (n = 18). Western blot was performed to determine the relative expression of HSPA8 in the nucleus pulposus in each group. Hematoxylin and eosin staining was performed to determine the number of nucleus pulposus cells, morphological differences, and cell densities of the degenerated intervertebral discs and normal intervertebral discs. Immunohistochemistry was performed to determine the expression of HSPA8 in nucleus pulposus tissues in each group. RESULTS: Hematoxylin and eosin staining results: There were significant differences in cell morphology and number between the control group and the experimental group. Furthermore, there were significant differences in cell density (F = 936.80, P < 0.01). Immunohistochemistry results: HSPA8 was expressed in lumbar intervertebral disc nucleus pulposus tissues, and its expression of gradually decreased with the severity of the disease, and the differences were significant (F = 2110.43, P < 0.01). Western blot results: The expression of HSPA8 in human degenerative nucleus pulposus tissues gradually decreased, and the differences were significant (F = 1841.72, P < 0.01). CONCLUSION: HSPA8 is stably expressed in human intervertebral disc nucleus pulposus tissues, and its expression is associated with the degree of intervertebral disc degeneration.

Research on expression and effects of host gene 3 of small nucleolar RNA in malignant tumors / 医学研究生学报

Increasingly, researches have shown that long non-coding RNA (lncRNA) plays an important role in the oncogenesis and development of various tumors. Small nucleoli RNA host gene 3 (SNHG3) is a newly discovered lncRNA whose abnormally high expression is closely related to the overall survival and prognosis of tumor patients. SNHG3 can regulate the oncogenesis and development of tumors by endogenous competitive adsorption of miRNA, regulating cell cycle, mediating epithelial and mesenchymal transformation, and activating multiple signaling pathways. Therefore, in-depth research on the carcinogenesis mechanism of SNHG3 is helpful for early diagnosis, targeted therapy and prognostic assessment of relevant tumors. This paper reviews latest research progress on the expression and mechanism of SNHG3 in breast cancer, ovarian cancer, kidney cancer, liver cancer, stomach cancer, colon cancer, osteosarcoma and head and neck tumors to provide references for future studies.

Research on expression and effects of host gene 3 of small nucleolar RNA in malignant tumors / 医学研究生学报

Increasingly, researches have shown that long non-coding RNA (lncRNA) plays an important role in the oncogenesis and development of various tumors. Small nucleoli RNA host gene 3 (SNHG3) is a newly discovered lncRNA whose abnormally high expression is closely related to the overall survival and prognosis of tumor patients. SNHG3 can regulate the oncogenesis and development of tumors by endogenous competitive adsorption of miRNA, regulating cell cycle, mediating epithelial and mesenchymal transformation, and activating multiple signaling pathways. Therefore, in-depth research on the carcinogenesis mechanism of SNHG3 is helpful for early diagnosis, targeted therapy and prognostic assessment of relevant tumors. This paper reviews latest research progress on the expression and mechanism of SNHG3 in breast cancer, ovarian cancer, kidney cancer, liver cancer, stomach cancer, colon cancer, osteosarcoma and head and neck tumors to provide references for future studies.

Value of quantitative MRI T2WI parameters in predicting surgical outcome of thoracic ossification of the ligamentum flavum / 中国组织工程研究

BACKGROUND: MRI has high sensitivity to thoracic myelopathy, which can assess the spinal cord injury by morphology and magnitude of cervical spinal cord compression. Additionally, it is a valuable tool for the prognosis evaluation of thoracic spinal stenosis. OBJECTIVE: To explore the value of quantitative MRI T2WI parameters in predicting surgical outcome of thoracic ossification of the ligamentum flavum, and to establish the prediction model of poor prognosis, so as to provide reference for prognosis evaluation. METHODS: From January 2010 to January 2019 at Cangzhou Central Hospital, clinical and imaging data of 87 cases of thoracic ossification of the ligamentum flavum treated by thoracic laminectomy were reviewed retrospectively. According to the JOA recovery rate at 6-month follow-up, the patients were divided into good recovery group (≥ 50%) and poor recovery group (< 50%). Age, sex, duration of disease, JOA score, Sato type of ossification, maximum spinal cord compression, cross-sectional area, distribution of hyperintense signal, signal intensity ratio, intramedullary signal size, local kyphosis, kyphosis correction, number of decompressed levels and incidence of cerebrospinal fluid were compared between two groups. Univariate analysis was used to analyze indicators with significant differences. Receiver operating characteristic curve was plotted to analyze prognosis. Areas under the curve and cut-off values were recorded. The independent predictors of poor recovery were estimated through multivariate logistic regression analysis and the prediction model was established. RESULTS AND CONCLUSION: (1) The duration of disease, JOA score, maximum spinal cord compression, cross-sectional area, signal intensity ratio and intramedullary signal size showed significant difference between good recovery and poor recovery groups (P < 0.05). (2) Receiver operating characteristic curve analysis showed that the area under the curve of the duration of disease, JOA score, maximum spinal cord compression, cross-sectional area, signal intensity ratio and intramedullary signal size was 0.670, 0.733, 0.647, 0.715, 0.753 and 0.765 respectively. The cut-off value was duration of 13 months, score 4, 29.8%, 0.25 cm2, 1.593 and 13.64 mm respectively. The duration of disease and maximum spinal cord compression had low discrimination power (the area under the curve < 0.7) in predicting poor recovery, whereas the JOA score, cross-sectional area, signal intensity ratio and intramedullary signal size had moderate discrimination power (the area under the curve 0.7-0.9). The area under the curve indicates good ability of signal intensity ratio and intramedullary signal size in combination (the area under the curve=0.791). (3) Logistic multivariate regression analysis showed that JOA score, cross-sectional area and combination of signal intensity ratio and intramedullary signal size were independent risk factors of poor recovery. A predicting model was built according to the result of the logistic regression analysis. It was shown that the area under the curve of this model was 0.890, which was significantly higher than that of the JOA score, cross-sectional area and combination of signal intensity ratio and intramedullary signal size (P < 0.05). (4) Combination of signal intensity ratio and intramedullary signal size had higher predictive ability than other MRI parameters. JOA score, together with quantitative MRI T2WI parameters may have a better predictive value for the risk of poor recovery in patients with thoracic ossification of the ligamentum flavum.

Alterations in atrial ion channels and tissue structure promote atrial fibrillation in hypothyroid rats.

PURPOSE: It is well known that hyperthyroidism is associated with atrial fibrillation (AF); however, the relationship between hypothyroidism and AF remains controversial. METHODS: Hypothyroidism was established in rats by two methods: methimazole-induced (MMI) and thyroidectomy (TX). MMI model includes control (n = 10), MMI (n = 10), and MMI + L-thyroxine (T4, n = 10). Methimazole was given intragastrically in MMI and MMI + T4 for 12 weeks, and T4 was added intragastrically in MMI + T4 at week 5. TX model includes sham (n = 10), TX (n = 10), and TX + T4 (n = 10). Four weeks after surgery, rats in TX + T4 received T4 for 8 weeks. Triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) were measured. Electrophysiology, tissue structure and function, and protein levels of potassium and L-type calcium channels were assessed in the atria. RESULTS: Severe changes in the atrial structure of hypothyroid rats were observed. Compared with euthyroid rats, atrial effective refractory period (AERP) in hypothyroid rats was significantly shortened; accordingly, inducibility and duration of AF were considerably increased. Protein levels of minK, Kv1.5, Kv4.2, Kv4.3, Kv7.1, and Cav1.2 were upregulated in hypothyroid rats, whereas there was only a tendency toward increased Kir2.1. Kv11.1 was statistically upregulated in the MMI model and had an increasing tendency in the TX model. Conversely, Kir3.1 and Kir3.4 were downregulated in hypothyroid rats. The above changes could be partially inhibited by T4 treatment. CONCLUSIONS: AERP shortening due to altered protein levels of ion channels and atrial structural changes increased the susceptibility to AF in hypothyroidism. Thyroid replacement therapy could prevent electrical and structural remodeling under hypothyroid condition.