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Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09%)were diagnosed with STB,and 54(40.91%)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68%and 66.67%,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95%CI:1.847-9.974,P<0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56%,higher than 67.42%of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.
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OBJECTIVE@#To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).@*METHODS@#From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12.@*RESULTS@#In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred.@*CONCLUSIONS@#GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).
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Humans , Percutaneous Coronary Intervention/adverse effects , Quality of Life , Depression , Coronary Disease/drug therapy , Drugs, Chinese Herbal/therapeutic use , Angina Pectoris/drug therapy , Prognosis , Anxiety , Treatment Outcome , Double-Blind MethodABSTRACT
Aim To investigate the mechanism of high salt-induced cerebral artery remodeling in mice by up-regulating TMEM16A. Methods Forty C57BL/6J mice were randomly divided into four groups (10 per group, 8 weeks of intervention), namely, blank control group (normal diet), low-salt group (2% high salt diet), medium-salt group (4% high salt diet) and high-salt group (8% high salt diet). HE staining was used to observe the morphological changes of cerebral arteries; blood vessel permeability test was used to compare the color and absorbance value of brain tissue. Immunofluorescence was employed to detect TMEM16A expression in cerebral arteries of mice in each group; PCR and Western blot were applied to detect the mRNA and protein expression of TMEM16A in cerebral arterial tissues; whole-cell patch clamp was use to record the calcium-activated chloride channel (CaCC) currents of mouse cerebral artery smooth muscle cells in each group. Results HE results showed that 2%, 4%, and 8% high salt diet could concentra-tion-dependently induce cerebral arterial wall thickening and lumen stenosis in C57BL/6J mice. The permeability test found that compared with the control group, the absorbance value of the brain tissue of the mice in the 2%, 4% and 8% high salt groups increased significantly. The results of isolated muscle tension showed that compared with the control group, the systolic response of isolated cerebral arteries to 60 mmol • L
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In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.
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ObjectiveTo study the chemical constituents of the seeds of Sophora tonkinensis. MethodThe chemical constituents were isolated and purified by chromatography with MCI resin, silica gel, Sephadex LH-20, and semi-preparative high performance liquid chromatography. Their structures were identified by physicochemical properties, spectral data as well as relevant references. Meanwhile, the antibacterial activities against Helicobacter pylori of these compounds were screened by agar dilution method. ResultA total of 22 compounds were isolated from the methanol extract of the seeds of S. tonkinensis, and characterized as 4′,7-dihydroxy-6-methoxy isoflavone (1), daidzein (2), wighteone (3), dalparvone (4), 5,7-dihydroxy-4′-methoxyisoflavone (5), prunetin (6), formononetin (7), genistein (8), 5-methoxydaidzein (9), ononin (10), 7,4′-dihydroxyflavone (11), liquiritigenin (12), bayin (13), 2,4-dihydroxybenzoate (14), methyparaben (15), 4-hydroxyacetophenone (16), p-anisaldehyde (17), methyl indole-3-carboxylate (18), 4-[β-D-apiofuranoyl-(1→6)-O-β-D-glucopyranosyloxy] phenylacetonitrile (19), (-)-methyl dihydrophaseate (20), methyl canavaliol ester (21), vomifoliol 3′-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (22). ConclusionCompounds 1, 5, 6, 9 and 16 are isolated from S. tonkinensis for the first time, compounds 4, 14, 17-22 are isolated from the genus of Sophora for the first time. In addition, compounds 10 and 13 display moderate antibacterial activities against H. pylori.
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Aim To investigate the effeets of prolifera¬tion and autophagy of BV2 eells in OGD/R models when the 18 ku transloeator protein( TSPO) was inhibi¬ted.Methods BV2 microglia were eultured in vitro and the model established by oxygen-glueose depriva- tion/reperfusion( OGD/R) , the eells were divided into eontrol group and OGD/R group, OGD/R + small hair¬pin RNA negative eontrol group ( OGD/R + NCshR- NA) , OGD/R + TSPO small hairpin RNA group (OGD/R + TSPOshRNA ).The expression of TSPO mRNA and TSPO protein were deteeted by qRT-PCR and Western blot, respectively.In order to study the effeet of TSPO on BV2 microglial eells in OGD/R inju¬ry and autophagy, the cell viability was tested by CCK- 8 assey, the cytotoxicity was deteeted by reactive oxy¬gen speeies ( ROS) , autophagy-related mRNA ( p62 mRNA, LC3B mRNA, Beolin-1 mRNA) expressions were detected by qRT-PCR, and the expression levels of autophagy -related proteins ( p62 , LC3 II /LC3 1 , Beclin-1 ) were detected by Western blot in each group.Result The expression of TSPO mRNA and protein increased significantly in OGD/R group while compared to control group, the cell death and cytotox¬icity increased significantly, the expression levels of LC3B mRNA and Beclin-1 mRNA increased, while the p62 mRNA decreased significantly, the levels of LC3 II/LC3 1 and Beclin-1 protein increased, the expres¬sion of p62 protein decreased significantly in OGD/R group, and the autophagy was activated; compared with OGD/R group, the different levels of cell viabili¬ty, cytotoxicity and autophagy in OGD/R + NCshRNA group were not statistically significant.But the survival rate of cells in OGD/R + TSPOshRNA group signifi¬cantly increased, the levels of cytotoxicity and autoph¬agy were significantly reduced.Conclusions The in¬hibition of TSPO has a significant protective effect on OGD/R injury model in BV2 microglial cells, which may be related to the inhibition of autophagy.
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Abstract Introduction The standard approach to thyroidectomy is a collar incision via the anterior neck, and the neck scar has always been a source of worry for patients. Acceptable wound cosmetology has become a focus for thyroid surgeons. Objective To verify the effectiveness and cosmetic results of thyroidectomy through a lateral supraclavicular incision. Methods 180 patients were randomly divided into two groups: a lateral supraclavicular approach and a conventional transcervical approach. The main outcomes included incision length, intraoperative blood loss, operative time, total drainage volume, hospitalization expense, early postoperative pain measured by visual analog scale, infection, and perceived cosmetic outcome. Results There were no statistical significances between the two groups in terms of age, gender, nodule size, intraoperative blood loss, operative time, total drainage volume, hospital expense and postoperative complications, whereas there were significant differences in terms of incision length (5.2 ± 1.04 cm vs. 6.9 ± 1.14 cm, p < 0.05). Conclusions The lateral supraclavicular incision is a safe and feasible approach for thyroidectomy. Compared with conventional approach, it provides a better cosmetic result.
Resumo Introdução A abordagem padrão para tireoidectomia é uma incisão em colar na face anterior do pescoço; a cicatriz no pescoço sempre foi uma fonte de preocupação para os pacientes; consequentemente, a cosmetologia aceitável da ferida tornou‐se um foco de atenção para os cirurgiões de cabeça e pescoço. Objetivos Verificar a eficácia e os resultados cosméticos da tireoidectomia por meio de incisão supraclavicular lateral. Método Foram divididos aleatoriamente 180 pacientes em dois grupos: um grupo supraclavicular lateral (Grupo LS) e outro transcervical convencional (Grupo TC). Os desfechos principais incluíram comprimento da incisão, perda de sangue intraoperatória, tempo cirúrgico, volume total de drenagem, despesas hospitalares, dor no pós‐operatório imediato medida através de escala visual analógica, infecção e resultado cosmético percebido. Resultados Não houve significância estatística entre os dois grupos em termos de idade, sexo, tamanho do nódulo, perda sanguínea intraoperatória, tempo cirúrgico, volume total de drenagem, custo hospitalar e complicações pós‐operatórias, mas houve diferença significante em termos de comprimento da incisão (5,2 ± 1,04 cm vs. 6,9 ± 1,14 cm, p < 0,05). Conclusão A incisão supraclavicular lateral é uma abordagem segura e viável para tireoidectomia. Em comparação com a abordagem convencional, oferece um melhor resultado cosmético.
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Objective To understand the real prevalence of Clonorchis sinensis infections in the freshwater fish in mainland China, so as to provide insights into clonorchiasis control and detection of freshwater fish. Methods All literatures reporting the prevalence of C. sinensis infections in the freshwater fish, the second intermediate host of the parasite, were jointly retrieved in Chinese and English electronic databases from January 1, 2010 to December 31, 2020, including Wanfang Data, CNKI, PubMed, Web of Science, Embase and Cochrane Library. All studies were screened based on inclusion and exclusion criteria, and the quality of all enrolled literatures was evaluated. The pooled prevalence of C. sinensis infections in freshwater fish and its 95% confidence interval (CI) were estimated using the software Stata version 15.0, and subgroup analyses were performed to investigate the region-, season- and sample source-specific pooled prevalence of C. sinensis infections in freshwater fish. In addition, the sensitivity and publication bias of all included studies were analyzed. Results A total of 40 eligible literatures were included in this study, including 37 Chinese literatures and 3 English literatures, and there were 10 high-quality literatures, 27 moderate-quality literatures and 3 low-quality literatures. A total of 53 species containing 37 959 freshwater fish were reported in these 40 studies, and 73.58% (39/53) of freshwater fish species were identified with C. sinensis infections. Meta-analysis showed 23.5% [95% CI: (0.19, 0.28)] pooled prevalence of C. sinensis infections in freshwater fish in mainland China, and subgroup analyses higher prevalence of C. sinensis infections in freshwater fish in northeastern China [35.7%, 95% CI: (0.22, 0.50)] than in central [25.9%, 95% CI: (0.04, 0.48)] and southern China [20.6%, 95% CI: (0.09, 0.32)], higher prevalence of C. sinensis infections in freshwater fish sampled in spring [44.1%, 95% CI: (0.35, 0.53)] than in autumn [6.7%, 95% CI: (0.05, 0.08)] and summer [3.3%, 95% CI: (−0.01, 0.07)], and higher prevalence of C. sinensis infections in freshwater fish sampled from natural water [25.2%, 95% CI: (0.17, 0.33)] than from retail trades [22.2%, 95% CI: (0.17, 0.28)] and breeding chain [12.3%, 95% CI: (0.03, 0.22)]. However, all included studies had a publication bias with a low sensitivity. Conclusions The prevalence of C. sinensis infections is high in freshwater fish in mainland China, and there are still challenges for clonorchiasis control. Reinforcement of health education, diagnostics development and food safety supervision is recommended in future clonorchiasis control programs.
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This article systematically reviews the research results related to the machine learning based suicide ideation prediction on social networking platforms, so as to provide references for group and individual suicide prediction. This article will address the current states (issues of algorithm accuracy and efficiency, privacy leakage and stigma) and limitations of machine learning based suicide prediction on different platforms (light blogging, acquaintance social platforms, forums, picture and video sharing applications and clinical databases).
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Diaporthe sp. fungi is one of the important sources of active natural products. Polyketides, alkaloids, terpenes, anthraquinones and other types of novel metabolic products are found from this genus, and many of them have significant anti-tumor, antibacterial, anti-hyperlipidemia, inhibition of pulmonary fibrosis, antioxidant and other biological activities. This paper reviewed source, structure and biological activity of natural products from Diaporthe sp. in the past two decades, and provided a reference for in-depth study of natural product of this genus fungus and innovative drug development.
Subject(s)
Anti-Bacterial Agents , Biological Products/pharmacology , Fungi , Polyketides , TerpenesABSTRACT
@#Objective To investigate the effect of sleep on quality of life in patients with first ischemic stroke.Method A total of 69 patients with the first ischemic stroke admitted to the department of neurology at the army medical center for specialty medicine from January to May 2019 were selected.Baseline data were evaluated after admission.Followed up by telephone one month after onset,and assessments of sleep and quality of life were improved.The Pittsburgh scale was used for sleep assessment,and the SF-36 scale was used for quality-of-life assessment.Results There were statistically significant differences between component A in Pittsburgh scale and BP,VT,SF and MH in SF-36 scale,between component C,D and VT(P<0.05).There were statistically significant differences between component E and VT and SF,between component F and RP,VT,SF,RE,MH (P<0.05).There were no statistically significant differences between component B,C,G and SF-36 score.While the total score of PSQI was statistically significant with VT and MH (P<0.05).Conclusion The insomnia disorder after the onset of the first ischemic stroke has a significant impact on the quality of life of patients.
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To compare the efficacies of the two techniques of "micro-hemostasis and micro-cutting" with straight bipolar electrocoagulation forceps and traditional clamp-ligation for hemostasia in thyroid surgery. A total of 228 patients who underwent surgical treatment for thyroid neoplasms in our hospital between January 2015 and December 2018 were retrospectively analyzed, including 50 males and 178 females, aged 23-68 years old. Of those, 150 cases as electric knife group received traditional thyroid surgery between January 2015 and December 2018 and 78 cases as bipolar electrocoagulation group received thyroid surgery by using the technique of bipolar electrocoagulation with meticulous anatomy between January 2018 and December 2018. The total operation time, single operation time, intraoperative hemorrhage, postoperative drainage volume on the first day, postoperative hoarseness and hypocalcemia were compared between the two groups. SPSS 16.0 was used to analyze the data. The total operation time and intraoperative hemorrhage in the bipolar electrocoagulation group were significantly lower than those in the electric knife group ((59.33±18.29)min (77.21±25.39)min, (14.83±9.22)ml (36.86±11.80)ml, all 0.01). The single operation time of the bipolar electrocoagulation group was shorter than that of the electric knife group((10.25±6.16) min (20.34±7.24)min, (16.25±7.15)min (35.68±8.25)min, (12.12±5.25)min (20.68±7.26)min, value was 3.948,16.262,8.238, all 0.01).There was no significant difference between the two groups in postoperative drainage volume on the first day (0.05) and the incidence of postoperative hoarseness (0.05), while the incidence of hypocalcemia in the bipolar electrocoagulation group(10.26%) was lower than that in the electric knife group(21.33%,χ(2)=4.353, 0.05). The fine dissection for thyroid operation can be achieved by using straight bipolar electrocoagulation tweezers. The use of "micro-hemostasis" and "micro-cutting" technique with bipolar electrocoagulation tweezers can greatly reduce intraoperative bleeding, operation time and postoperative complication.
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Paradoxical insomnia is a common clinical phenomenon.Due to the lack of comprehensive understanding of its pathogenesis, there were wide variability in diagnostic criteria and treatment outcomes, thus interfering with the correct statistics of its epidemiological data.Through the summary of previous studies, combination with our own research on the pathogenesis of chronic insomnia, we propose that the differences in the subjective and objective assessment of paradoxical insomnia are related to the asynchronous inactivation of the thalamus and cortex during the sleep initiation phase and the cortical activation sequence and intensity disorders in each region after sleep.Furthermore, the diagnosis of paradoxical insomnia and clinical characteristics are described according to the related pathogenesis and a targeted treatment strategy is formulated.Paradoxical insomnia is a type of insomnia with specific pathophysiological mechanism.
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Objective: To observe the improvement of androgen deficiency syndrome after endocrine therapy by "Jianpi Lishi Huayu Method" for advanced prostate cancer and its clinical effect. Methods: A total of 60 patients with advanced prostate cancer were randomly divided into observation group (30 cases) and control group (30 cases). The control group was treated with intermittent endocrine therapy (androgen blocking). The treatment group was treated with "Jianpi Lishi Huayu Decoction" on the basis of the control group. The end point of the study was the time to develop castration-resistant prostate cancer. ISS scale scores, disease progression-free survival, PSA, serum testosterone, I-PSS and TCM clinical symptom scores were compared between the two groups. Results: The median progression-free survival time of the patients in the observation group was 23 months, and there was no significant difference between the two groups. After treatment, the total ISS score, physical symptoms score, vasomotor symptoms score and psychosocial symptoms score in the observation group were significantly lower than those before treatment, and lower than those in the control group (P < 0.05). After treatment, the effective rate of ISS score in the observation group (73.33%) was significantly higher than that in the control group (16.67%); The PSA level in both groups decreased significantly after treatment, and the PSA level in the observation group (2.13 ± 0.58) ng/mL was better than that in the control group (5.30 ± 1.40) ng/mL (P < 0.05); There was no significant difference in serum testosterone between the two groups after treatment. After treatment, the I-PSS score and TCM clinical symptom score of the observation group and the control group were improved, and the observation group was better than the control group (P < 0.05). After treatment, the effective rate of the I-PSS score of the observation group (96.67%) and the improvement rate of TCM clinical symptom score (76.67%) were better than those of the control group (73.33%, 26.67%). Conclusion: On one hand, "invigorating spleen, draining dampness and removing blood stasis" method combined with endocrine therapy can prolong the time for hormone-dependent prostate cancer to develop into castrated resistant prostate cancer, improve clinical efficacy, reduce the level of tumor markers, stabilize the level of testosterone, and improve some androgen deficiency syndrome after endocrine therapy, especially in ovariectomized resistant prostate cancer. It has obvious advantages in improving physical symptoms, vasomotor symptoms and psycho-psychological symptoms. It can obviously alleviate adverse reactions after endocrine therapy. On the other hand, it can better improve clinical symptoms, reduce I-PSS scores and TCM clinical symptoms scores, improve the quality of life of patients, and give full play to the role of reducing TCM toxicity and increasing synergism efficiency.
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Traditional Chinese medicine has a history of more than 2 000 years with wide application in clinical practice. With the progress of diagnosis and treatment, the role of Chinese materia medica in extending the survival period of cancer patients and improving their quality of life has received increasing attention and recognition. The anti-tumor activity and mechanism of Chinese materia medica have the characteristics of multi-pathway, multi-target, and multi-pathway, such as inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor cell invasion and metastasis, regulating tumor microenvironment, anti-tumor angiogenesis, and reversing drug resistance. The mechanism of anti-tumor monomer in Chinese materia medica was reviewed in order to provide some ideas and theoretical basis for the anti-tumor research of traditional Chinese medicine.
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Objective: To investigate the efficacy of Xiaoyan Decoction in the treatment of non-small cell lung cancer (NSCLC) by retrospective study. Methods: Patients with NSCLC treated in the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 1, 2013 to December 30, 2017 were collected. The patients were divided into two groups: Xiaoyan Decoction plus subtractive prescription combined with symptomatic treatment group (46) and symptomatic treatment group (50). Analyze the survival of the two groups of patients, compare the Karnofsky scores of the two groups, and analyze the sex, age, smoking history, drinking history, histological grade, chemotherapy regimen, pathological type, TCM syndrome type, vascular invasion, and soft tissue invasion Correlation with patient prognosis. Results: There was a significant difference in median progression-free survival (mPFS) between the two groups (P 0.05).The quality of life of patients in Xiaoyan Decoction plus subtractive prescription combined with symptomatic treatment group was significantly improved (P < 0.05), among which, lung squamous cell carcinoma, no vascular, no soft tissue invasion, and patients with phlegm heat obstruction of lung syndrome had the best efficacy (P < 0.05). Conclusion: Xiaoyan Decoction combined with symptomatic maintenance therapy can prolong median progression-free survival (mPFS) and improve the quality of life of patients with advanced NSCLC. The best beneficiaries are patients with lung squamous cell carcinoma, phlegm-heat obstructive pulmonary syndrome without vascular or soft tissue invasion.
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The genus Carpesium plants contain many kinds of sesquiterpenes. Up to now, more than 201 sesquiterpene compounds have been isolated and identified, including 86 germacranolides, 30 eudesmanolides, 29 guaianolides, 23 sesquiterpene dimers, 9 pseudoguaianes, 9 carabranolides, 7 xanthanolides, 6 sesquiterpenes without lactone, 1 eremophilane and 1 tricyclo dodecane sesquiterpene. The reported sesquiterpenes possess a series of pharmacological properties, such as anti-tumor, anti-inflammatory, antibacterial, antiparasitic, insecticidal, and antiviral activities. This paper summarizes the 201 chemical structures and biological activities of sesquiterpenes in genus Carpesium, and provides the scientific basis for the further development and utilization.
Subject(s)
Anti-Bacterial Agents , Anti-Inflammatory Agents , Asteraceae/chemistry , Lactones , Molecular Structure , Phytochemicals/pharmacology , Sesquiterpenes/pharmacologyABSTRACT
OBJECTIVE@#Epstein-Barr virus associated gastric cancer (EBVaGC) is different from the traditional gastric cancer (Epstein-Barr virus non-associated gastric cancer, EBVnGC), and has unique clinicopathological features. This study investigated the largest single center cancer series so as to establish the clinicopathological and molecular characteristics of EBVaGC in China.@*METHODS@#A retrospective analysis was conducted on EBVaGC and EBVnGC patients diagnosed at Peking University Cancer Hospital from 2003 to 2018 by comparing their clinicopathological features and prognosis. The gastric cancer (GC) dataset of public database was analyzed to obtain differentially expressed genes. The expression of important genes and their association with prognosis of GC were verified in GC tissues from our hospital.@*RESULTS@#In this study, 3 241 GC patients were included, and a total of 163 EBVaGC (5.0%) patients were identified. Compared with EBVnGC, EBVaGC was higher in male and younger patients, and positively associated with remnant GC, poorly differentiated adenocarcinoma, and mixed type GC. EBVaGC was inversely related to lymph node metastasis. The 5-year survival rate of EBVnGC and EBVaGC was 59.6% and 63.2% respectively (P<0.05). In order to explore molecular features of EBVaGC, the Cancer Genome Atlas (TCGA) dataset was analyzed (n=240), and 7 404 significant differentially expressed genes were obtained, involving cell proliferation, apoptosis, invasion and metastasis. The down-regulated invasion/metastasis gene SALL4 and the up-regulated immune checkpoint gene PD-L1 were important molecular features of EBVaGC. Validation of these two genes in large GC series showed that the majority of the EBVaGC was SALL4 negative (1/92, 1.1%, lower than EBVnGC, 303/1 727, 17.5%), and that PD-L1 was mostly positive in EBVaGC (81/110, 73.6%, higher than EBVnGC, 649/2 350, 27.6%). GC patients with SALL4 negative and PD-L1 positive were often associated with better prognosis.@*CONCLUSION@#EBVaGC is a unique subtype of GC with less metastasis and a good prognosis. It also has a distinct molecular background. The down-regulation of invasion/metastasis gene SALL4 and up-regulation of immune checkpoint gene PD-L1 are important molecular features.
Subject(s)
Female , Humans , Male , China , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , Retrospective Studies , Stomach Neoplasms/etiologyABSTRACT
Objective To investigate the role of microRNA-10b (miR-10b) in the proliferation and invasion potential of osteosarcoma cell lines MG-63 and the exact underlying mechanism.Methods The expression level of miR-10b in human osteosarcoma tissue samples and adjacent normal bone tissues were detected by relative quantitative real-time PCR (qRT-PCR).miR-10b mimic and siRNA against Twist (Twist siRNA) were transfected into human osteosarcoma cell lines MG-63 respectively using lipofactamine 2000, and RT-PCR was used to detect the mRNA expression levels of miR-10b and Twist, and Twist protein expression level was detected by Western blot.The effect of miR-10b mimic and Twist siRNA on proliferation of MG-63 were detected by MTT[3- (4, 5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2 H-tetrazolium].The in-vitro cell invasion ability was determined by Transwell invasion assays after up-regulating miR-10b or knocking down of Twist.Results The expression levels of miR-10b was higher in human osteosarcoma tissue samples compared with adjacent normal bone tissues, the differences were extremely statistical significance (P<0.01).miR-10b directly up regulated the mRNA and protein expression levels of Twist, the differences were significant (P<0.05).In addition, miR-10b had enhanced the cell invasion and the proliferation (P<0.05), whereas the proliferation and invasion ability of MG-63 which transfected by both miR-10b mimic and Twist siRNA were significantly reduced than that transfected by miR-10b mimic (P<0.05).Conclusion miR-10b in MG-63 promotes the proliferation and invasion potential of human osteosarcoma cell lines MG-63, at least partly through the upregulation of Twist gene.
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Obesity is an important risk factor for cardiovascular diseases, which can lead to a variety of cardiovascular diseases including myocardial remodeling. Obesity may induce myocardial dysfunction by affecting hemodynamics, inducing autonomic imbalance, adipose tissue dysfunction, and mitochondrial dyshomeostasis. The key necessary biochemical functions for metabolic homeostasis are performed in mitochondria, and mitochondrial homeostasis is considered as one of the key determinants for cell viability. Mitochondrial homeostasis is regulated by dynamic regulation of mitochondrial fission and fusion, as well as mitochondrial cristae remodeling, biogenesis, autophagy, and oxidative stress. The mitochondrial fission-fusion and morphological changes of mitochondrial cristae maintain the integrity of the mitochondrial structure. The mitochondria maintain a "healthy" state by balancing biogenesis and autophagy, while reactive oxygen species can act as signaling molecules to regulate intracellular signaling. The excessive accumulation of lipids and lipid metabolism disorder in obesity leads to mitochondrial dyshomeostasis, which activate the apoptotic cascade and lead to myocardial remodeling. In this review, we provide an overview of the recent research progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis.