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Objective To explore the value of dynamic nomogram constructed by multi spiral computed tomography(MSCT)features combined with inflammatory indicators in predicting the status of microvascular invasion(MVI)of hepatocellular carcinoma(HCC)before surgery.Methods The clinical and imaging data of 137 patients with postoperative pathologically confirmed HCC were analyzed retrospectively.According to the status of the MVI,they were divided into positive group(44 cases)and negative group(93 cases).Multivariate logistic regression analysis was used to screen independent risk factors for predicting the MVI status of HCC patients,and a joint prediction model was constructed,which was displayed in the form of a dynamic nomogram.The receiver operating characteristic(ROC)curve,calibration curve and Hosmer-Lemeshow test were used to evaluate the diagnostic efficiency,calibration and goodness of fit of the model,Akaike information criterion(AIC)and Bayesian information criterion(BIC)were used for comparison between the models,and a 5-fold cross-validation and decision curve analysis(DCA)were also used to evaluate the stability and clinical applicability of the model.Results Multivariate logistic regression analysis showed that necrosis and delayed-phase enhancement(DEd),and alkaline phosphatase to lymphocyte ratio(ALR)were independent risk factors for predicting MVI status in HCC patients.The area under the curve(AUC)of the dynamic nomogram was 0.721,with the sensitivity of 0.705 and the specificity of 0.656.The AIC and BIC values were 152.372 and 158.212,respectively.The calibration curve and the Hosmer-Lemeshow test showed that the model had a high degree of calibration and goodness of fit(χ2=2.372,P=0.967),the average AUC of the 5-fold cross-validation was 0.787,and the DCA showed that the nomogram model had a good clinical applicability.Conclusion The dynamic nomogram model constructed by MSCT features combined with inflammatory indicators is feasible to predict the MVI status of HCC patients before surgery,and the dynamic nomogram can directly generate the prediction results of different individuals.
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Objective Meta-analysis was conducted to assess the risk of secondary infection caused by tocilizumab(TCZ)in the treatment of Corona Virus Disease 2019(COVID-19),in order to provide an evidence-based basis for the safety of tocilizumab in patients with COVID-19.Methods Cochrane Library,PubMed,Web of Science,CNKI,SinoMed and Wanfang databases were searched in computer to collect randomized controlled trial and cohort study of treating COVID-19 with tocilizumab from December 19,2019 to December 30,2022.A meta-analysis of the results of each study was performed using RevMan 5.4.1 software.Results A total of 1691 references were screened and eighteen studies involving 3933 patients were included.The incidence of secondary infection in the tocilizumab with the standard treatment group and standard treatment group was 19.14%(331/1729)and 12.11%(267/2204),respectively.Meta-analysis showed that the tocilizumab + standard treatment group had a higher incidence of secondary infection than the standard treatment group[RR = 1.35,95%CI(1.05,1.74),P = 0.02].The results of the subgroup analysis showed that the risk of secondary infection with different doses of tocilizumab was different.The incidence of secondary infection was significantly higher in the subgroup with doses of 400～800 mg/d tocilizumab than in the standard care group[RR = 1.48,95%CI(1.19,1.84),P = 0.0004].The incidence of secondary infection in subgroups with doses of≤400 mg/d tocilizumab was also significantly higher than that in the standard treatment group[RR = 1.87,95%CI(1.28,2.72),P = 0.001].However,there was no statistical significance between the subgroup 6～8 mg/kg tocilizumab and the standard treatment group.Conclusions Tocilizumab may increase the risk of secondary infection in patients with COVID-19 compared with standard treatment,and the benefits and risks of tocilizumab should be carefully evaluated before clinical administration.Moreover,large and high-quality studies are needed for further evaluation.
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Objective @# To explore the role of long non-coding RNA XR_378418 (LncRNA XR_378418) in the bi- ological behavior of hepatic stellate cells line JS-1 and to probe the potential molecular mechanism of LncRNA XR _378418 involved in liver fibrosis based on transcriptome sequencing．@*Methods @#In this study，the recombinant plasmid of pcDNA-LncRNA XR_378418 and control plasmid pcDNA-NC were constructed and transfected into JS-1 cells respectively．Then，the expression level of LncRNA XR_378418 was analyzed by quantitative real-time PCR (RT-qPCR) ．The effect of overexpression of LncRNA XR_378418 on proliferation and migration of JS-1 cells were detected by cell counting kit-8 assay ( CCK-8 ) and scratch assay，respectively． Finally，by high-throughput se- quencing analysis，the effect of XR_378418 on the transcriptomics of JS-1 cells was analyzed. @*Results @#T-qPCR results showed that the expression level of LncRNA XR_378418 in the overexpression group was significantly higher than that in the control group (P＜0. 05) ．The results of CCK-8 and scratch experiment suggested that the prolifer- ation and migration in the pcDNA-LncRNA XR _ 378418 group significantly increased． Furthermore ，the high- throughput sequencing analysis showed that a total of 248 genes were screened by gene differential analysis ，of which 127 were up-regulated ，and 117 were down-regulated． Gene Ontology ( GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that LncRNA XR_378418 could regulate cell adhesion，autophagy and Ca2 + signaling，etc．@*Conclusion @#LncRNA XR_378418 promotes the proliferation and migration of JS-1 cells and affects the expression of genes related to cell adhesion and calcium signaling in JS-1 cells.
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Objective To identify small molecule inhibitors of APC-mutant colon cancer and provide lead compounds for targeted therapy of colon cancer. Methods APC-mutant colon cancer cell lines that stably express 7*Tcf-GFP/SV40-Cherry (7TGC) dual fluorescence reporter system was constructed for small-molecule inhibitor screening. Cell viability, colony formation, EdU incorporation, and xenograft tumor assay were used to evaluate the inhibitory effect of these inhibitors on APC-mutant colon cancer in vitro and in vivo. Western blot and co-immunoprecipitation assays were used to explore the molecular mechanism. Results Four small molecules that inhibited Wnt activity in APC-mutant colon cancer cells were discovered. Shikonin exhibited significant inhibition of cell viability and proliferation while inducing apoptosis of APC-mutant colon cancer cells. Xenograft tumor assay demonstrated that shikonin significantly reduced tumor growth in vivo. Furthermore, Western blot and co-immunoprecipitation assays revealed that shikonin markedly decreased β-catenin levels. Conclusion Shikonin effectively inhibits Wnt activity and suppresses tumor growth in APC-mutant colon cancer.
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Objective:To investigate the prevalence of cataracts, the surgical coverage, and postoperative visual acuity of adults in Ningxia.Methods:A cross-sectional study using multistage cluster random sampling was conducted.Ten survey sites in Ningxia were selected and the population aged 18 years and over was surveyed with questionnaire, height and weight measurements, visual acuity, intraocular pressure, fundus photography and slit-lamp examinations.Cataract prevalence and its influencing factors were analyzed.Cataract prevalence, surgical coverage and presenting visual acuity (PVA) and best corrected visual acuity (BCVA) after surgery were investigated in different age groups of the examined population.The study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region (No.[2023]-LL-010).Participants signed informed consent prior to the examination.Results:A total of 6 145 people should be examined, and 5 721 people were actually examined, with an examination rate of 93.10%.The study population consisted of 2 558 males, accounting for 44.71%, and 3 163 females, accounting for 55.28%, with ages ranging from 18 to 93 years old and an average age of (64.27±13.48) years.Among them, 1 180 patients diagnosed with cataract, with a cataract prevalence of 20.62%.The prevalence of cataract increased with age and decreased with education level, showing statistically significant differences ( χ2=1 091.32, 581.92; both at P<0.01).The prevalence of cataract was significantly higher among people with hypertension, diabetes mellitus, hyperlipidemia, and coronary heart disease than those without these diseases ( χ2=274.65, 118.15, 78.05, 182.71; all at P<0.01).Cataract surgery was performed in 245 cases in the cataract patient population, with a surgical coverage rate of 20.76%.Of the 245 cases, 229 cases were implanted with IOLs, with an implantation rate of 93.40%.The social burden rate of cataract blindness was 2.29%, and increased with age.Of the 339 eyes that underwent cataract surgery, 241 had a PVA≥0.3, accounting for 71.09%, and 272 had a BCVA≥0.3, accounting for 80.24%. Conclusions:In Ningxia, cataracts are still the main cause of vision impairment and blindness in the elderly, and the social burden rate of cataract blindness is high.Moreover, the coverage rate of cataract surgery is low, so both the coverage and quality of surgery need improvement.
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Objective:To analyze the external quality control assessment results of salt iodine, urine iodine, and water iodine in iodine deficiency disorders (IDD) laboratories at all levels in Shandong Province, and provide reliable quality assurance for monitoring and prevention of IDD.Methods:The external quality control assessment of salt iodine, urine iodine and water iodine in provincial, municipal and county levels IDD laboratories in Shandong Province from 2017 to 2021 were conducted, and feedback rate and qualification rate were calculated.Results:From 2017 to 2021, the feedback rates and qualification rates of external quality control assessment of salt iodine, urine iodine and water iodine at provincial and municipal levels IDD laboratories in Shandong Province were all 100.0%. The feedback rates of county level laboratories participating in the salt iodine external quality control assessment were all 100.0%. The qualification rate in 2021 was 99.3% (135/136), and the other four years were all 100.0%. The feedback rates of county level laboratories participating in the urine iodine external quality control assessment were all 100.0%. The qualification rates in 2017 and 2021 were 98.4% (122/124) and 97.1% (132/136), respectively, and the other three years were all 100.0%. In 2021, the county level laboratories in Shandong Province participated in the water iodine external quality control assessment for the first year, and the feedback rate and qualification rate of 69 laboratories were both 100.0%.Conclusion:From 2017 to 2021, the detection capacity of IDD laboratories at the provincial and municipal levels in Shandong Province remains at a high level, and the detection capacity of salt iodine and urine iodine in some county level laboratories still needs to be further improved.
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The Internet has become an important carrier of medical information.Good electronic health literacy can enhance the public’s ability to obtain correct medical and health information with the help of electronic resources,which is helpful for the public to use health information to prevent diseases,avoid drug abuse,reduce the waste of medical resources and strengthen the self-management of chronic diseases.The improvement of electronic health literacy is of great value to the healthy development of citizens’ health literacy and healthy behavior.In view of the late start and slow development in the field of electronic health literacy in China,by combing the theoretical and practical research experience of electronic health literacy outside the region and combining with the COVID-19,this paper put forward new thinking on electronic health literacy in China,in order to provide useful reference for improving electronic health literacy of Chinese citizens,realizing self-care,self-management and disease prevention.
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Objective:To explore the clinical characteristics and risk factors of concurrent infection in adult patients with hypopituitarism (HP).Methods:Clinical data of patients diagnosed with HP in Fuyang People′s Hospital from October 2016 to August 2020 were collected. Patients were divided into infected group and non-infected group according to whether they were co-infected, and the differences in clinical characteristics between the two groups were compared. The risk factors of infection in HP patients were analyzed by binary logistic regression.Results:The top three clinical manifestations of 64 HP patients were decreased libido; lack of energy, fear of cold, and poor appetite; hyponatremia. Etiological analysis of 64 HP patients: 23 cases of Sheehan′s syndrome, 14 cases of postoperative brain tumors (pituitary adenoma, craniopharyngioma, meningioma), 8 cases of idiopathic, 7 cases of pituitary adenoma, 8 cases of pituitary volume and morphology changes, and 4 cases of empty sella turcica. 40.32%(25/62) of patients with adrenal axis dysfunction received glucocorticoid replacement therapy, with 80%(20/25) receiving prednisone and 20%(5/25) receiving hydrocortisone. The replacement dose was 2.5-25(6.77±3.90)mg of prednisone equivalent dose. 37.70%(23/61) of patients with low thyroid axis function received thyroid hormone replacement therapy, of which 52.17%(12/23) free thyroxine (FT4) levels were still lower than the lower normal limit. 20%(2/10) of males ≤60 years old and 5.56%(1/18) of females≤50 years old received hormone replacement therapy for patients with hypogonadism of the gonadal axis. Among 64 HP patients included, 29 were co-infected (infected group) and 35 were not co-infected (non infected group). There was no significant difference between the infected group and the non infected group in gender, etiology, number of pituitary axis involved, glucocorticoid replacement therapy dose, thyroid hormone replacement therapy dose, and sex hormone replacement therapy rate (all P>0.05). Compared with the non infected group, the infected group was older, had a longer course of disease, lower diastolic blood pressure (DBP) and albumin levels, with statistically significant difference (all P<0.05), while the other indicators showed no statistically significant difference (all P>0.05). The results of binary logistic regression analysis showed that age, course of disease, occupation, and albumin level were the influencing factors of HP complicated infection (all P<0.05). Conclusions:The most common cause of pituitary dysfunction in adults is Sheehan′s syndrome; Adult HP patients who are older, have a longer course of disease, work as farmers, and have hypoalbuminemia are more likely to develop concurrent infections.
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Objective:To compare the clinical effectiveness of propeller flap and vascular chain flap based on dorsal cutaneous branch of proper palmar digital artery for repair of wounds of fingertip or finger-pulp.Methods:From April 2018 to May 2021, a total of 55 patients (55 fingers) with wounds of fingertip or finger-pulp in the 2nd-5th fingers were treated in emergency surgery in the Department of Hand Surgery, the Second Hospital of Tangshan. The patients were randomly divided into 2 groups by the method of drawing lots. The wounds of 29 patients (29 fingers) were repaired by propeller flaps based on dorsal cutaneous branch of proper palmar digital artery (propeller group) and that of 26 patients(26 fingers) were treated by vascular chain flaps based on dorsal cutaneous branch of proper palmar digital artery(vascular chain group). Survival of the flaps and the skin grafts at donor sites were observed between the 2 groups. The operation and follow-up time in both groups were recorded. Postoperative follow-up included outpatient clinic visits, telephone reviews and WeChat video-clips. At final follow-up, the static TPD of the flaps, patient satisfaction with the appearance of flaps and donor sites and the Range of motion(ROM) of the injured fingers were recorded. The measurement and count data of both groups were compared by independent sample t-test, χ2 tests or Fisher's exact test, respectively. P<0.05 was considered a statistically significant. Results:All the flaps and skin grafts survived primarily in both groups. The operation time in propeller group was 57.55 minutes±4.35 minutes. It was less than what in the vascular chain group (61.12 minutes±4.58 minutes) and with statistically significant difference( P<0.05). The follow-up period was 14.55 months±2.89 months in propeller group and 15.15 months±3.78 months in the vascular chain group. There was no significant difference between the 2 groups( P>0.05). At final follow-up, the static TPD and patient satisfaction with the appearance of flaps in propeller group were 6.55 mm±1.24 mm and 4.59±0.50, which were better than 7.46 mm±1.27 mm and 4.31±0.47 in the vascular chain group with a statistically significant difference( P<0.05). The patient satisfaction with the appearance of donor sites and ROM of the injured digital joints in propeller group were 4.45±0.57 and 190.86°±8.56°, while what in the vascular chain group were 4.35±0.56 and 185.96°±10.58°. There was no significant difference between the 2 groups( P>0.05). Conclusion:The propeller flap and vascular chain flap are both based on dorsal cutaneous branch of proper palmar digital artery and are both suitable for repair of wounds of fingertip or finger-pulp. Compared with the vascular chain flap, the propeller flap has the advantages in shorter operation time, better flap sensation and appearance.
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ObjectiveTo study the mechanism of matrine in the treatment of inflammatory bowel disease （IBD） based on the zebrafish model and network pharmacology. MethodThe IBD model of zebrafish was established using 2，4，6-trinitro-benzenesulfonicacid （TNBS）， and the intestinal phagocytic function， goblet cell secretion， and neutrophil aggregation were evaluated using neutral red staining， alcian blue staining， and neutrophil number changes. Changes in tumor necrosis factor （TNF）-α and cholecystokinin （CCK） content in zebrafish were determined by using relevant reagent kits. Network pharmacology and molecular docking techniques were used to predict the potential mechanism of matrine in the treatment of IBD. Gene expression of relevant targets was verified through Real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the model group， the matrine administration group can increase the neutral red staining area in a dose-dependent manner and improve intestinal phagocytic function（P<0.05，P<0.01）. It can reduce the staining area of alcian blue and affect the secretion of intestinal goblet cells（P<0.01）. It can reduce the number of neutrophil granulocytes， relieve its aggregation， significantly reduce TNF-α content（P<0.01）， and increase the CCK content. Network pharmacology analysis identifies 28 potential targets for matrine in the treatment of IBD. The top five targets by protein-protein interaction （PPI） network analysis are CHRNA7， DRD1， CHRNA4， SLC6A3， and GRM5. The Kyoto encyclopedia of genes and genomes （KEGG） results show that the treatment of IBD with matrine may be related to neuroactive ligand-receptor interaction， cholinergic synapse， and neutrophil extracellular trap formation. Real-time PCR results show that matrine can affect the expression level of related target genes. Conclusionmatrine has a certain therapeutic effect on IBD and can affect the inflammatory response of IBD. Its therapeutic effect may be related to neuroactive ligand-receptor interaction and other pathways.
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OBJECTIVE@#To observe the intervention effect of damage control orthopaedic(DCO) strategy on fat embolism syndrome(FES) associated with long shaft fracture of lower limbs.@*METHODS@#Retrospective analysis was made on the clinical data of 163 patients with FES associated with lower limb long shaft fractures admitted from January 2015 to May 2021. They were divided into two groups based on the time point of implementing DCO strategy in January 2018. Total of 92 patients were admitted from January 2015 to December 2017 as the control group, and other 71 patients were admitted from January 2018 to May 2021 as the intervention group. The hospital mortality, arterial oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2) and oxygenation index (OI), hemoglobin (Hb), platelet count(PLT), Harris score of hip joint, HSS score of knee joint, AOFAS score of ankle joint, clinical efficacy and complications were observed and compared between two groups.@*RESULTS@#Total of 163 patients were followed up for 12 to 18 months with an average of (16.91±1.22) months. The in-hospital mortality rate in the intervention group was 2.82% (2/71), and that in the control group was 16.30% (15/92), the difference between two groups was statistically significant(χ2=6.455, P<0.05). After the intervention, SaO2, PaO2 and OI in two groups were higher than those before the intervention(P<0.05), and after the intervention, SaO2, PaO2 and OI in two groups were statistically significant(P<0.05). Hb and PLT in two groups after intervention were higher than those before intervention (P<0.001), and there was statistically significant difference in Hb and PLT between two groups after intervention (P<0.05). The Harris score of hip joint, HSS score of knee joint and AOFAS score of ankle joint in both groups after 3 months of treatment were better than those before treatment (P<0.05). The total clinical effective rate of the intervention group was higher than that of the control group(χ2=4.194, P<0.05). The total incidence of complications in the intervention group was lower than that in the control group(χ2=4.747, P<0.05).@*CONCLUSION@#DCO strategy is helpful to reduce the in-hospital mortality of patients with FES associated with long shaft fracture of lower extremities, eliminate FES symptoms and stabilize vital signs, gain time advantage for phase Ⅱ definitive surgery, and has significant clinical intervention effect, which is worth popularizing.
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Humans , Orthopedics , Retrospective Studies , Fractures, Bone , Treatment Outcome , Lower Extremity , Embolism, Fat/therapyالملخص
Mycoplasma pneumoniae pneumonia is an important component of community-acquired pneumonia, which can cause severe extrapulmonary complications of digestive, cardiovascular, blood, urinary and other systems.Accurate and effective biomarkers are significant for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia.Recent studies have shown that new biomarkers such as IL-35, IL-17, neutrophil to lymphocyte ratio(NLR) and S100 protein are involved in the development of Mycoplasma pneumoniae pneumonia.In order to provide reference for the clinical diagnosis and treatment of Mycoplasma pneumoniae pneumonia, this paper reviews the progress of new biomarkers in Mycoplasma pneumoniae pneumonia.
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Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of childbearing age, which seriously affects women's reproductive health. In recent years, more and more studies have found that serum anti-Müllerian hormone (AMH) has certain significance in the diagnosis and treatment evaluation of PCOS. In addition, with the improvement of detection methods, more attention has been paid to the significance of female androgens and AMH in the evaluation of PCOS. This article reviews the recent research progress of serum AMH and androgens in the evaluation of PCOS.
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Female , Humans , Polycystic Ovary Syndrome/diagnosis , Androgens , Anti-Mullerian Hormoneالملخص
Objective:To investigate the hemodynamic characteristics of the lenticulostriate artery (LSA) in cerebral small vessel disease (CSVD) patients with recent small subcortical infarcts (RSSI) using 7.0 T two-dimensional phase-contrast MRI (2D PC-MRI).Methods:A total of 16 CSVD patients with deep RSSI and 18 age-and sex-matched healthy controls (HC group) meeting the inclusion criteria were prospectively recruited from July 2021 to June 2022 at Beijing Tiantan Hospital, Capital Medical University. All participants underwent 7.0 T 2D PC-MRI with imaging plane localized at the level of the basal ganglia. A self-developed software (Flow analyze V1.0) was used to analyze the hemodynamic status of bilateral LSAs. The hemodynamic parameters including the maximum velocity (V max), average velocity (V avg), pulsatility index (PI), and resistance index (RI) of LSAs were calculated and recorded. As for the CSVD cases, the symptomatic side was defined as the ipsilateral side to the RSSI (CSVD symptomatic-side group), and the contralateral side was defined as the asymptomatic side (CSVD asymptomatic-side group). ANOVA or Mann-Whitney U test was used to compare hemodynamic parameters among the three groups. Results:Significant differences in V max, V avg and PI were observed among the CSVD symptomatic-side group, CSVD asymptomatic-side group, and HC group ( F=5.22, P=0.006; F=3.47, P=0.033; F=4.37, P=0.014). Specifically, CSVD symptomatic-side group showed significantly reduced V max ( P=0.004) and V avg ( P=0.017), and increased PI ( P=0.007) compared to the HC group. The CSVD asymptomatic-side group showed decreased V max ( P=0.026) and increased PI ( P=0.039) compared to the HC group. Conclusions:Hemodynamic assessment based on 7.0 T 2D PC-MRI reveal that CSVD patients with RSSI decrease blood flow velocity and increase arterial PI of LSAs. These findings suggest potential corresponding hemodynamic mechanisms associated with CSVD with RSSI lesions.
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Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the β-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC50 values of 12.97-65.01 μmol·L-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H2O2 and MPP+.
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Abietanes/pharmacology , Antimalarials , Hydrogen Peroxide , Biological Assay , Plant Components, Aerialالملخص
This study mainly explores the role of myeloid differentiation primary response protein 88 (MyD88) in tumorigenesis and development, to identify active compounds targeting MyD88. CRISPR/Cas9 system and xenograft tumor model were used to detect the effect of MyD88 deletion on tumor growth, and the experimental animal ethics review number was PZSHUTCM200828006. Microscale thermophoresis technology (MST) was used to identify compounds directly bind to MyD88 and further detect the impact of candidate small molecules on cell proliferation. Results showed that depletion of MyD88 significantly inhibited xenograft tumor growth of colon cancer, pancreatic cancer and skin cancer and the activity of NF-κB signaling pathway. MST showed that nordihydroguaiaretic acid (NDGA) bound to MyD88, with the binding dissociation constant Kd of 14.61 µmol·L-1. NDGA inhibited NF-κB reporting system activation and phosphorylation of p65, the key factor in NF-κB signal pathway. In addition, the results of colony formation assay showed that NDGA suppressed the proliferation of tumor cells. The above results show that, MyD88 is a potential therapeutic target for colon cancer, pancreatic cancer and skin cancer, NDGA directly binds to MyD88 and inhibits the activity of NF-κB signaling pathway, as well as inhibits the proliferation of pancreatic cancer, skin cancer and colon cancer cells.
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Eleven compounds were isolated from the 95% ethanol extract of the stems of Dendrobium officinale after water extraction by various modern chromatographic techniques, such as silica gel column chromatography(CC), octadecyl-silica(ODS) CC, Sephadex LH-20 CC, preparative thin layer chromatography(PTLC) and preparative high performance liquid chromatography(PHPLC). According to spectroscopic analyses(MS, 1D-NMR, 2D-NMR) combined with optical rotation data and calculated electronic circular dichroism(ECD), their structures were identified as dendrocandin Y(1), 4,4'-dihydroxybibenzyl(2), 3-hydroxy-4',5-dimethoxybibenzyl(3), 3,3'-dihydroxy-5-methoxybibenzyl(4), 3-hydroxy-3',4',5-trimethoxybibenzyl(5), crepidatin(6), alternariol(7), 4-hydroxy-3-methoxypropiophenone(8), 3-hydroxy-4,5-dimethoxypropiophenone(9), auriculatum A(10) and hyperalcohol(11). Among them, compound 1 was a new bibenzyl derivative; compounds 2 and 7-11 have not been previously reported from Dendrobium plants; compound 6 was reported from D.officinale for the first time. Compounds 3-6 exhibited potent antioxidant activity with IC_(50) values of 3.11-9.05 μmol·L~(-1) in ABTS radical scavenging assay. Compound 4 showed significant inhibitory effect on α-glucosidase, with IC_(50) value of 17.42 μmol·L~(-1), indicating that it boasted hypoglycemic activity.
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Dendrobium , Biological Assay , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Bibenzylsالملخص
Emerging evidence suggests that intron-detaining transcripts (IDTs) are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and stress. However, the underlying mechanisms of detained intron (DI) splicing are still largely unknown. Here, we suggest that post-transcriptional DI splicing is paused at the Bact state, an active spliceosome but not catalytically primed, which depends on Smad Nuclear Interacting Protein 1 (SNIP1) and RNPS1 (a serine-rich RNA binding protein) interaction. RNPS1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome pausing. Haploinsufficiency of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant U2 snRNA, a basal spliceosomal component. Snip1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes neurodegeneration. Therefore, we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing, and that its misregulation contributes to neurodegeneration.
الموضوعات
Spliceosomes/metabolism , Introns/genetics , RNA Splicing , RNA, Messenger/genetics , Cell Nucleus/metabolismالملخص
With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
الموضوعات
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutation , Tumor Microenvironment/geneticsالملخص
OBJECTIVE@#To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs.@*METHODS@#Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively.@*RESULTS@#JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05).@*CONCLUSION@#JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.