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OBJECTIVE To analyze the effects of tigecycline on coagulation function in patients with severe renal insufficiency， and to provide a reference for safe clinical drug use. METHODS Retrospective analysis was performed for the clinical data of patients with severe renal dysfunction complicated with infection receiving tigecycline admitted to nephrology department of our hospital from January 2021 to October 2022. The levels of prothrombin time （PT）， activated partial thromboplastin time （APTT）， international normalized ratio （INR）， platelet （PLT） and fibrinogen （FIB） were compared 3 days before medication， with 1-5， 6-10， 11-15 and 16-20 days after medication， 5 days after withdrawal and/or after symptomatic treatment. RESULTS Finally， 14 patients were included， and 9 patients developed coagulopathy， with an incidence of 64.29%. Compared with 3 days after medication， the levels of FIB at 6-10 and 11-15 days after medication， and PLT at 1-5 ， 6-10 and 11- 15 days after medication were decreased significantly， while the levels of PT at 1-5 and 6-10 days after medication， APTT at 1-5， 6-10 and 11-15 days after medication were significantly prolonged， and INR increased significantly at 1-5 and 6-10 days after medication （P＜0.05）. Compared with 3 days before medication， there were no statistically significant changes in FIB， PT， INR， APTT and PLT at 16-20 days after medication and 5 days after withdrawal and/or symptomatic treatment（P＞0.05）. CONCLUSIONS Patients with severe renal insufficiency should be cautious with tigecycline， which can lead to prolonged PT and APTT， increased INR， and decreased PLT and FIB. If medication time is over 14 days， dynamic monitoring of coagulation function indicators is recommended to reduce the risk of adverse reactions.
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Objective:To explore the effect of facial filling with autologous fat particles on the facial contour remodeling of patients with facial rejuvenation needs and its influence on the facial skin indicators of patients.Methods:From February 2019 to February 2020, 225 female patients, aged 25-52 years, with an average age of (42.5±5.2) years, received facial rejuvenation treatment in Zhengzhou Mylai Medical Beauty Hospital. They were divided into observation group (PPDO serrated line lifting combined with autologous fat granule filling), control group 1 (PPDO serrated line lifting alone) and control group 2 (simple autologous fat granule filling alone), with 75 cases in each group. After 6 months of follow-up, facial skin indexes, contour remodeling effect and adverse reactions after treatment were compared among the three groups.Results:At the last follow-up, the facial skin elasticity and moisture scores of the observation group (63.45±10.11, 56.71±9.38) were significantly higher than those of control group 1 (51.11±9.23, 43.69±7.65) and control group 2 (52.35±9.51, 42.47±7.53). The facial spots and lipid scores (41.31±7.24, 42.18±7.46) were significantly lower than those in control group 1 (48.67±9.15, 53.49±9.45) and control group 2 (48.26±9.21, 53.55±9.53) ( F=37.39, 68.98, 17.42, 40.91, P<0.001). At the last follow-up, the lower surface width of observation group (11.35±0.63) was lower than that of control group 1 (12.21±0.85) and control group 2 (12.38±0.65). The contour ratio of the lower part of the face (0.63±0.17) was higher than that of control group 1 (0.56±0.15) and control group 2 (0.57±0.15) ( F=44.49, 4.36, P<0.05). The change level of the ratio of lower facial area (0.12±0.03) was higher than that of control group 1 (0.07±0.02) and control group 2 (0.08±0.04) ( F=54.31, P<0.001). Conclusions:For patients who need facial rejuvenation treatment, the use of autologous fat granule facial filling therapy has good clinical effects, which can significantly improve the patient's facial skin elasticity, moisture, spots, and oil. The patient's facial contour reshaping effect is better, and the aesthetic score is significantly improved, and does not increase the risk of adverse reactions.
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ObjectiveAutonomic dysfunction is a common and serious complication in patients with early chronic kidney disease （CKD）. Sweat gland dysfunction is an initial sign of autonomic dysfunction. Electrochemical skin conductance （ESC） measurement by reverse iontophoresis and chronoamperometry to assess sweat gland function may detect patients with mild renal insufficiency in healthy population for early intervention and treatment to delay further deterioration of renal function. MethodsAn EZSCAN score （0~100） was calculated using a proprietary algorithm based on the chronoamperometry analysis. A total of 6 661 subjects who received physical examination from the physical examination center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to October 2020 were enrolled， including 2 075 （31.15%） subjects with reduced renal function （eGFR < 90 mL·min-1·1.73 m-2） as the case group and 4 586 （68.85%） subjects with normal renal function （90 mL·min-1·1.73 m-2≤ eGFR ≤120 mL·min-1·1.73 m-2） as the control group. Lasso regression was used to screen covariates， and the relationship between the risk score and eGFR was analyzed by loess curve and logistic regression. ResultsAfter multivariate adjustment， the risk score was correlated with the risk of eGFR decline. Compared with the group with the lowest risk value （Q1<24）， the OR（95%CI ）of Q2 （25-27）， Q3 （28-47）， and Q4 （48-75） were 1.85 （1.55， 2.21）， 2.53 （2.13， 3.00）， 2.49 （2.13， 2.93）， respectively. The maximum area under the ROC curve is 0.75（0.74，0.76）， the sensitivity is 73.98%， the specificity is 63%， the positive predictive value is 47.49%， the negative predictive value is 84.25%， and the Youden index is 0.369 72， the optimal cutoff value is 25. ConclusionsEZSCAN could be a useful screening tool to identify healthy individuals at increased risk of renal function decline， and the one with an EZSCAN score of more than 25% should undergo diagnostic laboratory testing.
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Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.
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Animals , Humans , Alzheimer Disease , Amyloid beta-Protein Precursor , Animals, Genetically Modified , Sirtuin 1 , SirtuinsABSTRACT
Objective:To compare the clinical value of visual analogue scale （VAS）, Lebel scale and total nasal symptom scores （TNSS） in evaluating nasal allergen provocation test （NAPT）. Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance（NAR） was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS（P>0.05）. The VAS differed significantly from Lebel and TNSS（P<0.05）. The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.
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Animals , Humans , Allergens , Nasal Provocation Tests/methods , Rhinitis, Allergic/diagnosis , Nose , PyroglyphidaeABSTRACT
OBJECTIVE@#To investigate the survival of patients with cardiac arrest and cardiopulmonary resuscitation (CA-CPR), and to analyze the factors influencing survival at 30 days after restoration of spontaneous circulation (ROSC).@*METHODS@#A retrospective cohort study was conducted. Clinical data of 538 patients with CA-CPR admitted to the People's Hospital of Ningxia Hui Autonomous Region from January 2013 to September 2020 were enrolled. The gender, age, underlying disease, cause of CA, type of CA, initial rhythm, presence or absence of endotracheal intubation, defibrillation, use of epinephrine, and 30-day survival rate of patients were collected. The etiology of CA and 30-day survival rate among patients with different ages were compared, as well as the clinical data between patients who survived and died at 30 days after ROSC were also compared. Multivariate Logistic regression was used to analyze the relevant factors affecting the 30-day survival rate of patients.@*RESULTS@#Among 538 patients with CA-CPR, 67 patients with incomplete information were excluded, and 471 patients were enrolled. Among 471 patients, 299 were males and 172 were females. Aged from 0 to 96 years old, 23 patients (4.9%) were < 18 years old, 205 patients (43.5%) were 18 to 64 years old, and 243 patients (51.6%) were ≥ 65 years old. 302 cases (64.1%) achieved ROSC, and 46 patients (9.8%) survived for more than 30 days. The 30-day survival rate of patients aged < 18 years old, 18-64 years old and ≥ 65 years old was 8.7% (2/23), 12.7% (26/205) and 7.4% (18/243), respectively. The main causes of CA in patients younger than 18 years were severe pneumonia (13.1%, 3/23), respiratory failure (13.1%, 3/23), and trauma (13.1%, 3/23). The main causes were acute myocardial infarction (AMI; 24.9%, 51/205), respiratory failure (9.8%, 20/205), and hypoxic brain injury (9.8%, 20/205) in patients aged 18-64 years old, and AMI (24.3%, 59/243) and respiratory failure (13.6%, 33/243) in patients aged ≥ 65 years old. Univariate analysis results revealed that the 30-day survival rate of patients with CA-CPR may be related to the the cause of CA was AMI, initial rhythm was ventricular tachycardia/ventricular fibrillation, endotracheal intubation and epinephrine. Multivariate Logistic regression analysis results showed that CA was caused by AMI [odds ratio (OR) = 0.395, 95% confidence interval (95%CI) was 0.194-0.808, P = 0.011] and endotracheal intubation (OR = 0.423, 95%CI was 0.204-0.877, P = 0.021) was a protective factor for 30 days of survival after ROSC in patients with CA-CPR.@*CONCLUSIONS@#The 30-day survival rate of CA-CPR patients was 9.8%. The 30-day survival rate of CA-CPR patients with AMI after ROSC is higher than that of patients with other CA causes, and early endotracheal intubation can improve the prognosis of patients.
Subject(s)
Female , Male , Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Survival Rate , Heart Arrest , Hospitals , Epinephrine , Ventricular FibrillationABSTRACT
UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.
Subject(s)
Animals , Tumor Necrosis Factor-alpha/genetics , Network Pharmacology , Capsules , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Reproducibility of Results , Tandem Mass SpectrometryABSTRACT
Introducing the concept of integration into medical curriculum reform is an important measure to promote the development of medical education. This research discusses the advantages and disadvantages of various teaching models by comparing the models of organ system integration courses at home and abroad, combining with the review of the development of integrated courses in Shanghai Jiao Tong University Medical College and the analysis of questionnaires from teachers and students, proposes a curriculum reform plan optimized with the concept of "Medical discipline in the new era", and puts forward targeted suggestions from the aspects of curriculum system setting, teacher security, etc., thus providing research support for the future development of organ system integration curriculum.
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Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during 2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.
Subject(s)
Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Stomach Neoplasms/therapyABSTRACT
Objectives: To analyze the current development status of gastric cancer (GC) randomized controlled trials (RCT) between 2000 and 2019, and to review the basic characteristics of published RCT. Methods: ClinicalTrials.gov was searched for phase 3 or 4 RCT conducted between January 2000 and December 2019 with the keyword "gastric cancer", and the development trend of different types of RCT during different time periods was described. Basic features of registered RCT such as intervention, study area, single-center or multicenter, sample size, and funding were presented. PubMed and Scopus databases were searched to judge the publication status of studies completed until June 2016. The adequacy of the report was estimated by the Consolidated Standards of Reporting Trials (CONSORT) checklist. Design flaws were evaluated by Cochrane tool and/or whether a systematic literature review was cited. The data was analyzed by χ2 test or Fisher exact test. Results: There were 262 RCT including in the present study. The number of GC-RCT registered on ClinicalTrials.gov had been on the rise from 1 case in 2000 to 30 cases in 2015. The proportion of RCT associated with targeted therapy or immunotherapy increased from 0 during 2000-2004 to 37.1% (36/97) during2015-2019. The RCT registered in Asia was 191 cases, while that in non-Asia region was 71 cases. The proportion of multi-center RCT from non-Asia was higher than that from Asia (70.4% (50/71) vs. 50.3% (96/191), χ²=8.527, P=0.003). The proportion of RCT published was 59.1% (81/137). Among the published RCT, 65 (80.2%) studies were reported adequately, but 63 (77.8%) studies had avoidable design limitations. Conclusions: Targeted therapy and immunotherapy have become research hotspots in the treatment of GC. At present, there are inadequate multicenter RCT in Asia, and the publication rate of RCT is low. A considerable number of published RCT are reported inadequately and have avoidable design flaws.
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Objective:To explore the teaching effect of organ system based integrated curriculum in the undergraduates of clinical medicine.Methods:A retrospective cohort study was conducted among 284 undergraduates majoring in clinical medicine from Batch 2011 to Batch 2016 in Shanghai Jiao Tong University School of Medicine. The observation group were 147 undergraduates from Batch 2014 to Batch 2016, taking organ system based integrated curriculum. The control group included 137 undergraduates from Batch 2011 to Batch 2013, taking the traditional mode of subject-centered curriculum. SPSS 21.0 was performed for independent sample t test, and questionnaires were issued to investigate students' evaluation of the teaching of organ system based integrated curriculum. Results:The examination scores of internal medicine problem based learning test, surgical theory test and surgical operation test were better in observation group than in control group [(86.34±2.74) vs. (85.51±3.36); (79.69±8.41) vs. (77.18±6.92); (81.43±10.72) vs. (76.78±11.29), P<0.05]. Obstetrics and pediatric theory test scores were lower in observation group than in control group ( P<0.05). There was no significant difference in test scores of internal medicine between the two groups ( P=0.935). The satisfaction rate of organ system based integrated curriculum in the observation group was 83.75%. Conclusion:The teaching of organ system based integrated curriculum can improve students' comprehensive abilities, and has certain requirements for students' learning autonomy.
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Exosomes are some small membrane-bound vesicles released by cells into extracellular spaces.They carry a variety of bioactive molecules, such as proteins, RNA and lipids for material exchange and communication in cells.Exosomes have been recognized as an important pathway in the nervous system in both normal and disease settings.Meanwhile, exosomes can pass through the blood-brain barrier.Therefore, exosomes provide a new strategy for the diagnosis and treatment of central nervous system diseases.In this review, general characteristics of exosomes, pathological and physiological functions of exosomes in central nervous systems and the progress of exosomes applied to the diagnosis and treatment of central nervous system diseases are discussed.
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Type Ⅰ cardiorenal syndrome is a common disease syndrome in clinic.Cardiac surgery and acute heart failure caused by various causes are common causes of type Ⅰ cardiorenal syndrome.More recognized pathogenesis includes overactivation of sympathetic nervous system and renin-angiotensin-aldosterone system, renal ischemia-reperfusion, inflammatory response and oxidative stress.In the current research, most of the renal injuries caused by type Ⅰ cardiorenal syndrome are related to renal tubular epithelial injury, but there are few reports on glomerular injury.With the continuous in-depth study, more and more people realize that glomerular injury plays an important role in the occurrence and progress of acute renal injury.This paper mainly reviews the research progress and future research direction of glomerular injury in type Ⅰ cardiorenal syndrome.
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Objective: To explore the mechanism of drug resistance in acute lymphoblastic leukemia and the anti-tumor effect of combination therapy of dehydroabietic acid and vincristine against acute lymphoblastic leukemia cells. Methods: Acute lymphoblastic leukemia cells REH and CCRF- CEM were employed to detect the anti-tumor effect of vincristine and doxorubicin on proliferation and apoptosis using EdU assay, human active caspase-3 Quantikine ELISA kit, and flow cytometry. Vincristine-resistant REH cells (REH-R), survivin knockdown and overexpressing REH cells were established to verify the role of survivin in drug resistance. Additionally, in vitro and in vivo assays were performed to determine the effect of dehydroabietic acid on the cytotoxicity of vincristine. Results: Vincristine and doxorubicin markedly suppressed proliferation and induced apoptosis of REH and CCRF-CEM cells. Survivin expression was upregulated in REH-R cells compared with REH cells. Knockdown of survivin expression obviously restored the sensitivity of REH-R cells to vincristine. Akt phosphorylation was also increased in REH-R cells compared to REH cells. In addition, LY294002, a PI3k/Akt pathway blocker, inhibited survivin expression and enhanced cytotoxicity of vincristine to REH-R cells. Dehydroabietic acid effectively reduced survivin expression in REH-R cells, thereby enhancing the therapeutic effect of vincristine on drug-resistant cells. Survivin overexpression markedly reduced the effect of dehydroabietic acid on enhancing the anti-proliferation and inducing apoptosis effect of vincristine. Moreover, the combination of dehydroabietic acid with vincristine significantly extended the survival rate in a mouse xenograft model of acute lymphoblastic leukemia, compared with vincristine treatment alone. Conclusions: Dehydroabietic acid may be used as a potential candidate for the treatment of acute lymphoblastic leukemia in combination with vincristine.
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ObjectiveTo reveal the effect of Wenxin prescription on mitochondrial energy metabolism and silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）/recombinant estrogen-related receptor α （ERRα） signaling pathway in rats with myocardial ischemia-reperfusion injury. MethodTotally 90 male Wistar rats of SPF grade were randomly assigned into a sham operation group， a model group， and low-， medium-， and high-dose Wenxin prescription groups， with 18 rats in each group. The rats in low-， medium-， and high-dose Wenxin prescription groups were administrated with 0.99， 1.98， and 3.96 g·kg-1 granules by gavage， respectively， and those in the sham operation group and model group with the same amount of normal saline. Twenty-one days after pre-administration， the rat model of myocardial ischemia-reperfusion injury was established by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 2 h， and the rats in the sham operation group were only threaded without ligation. Myocardial infarction area was observed through 2，3，5-triphenyl-2h-tetrazolium chloride （TTC） staining， and the myocardial histopathology through hematoxylin-eosin （HE） staining. The levels of creatine kinase-MB （CK-MB） and lactate dehydrogenase （LDH） in serum， cytochrome C oxidase （CCO） and succinate dehydrogenase （SDH） in mitochondrion， and ATP in myocardial tissue were detected according to kit instructions. The mRNA and protein levels of SIRT1， PGC-1α， ERRα， and mitochondrial transcription factor A （TFAM） in myocardial tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham operation group， the model group showed broken and disordered myocardial fibers， cytoplasmic edema， and pyknosis and deviation of nuclei. Moreover， the modeling increased the levels of CK-MB and LDH （P<0.05， P<0.01）， lowered the levels of ATP， CCO， and SDH （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of SIRT1， PGC-1α， ERRα， and TFAM in myocardial tissue （P<0.05， P<0.01）. Compared with the model group， Wenxin prescription reduced the myocardial infarction area （especially in the high-dose group， P<0.01）， restored the pathological changes， lowered the levels of CK-MB and LDH （P<0.05， P<0.01）， increased the levels of ATP， CCO， and SDH （especially in the high-dose group， P<0.01）， and up-regulated the mRNA and protein levels of SIRT1， PGC-1α， ERRα， and TFAM in myocardial tissue （P<0.05， P<0.01）. ConclusionWenxin prescription can protect rats from myocardial ischemia-reperfusion injury by regulating myocardial mitochondrial energy metabolism via the SIRT1/PGC-1α/ERRα signaling pathway.
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LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Subject(s)
Animals , Mice , Cell Differentiation , Embryo, Mammalian/metabolism , Embryonic Development , Pluripotent Stem Cells/metabolism , RNA, Messenger/genetics , RNA, Ribosomal , RNA-Binding Proteins/metabolism , Transcription Factors/metabolism , Zygote/metabolismABSTRACT
OBJECTIVE@#To compare the clinical effect of microsurgery and endovascular embolization in the treatment of spinal dural arteriovenous fistula (SDAVF) by meta-analysis.@*METHODS@#A systematic review was performed to retrieve all relevant literature about surgical treatment or endovascular embolization of SDAVF up to December 2019 through PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials Results, CNKI, Wanfang Data, and SinoMed. The Chinese and English key words included: "SDAVF", "spinal dural arteriovenous fistula", "spinal AVM", "spinal vascular malformation and treatment". The included studies were evaluated using the Newcastle-Ottawa scale. The early failure rate, long-term recurrence, neurological recovery, and complications were evaluated and the clinical effects of the two methods in the treatment of SDAVF were compared by using RevMan 5.3 software. And a further subgroup analysis of the therapeutic effect of endovascular embolization with different embolic agents was conducted.@*RESULTS@#A total of 46 studies involving 1 958 cases of SDAVF were included, in which 935 cases were treated by microsurgery and 1 023 cases were treated by endovascular embolization. The funnel plot demonstrated that there was no publication bias. The results of meta-analysis showed that the incidence of early surgical failure was lower than that of endovascular embolization (OR=0.20, 95%CI: 0.13-0.30, P < 0.05), and the long-term recurrence was also lower than that of endovascular embolization (OR=0.36, 95%CI: 0.22-0.58, P < 0.05). The improvement of neurological function in the surgical patients is significantly higher than that in the patients treated with endovascular embolization (OR=2.86, 95%CI: 1.36-5.99, P < 0.05). There was no significant difference in the occurrence of complications in these two groups (OR=1.52, 95%CI: 0.88-2.64, P=0.14). In the cases of endovascular embolization, the risk of treatment failure or recurrence was higher with Onyx glue than with n-butyl 2-cyanoacrylate (NBCA), and the difference was statistically significant (OR=4.70, 95%CI: 1.55-14.28, P < 0.05).@*CONCLUSION@#Although the treatment of dural arteriovenous fistulas by intravascular embolization has been widely used, the clinical effect of microsurgery is still better than that of endovascular embolization. Large scale and high-quality randomized controlled trials are required to validate the efficacy and safety of endovascular treatment in SDAVF patients.
Subject(s)
Humans , Central Nervous System Vascular Malformations/surgery , Embolization, Therapeutic/methods , Enbucrilate/therapeutic use , Endovascular Procedures/methods , Microsurgery/methods , Retrospective Studies , Treatment OutcomeABSTRACT
Objective:To investigate the effect of alendronate treatment and assess the value of bone turnover markers (BTMs) in predicting the changes of bone mineral densities (BMDs) in postmenopausal women with osteoporosis.Methods:In this retrospective study, 409 postmenopausal women with osteoporosis aged (64.86±7.21) years in the Department of Osteoporosis and Bone Disease, Shanghai Sixth People′s Hospital were enrolled from 2012 to 2020. BMDs at lumbar spine 1-4, femoral neck, and total hip, serum β cross-linked C-telopeptide of type 1 collagen (β-CTX), and osteocalcin (OC) were measured before and after treatment.Results:After alendronate treatment for 1 year, BMDs at lumbar spine 1-4, femoral neck and total hip increased 4.84%, 2.13%, and 2.89%, respectively ( P<0.05). At 6 months and 1 year on treatment, β-CTX and OC levels decreased by 77.7%, 42.3% and 78.2%, 49.5%, respectively ( P<0.05). Linear regression analysis showed that for every 10% decrease in the change of β-CTX at 6 months after alendronate treatment, the rate changes in BMDs at the lumbar spine 1-4, femoral neck, and total hip decreased by 0.417%, 0.127%, and 0.213% at 1 year after alendronate treatment; for every 10% decrease in OC, the change rates in BMDs at the lumbar spine 1-4, femoral neck, and total hip decreased by 0.582%, 0.258%, and 0.375%. Conclusions:Alendronate significantly increases BMDs and decreases BTMs levels in elderly women with osteoporosis. BTMs have a predictive value for the changes of BMDs, allowing early monitoring for the effect of alendronate treatment.
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Objective:To determine the blood level of homocysteine （Hcy） and its influencing factors among Shanghai rural residents with high risk of stroke and to verify if hyperhomocysteinemia （HHcy） is a main biomarker of stroke. Methods:With a clustered random sampling method， questionnaire survey and physical examination were conducted among 4 073 rural residents， aged 55 years and above， in Luojing community， Shanghai， in 2018. A total of 470 residents were at high-risk for stroke based on screening of plasma Hcy and other blood indicators. Multivariate logistic regression method was performed for data analysis. Results:The overall level of Hcy was （18.92±6.37）μmol/L， with （20.40±5.89）μmol/L for men and （17.87±2.12）μmol/L for women （t=5.431，P<0.001）. HHcy was detected in 78.94%（371/470） of the participants， in which 85.77%（235/274） were men and 69.39%（136/196） were women （χ2=12.400，P=0.001）. In the high-risk male group， subjects with smoking history， overweight or obesity， exercise frequency <1 h/d， and hypertension has a higher detection rate of HHcy than those without smoking history， normal body mass index， exercise frequency ≥1 h/d and without hypertension （χ2=11.340，8.170，8.200， and 12.400， respectively， all P<0.01）. However， there was no significant difference in HHcy detection rate in different age groups and between the patients with or without diabetes， and dyslipidemia（χ2=3.120，2.311， and 0.984， respectively， all P>0.05）. In the high-risk women group， HHcy detection rate increased with age （χ2=13.874，P<0.01）， and it was higher in participants with overweight or obesity， exercise frequency < 1 h/d， hypertension， and dyslipidemia（χ2=10.278， 13.840， 14.100， and 12.330， respectively， all P<0.01）. Unconditional logistic regression analysis showed that the factors affecting HHcy in the high-risk population of stroke include being male， smoking， hypertension， overweight and obesity. Conclusion:Screening of high-risk populations for stroke should include blood level of Hcy.
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OBJECTIVE@#To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia (Ph@*METHODS@#The WES/RNA-seq examination results of Ph@*RESULTS@#For Ph@*CONCLUSION@#There are obviously abnormal DNA damage repair pathways in children with Ph