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The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.
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Objective:To analyze the clinicopathological features of gastric oxyntic gland neo-plasms.Methods:Forty-nine cases of stomach oxyntic gland neoplasms including oxyntic gland adenoma(OGA)and gastric adenocarcinoma of the fundic gland type(GA-FG)diagnosed in the Sec-ond Hospital of Shandong University from January 2016 to December 2020 were selected.The clini cal information,endoscopic appearance,histological features and immunophenotype were analyzed retrospectively,and followed up.Results:Age of the gastric oxyntic gland neoplasm patients ranged from 19 to 83 years old,with an average age of(57.3±2.4)years old.The male-to-female ratio was 24:25.Most of the lesions were located in the gastric body(27/49)and fundus(15/49).There were four endoscopic phenotypes:flat bulging,polypoid,flat and depression.In some lesions,there were dilated dendritic vessels.48 cases were single onset.The mean maximum diameter of lesions was(3.9±0.5)mm(1.0～7.0 mm).Seven cases showed submucosal invasion,and the inva-sion depth was less than 500 μm.The tumor consists of the dense glandular and the glandular con-nects to form a strip shape,which is irregularly branched and labyrinthlike under the microscope.These tumor cells were well differentiated and the morphology was similar to oxyntic gland cells.The chief cells were the predominant cells.The nucleus was mildly enlarged with slight pleomorphism and the mitosis was uncommon.The oxyntic gland neoplasms of the stomach were diffusely posi-tive for Mucin-6(MUC6)(100％)and Pepsinogen Ⅰ(83％),focally positive for H+/K+-ATPase(58％).Conclusions:The stomach oxyntic gland neoplasm is a new histology type with unique clinico-pathological features.The incidence of this neoplasm is low and the prognosis is good but it still needs long-term follow-up.
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OBJECTIVE@#To obtain skin-derived induced pluripotent stem cells (iPSCs) from an Osteogenesis imperfecta (OI) patient carrying WNT1c.677C>T mutation in order to provide a new cell model for investigating the underlying molecular mechanism and stem cell therapy for OI.@*METHODS@#The pathogenic variant of the patient was identified by Sanger sequencing. With informed consent from the patient, skin tissue was biopsied, and primary skin fibroblasts were cultured. Skin fibroblasts were induced into iPSCs using Sendai virus-mediated non-genomic integration reprogramming method. The iPSC cell lines were characterized for pluripotency, differentiation capacity, and karyotyping assay.@*RESULTS@#The patient was found to carry homozygous missense c.677C>T (p.Ser226Leu) mutation of the WNT1 gene. The established iPSC lines possessed self-renewal and capacity for in vitro differentiation. It also has a diploid karyotype (46,XX).@*CONCLUSION@#A patient-specific WNT1 gene mutation (WNT1c.677C>T) iPSC line was established, which can provide a cell model for the study of OI caused by the mutation.
Subject(s)
Humans , Induced Pluripotent Stem Cells/pathology , Osteogenesis Imperfecta/genetics , Mutation , Cell Differentiation/genetics , Cell LineABSTRACT
Objective:To investigate the impact of QiliQiangXin Capsules on ventricular remodeling and cardiac contraction and relaxation function in aging rats with heart failure following myocardial infarction.Methods:From August 2022 to August 2023, a total of 30 old rats were randomly assigned to three groups: sham-operated group, model group, and treatment group, with 10 rats in each group selected through a digital lottery method.The model and treatment groups were created by ligating the anterior descending branch of the left coronary artery.The rats in the treatment group received daily administration of Astragalosa hebecarpa Drabanemerosa Strong Heart Capsule(1.0 g/kg)via gavage after 4 weeks.After the 4-week drug administration period, echocardiography was performed to measure various parameters including left ventricular end-diastolic internal diameter(LVIDd), left ventricular end-systolic internal diameter(LVIDs), left ventricular ejection fraction(LVEF), left ventricular anterior wall myocardial thickness(LVAWd), mitral valve early diastolic peak flow velocity(E peak), and early diastolic velocity of mitral annulus(e peak)detected by tissue Doppler(TDI). The E/e value was calculated based on these measurements.Additionally, serum levels of B-type brain natriuretic peptide(BNP), matrix metalloproteinase 2(MMP-2), matrix metalloproteinase 9(MMP-9), and tumor necrosis factor(TNF-α)were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE)staining was employed to observe the morphological changes in myocardial tissue.Results:Compared to rats in the model group, rats in the treatment group exhibited lower left ventricular internal dimension at end-diastole(LVIDd)(9.1±0.6 mm vs.11.4±0.8 mm, P<0.01), lower left ventricular internal dimension at end-systole(LVIDs)(5.9±0.8 mm vs.8.7±0.9 mm, P<0.01), lower E/e ratio(13.4±2.0 vs.16.3±2.8, P<0.05), higher left ventricular ejection fraction(LVEF)(68.8±7.1% vs.52.0±8.4%, P<0.01), and elevated left ventricular anterior wall thickness at end-diastole(LVAWd)(1.5±0.2 mm vs.1.2±0.3 mm, P<0.05). In addition, compared to rats in the model group, the treatment group showed a decrease in brain natriuretic peptide(BNP)(0.26±0.04 μg/L vs.0.34±0.05 μg/L, P<0.01), decreased matrix metalloproteinase-2(MMP-2)(3697.0±857.7 μg/L vs.4719.5±703.5 μg/L, P<0.01), decreased matrix metalloproteinase-9(MMP-9)(87.3±13.8 μg/L vs.116.5±9.6 μg/L, P<0.01), decreased tumor necrosis factor-alpha(TNF-α)(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01), and lower TNF-α levels(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01). Histological examination using hematoxylin and eosin(HE)staining revealed that the treatment group had less severe cardiac myocyte arrangement disorder and inflammatory reaction compared to the model group. Conclusions:Qiliqiangxin Capsules were found to effectively delay ventricular remodeling and improve myocardial contraction and relaxation function in aging rats with heart failure after acute myocardial infarction.
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Objective:To deeply understand the illness experience of patients with unruptured intracranial aneurysm undergoing interventional treatment, and to provide reference for formulating targeted nursing intervention programs.Methods:The semi-structured interview method of qualitative research was used to conduct in-depth interviews in 17 patients with unruptured intracranial aneurysm undergoing interventional treatment. Data were analyzed by content analysis method.Results:Five themes and ten sub-themes were extracted, including limited disease cognition (ignoring disease symptoms, wrong medical treatment behavior), uncertainty of disease (fear of aneurysm rupture, fear of disease recurrence), trusting in medical resources (trusting diagnosis and treatment technology, satisfactory medical service), desire for social support (hope for family members′companionship, expecting the concern of doctors and nurses), positive self-management (maintaining emotional stability, building health behaviors).Conclusions:Medical staff should pay attention to the physical and mental feelings of patients with unruptured intracranial aneurysm during the disease process, assess their needs, support and coping ability, and provide scientific and effective help to promote their physical and mental comfort.
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Objective To analyze the risk factors of colorectal adenoma,construct a nomogram prediction model for the risk of colo-rectal adenoma,and evaluate its predictive efficiency.Methods A total of 1066 patients who underwent colonoscopy in Qingdao Munici-pal Hospital from January 2018 to June 2019 were collected retrospectively.Among them,496 patients who were pathologically diagnosed with colorectal adenoma were included in the adenoma group,the other 570 patients had no obvious abnormality in colonoscopy,or patho-logical diagnosis of inflammatory or hyperplastic polyps were included in the non-adenoma group.The independent risk factors for color-ectal adenoma were analyzed by univariate and multivariate analysis;R software was used to establish a nomogram model for predicting the risk of colorectal adenoma,and the Bootstrap method was used for internal validation of the model.The Calibration curve and receiver op-erator characteristic curve was used to evaluate the predictive efficiency of the nomogram.Results The results of univariate and multiva-riate analysis showed that advanced age(OR=1.068,95％CI:1.049-1.087,P＜0.001),male(OR=0.593,95％CI:0.396-0.886,P=0.011),alcoholism(OR=1.847,95％CI:1.085-3.144,P=0.024),family history of tumor(OR=1.778,95％CI:1.241-2.547,P=0.002),changes in bowel habit(OR=3.508,95％CI:2.496-4.930,P＜0.001),diabetes(OR=1.832,95％CI:1.179-2.846,P=0.007),high neutrophil/lymphocyte ratio(OR=2.861,95％CI:2.055-3.982,P＜0.001),high carcino-embryonic antigen(OR=1.391,95％CI:1.229-1.574,P＜0.001)were independent risk factor for colorectal adenoma.The C-in-dex of the nomogram prediction model was 0.780,and the C-index of the validation model was 0.774.Conclusion The nomogram pre-diction model constructed in this study has high prediction accuracy,which can provide a basis for screening high-risk groups of colorec-tal adenoma and provide a reference for clinicians before endoscopy.
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Helicobacter pylori (Hp) infection is one of the main causes of gastric cancer. The virulence factors of Hp, cytotoxin⁃associated gene A (CagA) and vacuolating cytotoxin A (VacA), are closely related to the pathogenicity of Hp in European and American countries. However, the positivity rate of CagA is as high as 90% in East Asian countries, indicating that the above⁃mentioned virulence factors could not fully explain the differences in pathogenicity of Hp, and other pathogenic factors might be speculated. In our previous studies, thioredoxin⁃1 (Trx1) was found to be a virulence factor of highly pathogenic Hp, and a series of studies were conducted on Hp Trx1 in cytology, zoology and human histology. This article reviewed the progress in research on Hp Trx1.
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OBJECTIVE@#To explore the genetic basis for three Chinese patients with McCune-Albright syndrome (MAS).@*METHODS@#Three children who had respectively presented at Shandong Provincial Hospital in April 2019 and Peking Union Medical College Hospital in August 2020 and May 2021 were selected as the research subjects. Peripheral blood samples of the probands and their family members were taken for the extraction of genomic DNA. Potential variants were screened by whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing of the patients and their family members.@*RESULTS@#The proband from family 1 was found to harbor a heterozygous c.601C>T (p.R201C) missense variant in exon 8 of the GNAS gene, whilst the probands from families 2 and 3 were both found to harbor a heterozygous c.602G>A (p.R201H) missense variant in exon 8 of the GNAS gene. Both variants were known to be pathogenic, and all probands were found to be mosaics for the corresponding variants but with various degrees.@*CONSLUSION@#WES can effectively diagnose MAS and other somatic genetic disorders. In this study, the combined WES and Sanger sequencing have verified the degree of mosaicisms of pathogenic variants in the three MAS patients, albeit no apparent correlation was found between the degree of mosaicisms and the phenotype of patients. Above finding has provided a basis for genetic counseling and prenatal diagnosis for the affected families.
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Humans , Mutation , Fibrous Dysplasia, Polyostotic/genetics , East Asian People , Exons , Phenotype , PedigreeABSTRACT
The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.
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Humans , Multiple Myeloma/pathology , T-Lymphocytes, Regulatory/pathology , Immune Tolerance , Plasma Cells/pathology , Immunosuppression Therapy , Tumor MicroenvironmentABSTRACT
BACKGROUND@#Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2.@*METHODS@#Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2.@*RESULTS@#The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2.@*CONCLUSIONS@#miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD. .
Subject(s)
Humans , Lung Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung , Ferroptosis/genetics , Reactive Oxygen Species , Adenocarcinoma of Lung/genetics , MicroRNAs/genetics , 3,4-Methylenedioxyamphetamine , Cell Proliferation/genetics , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , AMP-Activated Protein KinasesABSTRACT
OBJECTIVE@#To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD).@*METHODS@#With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer.@*RESULTS@#Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c.515C>A (p.Pro172Gln) and c.5983G>A (p.Ala1995Thr) in fetus 1, and c.5920G>T (pGly1974) and c.9908T>C (p.He3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers.@*CONCLUSION@#The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.
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Humans , Fetus , Chloroform , Computational Biology , Ethnicity , RibsABSTRACT
Objective:To determine the effectiveness of individualized voice therapy in persistent pediatric voice disorders. Methods:Thirty-eight children who were admitted to the Department of Pediatric Otolaryngology Shenzhen Hospital, Southern Medical University due to persistent voice disorder from November 2021 to October 2022 were included. All children were evaluated by dynamic laryngoscopy before voice therapy. Two voice doctors performed GRBAS score and acoustic analysis on the children's voice samples to obtain the relevant parameters including F0, Jitter, Shimmer, and MPT; All children were given personalized voice therapy for 8 weeks. Results:Among 38 children with voice disorders, 75.8%（29 cases） were diagnosed with vocal nodules, 20.6%（8 cases） were vocal polyps, and 3.4%（1 case） were vocal cysts. And in all children. And 51.7%（20 cases） had the sign of supraglottic extrusion under dynamic laryngoscopy. GRBAS scores decreased from 1.93 ± 0.62, 1.82 ± 0.55, 0.98 ± 0.54, 0.65 ± 0.48, 1.05 ± 0.52 to 0.62 ± 0.60, 0.58 ± 0.53, 0.32 ± 0.40, 0.22 ± 0.36, 0.37 ± 0.36. F0, Jitter, Shimmer decreased from（243.11±39.73） Hz, （0.85±0.99）%, （9.96±3.78）% to（225.43±43.20） Hz, （0.33±0.57）%, （7.72±4.32）%, respectively MPT was prolonged from（5.82±2.30） s to（7.87±3.21） s after treatment. All parameters changes had statistical significance. Conclusion:Voice therapy can solve children's voice problems, improve their voice quality and effectively treat children's voice disorders.
Subject(s)
Humans , Child , Voice Disorders/diagnosis , Voice , Voice Quality , Acoustics , Speech Acoustics , Vocal Cords/surgeryABSTRACT
Objective:To investigate the protective effect of lipopolysaccharide (LPS) preconditioning on cerebral ischemia reperfusion in rats.Methods:One hundred and twenty adult male SD rats were randomly divided into sham operation group, model group, low-dose LPS group (0.05 mg/kg), medium-dose LPS group (0.15 mg/kg), and high-dose LPS group (0.45 mg/kg). LPS was injected intraperitoneally for preconditioning, once a day for 7 consecutive days. Twenty-four hours after the last injection, the left middle cerebral artery occlusion model was induced by suture-occluded method. The model was reperfused 1.5 h after ischemia. At 24 h after reperfusion, the neurological deficit was evaluated by neurobehavioral score. The volume of cerebral infarction was measured by triphenyltetrazolium chloride staining. The serum levels of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay. The expression of Toll-like receptor 4 (TLR4), matrix metalloproteinase (MMP) -2 and MMP-9 in ischemic brain tissue was detected by Western blot analysis.Results:Compared with the sham operation group, blood-brain barrier permeability was increased in the model group, serum IL-1β, IL-6 and TNF-α were up-regulated, and the expression of TLR4, MMP-2 and MMP-9 proteins in ischemic brain tissue was up-regulated. Compared with the model group, the neurological impairment of each LPS intervention group was significantly reduced, the volume of cerebral infarction was significantly reduced, the permeability of blood-brain barrier was significantly reduced, the serum IL-1β, IL-6 and TNF-α were down-regulated, and the expression of TLR4, MMP-2 and MMP-9 protein in ischemic brain tissue was down-regulated, especially in the medium-dose group and the high-dose group.Conclusions:LPS preconditioning can induce the formation of ischemic tolerance, inhibit the activation of TLR4-MMP-2/MMP-9 signal pathway, reduce the damage and inflammation of blood-brain barrier structure, and thus play a neuroprotective role in rats with cerebral ischemia reperfusion.
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Malunion is a common complication following a calcaneal fracture which was not treated or treated inappropriately.It is a therapeutic target and a great challenge as well to relieve pain, correct deformity and restore the function of the affected foot in clinical treatment of calcaneal malunion. As a result of researches by scholars at home and abroad focusing on the biomechanical mechanisms underlying the symptoms caused by calcaneal malunion, a variety of corrective calcaneal osteotomy has been widely applied in clinical practice to specifically correct the calcaneal deformity and restore normal calcaneal morphology. This review expounds on the techniques, outcomes, indications and complications of corrective calcaneal osteotomies commonly used in clinic.
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Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can self-renew and differentiate. Numerous studies have shown that MSCs have important roles in areas such as regenerative medicine and tissue engineering. However, it is worth noting that MSCs will gradually age during long-term in vitro expansion with decreased stemness such as weakened migration ability, slowed proliferation rate and decreased differentiation potential, which greatly hinders the application of MSCs. Currently, the microenvironment for cell growth is recognized as one of the factors causing senescence in MSCs. Recent studies point out that the latest technologies such as exogenous administration, oxygen concentration regulation and extracellular matrix (ECM) construction can delay stem cell senescence by simulating or regulating the microenvironment. Here, we review the current knowledge of the characteristics and molecular mechanisms of senescent MSCs and microenvironment strategies to maintain MSCs stemness, which can provide a reference for future large-scale application of MSCs preparations in tissue engineering and clinical studies.
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Cell Differentiation , Cell Proliferation , Cells, Cultured , Cellular Senescence , Extracellular Matrix , Mesenchymal Stem CellsABSTRACT
OBJECTIVE：To provide reference for the selection of more economical programmed death- 1（PD-1）/programmed death-ligand 1（PD-L1）inhibitors for National Medical Insurance List and the quality improvement of related economic evaluation. METHODS：Retrieved from CNKI ，VIP，Wanfang database ，PubMed，Web of Science and Ovid Embase ，economic evaluation studies including listed PD- 1/PD-L1 inhibitors of China were collected during the inception to Oct. 2020. CHEERS checklist was used to evaluate the quality of the included literatures ，and the methodological characteristics and economic evaluation results of the included studies were analyzed systematically. RESULTS ：A total of 14 literatures were included ，all of which were model-based and with moderate or high quality. However ，there were still some deficiencies in the included literatures ，mainly manifesting as the insufficient reports on the reasons for setting or selecting model parameters ，as well as the great uncertainty of clinical effect data and utility value. Only 3 of the 8 PD-1/PD-L1 inhibitors listed in China were involved in the included literatures. Compared with chemotherapy or targeted therapy plan ，9 literatures（64.29％）showed that the therapy plan containing PD- 1/PD-L1 inhibitors was not cost-effective. CONCLUSIONS ：The economic evidence of domestic PD- 1/PD-L1 inhibitors is lacking ，the higher price of imported PD- 1/PD-L1 inhibitors lead to poor economic performance. The existing economic evaluations has some shortcomings in methodological application and parameter selection. Pharmaceutical enterprises should fill in the data gaps and adjust the pricing strategy，researchers should improve the standardization of research ，and medical insurance decision-making departments should improve the judgment on the quality of economic evidences ，so as to promote more economical drugs to be included in the National Medical Insurance List.
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@#Objective To explore the factors that affect the accuracy of percutaneous thermal ablation of lung metastases and coping strategies. Methods We retrospectively analyzed the clinical data of 31 patients who met the conditions for thermal ablation of lung metastases in Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine between October 2019 and December 2020. There were 19 males and 12 females with a mean age of 40-81 (62.8±10.3) years. A total of 33 metastases tumors were thermally ablated, 12 were radiofrequency ablation and 19 were microwave ablation. Results Of the 33 metastatic tumors, 5 targets showed significant puncture deviation, 4 of them completed the ablation after adjustment and 1 failed. The result of the univariate logistic regression showed the distance within the lung parenchyma (P=0.043) and the maximum diameter of the tumor (P=0.025) were independent risk factors for the accuracy of percutaneous thermal ablation. In terms of correlation, there was a positive correlation between the accuracy of percutaneous thermal ablation and the distance within the lung parenchyma (P=0.033), and a negative correlation between the maximum diameter of metastases tumor (P=0.004) and hemoptysis (P=0.015). Complete ablation rate was 87.8% (29/33). Conclusion When we perform CT-guided percutaneous thermal ablation of lung metastases, we must fully prepare the deviation plan for the small diameter tumor, the long travel distance in the lung parenchyma, and hemoptysis during puncture. Complete ablation can be achieved by fully identifying the anatomical features of the tumor and its surrounding structures, shortening the travel distance in the lung parenchyma and increasing the ablation range.
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OBJECTIVE：To evaluate the pharmacoec onomics of Enalapril folic acid tablet and Enalapril tablet for stroke prevention in patients with hypertension. METHODS ：Markov model was constructed by using Excel 2016 software. Patients with essential hypertension were selected as the research object with 1 year cycle and 20 years horizon. From the perspective of health system，the pharmacoeconomics of Enalapril folic acid tablets versus Enalapril tablets for stroke prevention in patients with hypertension was compared by cost-effectiveness analysis ，and the stability of the research results was verified by sensitivity analysis. RESULTS ：Compared with Enalapril tablet ，the incremental cost-effectiveness ratio of Enalapril folic acid tablet was 221 323 yuan/QALY，which was higher than three times of China ’s per capita GDP in 2020（217 341.04 yuan）. The results of single factor sensitivity analysis and probabilistic sensitivity analysis were consistent with that of basic analysis. CONCLUSIONS ： Compared with Enalapril tablet ，Enalapril folic acid tablet doesn ’t have a better economy for patients with hypertension.
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OBJECTIVE：To pr ovide reference for the future pharmacoeconomic evaluation. METHODS ：Four typical cases of pharmacoeconomic evaluation showed the special situation that “not cost-effective at a zero price ”，defined the concept of “net value”to assist in theoretical analysis ，and summarized the possible causes of this situation . RESULTS & CONCLUSIONS ：The system（ATPS）：an overview and advances in its applica background treatment cost other than the target drug was too high ，the patient ’s quality of life during survival was too low ，the threshold of willingness to pay of incremental cost-effectiveness ratio was too low ，the cost of risk events during extended survival was too high or the health loss was too high ，and the price of the control scheme was too low ，which might affect the results of economic evaluation ，and even le d to the dilemma of pharmacoeconomic evaluation of “not cost-effective at a zero price ”. Pharmacoeconomic evaluation discusses the economy of intervention programs rather than the economy of drugs. The uneconomic results caused by various reasons need to be treated objectively ；theoretically，all“relevant”and“irrelevant”costs should be included in the calculation category in pharmacoeconomic evaluation ；pharmacoeconomics mainly solves the problem of “cost performance”comparison among several treatment schemes ，and the medical and health field often needs to face problems such as ethics and fairness. Therefore ，researchers may need to jump out of the framework of pharmacoeconomics analysis and conduct in-depth discussion from a higher and broader perspective.
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Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (