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Objective To explore the risk factors of apathy and correlations with cognitive function in patients with hypertension combined with cerebral small vessel disease(CSVD).Methods Totally 141 patients with hypertension combined with CSVD were prospectively enrolled and were divided into apathy group(n=43)and non-apathy group(n= 98)according to neuropsychiatric inventory-apathy scale(NPI-Apathy)scores.The general data,imaging marker scores and total imaging burden scores were compared between groups.In hypertension combined with CSVD patients,multivariate logistic regression analysis was performed to screen the independent risk factors of apathy,and Spearman correlation analysis was also performed to observe the correlation of apathy and cognitive function.Results The patients'age,high density lipoprotein cholesterol(HDL-C),Fazekas scores of lateral periventricular white matter hyper-intensity(WMH),cerebral microbleed of depth/infratentorial and total imaging burden scores of apathy group were all higher,while mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scores were both lower than those of non-apathy group(all P<0.05).HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy(both P<0.05),while NPI-Apathy scores were moderately negatively correlated with cognitive function in patients with hypertension combined with CSVD(r=-0.543,-0.484,both P<0.001).Conclusion HDL-C and Fazekas scores of lateral periventricular WMH were both independent risk factors for apathy in patients with hypertension combined with CSVD.The more severe the apathy,the lower the cognitive function.
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Objective @#To construct myeloid specific Spi1 gene knockout mice and analyze their genotypes , so as to provide animal model basis for the study of pathological mechanism of diseases and drug targets .@*Methods @#According to the principle of CRISPR/Cas9 technology and C re/LoxP system , sgRNA and Donor vectors were de signed and constructed . The transcript of Exon 2 ( Exon 2) was used as the knockout region , and Loxp elements were placed on both sides of Exon 2 . Cas9 protein , sgRNA and Donor vector were mixed and microinj ected into the fertilized eggs of C57BL/6J mice , the fertilized eggs were transplanted into the uterus of C57BL/6J pregnant female mice , and F0 generation was obtained after 19 ~ 20 days . Positive F0 mice were mated with C57BL/6J mice to ob tain stable F1 Spi1 flox/ + mice . Spi1 flox/ + mice of F1 generation were selfed to obtain Spi1 flox/flox mice . Spi1 flox/flox mated with Lyz2-Cre + mice to obtain Spi1 flox/ + /Lyz2-Cre + mice , and then mated with Spi1 flox/flox , the Spi1 flox/flox/Lyz2-Cre + mice were myeloid specific Spi1 gene knockout ( KO) mice . Spi1 flox/flox/Lyz2-cre - mice were used as wild type (WT) mice . DNA of WT and KO mice was extracted , and the genotypes were identified by agarose gel electro phoresis after PCR amplification . Western blot was used to detect the expression of spleen focus forming virus proviral integration oncogene , Spi - 1 /purine rich box - 1(PU . 1) in immune cells of WT and KO mice .@*Results@#The results of PCR identification showed that the genotype of mice with only 220 bp amplified by flox primer was Spi1 flox/flox homozygote , and the genotype of mice with 700 bp amplified by Lyz2-Cre primer was Lyz2-Cre + . Western blot showed that compared with WT group , the protein PU . 1 was not expressed in bone marrow derived macropha ges (BMDMs ) and peritoneal macrophages (PM) in KO group (P < 0.01) . There was no significant difference of statistics in the expression level of PU . 1 in T cells between KO mice and WT mice . The results of PCR and West ern blot showed that myeloid specific Spi1 KO mice were successfully constructed . @*Conclusion @#The myeloid spe cific Spi1 gene KO mice are successfully constructed and identified , which provides animal model basis for further revealing the potential mechanism of PU . 1 inimmune regulation .
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Objective:To select the differential prognostic lactic acid metabolism-related genes(LRGs)of the head and neck squamous cell carcinoma(HNSCC)to construct the LRGs prognostic model of HNSCC,and to clarify the potential mechanism.Methods:The HNSCC gene expression and clinical data were obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)Databases,the LRGs were identified through GeneCards Database,and R software was used to screen out the LRGs of HNSCC;univariate Cox regression analysis was used to identify prognosis-related genes;two different subtypes were identified based on the prognostis-related LRGs;Kaplan-Meier(K-M)curve analysis was used to compare the prognosis of the patients between two groups;CIBERSORT algorithm was used to perform the immuno-correlation analysis between two groups;multivariate Cox regression analysis and LASSO regression analysis were used to construct the prognostic model;receiver operating characteristic curve(ROC)and K-M survival curve were used to assess the relationship between LRGs and survival and prognosis of the HNSCC patients.The prognostic model was validated by GSE27020,GSE41613,and GSE65858 datasets.The experiment were grouped based on risk score,and immune-related analysis and tumor score analysis were performed.Results:The TCGA Database differential analysis results showed that 1 196 LRGs were identified from HNSCC samples;univariate Cox regression analysis selected 27 differentially expressed genes(DEGs)associated with the prognosis of the HNSCC patients.Two different LRGs subtypes(Group 1 and Group 2)were identified according to the prognosis-related genes.The K-M survival curves results showed that the overall survival(OS)of the patients in Group 2 was significantly higher than that in Group 1,and the immune cell expression amount of the patients in Group 2 was also higher than that in group 1.The multivariate Cox regression and LASSO regression analysis results screened out 9 LRGs,including hypoxanthine phosphoribosyltransferase 1(HPRT1),amyloid precursor protein(APP),glycogen phosphorylase L(PYGL),urokinase-type plasminogen activator(PLAU),cannabinoid receptor 2(CNR2),stanniocalcin 2(STC2),nucleotide binding oligomerization domain-like receptor protein 1(NLRP1),integrin-linked kinase(ILK),and forkhead box B1(FOXB1);the prognostic model was constructed.The K-M and ROC curve results indicated that the expression levels of above 9 genes were associated with the survival and prognosis of the HNSCC patients,providing good 1-year,2-year,and 3-year survival prediction effect,and the area under ROC curve(AUC)values were all greater than 0.650.Furthermore,the predictive ability of the prognosis model was validated in GSE27020,GSE41613,and GSE65858 datasets.The patients classified based on the risk scores had distinguishable immune statuses.Conclusion:The differentially expressed LRGs of HNSCC screened by bioinformatics methods are related to the survival and prognosis of the HNSCC patients;the prognostic model constructed by 9 LRGs can predict the survival status and treatment response of the HNSCC patients.
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Objective To explore the distribution of traditional Chinese medicine(TCM)syndrome elements in patients with multi-drug resistant bacteria-infected pneumonia.Methods Clinical data of 126 patients with multi-drug resistant bacteria-infected pneumonia admitted to the intensive care unit of Lung Disease Centre of Qingdao Hospital of Traditional Chinese Medicine from May 2020 to July 2022 were retrospectively collected.The clinical data included the patients'gender,age,underlying diseases,history of bad additions of smoking and alcohol,multi-drug resistant bacteria,and the information of four diagnostic methods of TCM,etc.The disease-nature syndrome elements in patients with drug-resistance to various strains of drug-resistant bacteria were extracted,and then deficiency-excess syndrome differentiation was carried out.Results(1)A total of 201 strains of multi-drug resistant bacteria were detected in 126 patients with multi-drug resistant bacterial pneumonia.The main pathogenic species were Gram-negative bacteria,and the proportion accounted for 95.52%(192/201),which was significantly higher than that of Gram-positive bacteria[4.48%(9/201)],with a statistically significant difference(χ2 = 166.612,P<0.001).Klebsiella pneumoniae accounted for the highest percentage of 23.38%in the gram-negative bacterium.(2)A total of 12 syndrome elements were extracted from the 126 patients.The excess syndrome elements were predominated by phlegm and heat,and the deficiency syndrome elements were predominated by yin deficiency.There was no statistically significant difference in the distribution of yin deficiency,blood deficiency,heat,phlegm,fluid-retention and damp syndrome elements among patients with different strains of drug-resistant bacterial infection(P>0.05).(3)Of the 126 patients,62 cases(49.21%)had simple excess syndrome,one case(0.79%)had simple deficiency syndrome,and 63 cases(50.00%)had concurrent deficiency-excess syndrome.Among the 126 patients,there were 19 cases of single syndrome element,41 cases of concurrent two-syndrome element,49 cases of concurrent three-syndrome element,16 cases of concurrent four-syndrome element,and one case of concurrent five-syndrome element.And the combined syndrome element of phlegm-heat-yin deficiency occurred most frequently for 26 times.Conclusion Gram-negative bacteria are the primary infectious pathogens for the patients with multi-drug resistant bacterial infections,and the TCM syndrome elements of the patients are characterized by the concurrence of deficiency and excess and simple excess syndrome,mainly manifesting as phlegm,heat,and yin deficiency.
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Objective @#To breed and identify the T lymphocyte-conditional Spi1 knockout mice for the further in- vestgation of the specific role of Spi1-encoded protein PU. 1 . @*Methods @#The Lck-Cre mice were mated with Spi1 flox/flox mice to obtain Lck-Cre ×Spi1 flox/flox mice (T lymphocyte-specific Spi1 knockout mice) , and the genotype was determined by polymerase chain reaction (PCR) and agarose gel electrophoresis . Magnetic beads were used to sort out the splenic T lymphocytes , and the knockdown efficiency of PU. 1 in T cells was detected by Western blot , quantitative real-time PCR ( qPCR) and flow cytometry. @*Results @#The Lck-Cre ×Spi1 flox/flox mouse genotype was stably inherited . Compared with Spi1 flox/flox mice , the expression level of PU. 1 was significantly reduced in splenic T cells of Lck-Cre ×Spi1 flox/flox mice . @*Conclusion @#In this study , the T lymphocyte-specific Spi1 knockout mice was successfully constructed by applying Cre/LoxP system and CRISPR/Cas9 technology , which provided a reliable an- imal model for the subsequent experiments of the specific role of PU. 1 in T cell-related diseases .
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OBJECTIVE: To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule (, QZJT) on diabetic kidney disease (DKD) treatment. METHODS: This experiment used db/db mice and podocytes (MPC5) to develop DKD model. Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters (24-h urinary albumin, serum creatinine, blood urine nitrogen), pathological kidney injury, and podocyte integrity. Moreover, autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy. Additionally, Western blotting was applied to detect the expression of podocyte marker protein (podocin), autophagy-associated proteins, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway changes and . RESULTS: QZJT significantly reduced urine protein, blood nitrogen urea, and serum creatinine and showed histological restoration of renal tissues. QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice. QZJT increased autophagic vesicles in mice and cultured podocytes. QZJT also upregulated microtubule-associated protein 1 light chain 3-II (LC3-II) / (LC3-I) and Beclin-1 and downregulated phosphorylated-PI3K (p-PI3K), p-AKT, and p-mTOR in db/db mice and MPC5 cells. However, autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells. CONCLUSIONS: These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.
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Diabetes Mellitus , Diabetic Nephropathies , Podocytes , Mice , Animals , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Creatinine/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Autophagy , Mammals/metabolism , Diabetes Mellitus/metabolismABSTRACT
OBJECTIVE To quantitatively and qualitatively analyze the progress of potentially inappropriate medication (PIM) research by means of bibliometrics, and to predict the hotspots and trends of PIM, so as to provide reference for PIM research in China. METHODS The research literature related to PIM were searched from Web of Science core database, and the publication trend of the literature was analyzed on the bibliometric online analysis platform and CiteSpace 5.8.R3 software. The research results were visualized and analyzed, and the research hotspots of PIM were summarized through gCLUTO. RESULTS About PIM research, the annual number of the literature issued from 2012 to 2021 showed a continuous growth trend totally; the United States had the largest number of literature (241 pieces); the University of Sydney in Australia was the research institution with the largest number of literature (59 pieces); O’Mahony D from University College Cork, Ireland, published the most literature (23 pieces); the research of PIM involved 57 disciplines, among which there was the largest number of literature about gerontology (384 pieces); International Journal of Clinical Pharmacy was the journal with the largest number of literature (61 pieces); Journal of the American Geriatrics Society was cited most frequently (1 197 times). The hotspots of PIM research mainly focused on seven aspects: the standard of PIM, the safety and economy research of PIM, the risk factors research of PIM, the PIM research of chronic patients, the PIM research of antipsychotics, the research of pharmacists’ participation in PIM management, and the PIM research about palliative care of tumor patients. CONCLUSIONS The heat of research on PIM has been on the rise, and there is little cooperation between countries and institutions, and more cooperation is needed. In the future, the focus of Chinese pharmacists’ research on PIM may be on the deep localization of PIM standards, PIM intervention and precise medication guidance, and PIM management of specific diseases and drugs.
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OBJECTIVE@#To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients.@*METHODS@#By exploring the half maximum inhibitory concentration (IC50) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance.@*RESULTS@#Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC50 were significantly higher than those of the sensitive cell lines (10.99 μmol/L, P < 0.01; 11.96 μmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 μmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib.@*CONCLUSION@#ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.
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Humans , Carcinoma, Renal Cell/metabolism , Axitinib/pharmacology , Kidney Neoplasms/metabolism , bcl-2-Associated X Protein , Nuclear Proteins , Cell Line, Tumor , Apoptosis , Cell ProliferationABSTRACT
Objective: To investigate the clinicopathological characteristics, pathological diagnosis of Ewing's sarcoma of the central nervous system. Methods: Six cases of Ewing's sarcoma of the central nervous system diagnosed at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from 2015 to 2022 were collected. The clinical manifestations, histological morphology, immunophenotype and molecular genetics of these cases were analyzed. The related literature was reviewed. Results: There were four males and two females, with a male to female ratio of 2∶1. The onset age was 17-40 years, with a median age of 23 years. All 6 tumors were located in the spinal cord (2 cases of cervical vertebra, 1 case of thoracic vertebra, 2 cases of lumbar vertebra, and 1 case of sacral vertebra). The patients' clinical manifestations were mostly lumbago, weakness and numbness of lower limbs/limbs. In 1 case, the tumor recurred and metastasized to the suprasellar region and the third ventricle. Microscopically, the tumor showed diffuse infiltrative growth. In some cases, the tumor was closely related to the spinal meninges. The tumor cells were arranged in sheet, lobular, thin-rope, and nest-like patterns. Homer-Wright rosette was visible. The tumor cells were small to medium in size, and most of them had scant cytoplasm. A few cells had clear cytoplasm. Some areas were rhabdoid. The tumor cell nuclei showed focal mild pleomorphism. The chromatin was uniform and delicate while the nucleoli were not obvious. Mitosis was commonly seen. The tumor was separated by fibrous connective tissue and may be accompanied by mucinous degeneration. Immunohistochemistry showed that all tumors were positive for CD99, NKX2.2, Fli1, ERG. ATRX, H3K27me3, INI1 and BRG1 were all retained. Immunohistochemical stains for EMA, GFAP and Olig2 were negative. The Ki-67 proliferation index was 30%-70%. EWSR1 break-apart FISH test was positive. Conclusions: Ewing's sarcoma is rare in the central nervous system and needs to be distinguished from a variety of neoplasms with primitive undifferentiated small cell morphology. Immunohistochemistry and molecular genetics may be required for a proper diagnosis.
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Humans , Male , Female , Young Adult , Adult , Adolescent , Sarcoma, Ewing/pathology , Proto-Oncogene Protein c-fli-1 , Immunohistochemistry , Biomarkers, Tumor/genetics , Central Nervous System/pathologyABSTRACT
Objective:To investigate the correlation between adiponectin gene polymorphism and osteoporosis in patients with differentiated thyroid after thyroid stimulating hormone (thyroid stimulating hormone, TSH) suppression therapy.Methods:A total of 79 patients who underwent resection of thyroid cancer and TSH suppression therapy were collected as research objects. After 5 years of follow-up, the bone mineral density of the patients was measured, and they were divided into normal bone mass group and osteoporosis group. The general data of the two groups of patients were compared, and the distribution frequencies of rs1063539, rs266729, rs3774261, and rs710445 genotypes in the two groups of patients were analyzed. The differences in bone mineral density of patients with different genotypes of rs1063539, rs266729, rs3774261, and rs710445 were analyzed. To explore the risk factors of osteoporosis in patients treated with TSH suppression after differentiated thyroid surgery.Results:General data analysis showed that the family history of osteoporosis ( P=0.021) and preoperative thyroid hormone status ( P=0.022) were significantly different between the two groups (all P<0.05). The genotype frequency deviations of rs1063539, rs266729, rs3774261, and rs710445 conformed to the Hardy-Weinberg equilibrium law. The distribution of the three genotypes of rs1063539 locus was significantly different between the two groups, and the bone mineral density T value of rs1063539 CC+CG genotype (-3.68±0.61) was significantly lower than that of GG type (-3.14±0.47) ( t=3.142, P=0.003). Logistic regression analysis showed that no family history of osteoporosis was a protective factor for osteoporosis in patients with TSH suppression after thyroid cancer surgery ( OR: 0.258, OR 95%CI: 0.082-0.773, P=0.020). Preoperative hyperthyroidism ( OR: 2.203, OR 95%CI: 1.134-4.541, P=0.025) and rs1063539 CC+CG genotype ( OR: 4.392, OR 95%CI: 1.248-17.652, P=0.027) were the risk factors inducing osteoporosis. Conclusion:Adiponectin rs1063539 gene polymorphism is associated with bone mineral density in patients, and rs1063539 CC+CG genotype can increase the risk of osteoporosis in patients treated with TSH suppression after differentiated thyroid surgery.
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Objective:To explore the application value of computed tomography (CT) plain scan and dynamic enhanced scan in the diagnosis of solitary pulmonary nodules.Methods:The clinical data of 120 patients with solitary pulmonary nodules detected by physical examination in Baoding First Central Hospital from January 2018 to December 2020 were retrospectively reviewed. All patients were confirmed by surgery and pathology, including 77 benign lesions and 43 malignant lesions; All patients underwent CT plain scan and dynamic enhanced scan before operation. The accuracy of the two examination methods in the diagnosis of benign and malignant lesions of solitary pulmonary nodules was analyzed and compared. The detection rate of CT dynamic enhanced scan imaging characteristics (vacuole sign, ground glass sign, spinous sign, lobulation sign, hair prick sign, blood vessel cluster, pleural depression) of benign and malignant lesions of solitary pulmonary nodules was compared, and the diagnostic value of CT plain scan and dynamic enhanced scan in the differential diagnosis of benign and malignant solitary pulmonary nodules was evaluated based on the results of surgical pathological diagnosis. The manifestations and characteristic curves of CT dynamic enhanced scan of solitary pulmonary nodules was analyzed.Results:The diagnostic accuracy of CT dynamic enhanced scan for solitary pulmonary nodules was 80.00% (96/120), which was higher than that of CT plain scan (63.33%) (76/120) ( P<0.05). The sensitivity, specificity, and negative predictive value of CT dynamic enhanced scan for the diagnosis of benign and malignant lesions of solitary pulmonary nodules were higher than those of CT plain scan (all P<0.05). Among the imaging characteristics of CT dynamic enhanced scans of malignant lesions, the ground glass sign, spinous process sign, lobulation sign, spiculation sign, vascular clustering and pleural indentation were detected more frequently than those of benign lesions (all P<0.05). Benign lesions usually showed homogeneous enhancement, and a few showed heterogeneous enhancement; Malignant nodules often showed uneven enhancement, and a few had even enhancement. The time density curves of dynamic enhanced CT values in the regions of interest of benign and malignant solitary pulmonary nodules were different. Conclusions:The value of dynamic enhanced CT scan in the differential diagnosis of benign and malignant lesions of solitary pulmonary nodules is higher than that of CT plain scan, and the imaging features are obvious, with higher sensitivity and specificity, which is worthy of application.
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Objective:To investigate the clinical characteristics, management and outcome of aortic dissection (AD) in pregnant women with pre-eclampsia.Methods:Clinical characteristics, management, and prognosis of nine patients with pre-eclampsia complicated by AD who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to April 2021 were retrospectively summarized using descriptive statistical analysis.Results:(1) Clinical features: The incidence of pre-eclampsia complicated by AD among the total deliveries and pre-eclampsia deliveries were 18/100 000 (9/49 166) and 182/100 000 (9/4 943), respectively. All the nine cases of pre-eclampsia complicated by AD, with an average age of (36.6±4.2) years, presented clinical symptoms in the second or the third trimester that were mainly manifested as chest and back pain (8/9) and the average gestational week at onset was (31.0±4.7) weeks. Seven cases were confirmed by transthoracic echocardiography (TTE) and computed tomography angiography (CTA), one by TTE and magnetic resonance angiography, and one by TTE+MRI+CTA. The main classification of AD was Stanford B (8/9). In the grading of blood pressure during pregnancy, except for one case without data, eight cases were severe. (2) Management: Four women did not receive any antihypertensive treatment. However, blood pressure remained uncontrolled in the other five cases despite antihypertensive managment. Except for one death before operation due to rapid deterioration, the other eight cases all received initial treatment and thoracic endovascular aortic repair (TEVAR). Four cases underwent TEVAR prior to the termination of pregnancy. Two cases were delivered by cesarean section first, and TEVAR was performed 5 and 6 days after delivery, respectively. The other two cases undenwent cesarean section and TEVAR at the same time. Lung infection ( n=6) was the main postoperative complication. (3) Delivery: Among the nine patients, one patient died, and the average termination time of the eight patients (six underwent cesarean section, including two cases with fetal death, two underwent vaginal delivery following fetal death) was (32.9±3.6) weeks and none of them had postpartum hemorrhage. (4) Maternal-infant outcomes: Follow-up of the eight surviving women showed that one had numbness in one side of the limbs, one with occasional heart palpitations, and the rest had good outcomes. There were four live births, including two with low birth weight and one with neonatal asphyxia, and five stillbirths. During the 7-83 months of follow-up, all four children grew well. Conclusions:Pregnant women with pre-eclampsia should actively control blood pressure to avoid AD. Once symptoms such as chest and back pain occur, the possibility of AD should be considered. Active treatment after diagnosis of AD can improve maternal and fetal survival rate.
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Objective The expression and prognosis significance of CD59 in pancreatic cancer were analyzed by bioinformatics.Methods Gene expression profiling interactive analysis 2(GEPIA2)and human protein atlas(HPA)databases were used to compare the expression of CD59 between pancreatic cancer tissues and adjacent tissues;Kaplan-Meier plotter database was used to evaluate the effect of CD59 on prognosis;String and Cytoscape3.9.1 were used to analyze the CD59 protein interaction network;DAVID6.8 performed gene enrichment and pathway enrichment analysis of CD59 with key interacting genes.Results Compared with normal tissues,the expression of CD59 in pancreatic cancer tissues was significantly up-regulated(P<0.05),and the overall survival time(HR=2.3,95%CI:1.52-3.50)and recurrence free survival(HR=4.31,95%CI:1.57-11.83)of pancreatic cancer patients with CD59 high expression was shorter than CD59 low expression patients.Protein interaction network analysis revealed that CD59 is closely related to several molecules such as CD55,GOLGA2,LMAN1,TMED2 and SERPINA1.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis indicated that CD59 was mainly involved in pathways such as complement activation,innate immune response and coronavirus-COVID-19.Conclusion CD59 is highly expressed in pancreatic cancer tissue and is affected by several immune-related genes.It is associated with poor prognosis of patients and can be used as one of biomarkers for early diagnosis and prognosis prediction of pancreatic cancer.
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Objective:To investigate the correlation between serum recombinant sclerostin (SOST) and dickkopf-related protein 1 (DKK-1) levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery.Methods:A total of 110 patients diagnosed with osteoporosis after differentiated thyroid cancer surgery were recruited as the study group, and another 110 patients without osteoporosis diagnosed after differentiated thyroid cancer surgery were recruited as the control group. The general data, bone mineral density, serum SOST, DKK-1 levels and bone metabolism indicators N-terminal propeptide of type I procollagen (PINP), bone alkaline phosphatase (BALP), beta-isomerized C-telopeptide (β-CTX), 25-hydroxyvitamin D3 [25- (OH) D3] levels were compared between the two groups. The correlation between serum SOST, DKK-1 levels and bone metabolism indexes was analyzed, and the risk factors affecting the formation of osteoporosis were explored.Results:The T value of bone mineral density in the study group (-3.27±0.92) was significantly lower than that in the control group (-1.23±0.27, t=22.32, P<0.001). The serum SOST (15.84±1.34, t=32.53, P<0.001) and DKK-1 (5.96±1.40, t=4.82, P<0.001) levels in the study group were significantly higher than those in the control group (SOST: 10.24±1.21, DKK-1: 5.05±1.40). The serum PINP (40.95±9.84, t=7.59, P<0.001), BALP (23.14±5.26, t=5.06, P<0.001) and β-CTX (1.07±0.54, t=4.96, P<0.001) in the study group were significantly higher than those in the control group (31.48±8.64, 19.64±4.99, 0.78±0.29), and the 25- (OH) D3 level (13.68±4.49) was significantly lower than that of the control group (18.31±5.72, t=6.68, P<0.001). Serum SOST was positively correlated with PINP ( r=0.33, P=0.001), BALP ( r=0.23, P=0.016) and β-CTX ( r=0.19, P=0.046), but not with 25- (OH) D3 ( r=-0.09, P=0.349). Serum DKK-1 was positively correlated with PINP ( r=0.19, P=0.044), BALP ( r=0.26, P=0.007) and β-CTX ( r=0.21, P=0.028), but not with 25- (OH) D3 ( r=-0.16, P=0.088). Serum SOST and DKK-1 levels were independent risk factors for osteoporosis (all P<0.05) . Conclusion:Serum SOST and DKK-1 levels are independent risk factors for the formation of osteoporosis, which are significantly positively correlated with bone metabolism indexes PINP, BALP, and β-CTX in patients with osteoporosis after differentiated thyroid cancer surgery.
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Background Experimental studies have shown that radiofrequency electromagnetic waves emitted by mobile phones can cause adverse effects on male reproductive health, including decreased semen quality and altered sex hormones. However, the results of epidemiological studies on the relationship between mobile phone use and male semen quality are inconsistent. Furthermore, there are few epidemiological studies on the association of mobile phone use with sex hormones. Objective To explore the associations of mobile phone use with male semen quality and sex hormones. Methods A total of 2045 men visited the reproductive medicine center of a hospital in Wuhan and ordered infertility examination were recruited from December 2018 to January 2020. Information on mobile phone use was obtained using a questionnaire. Among them, 1232 and 1694 men were eligible for semen quality analyses and sex hormone analyses, respectively. Multiple linear and logistic regression models were used to analyze the associations of mobile phone use with male semen quality and sex hormones. Results After adjusting for potential confounders, there was no statistically significant associations of mobile phone use with sperm progressive motility, sperm total motility, sperm concentration, sperm count, or serum luteinizing hormone (P>0.05). However, serum total testosterone showed a declined tendency with increasing daily duration of mobile phone use (Ptrend=0.08). Compared with men with daily mobile phone use of 0-2 h, men with daily mobile phone use of 2.1-5, 5.1-8, and >8 h showed decreased serum total testosterone concentrations by 6.29% (95%CI: 0.40%-11.84%), 6.01% (95%CI: 0.60%-12.19%), and 7.87% (95%CI: 0.40%-14.79%), respectively. Conclusion Mobile phone use is not associated with male semen quality and serum luteinizing hormone, but increasing daily duration of mobile phone use is potentially associated with a tendency to lower male serum total testosterone.
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The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People's Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8-18) and Group B (IPSS of 19-35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.
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Male , Humans , Retrospective Studies , Prostatic Hyperplasia/surgery , Follow-Up Studies , Holmium , Quality of Life , China , Treatment Outcome , Lower Urinary Tract Symptoms/surgery , Laser Therapy , Lasers, Solid-State/therapeutic useABSTRACT
Objective: To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Methods: Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. Results: The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different (P<0.05). Conclusions: DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.
Subject(s)
Humans , Adult , Male , Female , Middle Aged , Aged , Histones/genetics , Brain Neoplasms/pathology , Proto-Oncogene Proteins B-raf/metabolism , Glioma/pathology , Astrocytoma/pathology , MutationABSTRACT
Objective:To explore the effects of pregnancy complicated with Takayasu arteritis (TA) on maternal and fetal outcomes.Methods:The clinical data of 17 TA patients with pregnancy and finally terminated admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were collected and the maternal and infant outcomes were retrospectively analyzed.Results:Among the 24 pregnancies in 17 TA patients in our hispital, 11 patients in our hospital were primiparous (46%, 11/24) and 13 patients were multiparous (54%, 13/24); 4 cases of chronic hypertension before pregnancy (17%, 4/24), and 20 cases of non-hypertension (83%, 20/24) were abserved. Apart from the thoracoabdominal artery type, 15 cases (63%, 15/24) of brachiocephalic type, 8 cases (33%, 8/24) of extensive type, and 1 case of pulmonary artery type (4%, 1/24) were included in TA classification; the renal artery was damaged in 7 cases (7/8) of the extensive type. Among the 24 pregnancies of 17 TA patients, 8 cases of pregnancy complications occurred, including 4 cases (17%, 4/24) of preeclampsia, one case of (4%, 1/24) new-onset hypertension during pregnancy, exacerbation of existing hypertension, thrombocytopenia and ischemic stroke respectively; 3 cases of induced abortion, 1 case of induced labor, and 20 cases of final delivery were found. Of the 20 final deliveries, 3 cases (15%, 3/20) were delivered through the vagina; 17 cases (85%, 17/20) were delivered by cesarean section; 3 cases (15%, 3/20) of fetal growth restriction and 6 cases of oligohydramnios (30%, 6/20) were occurred. The median gestational age of pregnancy termination of 17 full-term neonates (85%, 17/20) and 3 premature neonates (15%, 3/20) was 38.4 weeks (range:29.6-40.9 weeks). All premature women were complicated with pre-eclampsia or severe pre-eclampsia, which lead to premature birth; the birth weight of the neonates was (2 791±783) g. Neonatal asphyxia occurred in 3 cases (15%, 3/20), and 6 cases (30%, 6/20) were admitted to the neonatal intensive care unit. None of the newborns died. The patients were followed up for 3 months to 7 years. Except for one case who underwent surgical treatment 3 years after delivery and died of intraoperative hemorrhage, the other 16 patients were in stable condition; all the newborns grew and developed well. The incidences of maternal and infant adverse events were higher in those with chronic hypertension, renal artery involvement, and no use of hormones and aspirin during pregnancy, but the differences were not statistically significant (all P>0.05). Conclusions:Pregnancy with TA has adverse effects on maternal and infant outcomes. To reduce the occurrence of maternal and child adverse events, the condition of TA patients should be fully assessed before pregnancy, multidisciplinary cooperation, regular treatment, strengthened monitoring of the condition, timely treatment of complications, selection of appropriate delivery methods after pregnancy, and vigilance of postpartum complications should be properly carried out.
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OBJECTIVE To investigate the situation ,influential factors and their re lationship of hospital pharmacy managers ’ servant leadership behavior and hospital pharmacists ’job satisfaction. METHODS The questionnaire survey method was adopted to stratified cluster sampling from primary ,secondary and tertiary hospitals ,five for each in Henan province. The personal basic data scale of pharmacists ,the hospital pharmaceutical service leadership behavior scale and the job satisfaction scale of pharmacists were used to conduct a questionnaire survey among hospital pharmacists. Excel 2019 and SPSS 23.0 software were used for statistical analysis. RESULTS A total of 956 questionnaires were distributed and 882 questionnaires were recovered ,including 841 valid questionnaires,with an effective recovery rate of 95.35%. The reliability coefficients Cronbach’s α of hospital pharmacy managers ’ servant leadership behavior scale and hospital pharmacists ’job satisfaction scale were 0.986 and 0.978,and the validity coefficients KMO were 0.908 and 0.977(P<0.01). The total score of hospital pharmacy managers ’servant leadership behavior was (110.73± 18.63). The total score of hospital pharmacists ’job satisfaction was (126.33±17.79). Hospital grade ,gender,age,professional title and highest education level all affected pharmacists ’recognition for managers ’servant leadership behavior (P<0.05). Hospital grade,age,professional title ,marital status ,highest education level and position all affected job satisfaction (P<0.05). The servant leadership behavior of hospital pharmacy managers was positively correlated with the job satisfaction of hospital pharmacists (correlation coefficient r was 0.521-0.698,all P<0.01). CONCLUSIONS The promotion and optimization the servant leadership behavior of hospital pharmacy managers can improve the job satisfaction of pharmacists ,stabilize the team of pharmacists ,and provide high-quality pharmaceutical care for patients ,so as to improve the core competitiveness of the hospital.
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Objective To investigate the anti-inflammatory role of α7 nicotinic acetylcholine receptor (α7nAChR) under inflammatory stress and its mechanisms. Methods PNU282987 was used for the activation of α7nAChR and LPS was administrated as inflammatory stressor. Realtime PCR was used for the detection of IL-1β, IL-6, TNF-α, M1 macrophage marker CD68, CD86 and M2 macrophage marker CD206, Arg1. Cell immunofluorescence was used for the detection of M1/M2 ratio and Western blot was applied for the detection of autophagy-related proteins. Results Under the stimulation of LPS, the mRNA levels of proinflammatory cytokines IL-1β, IL-6 and TNF-α, the proportion of M1 macrophage and autophagy process were increased in BV2 microglial cells. However, the administration of PNU282987 significantly decreased the mRNA levels of IL-1β, IL-6 and TNF-α and the proportion of M1 macrophage while increased the proportion of M2 macrophage and the level of autophagy process. Conclusion Activating α7nAChR plays an anti-inflammatory role in microglial cells under inflammatory stress due to the regulation of M1/M2 macrophage ratio and increase of autophagy level.