Objectives:To explore the impact of intensive lipid-lowering strategy on short-term prognosis of acute coronary syndrome(ACS)patients with multi-vessel disease. Methods:A total of 136 ACS patients with multi-vessel disease who received coronary stenting at Zhongnan Hospital of Wuhan University from August 2019 to November 2020 were enrolled in this study.Patients were divided into intensive lipid-lowering group(control low density lipoprotein cholesterol[LDL-C]below 1.0 mmol/L within 3 months,and continuously meet the standards within 12 months,n=69)or standard lipid-lowering group(gradually control LDL-C below 1.4 mmol/L within one year,n=67).The total cholesterol(TC),triglycerides(TG),LDL-C,high-density lipoprotein cholesterol(HDL-C),and lipoprotein(a)(Lp[a])data were collected.Incidence of major adverse cardiovascular events(MACE,including cardiac death,myocardial infarction,target vessel revascularization and stroke)were observed during 12 months of follow up. Results:The baseline data of the intensive lipid-lowering group and the standard lipid-lowering group were consistent before intervention.At the timeline of enrollment,there was no statistically significant difference in the blood lipid profiles(including TC,TG,LDL-C,HDL-C)between the two groups.After 3-months,patients in the intensive lipid-lowering group experienced significantly lower TC,TG,LDL-C and Lp(a)compared with baseline values(all P<0.05),while HDL-C remained unchanged(P>0.05).The standard lipid-lowering group showed a significant decrease in TC and LDL-C compared with baseline values(both P<0.05).The TC and LDL-C levels were significantly lower in the intensive lipid-lowering group than in the standard lipid-lowering group at 3/6/12 months follow up after discharge(all P<0.01).At 12 months follow-up,Kaplan-Meier survival analysis showed that the incidence of MACE was significantly lower in the intensive lipid-lowering group than in the standard lipid-lowering group(2.90%vs.14.93%,χ2=6.090,P=0.014).Multiple Cox regression analysis revealed that the intensive lipid-lowering strategy significantly reduced the risk of MACE compared with the standard lipid-lowering strategy(HR=0.177,95%CI:0.037-0.838,P=0.029). Conclusions:Our data show that intensive lipid-lowering strategy may probably reduce the incidence of short-term MACE in ASC patients with multi-vessel disease.Large-scale prospective multi-center studies are needed to further validate these results.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. METHODS: A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. RESULTS: The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. CONCLUSIONS Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Humans ; Middle Aged ; Young Adult ; Genotype ; Neutrophils ; Plasminogen Activator Inhibitor 1/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Retrospective Studies ; Sepsis/genetics*

Objective To explore the correlation between changes of gray matter volume and related cognitive impairment domains in patients with cognitive impairment of cerebral small vessel disease(CSVD)based on 7.0T magnetic resonance imaging(MRI)and voxel-based morphometry(VBM).Methods All subjects were recruited from the study on Correlation between Cerebral Deep Medullary Vein Morphology and Cognitive Impairment due to Cerebral Small Vessel Disease(registration No.:ChiCTR2100045136)from September 2021 to June 2023.We retrospectively enrolled CSVD patients with cognitive impairment as CSVD group and healthy controls with matched age,gender and education level as control group according to inclusion and exclusion criteria.Montreal cognitive assessment(MoCA)scale(Beijing version)score＜26 was divided into cognitive impairment.All subjects was assessed with MoCA,digit span test(DST),digit symbol substitution test(DSST),trail making test-A(TMT-A),verbal fluency test(VFT),Boston naming test(BNT)and auditory verbal learning test(AVLT).All subjects underwent 7.0T brain MRI scan to acquire T1-weighted three-dimensional magnetization prepared 2 rapid gradient echo(T1WI-MP2RAGE)for VBM analysis.General data and above cognitive function scores were compared between 2 groups.VBM analysis was used to compare the gray matter volume(GMV)between 2 groups and get mean GMV of significant brain regions of CSVD to explore the correlation between regions and cognitive function scores.Results(1)There were 18 individuals in control group,aged 55-70 years,and 19 individuals in CSVD group,aged 57-75 years.There was no significant difference in age,gender,education,body mass index,history of coronary heart disease,history of hyperlipidemia,smoking,drinking,total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein between the two groups(all P＞0.05).But the proportion of hypertension and diabetes history in the CSVD group was higher than control group,and there were significant differences between the two groups(12/19 vs.5/18,7/19 vs.0;all P＜0.05).(2)The scores of MoCA scale(22.0[20.0,23.0]vs.27.0[26.0,28.0],Z=-5.242),DSST(18±9 vs.40±4,t=5.212),DST(10.6±2.5 vs.13.9±2.0,t=4.364),VFT(38±11 vs.47±8,t=3.224),AVLT-immediate memory(13±3 vs.21±4,t=6.877),AVLT-short delay recall(3.4±2.5 vs.6.9±2.2,t=4.555)and BNT(22.7±3.6 vs.27.0±2.1,t=4.357)in CSVD group were lower than those in the control group.The time taken to complete TMT-A in CSVD group was longer than the control group(93.00[76.04,125.69]s vs.29.77[25.75,40.97]s,Z=-4.832).The difference of the above between two group was statistically significant(all P＜0.01).(3)Brain parenchymal fraction in CSVD group was lower than control group,and there was significant difference between two group([78.2±4.3]％vs.[80.9±3.7]％,t=2.079,P＜0.05).VBM analysis showed that gray matter volume of right inferior temporal gyrus(rITG)and right Crus 2 of cerebellar hemisphere(rCERCRU2)in CSVD group was significantly lower than control group(both P＜0.05 and corrected by false discovery rate).(4)Partial correlation analysis showed a positive correlation between gray matter volume in rITG and AVLT-short delay recall score(r=0.543,P=0.036).Conclusions CSVD patients with cognitive impairment had gray matter atrophy in rITG and rCERCRU2 and the gray matter volume in rITG was correlated with delayed memory impairment.The results of this study need to be further verified.

Objective:The clinical characteristics and prognosis of 20 patients with small B-lymphocyte proliferative disease with t (14;19) (q32; q13) were analyzed to improve the understanding of such rare cases.Methods:The clinical data of 20 patients with t (14; 19) (q32; q13) small B lymphocyte proliferative disease treated in the First Affiliated Hospital of Nanjing Medical University from April 2013 to December 2020 were retrospectively collected and analyzed. Among them, 10 cases were chronic lymphocytic leukemia (CLL) and 10 cases were other small B-cell malignancies.Results:Among the 20 cases, 10 were male and 10 were female, and the median age at diagnosis was 53.5 (35-88) years old. All patients had absolute lymphocytosis, 19 patients had lymphadenopathy, and 10 patients had splenomegaly. With a median follow-up of 36 (4-163) months, three patients died, and 11 patients had a time to treatment (TTT) ≤12 months. Ten patients (50%) were accompanied by +12, two patients (2/17, 12%) were accompanied by 13q-. Moreover, we found that t (14;19) was associated with unmutated immunoglobulin heavy-chain variable (IGHV) somatic mutation (17/19, 89%) and a biased use of IGHV4-39 (7/17, 41%) was observed. Next-generation sequencing detected one or more gene mutations in 14 (14/17, 82%) cases and a total of 25 gene mutations had been revealed, of which the most frequent were NOTCH1 (35%) , followed by SF3B1 (24%) and KMT2D (18%) . For 10 CLL patients, five (50%) were defined as Rai Ⅲ/Binet C. It is noteworthy that among the 20 cases, two cases actually involved Richter transformation.Conclusions:Small B-cell malignant tumors with abnormal t (14; 19) show unique clinical biological characteristics, often accompanied by a variety of adverse prognostic factors, and tend to have an aggressive clinical course.

OBJECTIVE：To compare the chemical constituents of petroleum ether fraction from ethanol extract of Aconitum sinomontanum before and after processing. METHODS ：After A. sinomontanum was purified with water ，the raw product decoction pieces were prepared ；the raw decoction pieces were steamed with licorice juice under high pressure to prepare processed decoction pieces of A. sinomontanum . The petroleum ether fractions of raw product and processed product were obtained after ultrasonic extraction with 95％ ethanol. The chemical constituents in the samples were analyzed by GC-MS. NIST 2014 mass spectrometry database was used to compare and match the components . The peak area normalization method was used to determine the relative percentage content of each component. RESULTS ：Before and after processing ，fatty acids and esters were the main components in the petroleum ether fraction from ethanol extract. Totally 18 chromatographic peaks were detected in the detection pieces of raw product，and 13 compounds were identified ，accounting for 94.60％ of the total content of volatile components. The components with relatively high content were （Z，Z，Z）-9，12，15-octadecatrienoic acid （26.13％），hexadecanoic acid ethyl ester （25.27％）， palmitoleic acid （10.84％），ethyl linoleic acid （10.67％），（Z，Z）-9，12-octadecenoic acid methyl ester （6.66％），pentadecanoic acid（5.11％）and so on. Totally 25 chromatographic peaks were detected in the decoction pieces of processed products，and 18 components were identified ，accounting for 82.40％ of the total content of volatile components. The components with relatively high content were palmitoleic acid （18.95％），（Z，Z）-9，12-octadecenoic acid methyl ester （17.93％），hexadecanoic acid ethyl ester（11.94％），（Z，Z，Z）-9，12，15-octadecatrienoic acid （10.54％），（Z，Z）-9，12-octadecenoic acid （5.51％），（Z）-11-hexadecanoic acid（5.30％）and so on. After processing ，7 new components were added ，5 of which were identified as （－）-eucalyptus globulus alcohol，ethyl 2-methyltetrade-canoate，6-methyl-4-phenylcoumarin，β-sitosterol，heptadecane. After processing ，no components disappeared，and the content of some components increased or decreased. CONCLUSIONS ：After processing ，the volatile components in the petroleum ether fraction from ethanol extract of A. sinomontanum are different ，and（－）-eucalyptus globulus alcohol and other components are added after processing.

Objective:The study aimed to analyze the clinical features and prognosis of chronic lymphocytic leukemia (CLL) with t (14;18) (q32;q21) and conduct a literature review.Methods:The clinical data of 8 patients with CLL carrying t (14;18) (q32;q21) seen in Jiangsu Province Hospital from November 2009 to November 2019 were collected and analyzed.Results:Among the 8 cases, 7 were male and 1 was female. The median age at diagnosis was 70 years old. The immunophenotype score was 5 in 3 patients. 4 patients were scored 4 and the remaining one scored 3. The bone marrow histopathology showed the typical manifestation of CLL. Karyotype analysis showed that all the cases carried t (14;18) (q32;q21) in the stemline. The t (14;18) (q32;q21) showed as the sole abnormality in 3 cases, with +12 in 4, and with 13q- in 1 case. 13q- was found in another 3 patients by FISH. Immunoglobulin heavy chain gene (IGHV) mutation status was detected in 6 cases and all of them were mutated. None of them used IGHV3-21. Only 1 case harbored TP53 mutation and no TP53, SF3B1, NOTCH1, or MYD88 mutations were found in the remaining cases who underwent the relevant tests. At a median follow-up of 30.9 months, 1 case died. The remaining 7 cases survived and 3 of them have not reached the treatment indication. 4 patients who received chemotherapy or immunotherapy were stable.Conclusions:The t (14;18) (q32;q21) is rare in CLL and often accompanied by +12 and mutated IGHV. CLL with t (14; 18) (q32; q21) tends to have a good prognosis.

Sex reversal, representing extraordinary sexual plasticity during the life cycle, not only triggers reproduction in animals but also affects reproductive and endocrine system-related diseases and cancers in humans. Sex reversal has been broadly reported in animals; however, an integrated resource hub of sex reversal information is still lacking. Here, we constructed a comprehensive database named ASER (Animal Sex Reversal) by integrating sex reversal-related data of 18 species from teleostei to mammalia. We systematically collected 40,018 published papers and mined the sex reversal-associated genes (SRGs), including their regulatory networks, from 1611 core papers. We annotated homologous genes and computed conservation scores for whole genomes across the 18 species. Furthermore, we collected available RNA-seq datasets and investigated the expression dynamics of SRGs during sex reversal or sex determination processes. In addition, we manually annotated 550 in situ hybridization (ISH), fluorescence in situ hybridization (FISH), and im-munohistochemistry (IHC) images of SRGs from the literature and described their spatial expression in the gonads. Collectively, ASER provides a unique and integrated resource for researchers to query and reuse organized data to explore the mechanisms and applications of SRGs in animal breeding and human health. The ASER database is publicly available at http://aser.ihb.ac.cn/.

Objective:To analysis and compare the burden of ischemic heart disease (IHD) attributable to metabolic risks in population aged 25 years and older in 2011 and 2017 in Nanjing.Methods:The data were extracted from the Nanjing Chronic Disease and Risk Factor Surveillance (2011 and 2017), the Nanjing Mortality Surveillance (2011 and 2017) and the 2016 Global Burden of Disease Study (GBD). Using GBD′s Comparative Risk Assessment Theory, the attribution burden was estimated by comparing the observed health outcomes with the health outcomes that may be observed when exposed to counterfactual levels. Based on population attributable fractions, the deaths and life expectancy losses of ischemic heart disease due to high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high total cholesterol (TC), high body mass index (BMI) and combination of four risks were estimated in 2011 and 2017. The average population structure of the world′s population from 2000 to 2025 wasusedas the standard population for standardization.Results:The number of IHD deaths attributable to four metabolic risks combination was 3 204, andwhich resulted in a loss of life expectancy of 0.90 years in 2017. High SBP appeared as the major cause of IHD deaths and Years of Life Lost (YLL). In 2017, the world standardized mortality rate (25.60×10 －5, 19.94×10 －5 and 6.83×10 －5) and the standardized YLL rate (389.31×10 －5, 335.16×10 －5, 134.60×10 －5) of the population due to high systolic blood pressure, high total cholesterol and high body mass index were significantly lower than those in 2011 (31.75×10 －5, 26.74×10 －5, 7.45×10 －5 and 469.07×10 －5, 463.70×10 －5, 142.66×10 －5); the world standardized rate and the standardized YLL rate due to high blood sugar (11.90×10 －5 and 174.61×10 －5) were significantly higher than those in 2011 (9.67×10 －5 and 150.61×10 －5) (all P<0.05). Males appeared to have higher standardized rate of YLL of IHD deaths than females, due to having metabolism risks( P<0.05). Conclusion:Metabolic exposures especially high SBP are the important risk factors whichleadto IHD deaths in Nanjing.

Objective To analyze the expression of CD160 antigen in patients with chronic lymphocytic leukemia (CLL), and to explore its clinical diagnostic value as well as the correlation of CD160 with genetic abnormalities. Methods A retrospective study was conducted from January 2015 to December 2017. Clinical data of 336 patients in the First Affiliated Hospital with Nanjing Medical University (Jiangsu Province) were collected. Among them, 200 patients were diagnosed with CLL according to WHO Classification Tumors of Hematopoietic and Lymphoid Tissues (the 4th edition of 2008), including 122 patients with typical CLL and 78 with atypical CLL based on Royal Marsden Hospital Immunomarker Integral System. Besides, there were 49 patients diagnosed with MCL and 87 patients with CD5-small B cell lymphoma (SBL). All patients' tumor cells were detected for CD160 expression and its mean fluorescence intensity (MFI) by flow cytometry. At the same time, fluorescence in situ hybridization (FISH) was used to detect P53 deletion, 13q14 deletion, ATM deletion, 6q23 deletion,+12 and IGH rearrangement in CLL cases. Molecular characteristics and genetic abnormalities were compared between CD160+ and CD160-CLL patients. Results The CD160 positive rate in typical CLL patients and atypical CLL patients was 59.8％(73/122) and 64.1％ (50/78), with MFI ranging from 14.9 to 173.9, and 29.6 to 193.7, respectively; while the CD160 positive rate in patients with CD5-SBL was 1.1％ (1 / 87) and all the MCL patients were CD160 negative. The CD160 positive rate was significantly higher in typical and atypical CLL patients than that in MCL patients or patients with CD5-SBL (P<0.01). The rearrangement rate of IGH was significantly higher in CD160+ CLL patients than that in CD160-CLL patients (62.1％ vs 31.6％, P<0.05). Conclusion CD160 has significant value for auxiliary diagnosis of CLL, especially can provide a reliable evidence for the diagnosis and differential diagnosis among atypical CLL, MCL, and SBL.

PURPOSE: MicroRNAs (miRNAs) are a group of small non-coding RNAs involved in different cancers, including lung cancer. Here, we aim to investigate the expression profiles of circulating miRNAs and their roles contributed to the progress of lung cancer. MATERIALS AND METHODS: The levels of circulating miRNA in lung cancer patients were investigated by miRNAs assay. Then we predicted the target genes of aberrantly expressing miRNAs by searching genetic databases. Based on the A549 cells transfected with miR-1246 mimics or miR-1246 inhibitor,we further measured the roles of miR-1246 involving in the epithelial-mesenchymal transition (EMT), migration and invasion capacities of lung cancer cells in vitro. Finally, we detected the effects of miR-1246 on glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway by immunofluorescence and Western blot, respectively. RESULTS: We identified that 14 miRNAs were aberrantly expressed in the serum of lung cancer patients. Among them, miR-1246 was the most up-regulated. The cell assays indicated that miR-1246 significantly increased the migration and invasion capabilities of A549 lung cancer cells. Meanwhile, immunofluorescence analysis revealed that miR-1246 promoted EMT process of A549 cells accompanying with decreasing E-cadherin expression, while increasing vimentin and transforming growth factor β (TGF-β) expression. Furthermore, an online tool predicated that miR-1246 might bind to 3′-untranslated region of GSK-3β, which was confirmed by overexpression and knockdown of miR-1246 assays. CONCLUSION: Taken together, the study illustrates that miR-1246 regulates Wnt/β-catenin pathway through targeting GSK-3β/β-catenin, which partly contributing to tumor metastasis. MiR-1246 may play an essential role in the diagnosis and therapeutic of lung cancer.
Blotting, Western ; Cadherins ; Databases, Genetic ; Diagnosis ; Epithelial-Mesenchymal Transition ; Fluorescent Antibody Technique ; Glycogen Synthase ; Humans ; In Vitro Techniques ; Lung Neoplasms ; MicroRNAs ; Neoplasm Metastasis ; RNA, Small Untranslated ; Transforming Growth Factors ; Vimentin