Objective To investigate the reasons for the inconsistent results between the vertical auto profile(VAP)method and bio-chemical homogeneous phase(BHP)method in detecting plasma low-density lipoprotein cholesterol(LDL-C),and provide experimen-tal basis for the accurate and quantitative detection of plasma LDL-C levels.Methods A total of 360 plasma samples from diabetes mellitus patients combined with carotid plaque admitted to the Department of Endocrinology of Ningbo Yinzhou Hospital of Traditional Chinese Medicine during January,2022 and January,2023 were collected.The LDL-C levels of these samples were detected by the VAP method and BHP method,respectively.The VAP method uses software to automatically calculate the area under the LDL-C curve after centrifugation of the sample as the LDL-C level(LDL-CVAP)and the BHP method directly detects the LDL-C level(LDL-CBHP)by the special surfactant method.360 samples were divided into the consistent group(group A)and inconsistent group(group B)ac-cording to the relative deviation between the LDL-CBHP and LDL-CVAP methods.Group B was further divided into the LDL-CBHP on the high side group(Group B1)and LDL-CBHP on the low side group(Group B2).Groups B1 and B2 were divided into B1-1,B1-2,B1-3 and B2-1 groups based on the degree of relative deviation.The percentages of samples and levels of lipoprotein a cholesterol[Lp(a)-C],intermediate-density lipoprotein cholesterol(IDL-C),Lp(a)-C and IDL-C[Lp(a)-C+IDL-C],very low-density lipo-protein cholesterol(VLDL-C),total cholesterol(TC)and total triglyceride(TG)in each group were compared.Results The LDL-CBHP levels of 360 samples were significantly higher than that of LDL-CVAP(P＜0.01).The percentage of samples in group B was significantly higher than that in group A,and that of group B1 was significantly higher than that of group B2(P＜0.05).The levels of Lp(a)-C,IDL-C and Lp(a)-C+IDL-C in groups B1-1,B1-2,and B1-3 were significantly higher than those in group A(P＜0.01).The relative deviation between LDL-CBHP and LDL-CVAP in 360 samples was significantly positively correlated with the levels of Lp(a)-C,IDL-C,and Lp(a)-C+IDL-C(P＜0.01).The maximum correlation coefficient was found in Lp(a)-C+IDL-C.Conclusion The results of plasma LDL-C in diabetes mellitus patients combined with carotid plaque detected by the BHP method are significantly different from those detected by the VAP method,which mainly shows that the results of the BHP method are on the high side.The higher the level of plasma Lp(a)-C+IDL-C,the greater the relative deviation between the BHP method and VAP method.The reason for the high results of LDL-C detected by the BHP method may be related to the fact that LDL-CBHP contains irremovable Lp(a)-C and cholesterol carried by IDL-C.The VAP method can be used as an accurate method for detecting real LDL-C without Lp(a)-C and IDL-C.

Objective To investigate the role and related mechanism of the soluble guanylate cyclase(sGC)-cGMP-protein kinase G(PKG)signaling pathway in the amelioration of isoproterenol(ISO)-induced cardiac hypertrophy in mice by aqueous extract of Curcuma kwangsiensis root tubers(GYJS).Methods 72 KM male mice were divided randomly into 6 groups:normal,model,propranolol control(40 mg/kg),and GYJS low-(1 g/kg),medium-(2 g/kg),and high-dose(4 g/kg)groups.Mice in the experimental groups were injected subcutaneously with ISO 10 mg/kg on days 1～3 and ISO 5 mg/kg on days 4～14 to establish a mouse cardiac hypertrophy model.4h after each subcutaneous injection of ISO,the mice in each group were administered the corresponding drugs orally for a dosing cycle of 14 days.The hearts were then removed and whole heart and left ventricle weight were measured.Myocardial tissue pathology was observed using hematoxylin and eosin and Masson staining,and sGC subunit beta-1(GUCY1B3)and transforming growth factor(TGF-β1)were detected by immunohistochemistry.Serum lactate dehydrogenase(LDH),creatine kinase(CK),and Nitric Oxide(NO),and myocardial superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were measured using respective kits.Serum cGMP was detected by enzyme-linked immunosorbent assay and quantitative reverse transcription PCR(RT-qPCR),and atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),GUCY1B3,PKG Ⅰ,and phosphodiesterase(PDE)5A mRNA expression levels were also determined by RT-qPCR.Results Compared with the model group,whole heart and left ventricle weights were significantly reduced in mice treated with propranolol or GYJS(P＜0.001 or P＜0.0001)and myocardial hypertrophy and myocardial fibrosis were significantly reversed.All the treatments significantly elevated myocardial expression of GUCY1B3(P＜0.05 or P＜0.01)and significantly reduced expression of TGF-β1(P＜0.05 or P＜0.01).The myocardial damage markers LDH and CK were significantly reduced(P＜0.05 or P＜0.01)while NO and cGMP were significantly elevated(P＜0.05 or P＜0.01),the myocardial oxidative stress indicator MDA was significantly reduced(P＜0.05 or P＜0.01)and SOD activity was significantly increased(P＜0.05 or P＜0.01).mRNA levels of the myocardial hypertrophy markers ANP,BNP,and PDE5A were significantly reduced(P＜0.05,P＜0.01,or P＜0.001)and the mRNA levels of GUCY1B3 and PKG Ⅰ were significantly increased(P＜0.01 or P＜0.001).Conclusions GYJS may improve cardiac hypertrophy by modulating the sGC-cGMP-PKG signaling pathway.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

OBJECTIVE: To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT). METHODS: From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up. RESULTS: The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA. CONCLUSION CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.
Female ; Humans ; Karyotyping ; Microarray Analysis ; Pregnancy ; Prenatal Diagnosis ; Trisomy 13 Syndrome/genetics* ; Trisomy 18 Syndrome

Objective:To compare the clinical characteristics, clinical efficacy and adverse drug reactions of rheumatoid factor (RF) positive (+ ) and negative (-) polyarticular juvenile idiopathic arthritis (PJIA).Methods:The clinical data of 67 PJIA patients admitted into Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to December 2018 were analyzed retrospectively.They were divided into RF-positive PJIA group [RF (+ ) group, 23 cases] and RF-negative PJIA group [RF (-) group, 44 cases] according to RF titer.The clinical characteristics, laboratory indexes and clinical efficacy evaluation of the two groups were compared.Results:(1)Distribution of affected joints: the top 3 affected joints in the RF (+ ) group were the knuckles (16 cases, 69.57%), the wrists (15 cases, 65.22%) and the ankles (13 cases, 56.52%), and those in the RF (-) group were the knees (33 cases, 75.00%), ankle joints (29 cases, 65.91%) and hip joints (26 cases, 59.09%). The wrist joint involvement of the RF (+ ) group was significantly higher than that of the RF (-) group, while the knee joint involvement was lower than that of the RF (-) group.The difference was statistically significant (all P<0.01). (2)Magnetic resonance changes of the affected joints: articular cavity effusion (54 cases, 84.38%), synovial thickening (44 cases, 68.75%) and bone edema (26 cases, 40.63%) are common in both groups.The incidence of bone destruction (7 cases, 70.00%) and soft tissue edema (7 cases, 70.00%) in the RF (+ ) group was higher than that in the RF (-) group (2 cases, 18.18% and 2 cases, 18.18%), the difference was statistically significant (all P<0.05). (3) Changes in laboratory indicators: the positive rates of C-reactive protein, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide antibody and anti-nuclear antibody in the RF(+ ) group were significantly higher than those in the RF(-) group, the difference was statistically significant (all P<0.05). (4)Juvenile arthritis disease activity score 27 (JADAS27): the score difference between RF(+ ) group and RF(-) group was not statistically significant [(22.83±5.60) scores vs.(23.07±6.66) scores, t=0.148, P>0.05]. (5) Efficacy analysis: 2 patients were lost to follow-up after discharge, and the remaining 65 patients were treated with traditional therapy, of which 30 were given biologics at the first hospitalization, 9 cases were treated with biologics after the failure of traditional treatments, and 35 patients were treated with biologics to control disease activity.In different dosage regimens, the disease remission rate in the RF(-) group is generally higher than that in the RF(+ ) group. Conclusions:PJIA patients have complicated joint involvement, RF-positive patients are more prone to joint destruction, and traditional treatments are less effective.Biological agents can effectively improve the symptoms of severe PJIA patients, especially those with poor prognosis.

Objective:To analyze the clinical characteristics and causes of death of 80 dead cases with confirmed coronavirus disease 2019 (COVID-19).Methods:The clinical data of 80 dead patients with COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 11 to February 11, 2020 were retrospectively analyzed.The laboratory examination indexes (including white blood cells, lymphocytes, procalcitonin (PCT), lactic acid, D-dimmer, fibrinogen degradation products, N-terminal pro-brain natriuretic peptide (N-proBNP), ultra sensitive-troponin I, lactate dehydrogenase (LDH) and CD4 + T lymphocyte) of the patients at the time of admission were compared with the indexes at the last time before death. Statistical analysis was conducted by using paired t test or Wilcoxon′s signed rank test. Results:The median age was 72 years old of the 80 patients, and 78.75%(63/80) of them were older than 60 years. Thirty-six cases (45.00%) were severe and 44(55.00%) were critical at admission. Fifty-eight cases (72.50%) had underlying diseases. The common underlying diseases were hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and chronic obstructive pulmonary disease. Comparing the patients′ first laboratory tests at admission with those before death, white blood cells increased (8.01(4.86, 12.29)×10 9/L vs 12.55(8.25, 17.66)×10 9/L), lymphocytes decreased (0.70(0.46, 0.88)×10 9/L vs 0.54(0.39, 0.75)×10 9/L), PCT increased (0.20(0.11, 0.74) μg/L vs 1.00(0.20, 1.99) μg/L), lactic acid increased (2.10(1.40, 3.10) mmol/L vs 3.10(2.60, 4.10) mmol/L), D-dimmer increased (4.33(0.97, 18.98) mg/L vs 15.29(5.17, 53.44) mg/L), fibrinogen degradation products increased (15.90(3.58, 76.60) mg/L vs 63.14(21.23, 110.67) mg/L), N-proBNP increased (1 078.00(347.35, 2 996.50) ng/L vs 3 439.50(1 576.00, 9 281.50) ng/L), ultra-sensitive troponin I increased (0.08(0.03, 0.17) μg/L vs 0.33(0.14, 2.47) μg/L), LDH increased (397.00(327.00, 523.50) U/L vs 624.00(481.00, 854.00) U/L) and CD4 + T lymphocyte decreased (137.00(104.00, 168.00)/μL vs 97.00(67.00, 128.00)/μL). The differences between the two groups were all statistically significant ( W=238.00, 1 053.50, 150.00, 152.00, 192.00, 190.00, 108.00, 57.00, 53.00 and 40.00, respectively, all P<0.05). All patients received antiviral and respiratory-support therapy and the main cause of death was respiratory failure caused by intractable hypoxemia and multiple organ failure. Among them, seven cases died in one day hospitalization, and 66 cases died in seven days hospitalization. Conclusions:Elderly patients with a variety of chronic underlying diseases have poor prognosis. It′s essential to pay more attention and deal with the above clinical characteristics at an early stage to improve the outcome of the COVID-19 patients.

Objective:To investigate the associations of brain white matter integrity deficits, and to explore the association of fractional anisotropy (FA) abnormality with clinical symptoms and cognitive impairments, as well as the prediction effect of the FA alterations on symptoms and cognitive function outcomes in the acute stage of schizophrenia from the whole brain level based on magnetic resonance diffusion tensor imaging (DTI).Methods:From November 2019 to December 2020, thirty-eight patients with first-episode schizophrenia and 38 healthy controls were recruited in this study. Wisconsin card classification test (WCST), digit span test (DST forward/backward), verbal fluency test, Stroop (A/B/C), trail making test (TMT-A/B), as well as positive and negative syndrome scale (PANSS) were utilized to evaluate patients' cognitive function and clinical symptoms both before and after 8 weeks of risperidone monotherapy. T1-weighted images and DTI data of all the subjects were collected . FSL and SPM8 were used to preprocess MRI data and compare the between-group differences of FA. Support vector machine (SVM) analysis was used to evaluate the accuracy of abnormal FA values in differentiating schizophrenic patients from healthy controls. Finally, stepwise multiple regression analysis or generalized linear models were used to explore the associations between white matter integrity and symptoms or cognition.Results:Before treatment, patients' FA values of right medial temporal lobe (mTL), cuneus, anterior cingulate gyrus (ACG) and inferior parietal lobe (IPL) were significantly lower than those in healthy controls ( P<0.01, GRF corrected), and patients' FA values of bilateral middle cingulate gyrus (mCG) were significantly higher than those in the control group ( P<0.01, GRF corrected). SVM analysis showed that four combinations could distinguish the patients from the control with the most accurate rate of 89.47%. Patients' baseline decreased FA values in the right IPL were positively associated with their increased total response time in WCST ( β=0.489, P=0.003, FDR corrected), correct response time in WCST ( β=0.450, P=0.008, FDR corrected), error response time in WCST ( β=0.435, P=0.008, FDR corrected), TMT-B ( β=0.296, P=0.042, FDR corrected), Stroop-C ( β=0.345, P=0.035, FDR corrected), and PANSS-P ( β=0.321, P=0.042, FDR corrected). Reduced FA values in the right mTL in patient group were significantly negatively related to the total time spent on the TMT-A ( β=-0.425, P=0.009, FDR corrected) and TMT-B ( β=-0.325, P=0.026 with FDR correction). Increased FA values in right mCG in patient group demonstrated positive associations with total response time in the WCST ( β=0.585, P=0.002, FDR corrected), correct response time in WCST ( β=0.524, P=0.003, FDR corrected), error response time in WCST ( β=0.536, P=0.003, FDR corrected) and total time consuming in TMT-B ( β=0.484, P=0.004, FDR corrected), as well as negative associations with DST-forward ( β=-0.319, P=0.042, FDR corrected). After treatment, patients' percentage changes in total response time of WCST ( β=0.715, P<0.001, FDR corrected), correct response time of WCST ( β=0.752, P<0.001, FDR corrected), as well as total time-consuming of TMT-A ( β=1.333, P=0.001, FDR corrected) showed positive correlations with baseline increased FA values in the left mCG. Percentage alteration of Stroop-B was negatively correlated with baseline FA values in the right cuneus ( β=-0.745, P=0.015, FDR corrected). Conclusions:The combination of abnormal FA values in multiple brain regions may be potential biomarkers to distinguish schizophrenic patients from healthy volunteers. There was regional dependence in the associations of the impairment of white matter integrity with the cognitive impairment, the severity of psychopathological symptoms as well as the prognosis of patients in the acute stage.

BACKGROUND: Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells (CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells. METHODS: BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells. Tumor growth and pulmonary metastasis were assessed. ALDEFLOUR™ assays were performed to identify aldehyde dehydrogenasebright (ALDHbr) tumor cells. ALDHbr cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry. The effects of CD8+ T cells on ALDHbr tumor cells were assessed in vitro and in vivo. The expression profiles of ALDHbr and ALDHdim 4T1 tumor cells were determined. The levels of plasma IFN-γ were measured by enzyme-linked immunosorbent assay, and their associations with the percentages of ALDHbr tumor cells were evaluated. The effects of IFN-γ on ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro. RESULTS: There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice (25.40 vs. 54.67, P < 0.050). CD8+ T cells decreased the percentages of ALDHbr 4T1 tumor cells in vitro (control vs. effector to target ratio of 1:1, 10.15% vs. 5.76%, P < 0.050) and in vivo (control vs. CD8+ T cell depletion, 10.15% vs. 21.75%, P < 0.001). The functions of upregulated genes in ALDHbr 4T1 tumor cells were enriched in the pathway of response to IFN-γ. The levels of plasma IFN-γ decreased gradually in tumor-bearing BALB/c mice, while the percentages of ALDHbr tumor cells in primary tumors increased. IFN-γ at a concentration of 26.68 ng/mL decreased the percentages of ALDHbr 4T1 tumor cells (22.88% vs. 9.88%, P < 0.050) and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells (0.86 vs. 0.49, P < 0.050) and inhibited the abilities of sphere formation (sphere diameter <200 μm, 159.50 vs. 72.0; ≥200 μm, 127.0 vs. 59.0; both P < 0.050) and invasion (89.67 vs. 67.67, P < 0.001) of 4T1 tumor cells. CONCLUSION CD8+ T cells and IFN-γ decreased CSC numbers in a 4T1 mouse model of breast cancer. The application of IFN-γ may be a potential strategy for reducing CSCs in breast cancer.
Aldehydes ; Animals ; Breast Neoplasms ; Cell Line, Tumor ; Female ; Humans ; Interferon-gamma ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplastic Stem Cells

OBJECTIVE: To carry out prenatal diagnosis on a fetus with abnormal findings by ultrasonography and non-invasive prenatal testing. METHODS: The fetus and both parents were subjected to chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis. RESULTS: The karyotypes of both parents were normal. The fetus carried a 46,N,der(X;16)(q28;q22) unbalanced translocation. SNP-array analysis confirmed that the derived chromosomal fragment of the fetus has originated from 16q. The fetus was diagnosed with 16q partial trisomy syndrome. CONCLUSION Combined chromosomal karyotyping analysis and SNP-array can detect chromosomal aberrations at submicroscopic level and enable accurate diagnosis of the fetus.

[摘 要] 目的：检测长链非编码RNA（long non-coding RNA，lncRNA）ARHGAP5-AS1在乳腺癌组织及细胞中的表达，分析其表达与患者临床病理参数及预后的相关性，并初步探讨其对乳腺癌细胞体外增殖、迁移和侵袭的影响。方法：通过对TCGA数据库中乳腺癌相关数据集的生物信息学分析，筛选出在乳腺癌中低表达且与患者不良预后相关的lncRNA ARHGAP5-AS1，采用qPCR方法在江南大学附属医院肿瘤科从2010年4月至2016年10月收集的乳腺癌组织中验证其表达。采用χ2检验分析ARHGAP5-AS1表达与乳腺癌患者临床病理参数之间的关系，Kaplan-Meier生存分析构建生存曲线，比较高、低表达组的总生存期和无复发生存期。CCK-8实验、划痕实验和Transwell实验分别检测ARHGAP5-AS1敲低对乳腺癌细胞MDA-MB-231和BT-549的增殖、迁移和侵袭的影响。结果：TCGA数据库分析结果显示，ARHGAP5-AS1在乳腺癌组织中的表达水平显著低于正常乳腺组织（P<0.01），其低表达与较大肿瘤直径（T3）、远处转移（M1）、ER和PR阴性以及较短的总生存期显著相关（均P<0.05）。乳腺癌组织中ARHGAP5-AS1表达水平显著低于癌旁组织（P<0.05），其低表达与较大的肿瘤直径和淋巴结转移相关（均P<0.05）。同样，ARHGAP5-AS1在6株人乳腺癌细胞系（MDA-MB-231、BT-549、MDA-MB-468、MCF-7、HCC1937、Hs578T）中的表达水平也显著低于正常乳腺上皮细胞系（MCF-10A）（均P<0.05）。细胞功能实验显示，ARHGAP5-AS1敲低促进MDA-MB-231和BT-549细胞的增殖、迁移和侵袭（均P<0.05）。结论：ARHGAP5-AS1异常低表达可能通过促进乳腺癌细胞的增殖、迁移和侵袭影响乳腺癌的发生发展。