Application of exercise testing in the diagnosis and evaluation of cardiovascular diseases in children / 国际儿科学杂志

In recent years, exercise testing has been increasingly used in pediatrics, especially in pediatric cardiovascular diseases.Its ability to monitor heart rate, blood pressure, electrocardiogram, oxygen saturation, and expiratory gas analysis is of great clinical value.In pediatric cardiovascular diseases, exercise testing can further evaluate arrhythmias, facilitate the differential diagnosis of syncope, and detect early myocardial perfusion defects in children with cardiomyopathy and Kawasaki disease; in addition, expiratory gas analysis of exercise testing can assess cardiorespiratory fitness in children and the operative results of congenital heart disease, etc.This article reviews the use of exercise testing in children with arrhythmias, cardiomyopathy, congenital heart disease, and Kawasaki disease.

Transcriptomic Effects of LINC01614 on Lung Cancer A549 Cells and Relevance of Drug Resistance / 肿瘤防治研究

Objective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells knocked down with LINC01614. We validated the transcriptomic differential genes MCAM and ABCC3 at the gene level and MCAM at the protein level, detected the IC50 changes of A549 cells after knockdown of LINC01614 under the effect of different concentrations of cisplatin, and detected the effect of knockdown of LINC01614 on the migration ability of A549 cells. Results Of the 2 713 DEGs after knockdown of LINC01614, a total of 1 626 genes were up-regulated and 1, 087 genes were down-regulated. GO analysis showed that DEGs were associated with intracellular signaling, cell adhesion, and so on. Meanwhile, the KEGG analysis showed that DEGs were associated with the Wnt signaling pathway, TGF-β signaling pathway, and Rap1 signaling pathway. Selection of drug resistance-associated gene ABCC3 from DEGs for validation with MCAM: qRT-PCR results showed that knockdown of LINC01614 significantly down-regulated the expression of MCAM (P<0.05) and upregulated the expression of ABCC3 on A549 cells (P<0.05). After knockdown of LINC01614, the protein expression of MCAM, was significantly decreased in A549 cells (P<0.05); the IC50 of A549 cells to cisplatin was significantly increased (P<0.05); and the scratch healing rate of A549 cells was also significantly decreased (P<0.05). Conclusion LINC01614 may be associated with the proliferation, invasion, and apoptotic pathways of A549 cells. In addition, LINC01614 may exert its migration ability through MCAM and chemoresistance to cisplatin through ABCC3.

Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome / 中国中药杂志

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, β-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

The Association between Exposure to Second-Hand Smoke and Disease in the Chinese Population: A Systematic Review and Meta-Analysis / 生物医学与环境科学（英文）

OBJECTIVE@#To analyze the association between exposure to second-hand smoke (SHS) and 23 diseases, categorized into four classifications, among the Chinese population.@*METHODS@#We searched the literature up to June 30, 2021, and eligible studies were identified according to the PECOS format: Participants and Competitors (Chinese population), Exposure (SHS), Outcomes (Disease or Death), and Study design (Case-control or Cohort).@*RESULTS@#In total, 53 studies were selected. The odds ratio (OR) for all types of cancer was 1.79 (1.56-2.05), and for individual cancers was 1.92 (1.42-2.59) for lung cancer, 1.57 (1.40-1.76) for breast cancer, 1.52 (1.12-2.05) for bladder cancer, and 1.37 (1.08-1.73) for liver cancer. The OR for circulatory system diseases was 1.92 (1.29-2.85), with a value of 2.29 (1.26-4.159) for stroke. The OR of respiratory system diseases was 1.76 (1.13-2.74), with a value of 1.82 (1.07-3.11) for childhood asthma. The original ORs were also shown for other diseases. Subgroup analyses were performed for lung and breast cancer. The ORs varied according to time period and were significant during exposure in the household; For lung cancer, the OR was significant in women.@*CONCLUSION@#The effect of SHS exposure in China was similar to that in Western countries, but its definition and characterization require further clarification. Studies on the association between SHS exposure and certain diseases with high incidence rates are insufficient.

Risk factors associated with malignant vasovagal syncope in children / 中华儿科杂志

Objective: To analyze the clinical characteristics and risk factors of malignant vasovagal syncope (VVS) in children. Methods: This was a case-control study. The data of 368 VVS patients who were treated in the Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics from June 2017 to December 2021 was collected and analyzed. They were divided into malignant VVS group and non-malignant VVS group according to the presence of sinus arrest, and then their demographic characteristics were compared. The children with malignant VVS and complete clinical information were recruited into the case group and were matched by age and sex (1∶4 ratio) with non-malignant VVS patients during the same period.Their clinical characteristics and lab tests were compared. Independent sample t test, Mann Whitney U or χ2 test was used for comparison between groups.Logistic regression was used to analyze the risk factors for malignant VVS in children. Results: Eleven malignant VVS and 342 non-malignant VVS met the inclusion and exclusion critera. Eleven malignant VVS and 44 non-malignant children were recruited in the case-control study. Ten patients of the 11 malignant VVS had a cardiac arrest occurring at 35 (28, 35) minutes of the head-up tilt test, and the duration of sinus arrest was (9±5) s. One patient had syncope occurring while waiting for drawing blood, and the duration of sinus arrest was 3.4 s. The children with malignant vasovagal syncope were younger than non-malignant VVS patients (9 (7, 10) vs. 12 (10, 14) years old, P<0.05), and had higher mean corpuscular hemoglobin concentration (MCHC) and standard deviation of the mean cardiac cycle over 5-minute period within 24 hours ((347±9) vs. (340±8) g/L, (124±9) vs. (113±28) ms, both P<0.05). Logistic regression analysis showed that MCHC was an independent risk factor for malignant VVS in pediatric patients (OR=1.13, 95%CI 1.02-1.26, P=0.024). Conclusions: The onset age of malignant VVS was younger, with no other special clinical manifestations. MCHC was an independent risk factor for malignant VVS.

The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells / 中华肿瘤杂志

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

Impact of Smoke-Free Legislation on Acute Myocardial Infarction and Subtypes of Stroke Incidence in Shenzhen, China, 2012-2016: An Interrupted Time Series Analysis / 生物医学与环境科学（英文）

OBJECTIVE@#This study assesses the impact of smoke-free legislation on the incidence rate for acute myocardial infarction (AMI) and stroke in Shenzhen.@*METHODS@#Data on ischemic ( n = 72,945) and hemorrhagic ( n = 18,659) stroke and AMI ( n = 17,431) incidence covering about 12 million people in Shenzhen from 2012 to 2016 were used. Immediate and gradual changes in incidence rates were analyzed using segmented Poisson regression.@*RESULTS@#Following the smoke-free legislation, a 9% (95% CI: 3%-15%) immediate reduction was observed in AMI incidence, especially in men (8%, 95% CI: 1%-14%) and in those aged 65 years and older (17%, 95% CI: 9%-25%). The gradual annual benefits were observed only in hemorrhagic and ischemic stroke incidence, with a 7% (95% CI: 2%-11%) and 6% (95% CI: 4%-8%) decrease per year, respectively. This health effect extended gradually to the 50-64 age group. In addition, neither the immediate nor gradual decrease in stroke and AMI incidence rates did not show statistical significance among the 35-49 age group ( P > 0.05).@*CONCLUSION@#Smoke-free legislation was enforced well in Shenzhen, which would generate good experiences for other cities to enact and enforce smoke-free laws. This study also provided more evidence of the health benefits of smoke-free laws on stroke and AMI.

Application of exosomes in the diagnosis and treatment of cardiovascular diseases / 国际儿科学杂志

The cardiovascular diseases, which have the increasing incidence and high mortality rate, have brought a great impact on people′s lives and health.Being lipid inclusions with 30~150 nm in diameter, exosomes can be secreted by most cells in the body, and proteins, lipids, nucleic acids and other substances derived from those cells are wrapped inside.Exosomes play a variety of biological roles in the communication between cells, such as mediating immune response, inflammatory response, cell migration and differentiation.Research on exosomes has made significant progress, and the roles of exosomes in cardiovascular diseases have consequently attracted more and more attention in recent years.The communication of exosomes between cardiomyocytes and between heart and peripheral tissues has provided new strategies for the diagnosis and treatment of cardiovascular diseases.Application of exosomes in the diagnosis and treatment of cardiovascular diseases such as heart failure, viral myocarditis, Kawasaki disease and dilated cardiomyopathy is summarized in this review.

Casticin inhibits the proliferation, migration and invasion of bladder cancer cells by inhibition of TM7SF4 expression / 中华肿瘤杂志

Objective: To explore the effect and mechanism of Casticin (CAS) on the proliferation, migration and invasion of bladder cancer T24 cells. Methods: T24 cells were cultured in vitro and divided into control group, 5, 10, 20 μmol/L CAS groups, si-NC group, si-TM7SF4 group, CAS+ pcDNA group and CAS+ pcDNA-TM7SF4 group. Cell counting kit-8 (CCK-8) was used to detect cell proliferation; Transwell was used to detect cell migration and invasion; western blot was used to detect the protein expressions of cyclin D1, p21, MMP-2, MMP-9 and TM7SF4, and real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of TM7SF4 mRNA. Results: The inhibition rates of T24 cells in the 5, 10, 20 μmol/L CAS groups were (17.68±1.41)%, (33.54±3.16)% and (61.44±5.50)%, respectively, higher than (0.00±0.00)% of the control group (P<0.001), but the numbers of migration and invasion were 72.83±5.66, 59.13±4.27, 41.25±3.22 and 55.83±5.15, 42.19±3.06, 31.13±3.22, respectively, lower than 86.11±5.16 and 68.82±5.29 of the control group (P<0.001). The protein expression levels of cyclin D1, MMP-2, MMP-9, TM7SF4 and the expression levels of TM7SF4 mRNA in the 5, 10, and 20 μmol/L CAS groups were lower than the control group (P<0.001). However, the protein expression levels of p21 were 0.37±0.03, 0.51±0.04, and 0.66±0.06, respectively, higher than 0.25±0.03 in the control group (P<0.001). The inhibition rate of T24 cells in the si-TM7SF4 group was (50.35±4.67)%, higher than (6.31±0.58)% in the si-NC group (P<0.001), but the numbers of migration and invasion were 53.51±4.18 and 42.92±3.81, lower than 85.26±4.99 and 67.93±4.64 of the si-NC group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2, MMP-9 in the si-TM7SF4 group were lower than the si-NC group (P<0.001). However, the protein expression level of p21 in the si-TM7SF4 group was higher than the si-NC group (P<0.001). The inhibitory rate of T24 cells in the CAS+ pcDNA-TM7SF4 group was (21.45±2.46)%, lower than (64.06±4.49)% of the CAS+ pcDNA group (P<0.001), but the number of migration and invasion in the CAS+ pcDNA-TM7SF4 group were 75.66±6.57 and 59.35±5.40, higher than 40.43±3.85 and 30.25±3.32 in the CAS+ pcDNA group (P<0.001). The protein expression levels of TM7SF4, CyclinD1, MMP-2 and MMP-9 in the CAS+ pcDNA-TM7SF4 group were higher than the CAS+ pcDNA group (P<0.001), but the protein expression level of p21 was lower than the CAS+ pcDNA group (P<0.001). Conclusion: CAS may suppress the proliferation, migration and invasion of bladder cancer T24 cells by inhibiting the expression of TM7SF4.

Effect of sacubitril valsartan sodium tablets on serum tenascin-C level and myocardial remodeling in patients of chronic left heart failure complicated with renal failure / 中国医师进修杂志

Objective:To study the effect of sacubitril valsartan sodium tablets on serum tenascin-C (TN-C) level and myocardial remodeling in patients of chronic left heart failure (CHF) complicated with renal failure.Methods:A total of 84 patients with chronic left heart failure complicated with renal failure admitted to Qinhuangdao Jungong Hospital from October 2020 to October 2021 were included and divided into the observation group (treated with sacubitril valsartan sodium tablets) and the control group (treated with valsartan), with 42 cases in each group according to the random number table method. The clinical efficacy of the two groups was compared after 3 months of treatment. The TN-C level and cardiac function index left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), troponin T (cTnT) and other index before the treatment and after 3 months of treatment were compared between the two groups.Results:After 3 months of treatment, the total effective rate between the two groups had no significant difference ( P>0.05). After 3 months of treatment, the TN-C level in the observation group was lower than that in the control group: (32.42 ± 4.22) μg/L vs. (37.32 ± 4.86) μg/L; and the LVEF in the observation group was higher than that in the control group: (41.21 ± 5.39)% vs. (37.76 ± 5.45)%, the differences were statistically significant ( P<0.05). The LVEDD and cTnT in the two groups had no significant differences ( P>0.05). After 3 months of treatment, neuroendocrine factors norepinephrine, aldosterone, angiotensin Ⅱlevels in the in the observation group were lower than those in the control group: (1 668.60 ± 251.19) pmol/L vs. (2 005.86 ± 280.91) pmol/L, (246.97 ± 13.99) ng/L vs. (275.41 ± 19.38) ng/L, (99.68 ± 8.57) ng/L vs. (112.20 ± 9.52) ng/L, the differences were statistically significant ( P<0.05). Conclusions:Sacubitril valsartan sodium tablets have a good effect in the treatment of CHF complicated with renal failure, which can improve the cardiac function and inhibit the over-activation of neuroendocrine hormones.

Correlation of plasma prolactin and cortisol with vasovagal syncope in children / 中华实用儿科临床杂志

Objective:To investigate the changes of plasma prolactin (PRL) and cortisol (Cor) in the head up tilt test (HUT) in children with vasovagal syncope (VVS), and their correlation with VVS.Methods:From May 2019 to May 2020, 75 children diagnosed as VVS through positive HUT in the Children′s Hospital, Capital Institute of Pediatrics were retrospectively recruited as VVS group, while 29 healthy children with negative HUT during the same period were collected in healthy control group.Heart rate (HR) and blood pressure [systolic and diastolic blood pressure (SBP, DBP)] were monitored using a noninvasive continuous blood pressure monitor.The changes of HR, SBP and DBP were analyzed and their differences between the supine position and positive reaction of HUT were compared.The contents of PRL and Cor in the supine position and positive reaction of HUT were measured using the electrochemiluminescence, and their changes (ΔPRL and ΔCor) were calculated.Differences between groups were analyzed by the two-tailed Student′s t-test or the Mann- Whitney test.Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of ΔPRL on VVS. Results:There were no significant differences in the age, gender, body mass index, blood electrolyte, syncope frequency and syncope course between VVS group and healthy control group (all P>0.05). There was no significant difference in syncope frequency and course of syncope among subtypes of VVS group (vasodepressor syncope, mixed syncope, cardioinhibitory syncope)(all P>0.05). Compared with healthy control group, PRL after HUT was significantly higher in VVS group[36.23 (22.08, 61.97) μg/L vs.11.47 (8.00, 23.25 ) μg/L, Z=-5.40, P<0.01]. Both ΔPRL [25.36( 9.92, 48.93) μg/L vs.-0.10(- 2.67, 9.32) μg/L, Z=-5.39, P<0.01] and ΔCor [(84.4±43.6) μg/L vs.(57.6±64.6) μg/L, t=-2.44, P<0.05 ] were significantly higher in VVS group than those of healthy control group.PRL at HUT positive reaction was negatively correlated with SBP and DBP ( r=- 0.46, -0.45, all P<0.01). In VVS group, PRL at HUT positive reaction was negatively correlated with SBP ( r=-0.38, -0.24, all P<0.05). In VVS group, ΔCor after HUT was negatively correlated with SBP ( r=-0.25, P<0.05). ROC curves revealed that the cut-off value of ΔPRL in predicting HUT was 4.03 μg/L, with the sensitivity of 89.3% and specificity of 72.4%. Conclusions:Plasma PRL and Cor increase during syncope in VVS children, and plasma PRL is correlated with blood pressure drop.The increased plasma level of PRL in VVS children with positive HUT is correlated with blood pressure, and ΔCor is correlated with SBP.Plasma PRL and Cor may be involved in the pathogenesis of VVS and ΔPRL presents the diagnostic potential of VVS in children.

Modified Linggui Zhugan Decoction () Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α Signaling Pathways in Obese Type 2 Diabetic Rats / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of modified Linggui Zhugan Decoction (, MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus (T2DM) rats.@*METHODS@#Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2DM (ob-T2DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M, 9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups, 10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance (IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or Akt)/the mammalian target of rapamycin (mTOR)-ribosome protein subunit 6 kinase 1 (S6K1 )/AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α) pathways were also studied.@*RESULTS@#MLZD dose-dependently reduced fasting blood glucose, fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2DM rats (P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2DM rats after 4-week treatment (P<0.05 or P<0.01). Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6 (P<0.05 or P<0.01). MLZD regulated the PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways and restored the tissue structure of liver and pancreas (P<0.05 or P<0.01).@*CONCLUSIONS@#MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways.

Association between MTHFR gene polymorphism and primary hypertension in children / 中国当代儿科杂志

OBJECTIVES@#To study the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in children with primary hypertension, and to explore the association between MTHFR C677T gene polymorphism and H-type hypertension in children.@*METHODS@#A total of 121 children with primary hypertension who were hospitalized in the department of cardiovascular medicine from January to July 2021, newly diagnosed, and untreated were retrospectively selected as the subjects. The children were divided into three groups: CC genotype (19 children), CT genotype (51 children), and TT genotype (51 children). According to the serum homocysteine (Hcy) level, they were divided two groups: H-type hypertension (47 children) and simple hypertension (74 children). The medical data were compared between the groups. The association between MTHFR C677T gene polymorphism and H-type hypertension was evaluated.@*RESULTS@#The mutation frequency of T allele in children with primary hypertension was significantly higher than that in healthy adults in Beijing and Chinese Han adults (P<0.001). The serum Hcy level in the TT genotype group was significantly higher than that in the CC and CT genotype groups (P<0.001). The serum Hcy level in the H-type hypertension group was significantly higher than that in the simple hypertension group (P<0.001), and MTHFR C677T was mostly TT genotype, which was associated with the risk of H-type hypertension (OR=12.71, P<0.001). There was no significant difference in the incidence rate of target organ damage between the H-type hypertension and simple hypertension groups (P>0.05). However, multiple organ involvement was observed in the H-type hypertension group at diagnosis, accounting for 11% (5/47).@*CONCLUSIONS@#The mutation rate of MTHFR C677T T allele in children with primary hypertension is high and associated with the serum Hcy level. TT genotype is an independent risk factor for H-type hypertension in children, and it may be related to the severity of early target organ damage.

Study of blood pressure variability in children with H-type hypertension / 中华实用儿科临床杂志

Objective:To summarize characteristics and rules of blood pressure variability (BPV) in children with H-type hypertension, in an attempt to explore some basis for further selection of the time points of treatment.Methods:A total of 117 children diagnosed as essential hypertension in Children′s Hospital Affiliated to Capital Institute of Pediatrics from March 2018 to September 2019 were selected as the research objective.According to the serum level of homocysteine (Hcy), those children were divided into the simple essential hypertension group (74 cases, Hcy≤13.9 μmol/L) and the H-type hypertension group (43 cases, Hcy>13.9 μmol/L). All children received 24 h ambulatory blood pressure monitoring (24 h ABPM), and BPV indexes were recorded and subject to group comparison.Meanwhile, the serum Hcy level was monitored.Besides, the demographic data and such blood biochemical indexes as blood glucose, blood fat and renal function were recorded or measured for an analysis of the correlation between BPV and each index.Results:There were no significant differences in gender, age, body mass index (BMI) and biochemical indexes between the simple essential hypertension group and the H-type hypertension group (all P>0.05). Compared with the simple essential hypertension group, the H-type hypertension group had a significantly higher 24 h systolic blood pressure standard deviation [24 h SSD, (11.21±3.23) mmHg vs.(9.64±2.73) mmHg, 1 mmHg=0.133 kPa, t=-2.806, P<0.05], nighttime systolic blood pressure standard deviation [nSSD, (10.79±3.89) mmHg vs.(9.26±3.23) mmHg, t=-2.292, P<0.05], and nighttime diastolic blood pressure standard deviation [nDSD, (10.23±3.53) mmHg vs.(8.73±2.93) mmHg, t=-2.617, P<0.05]. Pearson correlation analysis showed that the serum Hcy level was significantly positively correlated with 24 h, SSD, nSSD and nDSD ( r=0.194, 0.183, 0.182, all P<0.05). Conclusions:24 h SSD in children with H-type hypertension is significantly higher, with an obvious increase in both nSSD and nDSD, and the serum Hcy level was significantly positively correlated with BPV, which suggested that it was required to effectively control the serum Hcy level, reduce the range of blood pressure fluctuation and select the optimal time points of treatment, thus delaying the progress of hypertension.

Pandemic of the aging society - sporadic cerebral small vessel disease / 中华医学杂志(英文版)

Age-related sporadic cerebral small vessel disease (CSVD) has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population. The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers' understanding in the in vivo evolution of CSVD, its impact upon the brain, its risk factors, and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD. In this review, we aimed to provide an update on the pathophysiology, risk factors, biomarkers, and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML).@*METHODS@#Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M@*RESULTS@#Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M@*CONCLUSION@#The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

A retrospective study to compare the treatment outcomes with and without surgical navigation for fracture of the orbital wall / 中华创伤杂志(英文版)

PURPOSE@#To evaluate the outcomes with and without aid of a computer-assisted surgical navigation system (CASNS) for treatment of unilateral orbital wall fracture (OWF).@*METHODS@#Patients who came to our hospital for repairing unilateral traumatic OWF from 2014 to 2017 were included in this study. The patients were divided into the navigation group who accepted orbital wall reconstruction aided by CASNS and the conventional group. We evaluated the surgical precision in the navigation group by analyzing the difference between actual postoperative computed tomography data and preoperative virtual surgical plan through color order ratios. We also compared the duration of surgery, enophthalmos correction, restoration of orbital volumes, and improvement of clinical symptoms in both groups systemically. Quantitative data were presented as mean ± SD. Significance was determined by the two-sample t-test using SPSS Version 19.0 A p < 0.05 was considered statistically significant.@*RESULTS@#Seventy patients with unilateral OWF were included in the study cohort. The mean difference between preoperative virtual planning and actual reconstruction outcome was (0.869 ± 0.472) mm, which means the reconstruction result could match the navigation planning accurately. The mean duration of surgery in the navigation group was shorter than it is in the control group, but not significantly. Discrepancies between the reconstructed and unaffected orbital-cavity volume and eyeball projection in the navigation group were significantly less than that in the conventional group. One patient had remnant diplopia and two patients had enophthalmos after surgery in the navigation group; two patients had postoperative diplopia and four patients had postoperative enophthalmos in the conventional group.@*CONCLUSION@#Compare with the conventional treatment for OWF, the use of CASNS can provide a significantly better surgical precision, greater improvements in orbital-cavity volume and eyeball projection, and better clinical results, without increasing the duration of surgery.

Experimental Study on Effect of Modified Guilu Erxianjiao Decoction Combined with Cisplatin on Resistance-related Genes and IL-7-mediated Wnt/β-catenin Signaling Pathway in Mice with Lewis Lung Cancer / 中国实验方剂学杂志

Objective:To observe the effect of modified Guilu Erxianjiao decoction combined with cisplatin on the immune function， resistance-related genes and interleukin-7（IL-7）-mediated Wnt/<italic>β</italic>-serial protein（<italic>β</italic>-catenin）signaling pathway in Lewis lung cancer mice by establishing a mouse model of Lewis lung cancer with deficiency of both Qi and Yin. And the anti-cancer mechanism of modified Guilu Erxianjiao decoction was clarified， so as to provide a basis for its clinical application. Method:A Lewis lung cancer mouse model （type of deficiency of both Qi and Yin） was established. Mice were divided into a normal group （no modeling）， a model group （saline solution）， a cisplatin group （cisplatin， 2 mg·kg^-1）， a traditional Chinese medicine （TCM） group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1）， and a combined group （modified Guilu Erxianjiao decoction， 19.63 g·kg^-1·d^-1 + cisplatin， 2 mg·kg^-1）. The 10 mice in each group were administered separately for 21 days of intervention. The general conditions and organ indexes of mice were observed， and tumor inhibition rate was calculated. CD4⁺CD25⁺ regulatory T cell （CD4⁺CD25⁺ Treg） were detected by flow cytometry， the IL-7 level of cytokines in serum was detected by enzyme linked immunosorbent assay（ELISA）， and real-time quantitative polymerase chain reaction（Real-time PCR） was used to detect the gene expression level of drug resistance-related genes P-glycoprotein（P-gp）， and multidrug resistance protein1（MRP1）in tumor tissues. The protein expression of Wnt/<italic>β</italic>-serial protein（<italic>β</italic>-catenin）signaling pathway in tumor tissues were detected by Western blot. Result:In the TCM group and the combined group， the food intake increased， the mental state was better， the response was sensitive， and the body weight increased. Compared with the cisplatin group， the thymus index and spleen index in the combined group were significantly increased （<italic>P</italic><0.01）， and the tumor inhibition rate of the combined group was significantly increased （<italic>P</italic><0.01）. Compared with the cisplatin group， the percentage of CD4⁺CD25⁺Treg/CD4⁺ in the TCM group and the combined group was significantly reduced （<italic>P</italic><0.01）， and IL-7 in the TCM group and the combined group was significantly increased （<italic>P</italic><0.01）. Compared with the cisplatin group， the expressions of P-gp and MRP1 genes in the TCM group and the combined group were significantly reduced （<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expressions of secretory glycoprotein1（Wnt1）and <italic>β</italic>-serial protein（<italic>β</italic>-catenin）in the TCM group and the combined group were significantly reduced （<italic>P</italic><0.01）. Conclusion:The combined use of modified Guilu Erxianjiao decoction and cisplatin can significantly inhibit the growth of tumors in mice with Lewis lung cancer， and its mechanism of action may be related to the efficacy of m odified Guilu Erxianjiao decoction in relieving the body's immunosuppressive state， promoting the body to produce IL-7， regulating IL-7-mediated Wnt/<italic>β</italic>-catenin signaling pathway and reducing the expression of resistance-related genes in lung cancer tissues.

Correlation between cerebral microbleeds and lacunar infarction in patients with cerebral small vessel disease / 国际脑血管病杂志

Objective:To investigate the correlation between the location and volume of cerebral microbleeds (CMBs) and lacunar infarction (LI) in patients with cerebral small vessel disease (CSVD).Methods:Participants from the CSVD cohort in the Department of Neurology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School of Nanjing University from February 2017 to March 2019 were enrolled retrospectively. All participants underwent magnetic resonance imaging scans, standardized clinical assessment and diagnosis. AccuBrain, an automatic brain segmentation and quantification software developed by the Chinese University of Hong Kong, was used to quantitatively analyze the volume of CMBs and white matter hyperintensities (WMHs). Ordered multi-class logistic regression analysis was used to determine the independent influencing factors of LI, and then multiple linear regression analysis was used to investigate the correlation between the volume of deep or infratentorial CMBs (DI-CMBs) and the number of LI. Results:A total of 317 patients with CSVD were included in the analysis, including 214 (67.5%) in the non-LI group, 43 (13.6%) in the single LI group, and 60 (18.9%) in the multiple LI group. The comparison of the three groups showed that older age, male, smoking, drinking, history of previous stroke or transient ischemic attack (TIA), lower levels of high-density lipoprotein cholesterol, larger CMBs and WMHs volume, higher enlarged perivascular spaces (EPVS) grade might be the risk factors for LI. Ordinal multivariable logistic regression analysis showed that male (odds ratio [ OR] 2.058, 95% confidence interval [ CI] 1.084-3.909; P=0.027), previous stroke or TIA history ( OR 1.962, 95% CI 1.089-3.535; P=0.025), larger WMH volume ( OR 8.716, 95% CI 4.034-18.832; P<0.001), higher EPVS grade ( OR 1.915, 95% CI 1.292-2.839; P=0.001), larger DI-CMB volume ( OR 1.022, 95% CI 1.006-1.038; P=0.008) or more DI-CMB number ( OR 1.187, 95% CI 1.005-1.403; P=0.044) were the independent related factors of LI. Multiple linear regression analysis showed that there was a significant correlation between the volume of DI-CMB and the number of LI ( r=0.330, P<0.001). Conclusion:In patients with CSVD, there is a significant correlation between DI-CMBs and LI.

Clinical characteristics and prognostic analysis of secondary hemophagocytic syndrome in adults / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognosis of secondary hemophagocytic syndrome (HPS) in adults.Methods:The clinical data of 43 adult patients with primary secondary HPS in Mianyang Central Hospital of Sichuan Province from January 2014 to June 2020 were retrospectively analyzed. The patient's clinical manifestations and biochemical indicators were summarized. The clinical characteristics of patients between high-level ferritin (≥5 000 μg/L) group and low-level ferritin (<5 000 μg/L) group, lymphoma-related HPS group and infection-related HPS group were compared. Logistic regression model was used for multivariate survival analysis.Results:All patients had fever as the main complaint, and infections were manifested at the onset or during treatment. In all patients, 88.4% (38/43) had hemophagocytosis in the bone marrow; 88.4% (38/43) had varying degrees of cytopenia; 36.6% (15/41) had reduced fibrinogen [median value 0.93 g/L (0.50-1.35 g/L)]; 76.7% (33/43) had elevated aminotransferase. Compared with the low-level ferritin group (19 cases), the high-level group (21 cases) had a lower proportion of monocytes (0.081±0.040 vs. 0.163±0.076, P = 0.016), the incidence of fibrinogen reduction and the incidence of aminotransferase elevation were high [60.0% (12/20) vs. 11.1% (2/18), P = 0.002; 95.2% (20/21) vs. 52.6% (10/19), P = 0.006]. Compared with infection-related HPS patients, lymphoma-related HPS patients had a higher incidence of lymphadenopathy [72.7% (16/22) vs. 27.8% (5/18), χ2 = 8.021, P = 0.005] and a lower incidence of aminotransferase elevation [59.1% (13/22) vs. 94.4% (17/18), χ2 = 4.848, P = 0.028]. Multivariate analysis showed that the high proportion of neutrophils ( OR = 0.886, 95% CI 0.786-0.998, P = 0.046) and high-level albumin ( OR = 0.376, 95% CI 0.156-0.907, P = 0.030) after treatment were protective factors for survival of patients. Conclusions:Among adult patients with primary secondary HPS, the proportion of monocytes in patients with ferritin ≥5 000 μg/L is low, and liver damage and fibrinogen reduction are more likely to occur. Lymphoma-related HPS patients are more likely to have lymphadenopathy, and infection-related HPS patients are more likely to have liver damage. After treatment, a low proportion of neutrophils and hypoproteinemia indicate a poor prognosis in adult patients with secondary HPS.