In recent years, the incidence of chest malignant tumors in China has increased year by year, which has seriously threatened the health problems of people. Among them, early screening and intervention of patients with chest malignancies is the key to cancer prevention. Early detection, early diagnosis, and early treatment as the "three early prevention" of clinical practice are conducive to improve the survival rate of tumor patients. As a non-invasive and real-time reflection of tumor status, liquid biopsy has gradually received attention in clinical diagnosis and treatment. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes as liquid biopsy "Three carriages" are not only widely used in the diagnosis, monitoring and prognostic evaluation of chest malignancies, but also face many unknown challenges. In this article, the application of liquid biopsy in chest malignancies in recent years is elaborated in detail, which provides a reference for the formulation of clinical tumor prevention and diagnosis and treatment strategies.
Humans ; Circulating Tumor DNA/genetics* ; Liquid Biopsy/methods* ; Neoplastic Cells, Circulating/pathology* ; China ; Biomarkers, Tumor

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Diabetes Complications ; Diabetes Mellitus ; Humans ; Hypertension ; complications ; Male ; Prostatic Hyperplasia ; complications

AIM To investigate the dose-proportion relation of Tibetan medicine Siwei Jianghuang Prescription (SJP) for protective effects on diabetic nephropathy (DN),and the underlying mechanism.METHODS Diabetes mellitus rats induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) were randomly divided into model group,metformin support group,and eight SJP groups with dose-proportion variation (with reference to the uniform design method) for corresponding drug administration once a day,for four weeks.Measurement of fasting blood glucose (FBG) by a blood glucose meter,the concentrations of blood urea nitrogen (BUN),uric acid (UA),serum creatinine (SCr) and total protein (TP) by chemical methods,serum transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) by ELISA kits were conducted,the pathological morphology observation and glomerular basement membrane thickness detection by electron microscope were accomplished as well.Principal components analysis (PCA) and multivariate progressive regression analysis (MSRA) were employed to analyze the relationship between the dose-proportion to pharmacodynamics.RESULTS The resultant indexes revealed variant pharmacological improvement in each treatment group.MSRA results showed that the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr,and UA had correlative relations with a multiple linear or a multiple non-linear in all groups,which regression equation had a statistical significance (P ＜ 0.05);TGF-β1 level and total protein index with the dose-proportion had no linear or non-linear relation,which the regression equation statistical showed non-significance (P ＞ 0.05).In the global optimization comparison around the range of uniform design,the optimal dosage of the rats model was Curcumae Longae Rhizoma ∶ Berberidis dictyophyllae Cortex ∶ Phyllanthi Fructus ∶ Tribuli Fructus =1 ∶ 2 ∶ 1 ∶ 2.CONCLUSION Siwei Jianghuang Prescription shows better therapeutic effects on DN,which may be related to reducing the levels of BUN,renal index,FBG,glomerular basement membrane thickness,VEGF,Scr and UA.

OBJECTIVETo investigate the effect of c-Met inhibitor cabozantinib (XL-184) in inhibiting Listeria monocytogenes (LM) from invading Caco-2 cells to reduce the cell injury.

METHODSThe cell invasion capacity of LM was assayed in Caco-2 cells incubated with different doses of XL-184 for different durations. Caco-2 cells incubated with XL-184 were seeded on the upper room of the transwell chamber, and the cell monolayer was exposed to LM infection followed by addition of horseradish peroxidase (HRP). The trans-epithelial electric resistance (TEER), HRP concentration and LM colony-forming unit (CFU) were measured in the cell monolayer. Fluorescent staining was used to evaluate the cell viability, and LDH release from the cells was examined to assess the changes in cell membrane permeability.

RESULTSXL-184 significantly decreased LM invasion rate in Caco-2 cells in a dose- and time-dependent manner (P=0.000), and this effect was enhanced by co-incubation of the cells with ampicillin (P<0.05). In the cell membrane permeability assay in the monolayer cells, XL-184 markedly inhibited LM-induced reduction of TEER (P<0.05) and significantly suppressed LM-induced enhancement of cell membrane permeability shown by reduced HRP concentration and LM count in the lower chamber (P=0.000). The cells infected with LM showed significantly lowered cell viability, which was rescued by XL-184 (P<0.01); XL-184 also dose-dependently reduced LDH release from the cells (P<0.05).

CONCLUSIONSXL-184 can suppress LM invasion in Caco-2 cells to reduce the cell injury, suggesting its value as a promising candidate agent for prevention and treatment of LM infections.

Anilides ; pharmacology ; Caco-2 Cells ; Cell Membrane Permeability ; drug effects ; Cell Survival ; Humans ; Listeria monocytogenes ; drug effects ; Pyridines ; pharmacology

OBJECTIVETo observe the effect of Huanglian Jiedu Decoction (HLJDD) in in vivo regulating differentiation of monocytes in an apolipoprotein E knockout (ApoE(-/-)) mouse model, and to observe the effect of HLJDD-containing serum in in vitro regulating differentiation of macrophages and foam cells.

METHODSFifteen apoE(-/-) mice were randomly divided into the common diet group, the hyperlipidemia group, and the hyperlipidemia +HLJDD treatment group, 5 in each group. Mice in the common diet group were fed with a chow diet. Mice in the hyperlipidemia group were fed with high cholesterol wild diet (WD). Those in the hyperlipidemia +HLJDD treatment group were fed with high cholesterol WD supplemented with HLJDD. All mice were fed for 4 weeks. Five C57BL/6 wild types were recruited as the wild common diet control group. HLJDD was administered to mice in the hyperlipidemia + HLJDD treatment group by gastrogavage at the daily dose of 5 g/kg. Equal volume of purified water was given by gastrogavage to mice in the rest 3 groups. Four weeks later, subtypes of monocytes in the peripheral blood were detected by FACS. HLJDD administered to another 30 SD rats by gastrogavage at the daily dose of 5 g/kg, once for every 12 h for 5 times in total, thereby preparing 5% HLJDD containing serum to intervene the differentiation of in vitro primary bone marrow-derived macrophage (BMDM) and foam cells. The M2 subtype surface receptor CD206 of macrophages and foam cells were detected by FACS. The expression of Nos2 and Arg1 genes were assayed by Real-time PCR.

RESULTSThe ratio of inflammatory subset of monocytes (Ly6C(high)) increased in the peripheral blood after ApoE(-/-) mice were fed with high fat diet for 4 weeks. HLJDD significantly decreased the ratio of inflammatory subset of monocytes (P < 0.05). Compared with the vehicle serum, 5% HLJDD containing serum significantly increased differentiation of CD206 + M2 BMDM (P = 0.034). Results of real-time quantitative PCR showed that the expression level of Arg1 mRNA could be up-regulated by HLJDD containing serum (P < 0.05), and that of Nos2 mRNA down-regulated (P = 0.017). ox-LDL induced the differentiation of M2 subtype foam cells from BMDM, and HLJDD containing serum could further elevate the ratio of CD206 + M2 foam cells and increase the Arg1 mRNA expression level (both P < 0.01). HLJDD containing serum could inhibit the inversion of M2 subtype of foam cells to M1 subtype induced by Th1 factors, significantly elevate the Arg1 mRNA expression level, and decrease the Nos2 mRNA expression level (all P < 0.01).

CONCLUSIONSHLJDD could lower hyperlipidemia induced inflammatory monocyte subtype ratios in the peripheral blood of ApoE(-/-) mice. HLJDD containing serum promoted in vitro differentiation of M2 macrophages and foam cells. HLJDD attenuated and inhibited the occurrence and development of atherosclerosis induced by hyperlipidemia possibly through regulating the functional differentiation of monocytes, macrophages, and foam cells.

Animals ; Apolipoproteins E ; genetics ; Cell Differentiation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Foam Cells ; cytology ; drug effects ; Macrophages ; cytology ; drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes ; cytology ; drug effects

OBJECTIVETo observe the protection of Huanglian Jiedu Decoction (HJD) on high fat diet induced liver damage mice [hyperlipidemic mice lacking apolipoprotein E (ApoE(-/-))].

METHODSWild type mice were divided into the wild common food group and the wild hyperlipidemia group. ApoE(-/-) mice were divided into the ApoE(-/-) common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 5 in each group. In the present study, wild type mice and homozygous apoE(-/-) mice were fed with a chow diet or a high cholesterol Western diet for 4 weeks. HJD at the daily dose of 5 g/kg was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group by gastrogavage. The plasma levels of total cholesterol (TC), triglyceride (TG), low density cholesterol protein (LDL-C) were detected. The pathohistological changes of the liver were observed by Eosin and Hematoxylin (HE) staining. The liver macrophages and their subtype ratios, as well as macrophage surface receptor CD206 and CD36 were detected by flow cytometry.

RESULTSTypical pathological changes of simple fatty liver were manifested in the ApoE(-/-) hyperlipidemia group, TC, TG, and LDL-C increased, the macrophage ratio increased, the expression level of macrophage surface receptor CD206 decreased, showing statistical difference when compared with the ApoE(-/-) common food group (P < 0.01, P < 0.05). The ratio of alternatively activated macrophages (M2) subpopulations was lower in the ApoE(-/-) hyperlipidemia group than in the wild common food group (P < 0.05). There was no obvious change in the expression level of CD36. After intervened by HJD for 4 weeks, there was no obvious improvement in blood lipids. But the ratio of CD206+ M2 macrophages was significantly improved, when compared with the ApoE(-/-) hyperlipidemia group (P < 0.05). The pathological changes of fatty liver were significantly attenuated.

CONCLUSIONSThe liver protection effect of HJD might be associated with immunoregulation of M2 macrophage subpopulations and injured tissue repairmen. Its immunoregulation and liver protection were independent from lipids lowering.

Animals ; Apolipoproteins E ; genetics ; Cholesterol, LDL ; blood ; Diet, High-Fat ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Fatty Liver ; metabolism ; pathology ; prevention & control ; Hyperlipidemias ; metabolism ; pathology ; prevention & control ; Liver ; cytology ; metabolism ; pathology ; Macrophages ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Triglycerides ; blood

OBJECTIVETo observe the effect of Huanglian Jiedu IJecoction (HJU) on systemic and vascular immune responses of high fat diet fed apoE deficient (apoE(-/-)) mice.

METHODSEight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE(-/-) mice were randomly divided into the ApoE'common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 (TLR-4) and CD36 on the monocytes were detected. The pathological changes and expressions of cytokines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide (LPS) were analyzed. Results (1) Compared with the wild type common food group, TO, TG, and LDL-O significantly increased in the ApoE(-/-) common food group (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, TC and LDL-C significantly increased in the hyperlipidemia group (P < 0. 05). There was no statistical difference in each index between the ApoE(-/-) hyperlipidemia group and the ApoE(-/-) hyperlipidemia plus HJD group (P > 0.05). (2) Compared with the wild type common food group, no obvious change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level significantly increased in the ApoE'common food group (P < 0. 05). Compared with the ApoE common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly increased in the ApoE' hyperlipidemia group (P < 0.05). Compared with the ApoE(-/-) hyperlipidemia group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly decreased. Besides, the CD36 expression level also significantly decreased (P<0.05). (3) After stimulated by LPS for 3 h, compared with the wild type common food group, plasma TNF-ct and IL-b expressions significantly increased in the ApoE(-/-) common food group (P < 0.05). Compared with the ApoE(-/-) common food group, plasma expressions of IL-12, TNF-alpha, MCP-1, and IL-10 increased, but with no statistical difference in the ApoE(-/-) hyperlipidemia group (P > 0.05). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, the MCP-1 expression was significantly down-regulated, while the IL-10 expression significantly increased, showing statistical difference (P < 0.05). Compared with the wild type common food group, mRNA expression levels of IFN-gamma, MCP-1 , TNF-alpha, IL-10, and IL-1beta significantly increased (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, not only mRNA expression levels of IFN-gamma, MCP-1, TNF-alpha, and IL-1beta, further significantly increased, but also IL-12, IL-10, and TGF-beta significantly increased (P < 0. 05, P < 0. 01). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, mRNA expression levels of MCP-1, TNF-alpha, IL-1beta, and IL-12 significantly decreased in the ApoE(-/-) hyperlipidemia plus HJD group (P < 0.05, P < 0.01).

CONCLUSIONSHigh fat diet induced systemic reaction and inflammatory reactions of local vessels. The local inflammatory response of vessels exceeded systemic inflammatory response. Intervention of HJD could attenuate inflammatory response, especially in local arteries. Meanwhile, it enhanced systemic anti-inflammatory reactions.

Animals ; Aorta ; pathology ; Apolipoproteins E ; genetics ; CD36 Antigens ; metabolism ; Chemokine CCL2 ; metabolism ; Dietary Fats ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hyperlipidemias ; blood ; etiology ; immunology ; Inflammation ; Interleukin-10 ; blood ; Interleukin-12 ; blood ; Interleukin-1beta ; blood ; Leukocytes, Mononuclear ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Systemic Inflammatory Response Syndrome ; blood ; etiology ; immunology ; Toll-Like Receptor 4 ; metabolism ; Transforming Growth Factor beta ; blood ; Tumor Necrosis Factor-alpha ; blood