Association between the ratio of dietary vitamin A to body weight and hypertension in children / 中国学校卫生

Objective@#To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention.@*Methods@#Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension.@*Results@#The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01].@*Conclusions@#The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Aggressive treatment may be needed for idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions

SUMMARY OBJECTIVE: The purpose of this study was to analyze the clinical, pathological, prognostic features and treatment response of the coexistence of focal segmental glomerulosclerosis lesions with idiopathic membranous nephropathy. METHODS: This is a two-center retrospective cohort study. Patients of idiopathic membranous nephropathy were enrolled and divided into two groups with or without focal segmental glomerulosclerosis lesions according to the renal biopsy. Laboratory data and pathological manifestation were compared. Renal phospholipase A2 receptor was detected by immunofluorescence. During the follow-up, the effects of different therapies and renal function were estimated. RESULTS: A total of 236 patients were finally enrolled in this study, of which 60 and 176 idiopathic membranous nephropathy patients were enrolled in the FSGS+ and FSGS- groups, respectively. The FSGS+ group showed a higher percentage of hypertension history (38.3 vs. 20.0%, p=0.004), with a significantly higher level of systolic pressure [137 (120, 160) mmHg vs. 130 (120, 140) mmHg, p=0.009]. Main laboratory findings, including serial albumin (20.4±7.8 g/L vs. 24.5±6.7 g/L, p<0.001), 24-h proteinuria [5.61 (3.10, 7.87) g/day vs. 3.82 (2.31, 5.79) g/day, p=0.002], serial creatinine [80.8 (65.8, 97.9) μmol/L vs. 72.0 (58.7, 84.9) μmol/L, p=0.003], and estimated glomerular filtration rate [86 (66, 101) mL/min/1.73 m2 vs. 95 (81, 108) mL/min/1.73 m2, p=0.007] showed significant differences between the two groups. Pathologically, patients with focal segmental glomerulosclerosis lesions appeared with a higher percentage of crescents, a more severe degree of interstitial fibrosis, and a higher level of membranous nephropathy stage. Renal phospholipase A2 receptor showed a relatively lower positive rate of only 75.0% in the FSGS+ group in comparison with the positive rate of 90.3% in the FSGS- group (p=0.031). The prognosis was generally similar between the two groups. Among patients who were given non-immunosuppression treatment, those with focal segmental glomerulosclerosis lesions took a relatively longer period of time to achieve complete remission (29.3±7.0 m vs. 15.4±8.9 m, p=0.025) and experienced a higher rate of renal function deterioration (37.5 vs. 5.4%, p=0.033) compared with the other ones. While among those receiving immunosuppression treatment, both groups received similar remission rates. CONCLUSION: Compared with FSGS- group, idiopathic membranous nephropathy with focal segmental glomerulosclerosis lesions represented more severe nephrotic syndrome and worse renal function. In view of the renal function decline during the follow-up, more aggressive treatment with the use of immunosuppressants should be considered for idiopathic membranous nephropathy patients with focal segmental glomerulosclerosis lesions.

Variation of occipital protuberance and occipital bunning of Holocene Chinese population / 解剖学报

Objective To analyze the characteristics and variation of occipital protuberance and occipital bunning of Chinese Holocene population. Methods Based on 275 adult male skulls, Neolithic Age ( 49 cases ), Bronze and Iron Age (171 cases) and modern (55 cases), the occipital protuberance and occipital bunning were divided into several categories, and the occurrence rates were analyzed and compared among different time periods. Results The characteristics and variation of occipital protuberance and occipital bunning were also different in different ages. The degree of the occipital protuberance was more and more significant with the age, which changed greatly from Neolithic Age to Bronze and Iron Age. In the Holocene, most people did not appear occipital bunning on the skull, but the relatively significant occipital bunning appeared in the Bronze and Iron Age. Conclusion The variation of occipital protuberance may be related to the change of skull size and overuse of trapezius muscle in Holocene. The occipital bunning appearance may reflect the relative development speed of the brain and skull to some extent.

Application of geometric morphometrics in ancient human remains / 解剖学报

Based on the data collection and analysis of the sample landmarks, the geometric morphological method shows great prospect in the study of human remains. The purpose of this paper is to briefly outline the application of geometric morphological method in research of human remains and gives an outlook on the application of the method in the study of ancient children.

First-generation epithelial growth factor receptor tyrosine kinase inhibitor in the first-line treatment of advanced non-small cell lung cancer: 166 cases analysis of progression-free survival / 中国实用内科杂志

OBJECTIVE: Explore the clinical benefit factors of progression-free survival(PFS) in sensitive epithelial growth factor receptor(EGFR) gene mutated advanced non-small cell lung cancer patients treated with first-generation of EGFR tyrosine kinase inhibitor(TKI).METHODS: The clinical data of 166 patients who received first-line treatment with first-generation EGFR-TKI were retrospectively collected in 2016-2017 from Xiangya Hospital, Central South University. The patients were divided into three groups: PFS≤3 m,3 m

On Research Progress of Western and Chinese Medicine Treatment on Pre-Rheumatoid Arthritis / 中国结合医学杂志

Pre-rheumatoid arthritis is the inevitable phase before the actual onset of rheumatoid arthritis and has the crucial clinical significance of early controlling and preventing disease progression. Full understanding, from both Western medicine (WM) and Chinese medicine (CM), could offer new ideas for decision making in clinical and mechanism research. This paper reviews the novel studies of WM and CM to discuss the advantages and potential mechanisms working behind.

Severe pneumonia associated with sepsis-induced myopathy: one case report and literature review / 中国感染控制杂志

Clinical data of one patient with sepsis-induced myopathy (SIM) who was successfully treated were reviewed retrospectively, analysis was conducted combined with the relevant literatures. Patient was a middle-aged woman without underlying disease, she was admitted to hospital because of fever, cough, chest tightness and shortness of breath, during the treatment period, type II respiratory failure occurred repeatedly, and it was difficult in withdrawing respirator, patient was finally diagnosed with SIM. After anti-infective treatment and rehabilitation training, she was successfully withdrawn respirator, muscle strength was recovered. This case suggests that SIM can be completely cured through early identification, neuromuscular nutrition therapy, graded rehabilitation training and lung rehabilitation therapy.

Systemic disseminated Mycobacterium fortuitum infection:one case report and literature review / 中国感染控制杂志

Objective To explore the clinical characteristics of systemic disseminated infection caused by Mycobacterium fortuitum (M.fortuitum), and improve the diagnostic rate and understanding of the disease.Methods One case of systemic disseminated M.fortuituminfection was reported, and analyzed in combination with relevant literatures.Results Patient was with multiple systemic involvement (including lung, lymph node, skin, joint), lymph node tissue culture was positive for M.fortuitum, patient was given clarithromycin+levofloxacin+linezolid for treatment, disease was remitted.Conclusion Systemic disseminated M.fortuituminfection is rare, and patient with GATA2 deletion and IFN-γautoantibody may be a potential mechanism, diagnosis is mainly based on pathological morphology and microbiological detection, but positive rate is low, diagnosis is difficult.

Effects of Glucocorticoid-Induced Transcript 1 Gene Deficiency on Glucocorticoid Activation in Asthmatic Mice / 中华医学杂志(英文版)

Background@#Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown.@*Methods@#A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1) mice. Glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase 1 (MKP-1) expression were detected by polymerase chain reaction and Western blotting (WB). The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also detected by WB.@*Results@#In asthmatic patients, the change of FEV was well positively correlated with change of GLCCI1 expression (r = 0.430, P = 0.022). In animal experiment, GR and MKP-1 mRNA levels were significantly decreased in asthmatic mice than in control mice (wild-type: GR: 0.769 vs. 1.000, P = 0.022; MKP-1: 0.493 vs. 1.000, P < 0.001. GLCCI1: GR: 0.629 vs. 1.645, P < 0.001; MKP-1: 0.377 vs. 2.146, P < 0.001). Hydroprednisone treatment significantly increased GR and MKP-1 mRNA expression levels than in asthmatic groups; however, GLCCI1 asthmatic mice had less improvement (wild-type: GR: 1.517 vs. 0.769, P = 0.023; MKP-1: 1.036 vs. 0.493, P = 0.003. GLCCI1: GR: 0.846 vs. 0.629, P = 0.116; MKP-1: 0.475 vs. 0.377, P = 0.388). GLCCI1 asthmatic mice had more obvious phosphorylation of p38 MAPK than wild-type asthmatic mice (9.060 vs. 3.484, P < 0.001). It was still higher even though after hydroprednisone treatment (6.440 vs. 2.630, P < 0.001).@*Conclusions@#GLCCI1 deficiency in asthmatic mice inhibits the activation of GR and MKP-1 and leads to more obvious phosphorylation of p38 MAPK, leading to a decremental sensitivity to GCs.@*Trial Registration@#ChiCTR.org.cn, ChiCTR-RCC-13003634; http://www.chictr.org.cn/showproj.aspx?proj=5926.

Optic Nerve Crush Induces Changes of Hydrogen Sulfide Synthases Expression in the Rat Retina / 法医学杂志

Objective To investigate the expression changes of the hydrogen sulfide synthases cystathionineγ-lyase (CSE), cystathionineβ-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST), after optic nerve crush (ONC) in rat the retina.Methods The rat model of ONC was established.Rats were divided into normal control, ONC, and sham control groups.Histopathologic changes in retina, the number of retinal ganglion cells (RGC) and retinal thickness of inner part (RTIP) were measured.The changes of CSE, CBS and 3-MST mRNA expression were detected with quantitative real-time PCR.Results The retinal histostructure was normal in normal controls and with minor changes in sham controls, respectively.Compared with sham group, significant retina damages were found in the ONC group:a time-dependent reduction of RGC number and RTIP.Expressions of CSE, CBS and 3-MST mRNA in rat retina were detected in normal control.Compared with normal controls, the expressions of CSE, CBS and 3-MST mRNA did not show any significant changes in the sham controls.Compared with sham controls, CBS mRNA expressions showed a time-dependent increase at 3 d, 7 d and 14 d after crush in the ONC group;CSE mRNA expressions increased to the peak at 3 d and then slightly reduced at 14 d after crush;3-MST mRNA expressions showed the trend of increase at 3 d and 7 d and then enhanced remarkably at 14 d after crush.Conclusion Hydrogen sulfide synthases CSE, CBS and3-MST expressions were up-regulated in rat retina following ONC, which may cause an increase in local endogenous hydrogen sulfide production in the retina and a compensatory protective effect.

Progress in the Treatment of Acquired Hemophilia A / 昆明医科大学学报

Acquired hemophilia A is a deficiency disease caused by blood coagulation factor Ⅷ antibodies due to a variety of causes, The disease incidence rate is extremely low, but the mortality rate is high. This disease is often misdiagnosed,resulting in delays in treatment, so early diagnosis and timely treatment is crucial for reducing the mortality. The principle of treatment for the disease is mainly to control acute bleeding, eradicate inhibitor, and treat the primary disease,therefore, rational and personalized choices of treatment are also critical.

Effect of Lang-Chuang-Ding Decoction () on DNA Methylation of CD70 Gene Promoter in Peripheral Blood Mononuclear Cells of Female Patients with Systemic Lupus Erythematosus / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Lang-chuang-ding Decoction (, LCD) on the expression of DNA methylation of CD70 gene promoter in peripheral blood mononuclear cells (PBMCs) of females with systemic lupus erythematosus (SLE).</p><p><b>METHODS</b>PBMCs isolated from female patients with SLE or healthy donors were cultured and treated with LCD medicated serum or normal serum for 24 or 48 h. The mRNA expressions of CD70 gene in PBMCs were detected by reverse transcription polymerase chain reaction (PCR); the DNA methylation of the CD70 gene promoter region was detected by methylation-specific PCR.</p><p><b>RESULTS</b>After treated with medicated serum for 48 h, the mRNA expression levels of CD70 in PBMCs of SLE patients were signifificantly higher than those of healthy donors (P<0.05); the DNA methylation levels of CD70 promoter region in PBMCs of SLE patients treated with medicated serum for 48 h were signifificantly higher than those treated with fetal bovine serum (P<0.01).</p><p><b>CONCLUSION</b>LCD could inhibit CD70 gene expression in PBMCs of SLE patients by promoting the DNA methylation of CD70 gene promoter.</p>

Platelet Distribution Width on Admission Predicts In-Stent Restenosis in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Treated with Percutaneous Coronary Intervention / 中华医学杂志(英文版)

<p><b>Background</b>It is known that there is a definite association between platelet distribution width (PDW) and poor prognosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, there are no data available regarding the prognostic significance of PDW for in-stent restenosis (ISR) in patients with CAD and T2DM. We aimed to determine the value of PDW on admission that predicted ISR in patients with CAD and T2DM.</p><p><b>Methods</b>Between January 2012 and December 2013, a total of 5232 consecutive patients diagnosed with CAD and T2DM undergoing percutaneous coronary intervention were admitted. Three years of retrospective follow-up was undertaken. A total of 438 patients with second angiography operations were included. ISR was defined as ≥50% luminal stenosis of the stent or peri-stent segments. Continuous data were presented as the mean ± standard deviation or median (P, P) and were compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical variables were presented as percentages and were compared by Chi-square test or Fisher's exact test. The association between PDW and ISR was calculated by logistic regression analysis. A two-sided value of P < 0.05 was considered statistically significant. Statistical analyses were performed by SPSS version 22.0 for windows.</p><p><b>Results</b>Fifty-nine patients with ISR, accounting for 13.5% of the total, were included. ISR was significantly more frequent in patients with higher PDW quartiles compared with lower quartiles. We observed that PDW had a strong relationship with mean platelet volume (r = 0.647, 95% confidence interval [CI]: 0.535-0.750, P < 0.0001). The receiver-operating characteristic curves showed that the PDW cutoff value for predicting ISR rate was 13.65 fl with sensitivity of 59.3% and specificity of 72.4% (area under curve [AUC] = 0.701, 95% CI: 0.625-0.777, P < 0.001). Multivariate analysis showed that the risk of ISR increased approximately 30% when PDW increased one unit (odds ratio [OR]: 1.289, 95% CI: 1.110-1.498, P = 0.001). Patients with higher PDW, defined as more than 13.65 fl, had a 4-fold higher risk of ISR compared with lower PDW (OR: 4.241, 95% CI: 1.879-9.572, P = 0.001). Furthermore, when patients were divided by PDW quartiles values, PDW was able to predict ISR (Q2: OR = 0.762, 95% CI: 0.189-3.062, P = 0.762; Q3: OR = 2.782, 95% CI: 0.865-8.954, P = 0.086; and Q4: OR = 3.849, 95% CI: 1.225-12.097, P = 0.021, respectively; P for trend <0.0001).</p><p><b>Conclusion</b>PDW is an independent predictor of ISR in patients with CAD and T2DM.</p>

Clinical observation of flexible ureteroscopy combined with physical vibration lithecbole in treatment of massive upper urinary calculi / 中国内镜杂志

Objective To evaluate the clinical efficacy of flexible ureteroscopy combined with physical vibration lithecbole in treatment of massive upper urinary calculi. Methods The clinical data of 62 cases with massive upper urinary calculi from Feb 2016 to Mar 2017 were analyzed retrospectively. The average diameter of stones were (656.70 ± 275.40) mm2. The removal rate of stones, general conditions during the operation, the postoperative adverse reactions and renal function changes were observed. Results All 62 patients had successfully completed flexible ureteroscopy operation, and had physical vibration stone removal treatment after 1 week. The rate of stone removal was 61.29％ in the next day (38/62), 85.48％ (53/62) in the next 1 week and 96.77％ (60/62) in the next 3 weeks. Postoperative fever occurred in 2 cases, the overall complication rate was 3.23％. 18 patients had improved renal function while 4 patients keep stable after operation. Conclusion The flexible ureteroscopy combined with physical vibration lithecbole is a safe and effective therapeutic method for massive upper urinary calculi. It has high stone removal rate, less complications, little impact on renal function. It is valuable to advocate clinically.

Effects of HO-1 on Lipopolysaccharide-induced Endoplasmic Reticulum Stress of Rat Hepatocytes / 法医学杂志

OBJECTIVE@#To investigate effects of antioxidant stress protein heme oxygenase-1 (HO-1) on lipopolysaccharide (LPS)-induced endoplasmic reticulum stress (ERS) of rat hepatocytes.@*METHODS@#The BRL cells (rat hepatocyte cell line) were cultured. The hepatocytes were treated with LPS, LPS+HO-1 siRNA, HO-1 siRNA and PBS solution, respectively. The cell viability was measured by trypan blue exclusion test. The apoptosis cells were detected by the fluorescent dye Hoechst 33258. Expressions of GRP78, CHOP, caspase-12 and HO-1 were detected by Western blotting.@*RESULTS@#LPS caused an increase of HO-1 protein expression of rat hepatocytes in a dose-dependent and time-dependent manner, a up-regulation of GRP78, CHOP and caspase-12, a decrease in cell viability, and an increase in apoptosis rate of hepatocytes. Pretreatment of HO-1 siRNA inhibited the up-regulation of LPS-induced HO-1, however, aggravated ERS and cellular injury.@*CONCLUSION@#HO-1 inhibites ERS-mediated cellular injury of rat hepatocytes induced by LPS.

Human decorin regulates proliferation and migration of human lung cancer A549 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Decorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung cancer tissue and may be involved in regulation of lung cancer development.</p><p><b>METHODS</b>In this study, lentivirus-mediated RNA interference and over expression were employed to change the expression levels of decorin in lung cancer A549 cells. We tested the cell cycle of A549 cells and the expression of transforming growth factor (TGF)-β, cyclin D1, epidermal growth factor receptor (EGFR), P53, and P21.</p><p><b>RESULTS</b>We found that up-regulation of decorin could inhibit proliferation, block cell cycle at G1 and decrease invasive activity of A549 cells. Moreover, we also show that up-regulation of decorin induced significant decreases of TGF-β1, cyclin D1 expression, phosphorylation of EGFR, and increases of P53 and P21 expression. Opposite results were observed in A549 cells with down-regulation of decorin.</p><p><b>CONCLUSION</b>Our results suggest that decorin is a key regulator involved in proliferation and migration of A549 cells.</p>

Interferon regulatory factor-1 mediates the release of high mobility group box-1 in endotoxemia in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The extracellular release of the danger signal high mobility group box-1 (HMGB1) has been implicated in the pathogenesis and outcomes of sepsis. Understanding the mechanisms responsible for HMGB1 release can lead to the identification of targets that may inhibit this process. The transcription factor interferon regulatory factor-1 (IRF-1) is an important mediator of innate immune responses and has been shown to participate in mortality associated with endotoxemia; however, its role in mediating the release of HMGB1 in these settings is unknown.</p><p><b>METHODS</b>Male IRF-1 knockout (KO) and age matched C57BL/6 wild type (WT) mice were given intraperitoneal (IP) injections of lipopolysaccharide (LPS). In some experiments, 96 hours survival rates were observed. In other experiments, mice were sacrificed 12 hours after LPS administration and sera were harvested for future analysis. In in vitro study, RAW 264.7 murine monocyte/macrophage-like cells or primary peritoneal macrophage obtained from IRF-1 KO and WT mice were cultured for LPS mediated HMGB1 release analysis. And the mechanism for HMGB1 release was analyzed by immune-precipitation.</p><p><b>RESULTS</b>IRF-1 KO mice experienced less mortality, and released less systemic HMGB1 compared to their WT counterparts. Exogenous administration of recombinant HMGB1 to IRF-1 KO mice returned the mortality rate to that seen originally in IRF-1 WT mice. Using cultures of peritoneal macrophages or RAW264.7 cells, in vitro LPS stimulation induced the release of HMGB1 in an IRF-1 dependent manner. And the janus associated kinase (JAK)-IRF-1 signal pathway appeared to participate in the signaling mechanisms of LPS-induced HMGB1 release by mediating acetylation of HMGB1.</p><p><b>CONCLUSION</b>IRF-1 plays a role in LPS induced release of HMGB1 and therefore may serve as a novel target in sepsis.</p>

Inhibition of nuclear factor-κB activity enhanced chemosensitivity to cisplatin in human lung adeno-carcinoma A549 cells under chemical hypoxia conditions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tumor hypoxia, one of the features of solid tumors, is associated with chemo-resistance. Recently, nuclear factor-κB (NF-κB) was found to be activated during hypoxia. However, the impact of NF-κB activation on chemo-resistance during hypoxia remains unknown.</p><p><b>METHODS</b>Human lung adenocarcinoma A549 cells were transfected with NF-κB p65siRNA and treated with cobalt chloride (CoCl2) to mimic hypoxia in the presence or absence of cisplatin. NF-κB expression was measured by Western blotting, immune-fluorescence and real-time PCR. Hypoxia-inducible factor-1α (HIF-1α) and Bcl-2 expression were determined by Western blotting. Cell apoptosis and survival with half-maximum inhibitory concentration (IC50) of cisplatin were determined by Annexin V-FITC/PI and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), respectively.</p><p><b>RESULTS</b>Exposure of A549 cells to CoCl2 increased nuclear HIF-1a protein expression, and enhanced NF-κB p65 protein nuclear accumulation (the mark of NF-κB activation) in a time and dose dependant manner. CoCl2 did not promote apoptosis in A549 cells; on the contrary, it reduced cisplatin-induced apoptosis and increased the IC50 of cisplatin. However, when we inhibited CoCl2-induced activation of NF-κB through NF-κB p65siRNA, cisplatin-induced apoptosis was increased and IC50 of cisplatin was reduced to levels similar to those in control cells. Meanwhile, CoCl2-induced Bcl-2 overexpression was down-regulated in the presence of cisplatin when NF-κB activity was inhibited.</p><p><b>CONCLUSION</b>Up-regulating Bcl-2 might be involved in NF-κB activation induced resistance to cisplatin in A549 cells under CoCl2-induced chemical hypoxia.</p>

Treatment with EGCG in NSCLC leads to decreasing interstitial fluid pressure and hypoxia to improve chemotherapy efficacy through rebalance of Ang-1 and Ang-2 / 中国天然药物

AIM@#Microvasculature and microenvironment play important roles in proliferation, invasion, metastasis and prognosis in non-small cell lung cancer (NSCLC), which might be altered by many anti-angiogenic drugs. Epigallocatechin-3-gallate (EGCG), a natural anti-angiogenesis agent refined from green tea, was defined to have multiple effects on angiogenesis factors, such as endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and angiopoietins (ANGs). Hypothesizing that EGCG might regulate microvasculature and microenvironment in NSCLC, the effects of EGCG on microvessel density (MVD), expression of Ang-1 and Ang-2, interstitial fluid pressure (IFP), tumor hypoxia, and chemotherapy sensitivity were examined.@*METHODS AND RESULTS@#EGCG treatment of A549 cells in mice bearing xenografts in vivo led to a significant decrease of MVD detected by CD31, and of Ang-2 expression detected by quantum dots double-label immunofluorescence assessment, while Ang-1 decreased with no significance. Decreased IFP was measured by the Wink-in-needle method, while hypoxia was assessed by polarographic electrode and pimonidazole (PIMO) immunohistochemistry. Assuming that these changes would increase response to chemotherapy, tumor growth studies were p[erformed in nude mice with xenografts, which were then treated with EGCG and the chemotherapeutic agent cisplatin. EGCG therapy combined with cisplatin led to synergistic inhibition of tumor growth, compared with administration of each treatment separately (P < 0.001). According to linear regression analysis, IFP was positively correlated with PIMO staining (R(2) = 0.618, P = 0.002), Ang-2 was correlated with MVD (R(2) = 0.423, P = 0.022), IFP (R(2) = 0.663, P = 0.01) and PIMO staining (R(2) = 0.694, P = 0.01).@*CONCLUSION@#IFP and delivery of oxygen might be improved by rebalance of Ang-1/Ang-2 under the treatment of EGCG in NSCLC, which also acts as a sensitizer of chemotherapy. These studies established a new mechanism for using EGCG as an adjuvant chemotherapy agent through modifying microvasculature and microenvironment.