Huazhi Rougan Granules attenuates steatosis in cell model of nonalcoholic fatty liver disease by inducing autophagy / 中国中药杂志

To investigate the effect of Huazhi Rougan Granules(HZRG) on autophagy in a steatotic hepatocyte model of free fatty acid(FFA)-induced nonalcoholic fatty liver disease(NAFLD) and explore the possible mechanism. FFA solution prepared by mixing palmitic acid(PA) and oleic acid(OA) at the ratio of 1∶2 was used to induce hepatic steatosis in L02 cells after 24 h treatment, and an in vitro NAFLD cell model was established. After termination of incubation, cell counting kit-8(CCK-8) assay was performed to detect the cell viability; Oil red O staining was employed to detect the intracellular lipid accumulation; enzyme-linked immunosorbnent assay(ELISA) was performed to measure the level of triglyceride(TG); to monitor autophagy in L02 cells, transmission electron microscopy(TEM) was used to observe the autophagosomes; LysoBrite Red was used to detect the pH change in lysosome; transfection with mRFP-GFP-LC3 adenovirus was conducted to observe the autophagic flux; Western blot was performed to determine the expression of autophagy marker LC3B-Ⅰ/LC3B-Ⅱ, autophagy substrate p62 and silent information regulator 1(SIRT1)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway. NAFLD cell model was successfully induced by FFA at 0.2 mmol·L~(-1) PA and 0.4 mmol·L~(-1) OA. HZRG reduced the TG level(P<0.05, P<0.01) and the lipid accumulation of FFA-induced L02 cells, while elevated the number of autophagosomes and autophagolysosomes to generate autophagic flux. It also affected the functions of lysosomes by regulating their pH. Additionally, HZRG up-regulated the expression of LC3B-Ⅱ/LC3B-Ⅰ, SIRT1, p-AMPK and phospho-protein kinase A(p-PKA)(P<0.05, P<0.01), while down-regulated the expression of p62(P<0.01). Furthermore, 3-methyladenine(3-MA) or chloroquine(CQ) treatment obviously inhibited the above effects of HZRG. HZRG prevented FFA-induced steatosis in L02 cells, and its mechanism might be related to promoting autophagy and regulating SIRT1/AMPK signaling pathway.

Mechanism of Huangjing Qianshi Decoction in treatment of prediabetic mice based on transcriptome sequencing / 中国中药杂志

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.

Mechanism of Huangjing Qianshi Decoction in treatment of prediabetes based on network pharmacology and molecular docking / 中国中药杂志

This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.

A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province / 中国当代儿科杂志

OBJECTIVE@#To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province.@*METHODS@#The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017.@*RESULTS@#The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01).@*CONCLUSIONS@#Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.

Intra-tumor heterogeneity for endometrial cancer and its clinical significance / 中华医学杂志(英文版)

Background@#Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles.@*Methods@#A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC.@*Results@#The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc.@*Conclusions@#Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

Identification of new fusion genes and their clinical significance in endometrial cancer / 中华医学杂志(英文版)

Background@#Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC.@*Methods@#A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software.@*Results@#New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11–123O10.4–GRIP1, RP11–444D3.1–SOX5, RP11– 680G10.1–GSE1, NRIP1–AF127936.7, RP11–96H19.1–RP11–446N19.1, and DPH7–PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1–AF127936.7 and DPH7–PTP4A3 were found only in stage III patients with EC. DPH7–PTP4A3 was found in grades 2 and 3, and recurrent patients with EC.@*Conclusion@#Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1– AF127936.7 and DPH7–PTP4A3 might be related to stage, and DPH7–PTP4A3 be related to grade and recurrence.

Intra-tumor heterogeneity for endometrial cancer and its clinical significance / 中华医学杂志(英文版)

BACKGROUND@#Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles.@*METHODS@#A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC.@*RESULTS@#The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. CONCLUSIONS:: Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

Identification of new fusion genes and their clinical significance in endometrial cancer / 中华医学杂志(英文版)

BACKGROUND@#Fusion genes may play an important role in tumorigenesis, prognosis, and drug resistance; however, studies on fusion genes in endometrial cancer (EC) are rare. This study aimed to identify new fusion genes and to explore their clinical significance in EC.@*METHODS@#A total of 28 patients diagnosed with EC were enrolled in this study. RNA sequencing was used to obtain entire genomes and transcriptomes. STAR-comparison and STAR-fusion prediction were applied to predict the fusion genes. Chi-square tests and Student t tests were used to verify the clinical significance with SPSS 13.0 software.@*RESULTS@#New fusion genes were found, and the number of fusion genes varied from 3 to 110 among all patients with EC. The type of fusion genes varied and included messenger RNA (mRNA)-mRNA, long non-coding RNA (lncRNA)-lncRNA, and lncRNA-mRNA. There were six fusion genes with high fusion rates, namely, RP11-123O10.4-GRIP1, RP11-444D3.1-SOX5, RP11-680G10.1-GSE1, NRIP1-AF127936.7, RP11-96H19.1-RP11-446N19.1, and DPH7-PTP4A3. Further studies showed that these fusion genes are related to stage, grade, and recurrence, in which NRIP1-AF127936.7 and DPH7-PTP4A3 were found only in stage III patients with EC. DPH7-PTP4A3 was found in grades 2 and 3, and recurrent patients with EC.@*CONCLUSION@#Fusion genes play an essential role in EC. Six genes that are overexpressed with high fusion rates are identified. NRIP1-AF127936.7 and DPH7-PTP4A3 might be related to stage, and DPH7-PTP4A3 be related to grade and recurrence.

Orthogonal test on local temperature influenced by different parameters and manipulation types of An-pressing Xinshu (BL 15) / 针灸推拿医学（英文版）

Objective:To explore the optimal thermal effect parameter combination of An-pressing manipulation based on the pressing force, time and frequency, and to compare the thermal effect differences between the rhythmic and the continuous An-pressing manipulations. Methods:Three levels of light, moderate and heavy pressing forces were determined according to the An-pressing forces of the clinical tuina physicians; the pressing time and frequency parameters were determined according to the literatures about An-pressing manipulation. The volunteers were stimulated by the homemade An-pressing manipulation stimulator on the right Xinshu (BL 15), and then the three-factor and three-level orthogonal tests were carried out according to the test sequence specified by the L9(34) orthogonal table, and the temperature before and after pressing was recorded by an infrared thermal imaging system to screen the best parameters for the thermal effect of the An-pressing manipulation, thus to determine the optimal pressing parameters. The optimal parameters were then used for both continuous and rhythmic An-pressing manipulations to stimulate the bilateral Xinshu (BL 15). The temperature changes after pressing and the duration of the thermal effect (temperature difference ≤0.5℃ on both sides) were recorded by the infrared thermal imaging system, to explore the differences in the thermal effects of different An-pressing manipulations. Results:Among the three factors of pressing force, time and frequency, the influences of different pressing forces on temperature were significantly different (F=32.843,P=0.030), and the influence of 2.5 kg pressing force was the most significant; the effects of different pressing time on temperature were significantly different (F=54.102,P=0.018), and the pressing time of 7.5 min was the most significant; the influences of different pressing frequencies on temperature were not statistically significant (F=2.181,P=0.314), though the influence of 10 times/min pressing frequency was the largest. The influences on temperature difference of the rhythmic and the continuous An-pressing manipulations were significantly different (P=0.031 on the left side andP=0.045 on the right side), but there was no statistical difference in the duration of the thermal effect (P=0.690). Conclusion:The An-pressing manipulation parameters that significantly affect the temperature difference are pressing force and time. The optimal combination of thermal effect parameters is pressing force of 2.5 kg, time of 7.5 min, and frequency of 10 times/min. The local thermal effect of the rhythmic An-pressing manipulation is significantly greater than of the continuous An-pressing manipulation.

Study on Construction of Professional Degree Courses for Prevention and Health Care of TCM Postgraduates Based on Practical Ability / 中国中医药信息杂志

Objective To construct a suitable system of professional degree of prevention and health care of TCM postgraduates based on practical ability. Methods Dephi method was used to carry out two rounds of questionnaire survey on 30 experts from top three hospitals and TCM colleges and universities in different regions to evaluate the level of experts' initiative, authority and coordination. Results After 2 rounds of inquiry, it was concluded that the prevention and health care professional postgraduate training practical ability mainly included clinical ability (100%), research ability (73.3%), management ability (76.7%) and education ability (90.0%). On the basis of this, 11 compulsory courses and 5 elective courses were established, and clinical practice was built at the same time. Conclusion This study of professional degree courses for prevention and health care of TCM postgraduates on the construction based on practical ability training is feasible.

Study on Construction of Practice Ability Index System of TCM Prevention Health Major Degree through Delphi Method / 中国中医药信息杂志

Objective To construct practice ability index system of TCM prevention health major degree; To provide references for building of related postgraduate training mode. Methods Literature research and research group comments were comprehensively collected, to formulate practice ability index system of TCM prevention health major degree. Deplhi method was used to conduct two rounds of expert consultation to finalize the screening standard of practice index system and evaluate expert level of enthusiasm, authority degree and coordination degree. Results A total of 30 experts from top three hospitals in different regions and TCM colleges and universities attended the 2 rounds of consultation. Two rounds of effective questionnaires for recycling were 30 and 26 respectively. The effective recovery rates were 100.00% and 86.67%. After collecting, summarizing and analyzing the opinions of experts, a set of practical ability index system including 6 first-level indicators, 22 second-level indicators and 125 third-level indicators was constructed. Conclusion This study builds a reliable practice ability index system of TCM prevention health major degree.

Nalmefene improves prognosis in patients with a large cerebral infarction: study protocol for a randomized controlled prospective trial / 中国组织工程研究

BACKGROUND:Occlusion of the middle cerebral artery trunk can cause large infarctions.Clinically,thrombolytic therapy,defibrillation,vasodilation,and surgery are often used to treat these large infarctions.However,the therapeutic efficacy of these therapeutic interventions in promoting prognosis remains controversial.Nalmefene,an opioid receptor antagonist,exhibits a neuroprotective effect.Few clinical studies are reported on the therapeutic efficacy of nalmefene in the treatment of large cerebral infarctions.OBJECTIVE:To investigate the therapeutic efficacy of nalmefene in restoring the neurologic function of patients with middle cerebral artery trunk infarction in comparison with conventional treatment as a control.METHODS:A total of 236 patients with middle cerebral artery trunk infarction who will receive treatment at the First Hospital of Jilin University,China will be randomly divided into a control group (n=116) and a nalmefene group (n=120).Patients in the control group will receive conventional treatment.Patients in the nalmefene group will receive 10 successive days of intravenous nalmefene hydrochloride injection based on conventional treatment.The primary outcome of this study is the effective rate at 20 days (10 days after treatment).The secondary outcomes of this study include (1) the National Institutes of Health Stroke Scale (NIHSS) score at 20 days,used to evaluate neurologic function deficits;(2) Glasgow Coma Scale score at 0 (before treatment) and 10 days;(3) serum level of matrix metalloproteinase 9 at 0,5 and 10 days (before treatment and 5 and 10 days of treatment);(4) MRI perfusion imaging of the head at 0 and 10 days.This trial was ragistered with the Chinese Clinical Trial Registry (registration number:ChiCTR-IOR-17013871).RESULTS AND CONCLUSION:Preliminary experiment results ravealed that compared with the control group,NIHSS score was signficiantly decreased,effective rate was increased,Glasgow Coma Scale score was significantly increased,serum level of matrix metalloproteinase 9 was significantly decreased,cerebral blood flow and cerebral blood volume on the lesion side were signficiantly increased,and the mean transit time of contrast agent on the lesion side was significantly shortened in the nalmefene group.Findings from this study will provide clinical evidence for use of nalmefene in combination with conventional treatment for large cerebral infarctions and provide data support that this combined therapy can improve the prognosis in patients with large cerebral infarctions.

Risk factors for neonatal pulmonary hemorrhage in the neonatal intensive care unit of a municipal hospital / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors for neonatal pulmonary hemorrhage (NPH) in the neonatal intensive care unit (NICU) of a municipal hospital, and to provide a basis for the early identification and treatment of NPH.</p><p><b>METHODS</b>A total of 112 neonates who were admitted to the NICU of Shaoyang Central Hospital of Hunan Province and diagnosed with NPH were enrolled as the case group. A nested case-control method was used to select, as a control group (n=224), the neonates who underwent the treatment with an assisted mechanical ventilator and did not experience pulmonary hemorrhage. Univariate analysis and unconditional logistic regression analysis were used to identify the high risk factors for NPH.</p><p><b>RESULTS</b>The univariate analysis showed that compared with the control group, the case group had significantly higher incidence rates of gestational diabetes and cholestasis in mothers, cesarean delivery, gestational age <34 weeks, 5-minute Apgar score ≤5, birth weight <2 500 g, heart failure and disseminated intravascular coagulation (DIC) before the development of NPH, partial pressure of oxygen/fraction of inspired oxygen (oxygenation index, OI) ≤100, and a reduction in mean platelet volume. The multivariate logistic regression analysis showed that DIC, heart failure, and OI ≤100 were independent risk factors for NPH (OR=33.975, 3.975, 1.818 respectively; P<0.05).</p><p><b>CONCLUSIONS</b>Heart failure, OI ≤100, and DIC are risk factors for the development of NPH in the NICU of the municipal hospital.</p>

Chemical constituents from pseudobulb of Cremastra appendiculata / 中草药

Objective: To study the chemical constituents from the pseudobulbs of Cremastra appendiculata. Methods: The compounds were isolated by repeated column chromatography with silica gel, Sephadex LH-20, and ODS-HPLC. The structures were elucidated by analysis of spectroscopic (1H-NMR and 13C-NMR) data. Results: Eleven compounds were isolated from the EtOAc extract in the pseudobulbs of C. appendiculata. Their structures were identified as 3,5,3'-trihydroxybibenzyl (1), 7-hydroxy-4- methoxy-phenanthrene-2-O-β-D-glucoside (2), lignan glycosides (3), ibotanolide A (4), 3,3'-dihydroxy-5-methoxy-2,4-di (p- hydroxybenzyl) bibenzy (5), 5,4'-bihydroxy-bibenzyl-3-O-β-D-glucoside (6), 3'-β-D-glucopyranosyloxy-4,5'-dihydroxy-3-methoxy- 1,2-diphenylethane (7), cirrhopetalanthin (8), 7-hydroxy-2-4-dimethoxy-phenanthrene (9), β-daucosterin (10), and p-hydroxy benzaldehyde (11). Conclusion: Compounds 3-7 are isolated from the pseudobulbs of C. appendiculata for the first time.

Occupational Exposure to Indium of Indium Smelter Workers / 生物医学与环境科学（英文）

Case reports of indium-related lung disease in workers have raised public concern to the human toxicity of indium (In) and its compounds. However, studies evaluating the exposure or health of workers in In smelting plants are rare. Therefore, in this study, we focused on four In smelting plants, with the main objective of characterizing In in smelter plants in China and discussing the potential exposure biomarkers of In exposure. We recruited 494 subjectsat four In smelting plants in China. Personal air samples, first morning urine and spot blood samples were collected. In concentrations in samples were analyzed using inductively coupled plasma mass spectrometry. In concentrations in air samples did not exceed the permissible concentration-time weighed average, but the smelter workers had a higher internal exposure to In. Positive correlations were observed between the air In and urine In concentrations, and between the air In and blood In concentrations. This study provides basic data for the following In exposure and health risk assessment.

Correlation between the Expression of microRNA 451 in Red Blood Cells and Chronic Mountain Sickness / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between the expression of microRNA-451 in red blood cells and chronic mountain sickness(CMS).</p><p><b>METHODS</b>Peripheral blood samples were collected from emigrant CMS patients (28 cases), localized CMS patients (12 case), emigrant healthy people (24 case) and localized healthy people (22 case). The microRNA-451 expression in red blood cells was measured by the RT-PCR. The results combined with the clinical data of patients were analysed.</p><p><b>RESULTS</b>The expression of microRNA-451 in emigrant CMS patients was higher than that in emigrant healthy people (P<0.05); the expression of microRNA-451 in localized CMS patients was higher than that in localized healthy people (P<0.05); the microRNA-451 expression had no statistical difference between emargant and localized healthy people. The level of hemoglobin in CMS patients was positively correlated with the expression of microRNA-451 in red cells (r=0.701).</p><p><b>CONCLUSION</b>There is a certain level of microRNA-451 in healthy people, the expression of microRNA-451 in CMS patients is significantly higher than that in healthy people. MicroRNA-451 may play an important role in the process of chronic mountain sickness.</p>

Gonadotropin-releasing hormone agonists cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, conservative surgery is acceptable in young patients with borderline ovarian tumor and ovarian cancer. The preservation of these patients' future fertility has been the focus of recent interest. This study aimed to observe the effect of gonadotropin-releasing hormone agonists (GnRHa) cotreatment during chemotherapy in borderline ovarian tumor and ovarian cancer patients.</p><p><b>METHODS</b>Sixteen patients who were treated with fertility preservation surgery for borderline ovarian tumor and ovarian cancer and then administered GnRHa during chemotherapy in Peking University People's Hospital from January 2006 to July 2010 were retrospectively analyzed. This group was compared with a control group of 16 women who were treated concurrently with similar chemotherapy (n = 5) without GnRHa or were historical controls (n = 11). The disease recurrence, the menstruation status and reproductive outcome were followed up and compared between the two groups.</p><p><b>RESULTS</b>There were no significant differences between both groups regarding age, body weight, height, marriage status, classification of the tumors, stage of the disease, as were the cumulative doses of each chemotherapeutic agent. One (1/16) patient in the study group while 2 (2/16) patients in the control group relapsed 2 years after conclusion of the primary treatment (P > 0.05). All of the 16 women in the study group compared with 11 of the 16 patients in the control group resumed normal menses 6 months after the termination of the treatment (P < 0.05). There were 4 spontaneous pregnancies in the study group while 2 in the control group, all of the neonates were healthy.</p><p><b>CONCLUSIONS</b>GnRHa administration before and during chemotherapy in borderline ovarian tumor and ovarian cancer patients who had undergone fertility preservation operation may bring up higher rates of spontaneous resumption of menses and a better pregnancy rate. Long-term follow up and large scale clinical studies are required.</p>

Effects of insulin, insulin-like growth factor-I and -II on proliferation and intracellular signaling in endometrial carcinoma cells with different expression levels of insulin receptor isoform A / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hyperinsulinemia, insulin-like growth factor (IGF)-I and -II (IGF-II) are associated with increased risk of endometrial carcinoma. Insulin receptor isoform A (IR-A) is more frequently expressed in endometrial carcinoma than in normal endometrial tissues. To better understand their roles in endometrial carcinoma, we investigated the effects of insulin, IGF-I, and IGF-II in endometrial carcinomas cells with different IR-A expression levels.</p><p><b>METHODS</b>To explore the role of IR-A in mediating the activity of IGF-I, IGF-II, and insulin, we investigate the cellular proliferation of endometrial carcinoma cell lines RL95-2 and RL95-2-IR-A by MTS assays. Then we examined the protein kinase Akt phosphorylation and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in both cell lines by Western blotting. The effect of IGF-II and AG1024 on cell cycle progression and apoptosis was assessed by flowcytometry. To examine whether the effects of IGFs were mediated by IR-A, we blocked IGF-I receptor (IGF-IR) in both cell lines using AG1024, an IGF-IR-specific inhibitor.</p><p><b>RESULTS</b>IGF-I and IGF-II significantly enhanced proliferation of both cell lines (P < 0.05). By contrast, insulin significantly increased proliferation of RL95-2-IR-A cells only (P < 0.05). IGF-I and IGF-II significantly increased pAkt levels in RL95-2 cells and pERK1/2 levels in RL95-2-IR-A cells (all, P < 0.05). Insulin increased pERK1/2 levels in RL95-2-IR-A cells only (P < 0.05). LY294002 and PD98059 inhibited the specific signaling activities and cellular proliferation. After AG1024 pretreatment, neither IGF-I nor IGF-II affected pAkt levels in RL95-2 cells. IGF-II, but not IGF-I, increased pERK1/2 levels in RL95-2-IR-A cells. After AG1024 pretreatment, the proliferation rate and DNA content corresponding to the S phase increased and apoptosis decreased significantly in IGF-II-treated RL95-2-IR-A cells only (P < 0.05).</p><p><b>CONCLUSIONS</b>The proliferation effect of insulin is mediated by IR-A. When IR-A dominates in a cell line, IGF-II activated cell proliferation mainly through the ERK1/2 pathway. On the other hand, IGF-II activated cell proliferation mainly through the Akt pathway. IR-A can at least partly mediate the proliferative and anti-apoptotic effects of IGF-II through the ERK1/2 pathway.</p>

Clinical effectiveness of INSURE method in the treatment of neonatal respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical effectiveness and safety of intubation-surfactant-extubation (INSURE) method in the treatment of neonatal respiratory distress syndrome (NRDS), and to investigate its possible mechanisms.</p><p><b>METHODS</b>Sixty-four premature infants, who were admitted for NRDS and treated with pulmonary surfactant from March 2010 to March 2012, were enrolled in the study. They were randomly divided into INSURE (n=32) and conventional mechanical ventilation (CMV) groups (n=32). The two groups were compared in terms of respiratory function, ventilation time, duration of oxygen therapy, complications, and prognosis, as well as expression of interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and serum ferritin (SF).</p><p><b>RESULTS</b>Oxygenation index in the INSURE group was significantly higher than in the CMV group at 48 hours after treatment (P<0.05). Compared with the CMV group, the INSURE group showed significantly lower incidence of ventilator-associated pneumonia (VAP) and significantly shorter duration of oxygen therapy (P<0.05 for all comparisons). There were no significant differences in ventilation time and the incidence of pneumothorax, intracranial hemorrhage, necrotizing enteroolitis, bronchopulmonary dysplasia, and pneumorrhagia between the two groups (P>0.05). The levels of TNF-α and SF were significantly lower in the INSURE group than in the CMV group at 6, 24, 48, and 72 hours after treatment (P<0.05), while the level of IL-10 was significantly higher in the INSURE group than in the CMV group (P<0.05).</p><p><b>CONCLUSIONS</b>INSURE method can improve the oxygenation function of the lung, decrease the incidence of VAP and shorten the duration of oxygen therapy in neonates with NRDS, which is probably due to the fact that this method can reduce the production of TNF-α and SF and inhibit the decrease of IL-10.</p>

Molecular subtypes identified by gene expression profiling in early stage endometrioid endometrial adenocarcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Early stage (FIGO stage I-II) endometrioid endometrial adenocarcinoma (EEA) is very common in clinical practice. However, patients with the early stage EEA show various clinical behaviors due to biological heterogeneity. Hence, we aimed to discover distinct classes of tumors based on gene expression profiling, and analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters.</p><p><b>METHODS</b>Hierarchical clustering was performed for class discovery in 28 early stage EEA samples using a special cDNA microarray chip containing 492 genes designed for endometrial cancer. Correlations between clinicopathologic parameters and our classification were analyzed. And the significance analysis of microarrays (SAM) array was used to identify the signature genes according to the tumor grade and myometrial invasion.</p><p><b>RESULTS</b>Three tumor subtypes (subtypes I, II and III) were identified by hierarchical clustering, each subtype had different clinicopathological factors, such as tumor grade, myometrial invasion status, and FIGO stage. Moreover, SAM analysis showed 34 up-regulated genes in high grade tumors, and 38 up-regulated genes and 1 down-regulated in deep myometrial invasive tumors. The overlap genes between these two high-risk factors were markedly up-regulated in subtype I, but down-regulated in subtype III.</p><p><b>CONCLUSION</b>We have identified novel molecular subtypes in early stage EEA. Differential gene signatures characterize each tumor subtype, which could be used for recognizing the tumor risk and providing a basis for further treatment stratification.</p>