The performance of digital chest radiographs in the detection and diagnosis of pulmonary nodules and the consistency among readers / 中华肿瘤杂志

Objective: To investigate the detection and diagnostic efficacy of chest radiographs for ≤30 mm pulmonary nodules and the factors affecting them, and to compare the level of consistency among readers. Methods: A total of 43 patients with asymptomatic pulmonary nodules who consulted in Cancer Hospital, Chinese Academy of Medical Sciences from 2012 to 2014 and had chest CT and X-ray chest radiographs during the same period were retrospectively selected, and one nodule ≤30 mm was visible on chest CT images in the whole group (total 43 nodules in the whole group). One senior radiologist with more than 20 years of experience in imaging diagnosis reviewed CT images and recording the size, morphology, location, and density of nodules was selected retrospectively. Six radiologists with different levels of experience (2 residents, 2 attending physicians and 2 associate chief physicians independently reviewed the chest images and recorded the time of review, nodule detection, and diagnostic opinion. The CT imaging characteristics of detected and undetected nodules on X images were compared, and the factors affecting the detection of nodules on X-ray images were analyzed. Detection sensitivity and diagnosis accuracy rate of 6 radiologists were calculated, and the level of consistency among them was compared to analyze the influence of radiologists' seniority and reading time on the diagnosis results. Results: The number of nodules detected by all 6 radiologists was 17, with a sensitivity of detection of 39.5%(17/43). The number of nodules detected by ≥5, ≥4, ≥3, ≥2, and ≥1 physicians was 20, 21, 23, 25, and 28 nodules, respectively, with detection sensitivities of 46.5%, 48.8%, 53.5%, 58.1%, and 65.1%, respectively. Reasons for false-negative result of detection on X-ray images included the size, location, density, and morphology of the nodule. The sensitivity of detecting ≤30 mm, ≤20 mm, ≤15 mm, and ≤10 mm nodules was 46.5%-58.1%, 45.9%-54.1%, 36.0%-44.0%, and 36.4% for the 6 radiologists, respectively; the diagnosis accuracy rate was 19.0%-85.0%, 16.7%-6.5%, 18.2%-80.0%, and 0%-75.0%, respectively. The consistency of nodule detection among 6 doctors was good (Kappa value: 0.629-0.907) and the consistency of diagnostic results among them was moderate or poor (Kappa value: 0.350-0.653). The higher the radiologist's seniority, the shorter the time required to read the images. The reading time and the seniority of the radiologists had no significant influence on the detection and diagnosis results (P>0.05). Conclusions: The ability of radiographs to detect lung nodules ≤30 mm is limited, and the ability to determine the nature of the nodules is not sufficient, and the increase in reading time and seniority of the radiologists will not improve the diagnostic accuracy. X-ray film exam alone is not suitable for lung cancer diagnosis.

Research of first-degree relatives of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

@#Keratoconus(KC)is a progressive disease characterized by gradual corneal thinning and ectasia, resulting in irregular astigmatism, myopia, and mild to severe visual impairment. Although the pathogenesis of KC is still unclear, twin studies and family-based studies have identified that the occurrence of KC is closely related to genetic factors. First-degree relatives of KC patients including their parents, siblings and offspring are very important for the family aggregation analysis and polygenic analysis of diseases. This review summarized the current situation of clinical and genetic research about first-degree relatives of KC patients, hoping to deepen the understanding of clinical manifestations and genetic characteristics of first-degree relatives of KC, and to provide new ideas for exploring the role of genetic and environmental factors in the pathogenesis of KC.

Material manufacturability classification in high shear wet granulation process of Chinese medicine / 中国中药杂志

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.

Mechanism of uptake and retention of 18F-MyoZone in cardiomyocytes: A novel PET myocardial perfusion imaging agent / 解放军医学杂志

Objective To investigate the mechanism of uptake and retention of a novel PET myocardial perfusion imaging agent 18F-MyoZone in cardiomyocytes. Methods 1) Mechanism of inhibition of mitochondrial respiratory chain enzyme activity: With mitochondrial respiratory chain enzyme complex I (MC-I) activity assay kit, a sequence of 19F-MyoZone solution (start at 15 μmol/L, 3 times dilution, 12 points) was interacted with MC-I to detect the half inhibition rate (IC50) of 19F-MyoZone inhibiting mitochondrial respiratory chain activity. 2) Autoradiography experiment of 18F-MyoZone combining with MC-I: Myocardial tissue sections of neonatal rat were hatched with normal saline and 4 known MC-I inhibitors [rotenone (4 μmol/L), 19F-Flurpiridaz (4 μmol/L), 19F-MyoZone (4 μmol/L) and pyridaben (4 μmol/L)], and then 18F-MyoZone was added to autoradiography for detecting whether 18F-MyoZone can specifically bind the cardiomyocytes MC-I; and then the myocardial tissue sections of rat were hatched for 30 min with different concentrations of rotenone or 19F-MyoZone solution (0, 20 μmol/L, 2 μmol/L and 200 nmol/L, 20 nmol/L), then the 18F-MyoZone was added and hatched for 30 min again, developing for 10 min with phosphor storage screen after cleaning the slice, and analyzing and calculating the inhibition rate of each inhibitor concentration. 3) Experiment of rotenone inhibitting the uptake of 18F-MyoZone by cardiomyocytes: Neonate rats' primary cardiomyocytes were cultured for 15 min with different concentrations of 19F-MyoZone or equivalent rotenone (start at 10 μmol/L, 3 times dilution, 12 points), then 50 μl of 18F-MyoZone (about 17 kBq) was added and culturing for 30 min. The lysate was then collected, the radioactivity was counted and the IC50 of rotenone was calculated. 4) Outflow experiment of 18F-MyoZone from cardiomyocytes: Cultured neonate rats' primary cardiomyocytes were interacted with 500 μl of 18F-MyoZone (about 37 kBq) for 30 min, then the cell supernatant and lysate were separated to do photon counts at the time points of 0, 10, 20, 30, 60, 90, 120 and 150 min. The ratio of cardiomyocyte outflow rate was then calculated. Results Enzyme activity studies showed that 19F-MyoZone may effectively inhibit the activity of MC-I(IC50=229.9 nmol/L) in a dose dependent manner. MyoZone could specifically bind to MC-I with binding sites in accordance with the inhibitors rotenone, pyridaben and 19F-Flurpiridaz. Experiment of rotenone inhibitting the uptake of 18F-MyoZone by cardiomyocytes showed that 18F-MyoZone could be absorbed by rat's cardiomyocytes, and with the increase of rotenone concentration, the radio uptake of cardiomyocytes decreased gradually with inhibitor IC50 as 7 nmol/L. Outflow experiment showed that rat's cardiomyocytes could uptake 18F-MyoZone and stably detain over time. The outflow rate increased gradually within 0-30 min, and then maintained constantly from 60 min to 150 min. The amount of retention was about 20% of the entire uptake. Conclusions 18F-MyoZone may specifically bind MC-I and detain for a long time in rat's cardiomyocytes. 18F-MyoZone is a valuable myocardial perfusion imaging agent with great research value.

A prospective cohort study of the relationship between unhealthy lifestyle and gestational diabetes mellitus / 中华疾病控制杂志

Objective To analyze the incidence of gestational diabetes mellitus (GDM) among Chinese pregnant women and the distributions of unhealthy lifestyles. Exploring the association between these behaviors and GDM to provide some suggestions to GDM prevention. Methods Women who were enrolled by the Chinese Pregnant Women Cohort Study and delivered before the 31st December, 2018 were enrolled by this study. The characters of physical activity, sedentary lifestyle, tobacco exposure, alcohol consumption, unhealthy diet and low sleep level were assessed by questionnaire and also the pregnancy complications. Binary Logistic regression model was adopted to analyzed the relationship between the dependent and independent variables. Results A total of 3 162 women were enrolled in this study and 372 of them were diagnosed GDM. Single variable analysis showed that lack of leisure time physical activity (RR=1.015,95% CI=1.005-1.279，P=0.046) and low sleep quality (RR=1.019, 95% CI: 1.004-1.196，P=0.047) were two risk factors of GDM. Compared with women who showed none of these unhealthy lifestyle, those who showed all six unhealthy behaviors had higher risk of GDM (RR=1.530, 95% CI: 1.263-8.880，P=0.036). Conclusions The incidence of GDM among Chinese women was 11.76%. Lack of physical activity and poor sleep quality could increase the risk of GDM and the cluster of unhealthy lifestyles is associated with higher GDM risk. Adequate physical activity, no smoking and drinking, balanced diet and other healthy behaviors are important to GDM prevention.

Influence of reproduction history on depression during pregnancy: a prospective cohort study / 中华疾病控制杂志

@#Objective To explore the influence of reproduction history on depression during pregnancy． Methods Data on 3 792 pregnant women from the Chinese pregnant women cohort study with complete information on reproduction history and depression were used in the present study． The Edinburgh postnatal depression scale was used to assess depression status among pregnant women． A chi-square test was used for univariate analysis，and a Log－binomial regression was used for multivariate analysis． The adjusted relative risks ( ＲＲs) with 95% confidence intervals ( 95% CIs) were calculated，and were presented in a forest plot． Ｒesults The results of Log－binomial regression showed that a history of delivery could increase the risk of depression during the second trimester ( ＲＲ: 1. 04，95% CI: 1. 01 － 1. 08，P= 0. 042) and the third trimester ( ＲＲ: 1. 05，95% CI: 1. 01－1. 10，P= 0. 020) ． There was a 6% increase of risk on depression in women with a history of cesarean delivery compared with women without that during the third trimester ( ＲＲ: 1. 06，95% CI: 1. 01－1. 11，P = 0. 041) ． Conclusions There is asignificant influence of reproduction history on gestational depression． Maternal and child health personnel should focus on these pregnant women，and conduct targeted health education and mental nursing． In addition，medical personnel should also pay attention to the emotional changes of these women and provide them with several adjustment strategies．

Association of physical activity and cesarean section in the second trimester of pregnancy: a cohort study / 中华疾病控制杂志

@#Objective To explore the associations between cesarean section with different types and intensity of physical activity in the second trimester pregnant women． Methods Six hundred and seventy－two participants from the Chinese pregnant women cohort study ( CPWCS) were analyzed． The pregnancy physical activity questionnaire ( PPAQ) was used to collect the status of physical activities in pregnant women． The participants were followed up and the data of delivery way was collected． Logistic regression model was conducted to analyze the associations． Ｒesults A total of 273 pregnant women ( 40. 63%) were delivered by cesarean section． After adjusting age，pre-pregnancy BMI and history of childbirth，results of Logistic regression model showed that pregnant women with higher levels of exercise had a lower risk of cesarean section than those who did not participate in exercise ( OＲ= 0. 564，95% CI: 0. 338－0. 941) . In terms of physical activity intensity，pregnant women who participated in the higher level of moderate to vigorous physical activity had a lower risk of cesarean section than those who partici- pated in the lower level ( OＲ= 0．642，95% CI: 0．437－0．972) ． Conclusions Exercise and moderate to vigorous physical activity are protective factors for cesarean section． Health education should be further strengthened to encourage pregnant women to carry out appropriate physical activity during pregnancy．

Effect of pre－pregnancy body mass index and gestational weight gain on birth weight of infants: a prospective cohort study / 中华疾病控制杂志

@#Objective To analyze the relationship between pre － pregnancy body mass index ( BMI) ，gestational weight gain ( GWG) and the birth weight of infants，and explore the effect of weight change before and during pregnancy on low birth weight ( LBW) and macrosomia． Methods Women were enrolled by the Chinese Pregnant Women Cohort Study during first trimester． Each respondent＇s weight before and during pregnancy and the birth weight of infant were collected after fellow up． Prepregnancy BMI was divided into underweight，normal and overweight /obesity groups and GWG was divided into suitable， insufficient and excessive groups． Multivariate Logistic regression was adopted to explore the relationship be- tween pre－pregnancy BMI，GWG and newborn＇s birth weight． Ｒesults Women＇s prepregnancy BMI and GWG were associated with neonatal birth weight ( all P＜0. 05) ． Prepregnancy overweight or obesity ( OＲ=2. 339，95% CI: 1. 674－2. 282，P＜0. 001) and excessive GWG ( OＲ= 1. 398，95% CI: 1. 188－1. 978，P= 0. 048) were shown as risk factors for macrosomia． Insufficient GWG increased LBW risk ( OＲ = 1. 479， 95% CI: 1. 461－1. 679，P= 0. 035) while excessive GWG declined LBW risk ( OＲ= 0. 428，95% CI: 0. 225 －0. 817，P= 0. 010) ． Under weight－insufficient GWG was risk factor of LBW ( OＲ= 1. 335，95% CI: 1. 048 －2. 319，P= 0. 048) while normal BMI－excessive GWG ( OＲ= 1. 088，95% CI: 1. 016－1. 675，P= 0. 038) and overweight /obesity－excessive GWG ( OＲ= 1. 498，95% CI: 1. 244－2. 017，P= 0. 046) were associated with higher risk of delivering macrosomia． Conclusions Prepregnancy BMI and GWG were associated with infant＇s birth weight and women were suggested to maintain their weight in recommended range before and during pregnancy．

Content Comparison of Mannose,Glucose and Narinhenin in Dendrobium officinale and Dendrobium huoshanense / 中国实验方剂学杂志

Objective: To optimize the pre-column derivation high performance liquid chromatography (HPLC) content determination method of D-mannose and D-glucose as well as the content determination method of narinhenin in Dendrobium officinale and D. huoshanense, and compare the contents of D-mannose,D-glucose and narinhenin between D. officinale and D. huoshanense. Method: A pre-column derivation HPLC method modified by Chinese Pharmacopoeia(Ch.P) 2015 was used to simultaneously determine the contents of D-mannose and D-glucose,with acetonitrile-0.02 mol·L-1 ammonium acetate solution as mobile phase for gradient elution. Kromasil 100-5 C18 was performed with the wavelength set at 250 nm,and the flow rate was 1 mL·min-1;column temperature was 30℃. HPLC content determination of narinhenin was performed on Kromasil 100-5 C18 with the acetonitrile-methanol-0.4% phosphoric acid solution as mobile phase for gradient elution,and the wavelength was set at 290 nm; the flow rate was 0.8 mL·min-1,and column temperature was 40℃. Result: D-mannose and D-glucose showed a good linear relationship within the range of 0.15-3.0 μg and 0.075-2.25 μg (r=0.999 9); and their average recoveries were 99.01% (RSD 2.1%) and 101.69% (RSD 2.0%) respectively. In addition, the other methodological researches such as repeatability and durability all met the requirements. The contents of D-mannose(Cm),D-glucose(Cg) and sum of them (Cm+Cg) were 12.75%-36.40%,2.93%-18.39% and 19.23%-54.58% in 43 batch of D. officinale. Almost all of the results except very few samples reached the D-mannose standard in Ch.P 2015, and the total content of D-mannose and D-glucose was also up to the total polysccharide standard in Ch.P. The correlation between content and origin was not significant. The contents of D-mannose(Cm),D-glucose(Cg) and sum of them (Cm+Cg) were 14.33%-29.47%,6.64%-15.20%,and 25.73%-44.37% in 12 batch of D. huoshanense. These contents and ratio of peak areas of D-mannose to D-glucose (Am/Ag) were within the scope of D. officinale's; in addition, their average contents were basically the same with those in D. officinale (about 33%).Next,naringenin showed a good linear relationship within the range of 0.020 8-0.832 0 μg (r=0.999 9),and its average recovery was 101.96% (RSD 1.8%). The content of naringenin was 0.053 2-0.122 4 mg·g-1 (average value of 0.081 0 mg·g-1) in 11 batch of D. officinale, slightly higher than 0.040 3-0.090 0 mg ·g-1 (average value of 0.068 3 mg ·g-1) in 7 batch of D. huoshanense. All of these results of narinfenin did not reach the content lower limit in Ch.P. Conclusion: The method used to determinate the content of D-mannose and D-glucose is reproducible, and their sum content is possible to substitute the total polysccaride determination (with higher errors) in D. officinale; monosaccharide content determination can be used for quantitative quality control of D. huoshanense. However, it could not distinguish D. officinale and D. huoshanense by determining the contents of polysccharide,D-glucose,D-mannose and narinhenin, and shall be combined with other specificity methods for further identification.

HPLC Characteristic Spectrum Optimization of Flavonoid Glycosides on Dendrobium officinale and Characteristics Analysis of Different Provenances / 中国实验方剂学杂志

Objective: To optimize the HPLC characteristic spectrum of flavonoid glycosides of Dendrobium officinale,and identify the common and specific components of different provenances. Method: Kromasil 100-5 C18 column was adopted, with tetrahydrofuran-acetonitrile-methanol (10:22:5)-0.05% phosphoric acid as mobile phase (gradient elution). The detection wavelength was 340 nm,the column temperature was 30℃,and the flow rate was 1.0 mL ·min-1. Result: 13 flavonoid characteristic peaks were marked in 27 batches of D. officinale,and 7 characteristic peaks of 6 flavonoid C-glycosides (vicenin Ⅱ,vicenin Ⅰ,schaftoside,isoschaftoside,violanthin and isoviolanthin) and one flavonoid O-glycosides (rutin) was identified. 7-11 characteristic peaks were detected in different batches of samples. Among them,vicenin Ⅱ was a relatively stable common peak in different source samples,and the characteristic peaks of rutin,schaftoside and isoschaftoside were quite different. According to the relative abundance of the characteristic peaks,the samples could be divided into three categories. Among them,the first category had 10 batches of samples,which mainly came from Danxia landforms of Guangdong,Jiangxi,Fujian and Zhejiang (Wuyi) Province (which called "Danxia landform species") and characterized by detection of obvious peak of rutin. The second category had 11 batches of samples,which mainly came from Yunnan and Guangxi Province (which included "Yunnan Guangnan species" and "Guangxi Tiepilan species") and characterized by detection of violanthin and isoviolanthin. And the third category had 6 batches of samples, which were mainly derived from Zhejiang Province (which called "native species from Zhejiang") and characterized by detection of different degrees of rutin peak, but it was difficult to detect the characteristic peaks of violanthin and isoviolanthin. HPLC characteristic chromatograms of D. officinale in bionics wild cultivation and greenhouse of "Danxia landform species" and "Guangxi Tiepilan species" were compared. The results showed that the characteristic peaks in D. officinale planted in greenhouse could be detected stably,which verified the reliability of the source in D. officinale. Conclusion: The analytical method has a better separation effect on flavonoids of D. officinale, with a good reproducibility. The commonness and specificities of flavonoid glycosides components of D. officinale from different categories have basically confirmed. This suggests that Vicenin Ⅱ is suitable to be a reference peak for characteristic chromatogram. Both the relative abundance of rutin and the detection or relative abundance of violanthin and isoviolanthin peaks could be used as a reference to judge the categories of D. officinale in "Danxia landform species" or "Tiepilan species from Yunnan, South Guangdong and Guangxi" or "native species from Zhejiang".

Association between unhealthy diets and depression in early pregnancy / 中华疾病控制杂志

Objective To explore the association between unhealthy diets and depression in early pregnancy. Methods 7 976 women in early pregnancy were recruited and analyzed in this study from the Chinese Pregnant Women Cohort Study (CPWCS) from July 25th, 2017 to July 24th, 2018. Differences of baseline characteristics between the two groups were conducted by a chi-square test. The qualitative food frequency questionnaire and the edinburgh postnatal depression scale were used to assess depression status and food intake frequency during the first trimester respectively. Log-binomial regression was used to analyze the relationship between unhealthy diets and depression in early pregnancy. Prevalence ratio (PR) and its 95% confidence interval (95% CI) were calculated. Results Eating regularly (PR=0.45, 95% CI:0.38-0.54，P<0.001) and eating breakfast frequently (PR=0.80, 95% CI:0.72-0.90, P<0.001) were related to the low incidence of depression while frequent consumption of fried food (PR=1.25, 95% CI:1.03-1.53, P=0.027), Western-style fast food (PR=1.36, 95% CI:1.06-1.74, P=0.015) and puffed food (PR=1.37, 95% CI:1.11-1.70, P=0.003) as well as drinking sugar-sweetened beverage (PR=1.37, 95% CI:1.17-1.61, P<0.001),wine (PR=1.60, 95% CI:1.26-2.01, P<0.001) and liqueur (PR=1.26, 95% CI:1.00-1.59, P=0.047) were linked with the high incidence of depression. Conclusions There might be an association between unhealthy diets and depression in early pregnancy. Pregnant women should take the initiative to better understand what are healthy diets and reduce the frequency of unhealthy diets consumption to decrease the incidence of depression during pregnancy.

Development of animal model for lung injury in rats caused by unknown polymer via intratracheal instillation / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To establish an animal model of lung injury in SD rats using intratracheal instillation of unknown polymer and to provide the base for exploring the molecular mechanism of lung tissue injury induced by occupational exposure.</p><p><b>METHODS</b>One hundred forty SD rats were randomly divided into seven groups, including the control group 1 which was exposed to normal solution, the control group 2 which was not exposed to any one and five treatment groups which were exposed to 1 ml unknown polymer (0.5 ml for each lung) at the doses of 40, 30, 20, 10 and 5 mg/ml, respectively by intratracheal instillation. The rats were sacrificed on the 1st, 3rd, 7th, 10th, 14th, 21th and 28th day after exposure, then the lung tissues were examined pathologically and the blood bio-chemical analysis was conducted.</p><p><b>RESULTS</b>The results of blood biochemical analysis indicated that ALT and AST levels in rats exposed to 30 and 40 mg/ml unknown polymer were significantly higher than those in control groups. Intratracheal instillation of unknown polymer can causes PLF in experimental animals on the 14th days after exposure. The results of pathological examination exhibited that the lung tissue injury in rats exposed to unknown polymer for 14 days or more was found and the dose-effect relationship was observed.</p><p><b>CONCLUSION</b>An animal model of lung injury in SD rats induced by unknown polymer with intratracheal instillation was established successfully. The results of pathological examination showed that the types of rat lung injury were similar to the clinical lung injury after exposure to unknown polymer, which provided a base for studying the mechanism of lung injury caused by occupational exposure to unknown polymer.</p>

Programmed death 1 mRNA in peripheral blood as biomarker of acute renal allograft rejection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Invasive kidney biopsy is a priority diagnostic method for the acute rejection after renal transplantation for the past decades. However, no effective and noninvasive assay for predicting the severity of acute rejection is in wide use at present. This study was designed to investigate the predictive value of programmed death 1 (PD-1) mRNA for acute rejection after renal transplantation with real-time reverse transcriptase polymerase chain reaction (RT-PCR). A noninvasive diagnostic method has been expected to replace the traditional kidney biopsy for the diagnosis of acute rejection and prediction of the outcome after kidney transplantation.</p><p><b>METHODS</b>The whole blood samples from 19 subjects with acute rejection, 20 subjects with delayed graft function (DGF) and 21 subjects with stable recipients after kidney transplantation in a single kidney transplantation center between 2006 and 2009 were collected. The messenger RNA (mRNA) of PD-1 was analyzed with real-time RT-PCR. The associations of PD-1 mRNA levels with acute rejection and disease severity were investigated.</p><p><b>RESULTS</b>The log-transformed ratio of PD-1 mRNA to GAPDH mRNA was higher in peripheral blood mononuclear cell (PBMC) from the group with acute rejection (4.52 ± 1.1) than that from the group with DGF (1.12 ± 0.6) or the group with normal biopsy results (0.7 ± 0.4) (P < 0.01, by the Kruskal-Wallis test). PD-1 mRNA levels were correlated with serum creatinine levels measured at the time of biopsy in the acute rejection group (Spearman's correlation coefficient, r = 0.81, P = 0.03), but not in the group with DGF or the group with normal biopsy results. PD-1 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection.</p><p><b>CONCLUSIONS</b>Our data suggest that PD-1 status may be a new predictor of acute rejection and the levels of PD-1 mRNA in whole blood cells may positively correlate with the severity of acute rejection after renal transplantation. Meanwhile, the data provide the rational for interfering into the PD-1/PD-L1 as a novel therapy against the acute rejection after renal transplantation in clinical settings.</p>

Analysis for the association between genetic polymorphisms of XRCC1, XPD, XRCC3, CCND1 and the latency of the occupational chronic benzene poisoning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the association between genetic polymorphisms of XRCC1, XPD, XRCC3 and CCND1 and latency of occupational chronic benzene poisoning.</p><p><b>METHODS</b>80 patients diagnosed with occupational chronic benzene poisoning were investigated. PCR-RFLP was applied to detect the single nucleotide polymorphisms of C26304T, G27466A, G28152A, G36189A of XRCC1, C22541A, C23591T, A35931C of XPD, C18067T of XRCC3 and G870A of CCND1. Their relationship with the latency of chronic benzene poisoning was analyzed by Kaplan-Meier method.</p><p><b>RESULTS</b>The association of XRCC1 G27466A subgroup with the latency of chronic benzene poisoning was observed, as well as that of CCDN1G870A subgroup. The benzene-exposed workers with XRCC1 27466G/G homozygous wild genotype developed chronic benzene poisoning 6.9 years later than those had homozygous (27466A/A) or heterozygous (27466G/A) mutant alleles. On the other hand, the latency developing chronic benzene poisoning was longer in workers with homozygous (CCND1 870A/A) or heterozygous (CCND1 870G/A) mutant alleles than in those carrying 870G/G homozygous wild genotype (14.9 vs. 8.7 years).</p><p><b>CONCLUSION</b>The polymorphisms of XRCC1 and CCND1 potentially modify the latency of the chronic benzene poisoning among workers exposed to benzene.</p>

Association between genetic polymorphisms of DNA repair genes XRCC1, XRCC3 and susceptibility to chronic benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the association between genetic polymorphisms of DNA repair genes XRCC1, XRCC3 and susceptibility to chronic benzene poisoning.</p><p><b>METHODS</b>A case-control study was conducted. Eighty patients with chronic benzene poisoning and 62 workers occupationally exposed to benzene who were engaged in the same working time and job title as patients were investigated. Polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) was used to detect the single nucleotide polymorphisms on C26304T, G27466A, G28152A, G36189A of XRCC1 and C18067T of XRCC3. The relationship between them and latency of chronic benzene poisoning was analyzed by Kaplan-Meier method.</p><p><b>RESULTS</b>A correlation for XRCC3 18067C/T compared with C/C genotype was found (OR=0.233, 95% CI 0.085 approximately 0.639, P=0.0046). Patients who were XRCC1 27466G/G homozygous wild genotype developed chronic benzene poisoning average 6 years later than those had homozygous (27466A/A) or heterozygous (27466G/A) mutant alleles.</p><p><b>CONCLUSION</b>Subjects with XRCC3 18067T variant allele are tolerance sub-group to benzene poisoning. Patients carrying XRCC1 27466 G/G genotype develop chronic benzene poisoning later.</p>

Alteration of signal transduction-associated gene expression in rat cardiac fibroblasts induced by blocking angiotensin II receptors / 生理学报

To investigate the molecular mechanism of angiotensin II (Ang II) receptor activation in adult rat cardiac fibroblasts, the expressions of cell signal transduction-associated genes were studied by using cDNA microarray. Cardiac fibroblasts of adult Sprague-Dawley rats (230~250 g) were isolated and cultured. The cells were divided into 4 groups: Ang II, Ang II + losartan, Ang II + PD123319, Ang II + losartan + PD123319. The expressions of Ang II receptors were studied by immunohistochemical staining. Total RNA was extracted and purified. After cDNA synthesis and biotin-16-dUTP labeling, the probes were denatured and hybridized with GEArray Q Series mouse G Protein-coupled Receptors Signaling Pathway Finder Gene Array (MM-025) containing 96 genes associated with 11 pathways. The arrays were scanned with a Uniscand1000 scanner and further analyzed with GEArray Analyzer software. RT-PCR was used to further confirm the results of gene microarray. The results of immunohistochemical staining showed that the expression of Ang II type 2 (AT2) receptor was evidently induced by Ang II stimulation when Ang II type 1 (AT1) receptor was blocked. The results of gene array indicated that blocking AT1 receptor changed 34 genes (more than 2 folds), 30 were down-regulated and 4 were up-regulated. The maximum change was not beyond 20 folds. The following 9 pathways were activated: cAMP/PKA, Ca2+, PKC, PLC, MAPK, PI-3 kinase, NO-cGMP, Rho, NF-kappaB pathways. Blockade of AT2 receptor caused 64 genes changing more than 2 folds (48 were down-regulated and 16 were up-regulated). Eleven pathways were basically activated. The change of the following 7 genes was over 30 folds: Cyp19a1 (37 folds), Il1r2 (42 folds), Cflar (53 folds), Bcl21 (31 folds), Pik3cg (278 folds), Cdkn1a (90 folds), Agt (162 folds). According to the activated extent, the signal transduction pathways in turn were PI-3 kinase, NF-kappaB and JAK-STAT pathways. Blocking both AT1 and AT2 receptors changed 46 genes more than 2 folds (36 were down-regulated and 10 were up-regulated). Eleven pathways were basically activated. The results of RT-PCR of IL-1beta and TNF-alpha confirmed the observations in gene microarray. Our results show that Ang II can induce a high expression of AT2 receptor in adult rat cardiac fibroblasts when AT1 receptor is blocked, and the signal mechanism of AT2 receptor is clearly different from that of AT1 receptor.

Association between polymorphisms of XPD gene and susceptibility to chronic benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the relationship between genetic polymorphisms of XPD gene and susceptibility to chronic benzene poisoning.</p><p><b>METHODS</b>A case control study was conducted. Eighty patients diagnosed with chronic benzene poisoning and 62 workers occupationally exposed to benzene who were engaged in the same working time and job title as patients were investigated. PCR-RFLP was used for detecting the single nucleotide polymorphisms (SNPs) on codon156, codon312 and codon751 of XPD gene.</p><p><b>RESULTS</b>There was a 2.903 times (95% CI: 1.054 - 7.959, P = 0.039 2) increased risk of chronic benzene poisoning in the subjects carrying XPD 751Gln variant allele compared with those carrying XPD 751Lys/Lys genotype, after adjusted for sex, length of service, smoking and drinking status.</p><p><b>CONCLUSION</b>The subjects with XPD 751Gln variant allele are more susceptive to benzene.</p>

The role of endogenous opioid peptides in paraventricular nucleus of hypothalamus in the antagonism to myocardial ischemia by electroacupuncture at acupoint "Neiguan" (PC 6) / 中国针灸

<p><b>OBJECTIVE</b>To explore the mechanism of electroacupuncture at "Neiguan" (PC 6) antagonizing myocardial ischemia injury.</p><p><b>METHODS</b>Forty rabbits were randomly divided into 4 groups, model control group, naloxone control group, electroacupuncture plus cerebral spinal fluid group, and electroacupuncture plus naloxone group, 10 rabbits in each group. The effects of electroacupuncture at "Neiguan" (PC 6) after injection of naloxone into the paraventricular nucleus (PVN) of the hypothalamus on myocardial ultrastructure, II lead ECG and transmembrane potentials of the ischemic myocardial cell in the rabbit of myocardial ischemia were investigated.</p><p><b>RESULTS</b>The injection of naloxone into PVN has no effect on myocardial functions in the normal rabbit and a little effect on ischemic myocardial functions, but at 60 min after myocardial ischemia, this has a certain protective action on myocardial functions (P < 0.05); electroacupuncture at "Neiguan" has obvious protective action on ischemic myocardium, which can be reduced by injection of naloxone into PVN (P < 0.05), but can not be blocked.</p><p><b>CONCLUSION</b>(1) PVN plays an important role in the process of antagonizing myocardial ischemia by electroacupuncture at "Neiguan"; (2) endogenous opioid pepetides in PVN are involved in the acupuncture effect of antagonizing myocardial ischemia; (3) other transmitters in PVN and other nucleus groups in the center also can produce obvious effects in the antagonism to myocardial ischemia by electroacupuncture at "Neiguan".</p>

Identification of up-regulated genes induced by angiotensin II in cardiac fibroblasts / 生理学报

To identify up-regulated genes in adult rat cardiac fibroblasts (CF) induced by angiotensin II (Ang II), suppression subtractive hybridization (SSH) was performed between the CF stimulated by Ang II (tester) and unstimulated CF (driver) to generate subtractive cDNA library. The library was screened with dot blots hybridization to further verify the differentially expressed cDNA clones. Partial positive clones (19 up-regulated genes) were sequenced and BLAST analyzed. Twelve up-regulated genes related to extracellular matrix, cell cycle, intracellular signal transduction, cell cytoskeleton, cell metabolism and 7 new expressed sequence tags (EST) were acquired (GenBank accession number: CN382808, CN382809, CN382810, CN382811, CN382812, CN382813, CN382814). Our data reveal that SSH is a powerful technique of high sensitivity for the detection and cloning of up-regulated genes expressed in CF induced by Ang II, which may be helpful to clarify the mechanism of cardiac remodeling.

Genetic damage in peripheral blood lymphocyte of coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs).</p><p><b>METHODS</b>One hundred and thirty-seven coke oven workers and 50 controls without occupational PAHs exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. Urinary 1-hydroxypyrene level was used to assess the personal internal PAHs exposure dose. Personal information including occupational history, age, sex, smoking and drinking status was collected by questionnaire.</p><p><b>RESULTS</b>Urinary 1-hydroxypyrene level in coke oven workers [(5.76 +/- 1.04) micro mol/mol Cr] was significantly higher than that in controls [(0.70 +/- 0.32) micro mol/mol Cr]. The rate of CBMN and comet tail moment of lymphocyte in coke oven workers [8.0 per thousand (0.0 per thousand - 30.0 per thousand ) and 2.09 (0.31 - 75.41), respectively] were higher than those in controls [3.5 per thousand (0.0 per thousand - 13.0 per thousand ) and 1.05 (0.11 - 6.63), P < 0.05]. In controls, the comet moment in smokers was significantly higher than that in non-smokers [1.44 (0.23 - 6.63) vs 0.81 (0.11 - 3.47), P < 0.05]. According to the length of work, 137 coke oven workers were classified into 3 groups i.e. 0.5 yrs , 16.0 yrs and 22.0 yrs group, and the comet moments were 1.34 (0.31 - 37.84), 2.32 (0.49 - 52.97) and 3.20 (0.45 - 75.41) respectively after adjusting the age, sex, smoking, drinking and level of urinary 1-hydroxy-pyrene. There was a rising tendency along with the increase in length of work.</p><p><b>CONCLUSION</b>Under present PAHs exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect PAHs-induced genotoxicity in coke oven workers, and comet assay is more suitable to assess the cumulative damage effect on DNA.</p>