Objective To study the effects of Qingzao Runfei Huazhuo Xingxue decoction (QRHXD) on inflammatory reaction and histopathology in mice with PM2.5-induced pulmonary injury, and to approach the possible mechanism of prevention and treatment of traditional Chinese medicine on lung injury induced by haze.Methods Fifty healthy male C57BL/6 mice were randomly divided into five groups (n = 10): namely control, PM2.5, PM2.5+ low-, moderate-, and high-dose groups. The PM2.5 suspensions at a dosage of 40 mg/kg was respectively given to mice by the nasal instillation for reproduction of mouse model of lung injury induced by PM2.5, and the mice in control group were given the same volume of normal saline. The mice in PM2.5+ low-, moderate-, and high-dose QRHXD groups were given 15, 25, 50 mL·kg-1·d-1 QRHXD by oral perfusion daily for consecutive 21 days at the next day of model reproduction (the QRHXD included: Pear 75 g,Bulbus Fritillariae Cirrhosae 10 g, Radix Stemonae 8 g,Rhizoma Pinelliae 8 g,Radix Platycodi 6 g, Aster 10 g, Almond 5 g, Lily 6 g, Rhodiola 4 g, Lotus 3 g,Fructrs Liquidambaris 6 g,Radix Paeoniae Rubra 5 g, Semen Cassiae 6 g). The mice in control and PM2.5 groups were given equivalent volume of normal saline respectively. After treatment for 21 days, the mice were sacrificed, and the left lung was harvested for bronchoalveolar lavage, and the bronchoalveolar lavage fluid (BALF) was collected for determination of levels of acid phosphatase (ACP), alkaline phosphatase (AKP), lactic dehydrogenase (LDH), and albumin (ALB). The right lung was harvested for histopathology observation under light microscope using hematoxylin and eosine (HE) staining.Results After intranasal instillation of PM2.5 suspension, the levels of ACP, AKP, LDH, and ALB in PM2.5 group were significantly higher than those in control group [ACP (U/L): 3.9±0.4 vs. 1.7±0.3, AKP (U/L): 9.0±1.5 vs. 4.8±0.3, LDH (U/L): 416.7±44.4 vs. 112.5±20.3, ALB (mg/L): 198.7±32.4 vs. 65.8±21.3, all P < 0.05]. Under light microscope, the PM2.5 particles were collected, the alveolar septa were thickened, and the inflammatory cells in the alveolar cavity and pulmonary interstitium were found. On the contrary, after administration of QRHXD, a significant reduction of biochemical indexes was found, which showed a dose-dependent manner. The parameters of PM2.5+ high-dose QRHXD group were significantly lower than those in PM2.5 group [ACP (U/L): 2.1±0.8 vs. 3.9±0.4, AKP (U/L): 5.3±1.4 vs. 9.0±1.5, LDH (U/L): 146.6±29.8 vs. 416.7±44.4, ALB (mg/L): 88.5±26.7 vs. 198.7±32.4, all P < 0.05]. At the same time, the pathological changes in lung tissue were better with the increase of the dose.Conclusions QRHXD can reduce the pulmonary inflammatory response and tissue damage caused by PM2.5, with the increase concentration of Chinese medicine, and the effect is more obvious. This may be related to the immune response of the human body to regulate inflammatory mediators, which provide basis for the treatment of pulmonary injury induced by PM2.5.

Objective To study the influence of Qingzao Runfei Huazhuo Xingxue decoction on pulmonary tissue and lung function in mouse model of lung injury induced by PM2.5, and to provide an idea of clinical prevention and treatment of respiratory diseases induced by PM2.5. Methods Totally 30 clean level male ICR mice were randomly divided into three groups: normal control group, model group and Qingzao Runfei Huazhuo Xingxue decoction intervention group, with 10 mice in each group. Model of PM2.5-induced respiratory disease in mice was reproduced by instilling nasal cavity drip PM2.5 suspension 40 mg/kg once a day for 6 weeks. In the treatment group, the mice were fed with the Qingzao Runfei Huazhuo Xingxue decoction twice a day from the 4th week of instilling PM2.5 suspension until the end of experiment. In the normal control group, the mice were fed as usual. At the end of the experiment, the total protein content in bronchoalveolar lavage fluid (BALF), and lung wet/dry weight (W/D) ratio was determined. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue under light microscope. The inflammatory mediators levels in lung tissue were determined by antibody-sandwich enzyme linked immunosorbent assay (ELISA). Results Respiratory system damage model was successfully reproduced by dripping of PM2.5 suspension in nasal cavity. Compared with normal control group, inflammatory changes and inflammatory cell infiltration in model group were significant, and lung W/D ratio (4.71±0.33 vs. 3.13±0.12), total protein content in BALF (mg/L: 363.98±18.24 vs. 82.13±12.78), tumor necrosis factor-α [TNF-α (ng/L): 185.72±0.23 vs. 31.03±0.16], interleukin-8 [IL-8 (ng/L): 531.85±37.83 vs. 72.64±16.72], and leukotriene B4 [LTB4 (ng/L): 931.74±48.64 vs. 483.81±41.74] in lung tissue were significantly increased (all P < 0.05). Compared with the model group, the inflammatory changes of lung tissue in Qingzao Runfei Huazhuo Xingxue decoction intervention group were significantly reduced, lung W/D ratio (3.92±0.41 vs. 4.71±0.33), total protein content in BALF (mg/L: 213.21±19.62 vs. 363.98±18.24), TNF-α (ng/L: 124.15±0.27 vs. 185.72±0.23), IL-8 (ng/L: 238.42±35.82 vs. 531.85±37.83) and LTB4 (ng/L: 582.85±31.00 vs. 931.74±48.64) levels in lung tissue in Qingzao Runfei Huazhuo Xingxue decoction intervention group were significantly decreased (all P < 0.05). Conclusion Qingzao Runfei Huazhuo Xingxue decoction can improve PM2.5-induced damage and pathological inflammatory changes in lung tissue, which provided some new ideas for the treatment of PM2.5-induced respiratory diseases.

Objective To study the association between brachial-ankle index (BAI) and severe subclavian artery stenosis.Methods Seventy severe subclavian artery stenosis patients with a stenosis rate ≥70％ admitted to our hospital served as a stenosis group and 70 subclavian artery stenosis-free patients served as a control group in this study.Their BAI,pulse wave upstroke time (UT) and pulse wave form were recorded with a noninvasive automatic peripheral arterial device.The sensitivity,specificity,accuracy,positive and negative prediction value of BAI in diagnosis of subclavian artery stenosis were calculated.Results The BAI of stenosis-involved extrmities was significantly lower while the pulse wave UT was significantly longer in stenosis group than in control group (0.6±0.1 vs 0.9±0.1 and 0.9±0.1,261.0±11.8 vs 188.0±12.1 ms and 186.0±12.6 ms,P＜0.01).The low obtuse pulse wave form and low plain pulse wave form were detected respectively in stenosis involved extrmities of 58 patients (82.9％) and 11 patients (15.7％) of stenosis group.The sensitivity,specifity,accuracy,positive and negative prediction value of BAI in diagnosis of severe subclavian artery stenosis were 44.3％,92.9％,68.6％,86.1％ and 62.5％ respectively.Conclusion The specifity,positive prediction value and accuracy of BAI＜ 0.70 are rather high in diagnosis of severe subclavian artery stenosis.

OBJECTIVETo explore the clinicopathological, immunohistochemical, and molecular biologic characteristics of esophageal stromal tumors and smooth muscle tumors.

METHODSTwenty four cases of esophageal mesenchymal tumors were reclassified by a panel of antibodies such as CD117, CD34 etc. The sequence of 11 exon of c-kit gene were detected in some cases.

RESULTSThere were 3 cases of esophageal stromal tumors, 20 leiomyomas, and 1 leiomyosarcoma. The 3 esophageal stromal tumors occurred in 3 men aged 71, 56 and 60 years respectively. The tumors originated from muscularis propria with the size of 4 cm, 8 cm and 14 cm in diameter. Microscopically, the tumor cells were spindle and epithelioid shaped with slightly basophilic appearance, arranged in intersecting fascicles, diffusing and palisading patterns. Immunohistochemically, the tumors were positive for CD117 and CD34. The mutation of 11 exon of c-kit gene was detected in one case. In comparison, esophageal leiomyomas occurred in a younger population. The age ranged from 30 to 60 years (mean age 41.6 years), 12 male cases, 8 female cases. 15 cases of esophageal leiomyomas were intramural tumors with a diameter of 0.8 - 10.5 cm (mean 4.5 cm) originating from muscularis propria and 5 cases which were intraluminal polyps with a diameter of 0.2 - 1.0 cm originating from muscularis mucosae. Leiomyomas were strongly eosinophilic in appearance, diffuse positivity for alpha-SMA, MSA, and desmin, and no c-kit gene mutation. One male case of leiomyosarcoma had a diameter of 5 cm and originated from muscularis mucosae and displayed a sausage-shaped polyp.

CONCLUSIONSLeiomyoma is still the most common mesenchymal tumor of the esophagus, the stromal tumor can be similar to gastrointestinal stromal tumors. Typical esophageal leiomyosarcoma is very rare and has different clinicopathologic and molecular biologic features.

Actins ; analysis ; Adult ; Aged ; Antigens, CD34 ; analysis ; Base Sequence ; Desmin ; analysis ; Esophageal Neoplasms ; genetics ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Leiomyoma ; genetics ; metabolism ; pathology ; Leiomyosarcoma ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Muscle, Smooth ; metabolism ; pathology ; Mutation ; Proto-Oncogene Proteins c-kit ; analysis ; genetics ; Stromal Cells ; metabolism ; pathology

OBJECTIVETo study the morphologic and immunohistochemical features of gastrointestinal stromal tumors (GISTs) and to explore the reference parameters for malignancy.

METHODSSeventy six (76) cases of primary GISTs were distinguished from a group of gastrointestinal mesenchymal tumors by use of a panel of antibodies such as CD117, CD34 by immunohistochemical EnVision method, their biologic behaviors were analyzed by including their follow-up data.

RESULTSAll patients were adults, age range 32 to 81 years (mean 54 year), male 39 cases and female 37 cases; the tumors were situated in stomach (36 cases), in small intestine (23 cases), colon (2 cases) and rectum (15 cases). The most common symptoms were abdomen mass, vague pain and GI bleeding. Forty eight (48) cases were mainly located within the muscularis propria, 25 cases outside the serosa, and 3 cases below the mucosa. Grossly, they were of soft consistency often with hemorrhage, cystification or necrosis. Microscopically, the tumors were composed of spindle cells (46 cases) or epithelioid cells (9 cases) and of both cells (21 cases), arranged in interlacing fasicles, diffusing sheets, pallisading, whirling, alveolar and giant pseudo-rosette shapes. Tumor cells often had abundant cytoplasm with light to moderate eosinophilic or slight basophilic in staining, the nuclei generally showed spindle, blunted ends, round or signet in shape with nucleoli. Immunohistochemically, CD117 and CD34 showed diffuse strong expression, the positive rates were 98.7% and 68.4% respectively, alpha-SMA, MSA, S-100, PGP9.5 showed focal expression, the positive rates were 25.0%, 19.7%, 23.7% and 17.1% respectively, vimentin were all positive and desmin, GFAP, NF were all negative. Nine cases were benign, 19 cases borderline and 48 cases malignant. Follow-up of 20 cases with benign and borderline tumors found patients alive without tumor. In the malignant group of 34 cases, 10 cases were alive without tumor, 10 cases developed recurrence or metastasis, and 14 cases died of tumor. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity and obvious pleomorphism were all in the malignant group. In this group, tumor necrosis, adhesion in operation, tumor, over 5 cm in diameter, mitotic activity over 5/50HPF had significant differences among three groups and the 3 years survival rate had a significant difference in tumors with or without coagulative necrosis and also in tumors with or without mitotic activity over 5/50HPF.

CONCLUSIONSGISTs predominantly occurred in middle aged or old patients, the tumors had varied cell types and different arrangements, the immunohistochemical characters were positive for CD117 and CD34, negative for desmin, occasional positive for alpha-SMA, MSA, S-100 and PGP9.5, which were helpful to differentiate GIST from leiomyomas and Schwannomas. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity with obvious pleomorphism were also helpful parameters for diagnosis of malignancy aside from metastasis and invasion. Adhesion, over 5 cm in diameter and mitotic activity over 5/50HPF but less than 10/50HPF might be the potential malignant parameters.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Intestinal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Rectal Neoplasms ; metabolism ; pathology ; Statistics as Topic ; Stomach Neoplasms ; metabolism ; pathology

Objective: To evaluate the value of non-invasive prenatal testing (NIPT) in pregnancies with anomaly in prenatal screening. Methods: This was a retrospective study of 2 837 singleton pregnancies who performed NIPT indicated by isolated anomaly in prenatal screening at Guangdong Women and Children Hospital between November 2014 and August 2016. All pregnancies were divided into 3 groups by single indication: advanced maternal age ( AMA, ≥35), abnormal multiples of the median (MoM) in standard screening, increased nuchal translucency thickness (NT, 2.5-3.0 mm). High risk results were verified by prenatal diagnosis. Low risk cases were followed by a 22-26 week anatomical ultrasound examination. All of the cases were followed up and the performance of NIPT for every single indication was evaluated. Results: There were total of 2 837 pregnant women who underwent NIPT. Twenty-five of 2 448 pregnancies indicated by AMA had high risk results, among which 17 were confirmed by invasive genetic testing, except 1 case rejecting prenatal diagnosis. In 351 pregnant women with abnormal MoM, NIPT found 3 cases of sex chromosome aneuploidies (SCA) and 2 of them were validated by invasive prenatal diagnosis. Increased NT group included 38 cases, NIPT found 1 case of trisomy 21 which was consistent with karyotype analysis. For common aneuploidies and SCA, the performance of NIPT in the pregnant women who indicated by AMA, abnormal MoM and increased NT were as the follows: the sensitivity were 17/17, 2/2 and 1/1 respectively, the specificity were 99.7% (2 423/2 431), 99.7% (348/349) and 100%(37/37), the positive predictive value were 68% (17/25), 2/3 and 1/1, the negative predictive value were 100% (2 423/2 423), 100% (348/348) and 100% (38/38), respectively. By follow-up survey, a total of 8 cases of abnormal fetus were recorded in NIPT low-risk women, including 5 cases of termination of pregnancy due to abnormal ultrasound findings, 2 cases of abortion as a result of severe obstetric complications and 1 case of stillbirth. Conclusions To the pregnant women who indicated by advanced maternal age, abnormal MoM and increased NT (2.5-3.0 mm), NIPT had satisfactory performance for common aneuploidies, and also had potential value for SCA, resulting in a significant reduction in diagnostic procedures. However, for NIPT low-risk pregnancies, routine antenatal examination and anatomical ultrasound detection would be highly necessary to avoid missing abnormal fetuses.(Chin J Lab Med, 2018, 41: 509-513)

Objective To evaluate the efficacy and safety of continuous erythropoietin receptor activator (C.E.R.A.) once every 4 weeks by subcutaneous administration on hemoglobin (Hb)maintenance in dialytic patients with chronic renal anemia who had been treated with stable dose of erythropoietin (EPO).Methods This was an open,randomized,controlled,multi-center trial.All the hemodialysis or peritoneal dialytic patients in EPO maintenance treatment received subcutaneous EPO-β during the 6-week pre-treatment period to maintain Hb level between 100 g/L and 120 g/L.Eligible patients were randomized (2∶1 ) to accept either C.E.R.A.once every 4 weeks by subcutaneous administration ( C.E.R.A.group,n =187 ) or subcutaneous EPO-β 1-3 times weekly ( EPO group,n =94) for 28 weeks (including 20-week dose titration period and 8-week efficacy evaluation period ). The starting dose of C.E.R.A.was converted according to the dose of EPO-β administered in the week preceding the first study drug administration.The primary outcome was the change of Hb level between the baseline and that in the efficacy evaluation period.Results Totally 253 patients completed the whole 28-week treatment.The change of baseline-adjusted mean Hb was +2.57 g/L for C.E.R.A.group and + 1.23 g/L for EPO group,resulting in a treatment difference of 1.34 g/L (95％ CI - 1.11-3.78 g/L).Since the lower limit of 95％ CI was greater than the pre-defined non-inferiority margin -7.5 g/L( P ＜ 0.0001 ),C.E.R.A.once every 4 weeks by subcutaneous administration was clinically non-inferior to EPO regarding the maintenance of stable Hb level.The proportion of patients maintaining Hb level within the range of 100-120 g/L through efficacy evaluation period was similar between the two groups ( 69.0％ for C.E.R.A.group vs 68.9％ for EPO group,P ＞0.05 ).The overall incidence of adverse events was similar between the C.E.R.A.(41.7％)and EPO (46.2％ ) groups ( P ＞ 0.05 ).The safety findings were in accordance with the patients' primary diseases rather than the administration.Conclusions Conversion from EPO to C.E.R.A.once every 4 weeks by subcutaneous injection could maintain the Hb in target level in dialytic patients with renal anemia,and it was non-inferior to EPO.In general,subcutaneous administration of C.E.R.A.is well tolerated in dialytic patients with chronic renal anemia.

Objectives:To investigate the relationship between visceral adipose index and glomerular filtration rate in patients with type 2 diabetes mellitus.Methods:A total of 1 036 patients with type 2 diabetes mellitus who received treatment in The Second Affiliated Hospital of Xi'an Jiaotong University from May 2017 to May 2018 were included in this study. The visceral adipose index was detected using a bioresistance assay. These patients were divided into four groups using the quartile method: Visceral adipose index < 8.10 (q1 group, n = 246), 9.60 > visceral adipose index ≥ 8.10 (q2 group, n = 64), 11.10 > visceral adipose index ≥ 9.60 (q3 group, n = 423), visceral adipose index ≥ 11.10 (q4 group, n = 233). One-way analysis of variance was performed to compare the differences among groups. Partial correlation and multiple regression were used to analyze the correlation between body mass index, waist circumference, waist-to-height ratio, waist-to-hip ratio, body fat content, visceral adipose index, and urinary microalbumin and glomerular filtration rate. Results:With the increase in the visceral adipose index, the glomerular filtration rate gradually decreased. The glomerular filtration rate in the q1, q2, q3, q4 groups was (112.19 ± 31.74) mL·min -1·1.73 m -2, (106.14 ± 28.26) mL·min -1·1.73 m -2, (104.73 ± 23.63) mL·min -1·1.73 m -2, (103.40 ± 27.51) mL·min -1·1.73 m -2, respectively. In the female group, with the increase in visceral adipose index, the glomerular filtration rate decreased gradually. After controlling for age, sex, diabetes, and hypertension, the visceral adipose index was significantly correlated with the glomerular filtration rate ( r = -0.10, P < 0.001). Multiple regression analysis showed that visceral adipose index and waist-to-height ratio were closely related to glomerular filtration rate ( F = 6.00, P < 0.001). Conclusion:With the increase of visceral adipose index, body mass index, waist circumference, waist-to-height ratio, waist-to-hip ratio, body fat content, and urinary microalbumin increased gradually. When the visceral adipose index is greater than 9.60, the glomerular filtration rate is significantly decreased. Therefore, it is suggested to adopt various methods to evaluate obesity in clinical work, and visceral fat index should be paid more attention, especially when the visceral fat index is greater than 9.60.

Objective:To explore the association between H3K18 acetylation (H3K18ac) and hepatic injury induced by arsenic in rats, which might to provide a new target for the study of mechanism and intervention of hepatic injury induced by arsenic.Methods:Twenty-four healthy Wistar rats, half male and half female, were selected and divided into control group, low, medium and high arsenic dose groups according to body weight (80-100 g) by random number table method, 6 rats in each group. The control group was given deionized water by gavage, and the low, medium and high arsenic dose groups were given 2.00 g/L sodium arsenite (NaAsO 2) by gavage according to their body weight for 6 days every week, the concentrations of NaAsO 2 in the low, medium and high arsenic dose groups were 2.5, 5.0 and 10.0 mg/kg·bw, respectively. After 4 months treatment, liver tissue and peripheral blood samples of rats were collected. The content of arsenic in liver was measured by inductively coupled plasma mass spectrometry (ICP-MS). Histone was extracted from the liver of rats by acid extraction, and the level of H3K18ac was measured with enzyme-linked immunesorbent assay (ELISA). The serum total bile acid (TBA) and γ-glutamyl transpeptidase (γ-GT) levels were measured by fully automatic biochemical instrument. Results:The difference of arsenic content in liver among the control group, low, medium and high arsenic dose groups [median (quartile range): 2.41 (1.83, 2.99), 62.64 (56.26, 65.17), 68.81 (62.58, 77.24), 88.48 (74.47, 98.99) μg/g] was statistically significant ( H=18.98, P < 0.01). The arsenic contents in liver in the low, medium and high arsenic dose groups were higher than that of the control group ( P < 0.05), and the arsenic content in liver increased gradually with the increase of arsenic dose ( Ztrend=5.04, P < 0.01). The differences of serum TBA and γ-GT levels among the control group and low, medium and high arsenic dose groups were statistically significant ( F=11.11, 12.26, P < 0.05). The TBA and γ-GT levels increased gradually with the increase of arsenic dose ( Ftrend=32.09, 33.22, P < 0.01). The difference of H3K18ac levels among the control group, low, medium and high arsenic dose groups was statistically significant ( F=4.62, P < 0.05). Compared with the control group, the levels of H3K18ac in the medium and high arsenic dose groups decreased ( P < 0.05), and the level of H3K18ac in liver decreased gradually with the increase of arsenic dose ( Ftrend=12.82, P < 0.01). The results of correlation analysis showed that there were positive correlation between liver arsenic content and the liver function indicators of TBA and γ-GT levels( r=0.631, 0.863, P < 0.01), while the liver arsenic content were negatively correlated with H3K18ac level ( r=- 0.476, P < 0.05). And the level of H3K18ac were negatively correlated with the liver function indicators of TBA and γ-GT levels ( r=- 0.628,-0.544, P < 0.05). The results of the mediating effect analysis showed that the H3K18ac had a partly mediating effect on the effect of arsenic exposure on liver function indicators of TBA and γ-GT, and the proportion of mediating effect on TBA and γ-GT to total effect was 37.10% [95% confidence interval ( CI): 9.71%-92.45%] and 20.05% (95% CI: 2.61%-52.89%), respectively. Conclusion:The level of H3K18ac in the liver of rats is not only respond to arsenic exposure, but is also closely related to hepatic injury induced by arsenic, suggesting that H3K18ac may be used as a new target for the study of liver injury mechanism and intervention of hepatic injury induced by arsenic.