[Clinical features and prognostic factors of advanced myelodysplastic syndromes in children].

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

[A panel study on the association of organophosphate ester flame retardant exposure with thyroid function related hormones in healthy older adults].

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M (Q1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M (Q1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M (Q1, Q3) for TSH, T3, and T4 was 3.74 (2.55, 5.69) µIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%CI:-15.17%, -4.36%) and 11.14% (95%CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

[Perioperative efficacy of laparoscopic duodenal-preserving pancreatic head resection].

Objective: To compare the perioperative outcomes of laparoscopic duodenal-preserving pancreatic head resection(LDPPHR) with laparoscopic pancreaticoduodenectomy(LPD) in the treatment of borderline and benign diseases of the pancreatic head. Methods: This is a retrospective cohort study. Perioperative data from 87 patients with non-malignant pancreatic head diseases who underwent LDPPHR or LPD were retrospectively collected in the Department of Biliary-Pancreatic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from January 2020 to December 2022. There were 49 male and 38 female patients with an age (M(IQR)) of 57.0(16.5) years (range: 20 to 75 years). Forty patients underwent LDPPHR and 47 patients underwent LPD. Quantitative data following a normal distribution were compared using Student's t-test, while quantitative data not following a normal distribution were compared using the Mann-Whitney U test. Comparisons of categorical or ordinal variables were made using χ2 test or Fisher's exact test. Logistic regression analysis was used to estimate the risk factors associated with the rate of complications. Results: There were no statistically significant differences between the LDPPHR group and the LPD group in terms of reoperation rate,total hospital stay duration,postoperative hospital stay duration,90-day mortality rate,30-day and 90-day readmission rates,and 2-year tumor recurrence rate (all P>0.05). The complication rate was higher in the LDPPHR group compared to the LPD group (80.0%(32/40) vs. 51.1%(24/47), χ2=7.89,P=0.005),but there was no difference in the rate of Clavien-Dindo classification of surgical complications ≥Ⅲ between the two groups (10.0%(4/40) vs. 12.8%(6/47), χ2<0.01, P=0.947). Additionally,the rate of delayed gastric emptying (DGE) was higher in the LDPPHR group compared to the LPD group (χ2=10.79,P=0.001),but there was no statistically significant difference in the rate of B,C grade DGE between the two groups (χ2=0.48, P=0.487). There were no statistically significant differences in the rates of postoperative pancreatic fistula,bile leakage,post-pancreatectomy hemorrhage,intra-abdominal infection,and pulmonary infection between the two groups (all P>0.05). The results of the univariate logistic regression analysis showed that LDPPHR (compared to LPD, OR=3.83, 95%CI: 1.46 to 10.04, Z=2.73,P=0.006) and preoperative biliary stent placement (compared to non-use of biliary stent, OR=5.30, 95%CI: 1.13 to 25.00, Z=2.11, P=0.035) were risk factors for the complication rate,but neither was an independent risk factor for complication rate (all P>0.05). Conclusion: The preliminary results suggest that LDPPHR can achieve perioperative safety and effectiveness comparable to LPD.

[Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers].

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

[Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia].

Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.

[Safety and efficacy of percutaneous mechanical thrombectomy through ipsilateral calf venous access in the treatment of entire-limb acute deep venous thrombosis].

Objective: To evaluate the safety and clinical efficacy of percutaneous mechanical thrombectomy (PMT) through ipsilateral calf venous access in the treatment of entire-limb acute deep vein thrombosis (DVT). Methods: From July 2017 to August 2020, the clinical data of patients with entire-limb acute DVT at Renji Hospital, School of Medicine, Shanghai Jiaotong University treated by AngioJet through ipsilateral calf venous access were analyzed retrospectively. All patients received rivaroxaban or warfarin anticoagulant therapy for at least 6 months after operation. Pressure gradient socks were given routinely after operation. All patients were followed up at 3, 6, 12 months and every year after operation. The primary end points were the 12-month primary patency rate and the incidence of post thrombotic syndrome (PTS). The secondary end points included the thrombus clearance rate, total complication rate, bleeding complication rate and the 12-month incidence of moderate to severe PTS. Results: A total of 31 patients were included in the study. The age ranged from 31 to 80 (63±14) years, including 16 males and 15 females, 23 left lower limb DVT and 8 right lower limb DVT. There were 15 cases treated through peroneal venous access, 6 cases through anterior tibial venous access and 10 cases through posterior tibial venous access. Moreover, 9 cases underwent combined catheter-directed thrombolysis, 25 cases underwent iliac vein percutaneous transluminal angioplasty (PTA), and 10 cases underwent iliac vein stenting. The thrombus clearance rate was grade Ⅱ in 19 cases (61.3%) and grade Ⅲ in 12 cases (38.7%). One patient (3.2%) with anterior tibial venous access developed hematoma at the puncture site, which was improved after pressure bandage, and there were no other bleeding and serious complications. All the 31 patients were followed up for at least 12 months, with an average follow-up period of (22±9) months. The 12-month primary patency rate was 77.4% (24/31). The 12-month incidence of PTS was 16.1% (5/31) and the incidence of moderate to severe PTS was 3.2% (1/31). Conclusions: PMT through ipsilateral calf venous access is safe and effective in the treatment of entire-limb acute DVT. Thrombus in the distal popliteal vein can be one-stage removed and the incidence of PTS is low. It is considered as the first choice of access for the endovascular treatment of entire-limb acute DVT.

DNA Methylation Differences in Peripheral Blood of Patients with Anaphylaxis.

ABSTRACT: Objective To study the DNA methylation of nucleated cells in peripheral blood of patients died from anaphylactic shock caused by cephalosporin drugs and to provide a new research direction and basis for the forensic diagnosis of shock caused by drug hypersensitiveness. Methods Methylation microarray was used to detect DNA methylation of nucleated cells in peripheral blood of patients died from anaphylactic shock caused by cephalosporin drugs and normal subjects. Sequencing data and chip data were analyzed for differences in DNA methylation using R language methylkit, ChAMP package. Random forest algorithm was used to evaluate the importance of the DNA methylation differential sites. Results Differential sites of DNA methylation highly associated with anaphylaxis caused by cephalosporin drugs were obtained at loci such as ETS1, PRR23B and GNAS. Conclusion Cephalosporin allergy is associated with DNA methylation, and DNA methylation may be a new strategy for forensic identification of anaphylactic shock and death.

Inhibition of heat shock protein 90 suppresses Bombyx mori nucleopolyhedrovirus replication in B. mori.

Heat shock protein 90 (Hsp90) plays a very important role in facilitating the replication of many viruses. Until now, little has been known about the role of Hsp90 in Bombyx mori virus infection. In this study, we explored the role of BmHsp90 in B. mori nucleopolyhedrovirus (BmNPV) replication. We found that BmHsp90 inhibition by geldanamycin (GA) significantly reduced the BmNPV titre, the protein expression level of BmNPV nucleocapsid protein 39 (VP39) and the transcript level of BmNPV genes. Silencing the hsp90 gene in BmN cells by small interfering RNA suppressed BmNPV replication whereas overexpression of hsp90 promoted the replication of BmNPV. After inhibition of Hsp90, the expression of three key genes [signal transducing activator of transcription (stat), suppressor of cytokine signalling protein 2 (socs2), socs6] involved in the Janus kinase/STAT pathway significantly changed, with up-regulation of stat and down-regulation of socs2 and socs6. In addition, the expression of two antiapoptosis genes, BmNPV inhibitor of apoptosis protein1 (BmNPV-iap1) and Bmiap2, was greatly decreased in GA-treated cells, whereas their expression was significantly increased in hsp90-overexpressed silkworm larvae. Our results indicated that inhibition of Hsp90 can suppress BmNPV proliferation in B. mori. Our findings may provide new clues to elucidate the molecular mechanisms of silkworm-virus interactions.

An office building outbreak: the changing epidemiology of tuberculosis in Shenzhen, China.

Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.

[A rare case of cystadenoma in the small intestine].

In recent years, there have been more and more reports about cystadenoma. Cystadenoma can occur in many parts of the body, and cystadenoma in different parts may show different clinical symptoms, however, some patients with cystadenoma have no symptoms. The vast majority of cystadenomas are benign lesions, but a small number of cystadenomas can be malignant. For example, a small number of ovarian cystadenomas and pancreatic cystadenomas may be malignant. This study reported a patient with small intestinal cystadenoma diagnosed by pathology. The patient's physical examination revealed a lesion in the left upper abdomen. He had only abdominal distension and no other discomfort. His laboratory examination results were basically normal, i.e. blood routine, urine routine, stool routine, liver function, kidney function, myocardial enzyme, tumor marker, etc. The patient underwent sectional small intestine resection and the pathological sample was analyzed. The histological findings of the resected intestinal sample were consistent with cystadenoma. Computed tomography scan of the abdomen was performed 4 months after the surgery. No recurrence of the tumor was found. The patient recovered in good condition. By consulting the literature, I found very few reports of small intestinal cystadenoma before, it was very rare. This article described the clinical manifestation, diagnosis and differential diagnosis, treatment and prognosis of a case of small intestinal cystadenoma, it suggested that cystadenoma can occur in the small intestine, other than the ovary, pancreas, liver, lung, thyroid, prostate, seminal vesicle, skin, etc. The cystadenoma in small intestine is easy to be mistaken with other tumors, such as small intestine stromal tumor, small intestine adenocarcinoma, small intestine lipoma, small intestine hemangiomas, etc., and it is difficult to fully confirm through imaging examinations, such as computed tomography and magnetic resonance imaging. Laparotomy and histopathological examination are necessary before definitive diagnosis. This disease can be treated by small bowel resection at the affected region and good prognosis can be achieved.

[Clinical features of 54 cases of lung adenocarcinomas with c-ROS oncogene 1 fusion].

Objective: To study the prevalence of c-ros oncogene 1 fusion in lung adenocarcinoma and to evaluate its relationship with clinical characteristics. Methods: We retrospectively analyzed epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) fusion in 1 482 patients with adenocarcinoma from March 2014 to January 2017 in the first affiliated hospital of Zhejiang University. Furthermore, ROS1 fusion positive patients diagnosed between February 2017 and December 2017 were also included in ROS1 positive group. The data of age, sex, smoking history, TNM stage and chest computed tomography were collected by Electronic Medical Record (EMR). The clinical data were compared by the chi-squared test or Mann-Whitney test. Results: Of these 1 482 patients,54 cases were diagnosed with ROS1 rearrangement, including 19 males and 35 females, while 73 cases were diagnosed with ALK rearrangement, including 28 males and 45 females, and 679 cases diagnosed with EGFR mutation including 293 males and 386 females. And there were 676 patients without driven genes mutation. The mean age in ROS1 fusion group (54±12) was lower than EGFR mutation group (60±11, z=-3.982, P<0.001) and WT group (62±10, z=-4.944, P<0.001). Female proportion in ROS1 fusion group (64.8%, 35/54) was higher than WT group (28.4%, 192/676, χ(2)=30.94, P<0.001). Non-smoker percentages in ROS1 fusion group (72.2%, 39/54) was significantly higher than WT group (38.0%,257/676, χ(2)=24.27, P<0.001). ROS1 fusion group was similar to ALK fusion group in sex, age and smoking history, and there were no significant difference in TNM stage among these groups. On chest CT, adenocarcinomas with ROS1 fusion were found to be more peripheral in location (71.4%, 20/28) and solid in density (75%, 21/28), usually with lobulated margins (75.0%, 21/28) and spiculated in contour (57.1%,16/28). Conclusion: In our study lung adenocarcinoma with c-ROS oncogene 1 fusion was a rare subtype lung cancer and was usually detected in young, never smoking, and female patients.

Determination of Escitalopram in Biological Samples by Dispersive Liquid-Liquid Microextraction Combined with GC-MS/MS.

ABSTRACT: Objective To establish a method for determination of escitalopram in biological samples by ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with gas chromatography-tandem mass spectrometry （GC-MS/MS） and provide evidences for forensic determination of cases related to escitalopram. Methods The 1-hexyl-3-methylimidazolium hexafluorophosphate （[C6MIM][PF6]） was selected as an extract solvent to process biological samples. Ultrasound-assisted extraction was used on the samples. Then the samples were detected by GC-MS/MS. Results The linear range of escitalopram in blood and liver were 5.56-1 111.10 ng/mL and 0.025-5.00 mg/g, respectively. The correlation coefficient （r） were greater than 0.999, limit of detection （LOD） were 4.00 ng/mL and 2.00 µg/g, limit of quantitation （LOQ） were 14.00 ng/mL and 6.00 µg/g, respectively. The extraction recovery rates were all greater than 50%, the interday and intraday precision were less than 20%. Escitalopram was detected in blood and liver samples from the actual poisoning case by this method with a content of 1.26 µg/mL and 0.44 mg/g, respectively. Conclusion The ultrasound-assisted ionic liquid-dispersive liquid-liquid microextraction combined with GC-MS/MS is environment friendly, rapid, has good enriching effect and consumes less organic solvent and can be used for forensic determination of escitalopram related cases.

[Assessing right ventricular function in patients with pulmonary artery hypertension based on noninvasive measurements: correlation between cardiac MRI, ultrasonic cardiogram, multidetector CT and right heart catheterization].

Objective: To compare the value of cardiac MRI (CMRI), ultrasonic cardiogram (UCG), multidetector CT (MDCT) in assessing right ventricular function (RV) in patients with PAH. Methods: A total of 31 consecutive patients with PAH (17 males and 14 females, 55±12 years) in Beijing Chao-Yang Hospital from August 2012 to February 2014 were prospectively enrolled. All patients underwent CMRI to get parameters including right ventricular end-systolic volume (ESV), end-diastolic dimension (EDV), stroke volume (SV), ejection fraction (EF), ventricular mass index (VMI). UCG parameters included Tei index, RV fractional area change (FAC), ESV, EDV. MDCT parameters included right /left ventricular internal diameter (RVd/LVd), right /left ventricular diastole maximum area (RVa/LVa), Cobb angle.These parameters obtained by MRI, UCG and MDCT were correlated with those of RHC respectively by Spearman or Pearson correlation analysis. Results: Six minutes walk distance had moderate negative correlation with CMRI-EF (40±9), VMI 44-115(71±20) g/m(2,) Cobb angle(67°±12°); RHC-SV had moderate negative correlation with CMRI-SV(57±21) ml, EF, VMI, UCG-EF(41±14), Tei(0.82±0.29), FAC(30±9), RVd(45±7) mm, RVa(2 484±596) mm(2), Cobb angle ; Right cardiac work index had moderate negative correlation with CMRI-EF, RVd and Cobb angle. Conclusions: MRI-EF is the best parameter to reflect RV function. CMRI is the optimal method to assess RV function, and then is the MDCT and the last is UCG.

[Clinicopathologic characterization of malignant mixed tumor of the skin accompanied by eccrine porocarcinoma].

Objective: To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT). Methods: Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature. Results: A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin. Conclusions: MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.

Novel screening strategy reveals a potent Bacillus antagonist capable of mitigating wheat take-all disease caused by Gaeumannomyces graminis var. tritici.

Take-all is a severe root disease of wheat worldwide that is caused by the soilborne fungal pathogen Gaeumannomyces graminis var. tritici (Ggt). In this study, 272 Bacillus isolates were screened for their antifungal activity in vitro to Ggt. Of the 128 strains that demonstrated an antagonistic action, 24 of these exhibited at least three of the four plant growth promotion parameters (i.e. indole acetic acid and siderophore production, inorganic phosphorus solubilization and organic phosphorus solubilization) that were tested in wheat plants. The most effective strain found was Bacillus subtilis Pnf-12; its disease reduction effect reached 69%. Pnf-12 also caused a significant improvement (P < 0·05) in the root and shoot weights of wheat plants, though their root length and shoot height were similar to the noninoculated treatment (P > 0·05). The mechanism for this disease control may be linked to the production of the antifungal lipopeptides surfactin, iturin and fengycin production, all of which were detected in the cell-free supernatant of Pnf-12. SIGNIFICANCE AND IMPACT OF THE STUDY: Take-all, which is caused by the soilborne fungal pathogen Gaeumannomyces graminis var. tritici (Ggt), is one of the most widespread and devastating root diseases of wheat plants. This study focuses on a novel screening strategy of Bacillus isolates to evaluate their potential biological control capacity for suppressing wheat take-all. The joint assessment of antifungal activities, growth promotion factors and variety of antibiotic synthesis genes, in addition to greenhouse experiments, allowed for the identification and demonstration of the Bacillus isolate Pnf-12 as an effective disease control agent.

[Expression of proBNP and NT-proBNP in Sudden Death of Coronary Heart Disease].

OBJECTIVES: To study the expression change of pro-brain natriuretic peptide （proBNP） and N-terminal pro-brain natriuretic peptide （NT-proBNP） in sudden death of coronary atherosclerotic heart disease, and to explore its application in forensic diagnosis. METHODS: Myocardial and blood samples were collected from normal control group, sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group （20 cases in each group）. The expression of proBNP in myocardial samples were detected by immunohistochemical staining and Western blotting, and that of BNP mRNA were detected by reverse transcription PCR （RT-PCR）. The content of NT-proBNP in plasma were detected by ELISA. RESULTS: Immunohistochemical staining showed positive expression of proBNP in both sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group. There was no positive expression in normal control group. For sudden death of coronary atherosclerotic heart disease group and single coronary stenosis group, the relative expression of proBNP protein and BNP mRNA in myocardial tissue and the NT-proBNP content in plasma were higher than that of normal control group （P<0.05）. The NT-proBNP content in plasma of sudden death of coronary atherosclerotic heart disease group was higher than that of single coronary stenosis group （P<0.05）. CONCLUSIONS: In myocardial ischemia condition, the higher expression of proBNP in cardiac muscle cell shows that the detection of NT-proBNP in plasma can be useful to differentially diagnose the degree of coronary atherosclerotic heart disease and determine whether the sudden death due to coronary atherosclerotic heart disease.

Expressions of Mast Cell Tryptase and Brain Natriuretic Peptide in Myocardium of Sudden Death due to Hypersensitivity and Coronary Atherosclerotic Heart Disease.

OBJECTIVES: To explore the value of mast cell tryptase and brain natriuretic peptide（BNP） in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart disease. METHODS: Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010-2015. All samples were divided into three groups： death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting. RESULTS: Immunofluorescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison （P<0.05）; The expression level of BNP in sudden death of coronary atherosclerotic heart disease group were significantly higher than the sudden death of hypersensitivity group and death of craniocerebral injury group （P<0.05）. The difference of the expression level of BNP between the sudden death of hypersensitivity group and the death of craniocerebral injury group had no statistical significance （P>0.05）. CONCLUSIONS: The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease.

Correlation between carbonic anhydrase IX (CA-9), XII (CA-12) and hypoxia inducible factor-2α (HIF-2α) in breast cancer.

Hypoxia inducible factor 2α (HIF-2α) can trigger the expression of several genes related to many aspects of tumor progress under hypoxia. As an independent factor, the role of HIF-2α is different from other hypoxia-mediated elements, including HIF-1α. Carbonic anhydrase (CA) were also regarded as important enzymes that involve in the tumor microenvironment pH. To find clinical-pathological features of breast cancer in plateau and explore the impact of CAIX, XII (CA-9, CA-12) and HIF-2α on patients with breast cancer. Clinical data were collected and summarized in 94 patients with breast cancer. The expression of HIF-2α, CA-9 and CA-12 were detected, using immunohistochemistry of specimens. The relation between expressions and clinical-pathology was analyzed. Under normoxia, hypoxia, and after being pretreated with the JNK inhibitor SP600125, HIF- 2α, CA-9 and CA-12 expressions were detected, and adhesion and invasion assays were performed in MCF-7 cells and HIF- 2α shRNA cells, respectively. There are higher expressions of HIF-2α in tumor classification 2 and clinical stage 2 (P < 0.05). High expression of CA-12 was observed in clinical stage 2 (P < 0.05). CA-9 expression is significantly correlated with CA-12 expression (r = 0.376, P = 0.0001). HIF-2α expression is not correlated with both CA-9 expression (P = 0.21) and CA-12 expression (P = 0.27). Breast cancer cells in vitro showed that HIF-2α, CA-9 or CA-12 had an increase expression under hypoxia (1% O2). CA-9 or CA-12 expression was observed in HIF-2α shRNA cells. JNK inhibitor SP 600125 reduced the HIF-2α expression and inhibited the adhesion and invasion of breast cancer cell. Slight inhibition effect on CA-9 and CA-12 expression was found. In conclusion, HIF-2α, CA-9 and CA-12 are important hypoxia responsive elements in breast cancer. HIF-2α was involved in metastasis and invasion of breast cancer cells under hypoxia, by the involvement of c-Jun NH2-terminal kinase (JNK) signal pathway. CA-9 and CA-12 may tend to be regulated by HIF-1α more often than by HIF-2α under hypoxia.