[Analysis of clinicopathological and molecular abnormalities of angioimmunoblastic T-cell lymphoma].

OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR+/IG-, 26.3% (5/19) TCR+/IG+, 10.5% (2/19) were TCR－/IG－, and 5.3% (1/19) TCR－/IG+. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR－/IG－, 1 case with TCR－/IG+, and 1 case with TCR+/IG+; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR－/IG－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION: Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.

[Application value of neutrophil lymphocyte ratio combined with age in the diagnosis of dual-phenotype hepatocellular carcinoma].

Objective: This study retrospectively analyzed the clinical medical records of patients with dual phenotypic liver cancer (DPHCC) and those (non-DPHCC) in the same period to seek quick and effective biomarkers for differential diagnosis. Methods: A retrospective study was conducted on 164 patients who underwent radical hepatocellular carcinoma resection at Affiliated Hospital of Nantong University from May 2017 to May 2020, including 29 patients with DPHCC, accounting for 17.7% (age: 53.9±10.0). There were 135 non-DPHCC patients, accounting for 82.3% (age, 62.6±9.1). The clinical records of the above patients were collected,including the basic information of the patients, clinical symptoms and signs, history of infection, laboratory test indexes one day before surgery, postoperative pathological report and other relevant data, The follow-up time was 18 months and the data were complete. By analyzing the clinical data of DPHCC patients and non-DPHCC patients in the same period, to find quick and effective differential diagnostic indicators, and to explore the indicators indicating poor prognosis of DPHCC patients. Results: One-way ANOVA showed significant differences in age, AFP[143(4.8-984.8) vs 9.9(2.8-71.3) µg/L], NLR (3.650±1.924 vs 2.220±1.486), neutrophil count, lymphocyte count, vascular infiltration rate, TNM stage, Chinese Hepatocellular carcinoma Staging (CNLC), Child grade, and Japanese General Staging Score (JIS) (P<0.05). Multivariate logistic regression analysis identified age(OR score:0.967,95%CI:0.860-0.957) and NLR(OR score:1.564,95%CI:1.205-2.029) as independent risk factors for DPHCC differential diagnosis. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficiency of NLR, and the best cut-off value was 2.586. The combination of age at onset improved the efficiency of differential diagnosis. When reaching the maximum diagnostic efficiency, the area under curve(AUC) was 0.836, the sensitivity was 89.66%, and the specificity was 65.93%. Conclusion: NLR combined with the age of disease has certain feasibility in predicting DPHCC and may be an effective index to distinguish DPHCC from non-DPHCC patients.

[Effect of intestinal obstruction stent combined with neoadjuvant chemotherapy on the pathological characteristics of surgical specimens in patients with complete obstructive colorectal cancer].

Objective: To compare the effects of three treatment options: emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery, on the pathological characteris- tics of surgically-resected specimens from patients with completely obstructive colorectal cancer. Methods: This was a retrospective cohort study analyzing clinicopathological data of patients with complete obstructive colorectal cancer who were admitted to the General Surgery Department of Beijing Chaoyang Hospital, Capital Medical University, between May 2012 and August 2020. The inclusion criteria were diagnosed with complete colorectal obstruction, pathologically confirmed as adenocarcinoma, resectable on imaging assessment, and without distant metastasis, combined with the patients' clinical manifestations and imaging examination findings. Patients with multiple colorectal cancers, refusal to undergo surgery, and concurrent peritonitis or intestinal perforation before stenting of the intestinal obstruction were excluded. Eighty-nine patients with completely obstructive colorectal cancer were enrolled in the study and were divided into emergency surgery group (n=30), stent-surgery group (n=34), and stent-neoadjuvant chemotherapy- surgery group (n=25) according to the treatment strategy. Differences in the pathological features (namely perineural infiltration, lymphovascular infiltration, tumor deposits, specimen intravascular necrosis, inflammatory infiltration, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cell ratio) and biomolecular markers (namely cluster of differentiation (CD)34, Ki67, Bcl-2, matrix metalloproteinase-9, and hypoxia-inducible factor alpha) were recorded. Pathological evaluation was based on the presence or absence of qualitative evaluation of pathological features, such as peripheral nerve infiltration, vascular infiltration, and cancer nodules within the specimens. The evaluation criteria for the pathological features of the specimens were as follows: Semi-quantitative graded evaluation based on the proportion of tissue necrosis, inflammatory infiltrates, abscesses, mucus lake formation, foreign body giant cells, calcification, and tumor cells in the field of view within the specimen were classified as: grade 0: not seen within the specimen; grade 1: 0-25%; grade 2: 25%-50%; grade 3: 50%-75%; and grade 4: 75%-100%. The intensity of cellular immunity was classified as none (0 points), weak (1 point), moderate (2 points), and strong (3 points). The two evaluation scores were then multiplied to obtain a total score of 0-12. The immunohistochemical results were also evaluated comprehensively, and the results were defined as: negative (grade 0): 0 points; weakly positive (grade 1): 1-3 points; moderately positive (grade 2): 4-6 points; strongly positive (grade 3): 7-9 points; and very strong positive (grade 4): 10-12 points. Normally-distributed values were expressed as mean±standard deviation, and one-way analysis of variance was used to analyze the differences between the groups. Non-normally-distributed values were expressed as median (interquartile range: Q1, Q3). A nonparametric test (Kruskal-Wallis H test) was used for comparisons between groups. Results: The differences were not statistically significant when comparing the baseline data for age, gender, tumor site, American Society of Anesthesiologists score, tumor T-stage, N-stage, and degree of differentiation among the three groups (all P>0.05). The differences were not statistically significant when comparing the pathological characteristics of the resected tumor specimens, such as foreign body giant cells, inflammatory infiltration, and mucus lake formation among the three groups (all P>0.05). The rates of vascular infiltration were 56.6% (17/30), 41.2% (15/34), and 20.0% (5/25) in the emergency surgery, stent-surgery, and stent- neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences between the groups (χ2=7.142, P=0.028). Additionally, the rate of vascular infiltration was significantly lower in the stent-neoadjuvant chemotherapy-surgery group than that in the emergency surgery group (P=0.038). Peripheral nerve infiltration rates were 55.3% (16/30), 41.2% (14/34), and 16.0% (4/25), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (χ2=7.735, P=0.021). The infiltration peripheral nerve rates in the stent-neoadjuvant chemotherapy-surgery group were significantly lower than those in the emergency surgery group (P=0.032). The necrosis grade was 2 (1, 2), 2 (1, 3), and 2 (2, 3) in the emergency surgery, stent- surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=10.090, P=0.006). Post hoc comparison revealed that the necrosis grade was higher in the stent-surgery and stent-neoadjuvant chemotherapy-surgery groups compared with the emergency surgery group (both P<0.05). The abscess grade was 2 (1, 2), 3 (1, 3), and 2 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=6.584, P=0.037). Post hoc comparison revealed that the abscess grade in the emergency surgery group was significantly lower than that in the stent-surgery group (P=0.037). The fibrosis grade was 2 (1, 3), 3 (2, 3), and 3 (2, 3), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=11.078, P=0.004). Post hoc analysis revealed that the fibrosis degree was higher in both the stent-surgery group and the stent- neoadjuvant chemotherapy-surgery group compared with the emergency surgery group (both, P<0.05). The tumor cell ratio grades were 4 (3, 4), 4 (3, 4), and 3 (2, 4), in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, with statistically significant differences (H=8.594, P=0.014). Post hoc analysis showed that the tumor cell ratio in the stent-neoadjuvant chemotherapy-surgery group was significantly lower than that in the emergency surgery group (P=0.012). The CD34 grades were 2 (2, 3), 3 (2, 4), and 3 (2, 3) in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups, respectively, and the difference was statistically significant (H=9.786, P=0.007). Post hoc analysis showed that the CD34 grades in the emergency surgery, stent-surgery, and stent-neoadjuvant chemotherapy-surgery groups were 2 (2, 3), 3 (2, 4), and 3 (2,3), respectively. Post hoc analysis revealed that the CD34 concentration was higher in the stent-surgery group than that in the emergency surgery group (P=0.005). Conclusion: Stenting may increase the risk of distant metastases in obstructive colorectal cancer. The stent-neoadjuvant chemotherapy-surgery treatment model promotes tumor cell necrosis and fibrosis and reduces the proportion of tumor cells, vascular infiltration, and peripheral nerve infiltration, which may help decrease local tumor infiltration and distant metastasis in completely obstructive colorectal cancer after stent placement.

[Clinical analysis of pulmonary nocardiosis associated with bronchiectasis].

Objective: To better understand the clinical characteristics of pulmonary nocardiosis associated with bronchiectasis. Methods: Patients diagnosed as bronchiectasis complicated with pulmonary nocardiosis in 9 tertiary general hospitals in China were enrolled from March 2016 to March 2020, with the record of general data, imaging performance and pathogen. The literature was reviewed. Results: Totally 17 patients were included. There were 12 females and 5 males. The ages ranged from 45 to 79 years, with an average of (63±9) years. There were 15 nonsmokers and 2 smokers, all of whom with chronic course. The clinical manifestations were mostly cough, expectoration, hemoptysis, fever, and dyspnea. The imaging manifestation was bronchiectasis in both lungs, with the most common involvement in the left lower lung, right middle lobe and left lingual lobe. Sputum cultures were positive in 10 cases, bronchoalveolar lavage fluid (BALF) cultures were positive in 6 cases, and next generation gene sequencings were positive in 4 cases, including 2 cases of Nocardia gelsenkii, 2 cases of Nocardia abscess, 2 cases of Nocardia stellate, 1 case of Nocardia mexicana, 1 case of Nocardia otitis caviae, and 9 cases of undetermined Nocardia. There were 3 cases of Klebsiella pneumoniae, 2 cases of Pseudomonas aeruginosa and 2 cases of Aspergillus. The symptoms and imaging of all patients were improved after anti Nocardia therapy. Conclusions: Bronchiectasis combined with nocardiosis is more common in middle-aged and elderly women without smoking, which is similar to the clinical manifestations of Lady Windermere syndrome. Bronchiectasis often involves the left lower lobe, right middle lobe and left lingual lobe. Nocardia infection might further precipitate the initiation and progression of bronchiectasis.

Retrospective analysis of molecular biology mechanism of ABO blood group typing discrepancy among blood donors in Jinan blood station.

BACKGROUND: To accurately identify ABO blood typing in pre-transfusion testing is very important to ensure blood transfusion safely, which is a major responsibility of blood station. METHODS: Eighty-one blood donors samples with ABO blood group typing discrepancy was collected among 61952 donor samples in our blood station from January 2019 to July 2020. Blood group serological method was used to detect ABO blood group. DNA Sequencing was used to determine the genotype. The antibody screening test detects antibodies other than ABO. RESULTS: In total, 61,952 donor samples were analysed for ABO typing discrepancies. The incidence among blood donors was 0.13% (81/61952). The most common reason of ABO typing discrepancies was due to specific antibody or non-specific agglutination (54.32%, 44/81), mainly anti-M antibody, cold autoantibody, anti-D antibody, anti-N antibody and anti-Lea antibody. The major cause of forward typing discrepancies among blood donors was ABO subgroups (25.93%, 21/81), including 10 cases of A subtype (1 case of A2, 2 cases of A3, 2 cases of Ax, 3 cases of AxB, 1 case of Ael, 1 case of Ahm), 6 cases of B subtype (2 cases of B3, 1 case of Bel, 3 cases of AB3), 2 cases of B subtype (A), 1 case of cisAB, and 2 cases of acquired B. The serum antibody was weakened in 16 cases (19.75%). CONCLUSIONS: The blood types should be correctly identified by combining serology with gene sequencing to ensure the safety of clinical blood transfusion, when the forward and reverse typing discrepancies among the blood donors.

[Current status of hyperkalemia in dialysis patients in China].

Objective: To investigate the prevalence and associated factors of hyperkalemia in dialysis patients. Methods: Patients underwent hemodialysis (HD) and peritoneal dialysis (PD) from multi-center databases were recruited from January 2017 to December 2019, and those aged ≥18 years and with dialysis duration ≥3 months were included to analyze the prevalence and related factors of hyperkalemia. Results: A total of 12 364 patients were enrolled in the study, and 6 836 cases were men. The average age of the patients was (51±15) years. Among these patients, 4 230 cases underwent HD while 8 134 received PD. Hyperkalemia was detected in 20.7% (2 554/12 364) of the patients while hypokalemia was found in 17.0%(2 102/12 364) of the patients. Multivariate logistic regression showed that HD (OR=2.25, 95%CI: 1.54-3.30), diabetes mellitus (DM) (OR=1.65, 95%CI: 1.17-2.32), high body mass index (BMI) (OR=1.06, 95%CI: 1.03-1.09), high levels of serum albumin (OR=1.04, 95%CI: 1.01-1.07) and phosphorus (OR=3.12, 95%CI: 2.44-4.00), low levels of serum bicarbonate (OR=0.89, 95%CI: 0.87-0.92), triglycerides (OR=0.76, 95%CI: 0.68-0.85) and creatinine (OR=0.95, 95%CI: 0.90-0.99), usage of angiotensin converting enzyme inhibitor/Angiotensin Ⅱ receptor antagonist (ACEI/ARB, OR=1.38, 95%CI: 1.11-1.72) and beta-blocker (OR=1.32, 95%CI: 1.07-1.64) were associated with hyperkalemia. Conclusions: Hyperkalemia occurred in 20.7% of the dialysis patients. HD, DM, high BMI, high levels of serum albumin and phosphorus, low levels of serum bicarbonate, triglycerides and creatinine, use of ACEI/ARB were associated with hyperkalemia.

Protective effects of L-carnitine on reproductive capacity in rats with diabetes.

To explore the protective effects of L-carnitine on erectile function and reproductive function in rats with diabetes. A total of 60 male diabetes mellitus induced-erectile dysfunction (DMED) rats were randomly divided into three groups, 20 rats in each group. The blank group was fed normally, the control group was fed with 0.9% sodium chloride solution 5 ml/kg/day, and the experimental group was given L-carnitine 300 mg/kg/day. After six weeks, the Corpus cavernosum penis pressure (ICP) and mean arterial pressure (MAP) were measured. The sperm of epididymis were taken to detect the parameters of sperm. After six weeks of treatment, ICP and MAP in the experimental group were significantly higher than those in the control group and blank group (p < 0.05), and sperm density and PR in the experimental group were significantly higher than those in the control group and the blank group (p < 0.05). Superoxide dismutase (SOD) in the experimental group was significantly higher than that in the control group and blank group (p < 0.05). Malondialdehyde (MDA) in the experimental group was significantly lower than that in the control group and blank group (p < 0.05). The follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone in the experimental group were significantly higher than those in the control group and blank group (p < 0.05). We conclude that L-carnitine can significantly improve erectile function and reproductive function in rats with diabetes and it has great potential in the treatment of systemic organ damage in DMED rats.

Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

Alcohol consumption promotes colorectal cancer by altering intestinal permeability.

OBJECTIVE: The purpose of this study was to uncover the potential impact of alcohol consumption on the tumorigenesis of colorectal cancer (CRC) and the underlying mechanism. PATIENTS AND METHODS: Overall survival was compared in CRC patients either with alcohol consumption or not. Subsequently, a mouse model of CRC was established by azoxymethane (AOM) administration. Tumor number and size were compared in CRC mice fed with Lieber-DeCarli liquid diet or normal diet. At last, pathological differences in cell proliferation, apoptosis, inflammation, and intestinal permeability, in intestines harvested from CRC mice fed with Lieber-DeCarli liquid diet or normal diet were assessed. RESULTS: It was found that the prognosis was worse in CRC patients with alcohol consumption. In CRC mice fed with Lieber-DeCarli liquid diet, more tumor tissues were found than those in the controls. Besides, alcohol consumption remarkably impaired intestinal permeability, making it easier for bacteria to invade epithelial cells. Moreover, oral gavage of probiotics markedly improved intestinal permeability and reduced tumor number in CRC mice fed with Lieber-DeCarli liquid diet. CONCLUSIONS: Probiotics can inhibit the development of alcohol-induced CRC by protecting intestinal permeability.

Genetic investigation of nodal melanocytic nevi in cases of giant congenital melanocytic nevus.

Nodal melanocytic nevi are common incidental findings in lymph nodes that have been removed during sentinel lymph node biopsy for melanoma. They can also occur in the local lymph nodes of the giant congenital nevus (GCN), but very little is known regarding nodal melanocytic nevi in the giant congenital nevus, especially at the genetic level. There are two theories that explain the possible pathogenesis of nodal melanocytic nevi, mechanical transport and arrested migration during embryogenesis. However, there have been few tests of these two theories at the molecular biology level until now. We used whole-exon sequencing to test these two theories at the gene level for the first time. In clonal evolution analysis of patient 1, whose tumor mutation burden (TMB) value was relatively stable, showed that the GCN and nodal nevus had the same initial origin and then diverged into two branches as a result of gene mutations. In contrast, analysis indicated that in the other patient, whose TMB value declined from 68.02/Mb in a GCN to 17.55/Mb in associated nodal nevi, these two samples were from different origins at the beginning, each with its own gene mutation. These results are consistent with the two respective theories at the molecular biological level. We provided the first tests of the two theories of pathogenesis of nodal melanocytic nevi at the gene level, and these findings may provide some clues for further study. In addition, not all nodal nevi should be treated as lymph node metastasis in clinical diagnosis, and we should make a comprehensive assessment and judgment of nodal melanocytic nevi based on morphology, immunological characteristics and fluorescence in situ hybridization (FISH) tests.

[Pulmonary cavities with Takayasu arteritis: report of 3 cases and literature review].

Objective: To analyze the clinical features of 3 cases of Takayasu arteritis(TA) with pulmonary cavities on chest computed tomography(CT). Methods: The clinical data of 3 TA patients with cavities on the chest CT who were admitted into Beijing Chaoyang Hospital were retrospectively analyzed. A literature search was performed with "Takayasu arteritis" and "pulmonary" as the key words in China Knowledge Resource Intergrated Database (CNKI) and Pubmed Database for publications from Jan 1, 2000 to Dec. 31,2017. The relevant literatures were reviewed. Results: Among the 3 patients, 2 were males and 1 was female, aging 49, 28 and 28 years, respectively. They presented with cough, fever and chest pain, and chest CT showed cavities, single or multiple, either with thick or thin wall, or wedge-shaped consolidation, residual stripes after being absorbed, and one case had pulmonary biopsy results which showed hemorrhagic infarction. They were all misdiagnosed before as pneumonia, pulmonary tuberculosis, pulmonary thromboembolism. After being treated by combination therapy of glucocorticoids and immunosuppressive agents, the disease improved significantly. A total of 777 cases with TA involving pulmonary arteries were reported, from which 13 cases with involvement of pulmonary parenchyma were described. Therefore total 16 cases including the 3 cases in this article were included for analysis. Twelve cases showed patchy or wedge-shaped ground-glass opacity and consolidation, and peripheral lung stripes remained after being absorbed. Two cases showed pleural effusion, and 4 cases showed cavities, 3 cases were misdiagnosed as pulmonary tuberculosis, 7 as pulmonary infection, and 5 as pulmonary thromboembolism. Conclusions: TA with pulmonary arteries involved is susceptible to be misdiagnosed and missed, and therefore, in patients with cough, hemoptysis, chest pain and cavities in pulmonary parenchyma, TA should be suspected. Early diagnosis and appropriate treatment can lead to a better prognosis.

Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay.

Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not unequivocably demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the intravenous (IV) route, which requires blood-brain barrier penetration. To address these questions, we developed a sensitive and specific quantitative mass spectrometry assay that distinguishes labeled (d5-deuterated) from endogenous (d0) OT. We administered d5 OT (80 IU) to six nonhuman primates via IN and IV routes as well as IN saline as a control condition. We measured plasma and CSF concentrations of administered and endogenous OT before (t=0) and after (t=10, 20, 30, 45 and 60 min) d5 OT dosing. We demonstrate CSF penetrance of d5, exogenous OT delivered by IN and IV administration. Peripheral administration of d5 OT did not lead to increased d0, endogenous OT in the CSF. This suggests that peripheral administration of OT does not lead to central release of endogenous OT. We also did not find that IN administration offered an advantage compared to IV administration with respect to achieving greater CSF concentrations of OT.

[Impact of platelet distribution width on the extent and long-term outcome of patients with stable coronary artery disease post percutaneous coronary intervention].

Objective: To evaluate the relationship between platelet distribution width(PDW) and the extent of coronary artery disease and 2-year outcome in patients received percutaneous coronary artery intervention(PCI) because of stable coronary artery disease(SCAD). Methods: We consecutively enrolled 4 293 patients who received PCI because of SCAD in Fuwai Hospital from Jan 2013 to Dec 2013, patients were followed up for 2 years. Patients were divided into three groups according to tertiles values of PDW as follows: PDW≤11.4%(1 402 patients), 11.4%12.9% (1 450 patients). Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as the occurrence of death, myocardial infarction, target vessel revascularization, intra stent thrombosis and stroke during follow-up. Multivariable logistic regression was used to evaluate the relationship between PDW and the extent of CAD. Multivariable Cox regression was used to evaluate the relationship between PDW and prognosis of SCAD patients. Results: PDW was associated with diabetes mellitus, body mass index, red cell distribution width, mean platelet volume (MPV), platelet counts and glycosylated haemoglobin (P<0.05), but not associated with age, sex, estimated glomerular filtration rate (P>0.05). PDW was not correlated with the extent of CAD(P=0.990), SYNTAX score(P=0.721), no-reflow phenomenon after PCI(P=0.978). Multivariable logistic regression also showed no relationship between PDW and extent of CAD (OR=0.994, 95%CI 0.961-1.029, P=0.73). PDW was found to be an independent risk factor of 2-year cardiac death (HR=1.242, 95%CI 1.031-1.497, P=0.022), but was not an independent risk factor of all-cause death and MACCE. Conclusions: PDW is not related with the extent of coronary artery disease. PDW is an independent risk factor of 2-year cardiac death, but is not an independent risk factor of all-cause death and MACCE in this patient cohort.

Approaches, Challenges, and Advances in Metabolism of New Synthetic Cannabinoids and Identification of Optimal Urinary Marker Metabolites.

We review approaches for determining metabolism of new synthetic cannabinoids (SCs), and challenges and advances in identifying optimal urinary marker metabolites of SC intake. Metabolic patterns of different SC generations are evaluated, and a practical strategy offered for selecting SC urinary marker metabolites. Novel SCs are incubated with human hepatocytes, the most abundant and characteristic metabolites are identified with high-resolution mass spectrometry, and proposed hepatocyte marker metabolites are confirmed in authentic positive urine samples.

[Clinical application of modified minimally cardiopulmonary bypass: compared with conventional cardiopulmonary bypass].

OBJECTIVE: To evaluate the safety and effects on blood transfusion of modified minimally cardiopulmonary bypass (CPB). METHODS: From April 2013 to February 2016, 1 103 elective cardiac surgery cases in National Center for Cardiovascular Diseases China, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were prospectively enrolled in the study. Patients undergoing modified minimally CPB were assigned to mini-CPB group (n=553), the others undergoing conventional CPB were assigned to conventional group (n=550). In mini-CPB group, oxygenator with integrated arterial filter, modified minimized circuit, mini-cardioplegia and vacuum assisted venous drainage(VAVD) were used. In conventional group, conventional CPB was composed with conventional oxygenator from the same manufactory, conventional circuit and 1∶4 blood cardioplegia. Analysis was performed with t test, t' test, Wilcoxon rank-sum test, χ(2) test, and Fisher exact test. RESULTS: No CPB accidents and peri-operative stroke were observed. There was no statistical difference in postoperative mechanical ventilation time, length of ICU stay, postoperative complications and mortality between the two groups. The incidence of erythrocyte transfusion (13.7% vs. 27.6%, χ(2)=32.458, P=0.000) and the incidence of ultrafilter (11.0% vs. 33.7%, χ(2)=76.019, P=0.000) were lower in the mini-CPB group. Postoperative hematocrit (M(QR): 32.9 (5.7) vs. 32.2 (5.7), Z=3.403, P=0.001) and 12-hour chest drainage ((228±154) ml vs.(260±197) ml, t'=3.004, P=0.003) of mini-CPB were imporved compared with conventional group. CONCLUSIONS: Modified minimally CPB is safe. It might reduce erythrocyte transfusion for adult cardiac surgery, warranting widely adoption.

Myeloid Sarcoma Presenting With Multiple Skin and Subcutaneous Mass Without Leukemic Manifestations After Renal Transplantation.

BACKGROUND: Myeloid sarcoma is well described and known in clinical practice, however, it is a rare condition after receiving renal transplantation. Immunosuppressive therapy is thought to be the main cause in these cases. CASE REPORT: A 45-year-old woman accepted a right kidney transplantation because of her chronic renal insufficiency and uremia in May 2011. She had to receive a left kidney transplantation again in February 2012 because she had renal failure again after receiving the right kidney transplantation. She received immune inhibitors treatment. After the latter operation, her renal function was normal. The third operation was done to remove the right transplanted kidney in July 2012. The diagnosis of the kidney was myeloid sarcoma. The blood and bone marrow biopsy had no evidence of leukemia. She then received chemotherapy. There was a small skin nodule on the left arm of approximately 0.5 cm in August 2012; after that its diameter enlarged progressively to about 5 cm and more nodules and masses gradually appeared on her face, arms, trunk, lower limbs, and feet over the course of 1 year. The skin biopsy specimen obtained from her left arm showed myeloid sarcoma too. She was admitted to the Orthopedics Department for severe pain and swelling in the left foot in September 2014 and underwent an operation for resecting the mass in the left foot. Pain was apparently alleviated and the incision healed well. CONCLUSIONS: The patient is still alive with no evidence of leukemia after a 30-month follow-up.

The detection of ß-amyloid plaques in an Alzheimer's disease rat model with DDNP-SPIO.

AIM: To detect the ß-amyloid plaques (Aß) in a rat model of Alzheimer's disease (AD) using superparamagnetic iron oxide nanoparticles coated with 1,1-dicyano-2-[6-(dimethylamino)-naphthalene-2-yl] propene carboxyl derivative (DDNP-SPIO). MATERIALS AND METHODS: DDNP-SPIO was prepared in a previous trial. The binding affinity of DDNP-SPIO to Aß was tested using fluorescence spectrophotometry in vitro. In vivo, five AD rats and five non-AD rats were intravenously injected with DDNP-SPIO at a dose of 76 µmol Fe/kg. Coronal T2*-weighted images were collected at baseline and repeated at 10, 30, and 60 min post-injection. Enhancement features of the two groups were analysed. After imaging, brain specimens were resected for Congo red and Prussian blue staining to assess the binding of DDNP-SPIO to Aß deposits. RESULTS: In vitro experiments indicated that the DDNP-SPIO nanoparticles displayed high binding affinities towards Aß with a Kd value of 29.4 nmol/l. A significant decrease in SI was detected in the hippocampal area of AD rats after intravenous injection of the nanoparticles, but not in non-AD rats. The measurement of the percentage signal loss decreased to 52% in AD rats. In non-AD rats, only 10% signal loss was observed. There was a significant difference between the two groups (t = 4.533, p < 0.05). The signal decrease resulted from the binding of the DDNP-SPIO nanoparticles to the Aß plaques, which was identified with Congo red and Prussian blue staining. CONCLUSION: The DDNP-SPIO nanoparticles could potentially be used for visualizing Aß plaques, which may be helpful for diagnosing the early stages of AD and monitoring the effects of drug therapy.

Screening of feature genes of the renal cell carcinoma with DNA microarray.

AIM: To investigate the underlying molecular mechanisms of renal cell carcinoma (RCC) by using the microarray expression profiles of normal kidney and RCC tissue for early diagnosis and treatment of RCC. MATERIALS AND METHODS: The gene expression profile of GES781 was downloaded from Gene Expression Omnibus database, including including nine tissue samples of RCC tissues removed from nine patients and eight adjacent normal renal tissue samples. We identified the differentially expressed genes (DEGs) by Multtest package in R software. The screened DEGs were further analyzed by bioinformatics methods. Firstly, the comparison of the DEGs expression degree was performed by cluster analysis. Secondly, DAVID was used to perform functional analysis of up- and down- regulated genes and the protein-protein interaction (PPI) networks were constructed by prePPI. Finally, the pathways of genes in PPI networks were discovered by WebGestalt. RESULTS: Compared with the control, we screened 648 down-regulated and 681 up-regulated DEGs. And the down- and up-regulated DEGs with maximum expression degree were UMOD (uromodulin) and FABP7 (fatty acid binding protein 7), respectively. There was significant difference in the gene expression between the normal kidney and RCC tissue. The up-regulated DEGs in RCC tissue were significantly related to the immune responses and the down-regulated DEGs were significantly related to the oxidation reduction. The most significant pathway in the PPI network of UMOD was cytokine-cytokine receptor interaction. CONCLUSIONS: The screened DEGs have the potential to become candidate target molecules to monitor, diagnose and treat the RCC, and might be beneficial for the early diagnosis and medication control of RCC.

Feasibility of MR imaging in evaluating breast cancer lymphangiogenesis using Polyethylene glycol-GoldMag nanoparticles.

AIM: To investigate the feasibility of evaluating tumour lymphangiogenesis using magnetic resonance imaging (MRI) in vivo. MATERIALS AND METHODS: Water-soluble polyethylene glycol (PEG)-GoldMag nanoparticles were obtained by combining GoldMag with PEG. The PEG-GoldMag nanoparticles were bound to anti-podoplanin antibody (PodAb) to construct PEG-GoldMag-pod molecular probes targeting lymphatic endothelial cells (LECs). The characteristics of the PEG-GoldMag-pod nanoparticles were tested. Using these nanoparticles, tumour lymphangiogenesis was evaluated using MRI in vitro and in vivo. RESULTS: The average size of PEG-GoldMag nanoparticles was about 66.8 nm, and the nanoparticles were stably dispersed in the liquid phase for at least 15 days. After incubation for 24 h at different iron concentrations ranging from 5-45 µg/ml, the LECs were labelled with PEG-GoldMag-pod nanoparticles, in particular the breast cancer LECs. Dose-dependence was observed in the labelling efficiencies and MRI images of the labelled cells. In vitro, the labelling efficiencies and MRI images showed that the nanoparticles could detect podoplanin expression in LECs. In induced rat models of breast cancer, PEG-GoldMag-pod nanoparticles combined with lymphatic vessels were significantly detectable at MRI 60 min after nanoparticle administration, the signal intensity was negatively correlated with the lymphatic vessel density of breast cancer (r = -0.864, P = 0.000). CONCLUSIONS: The present study proves the feasibility of evaluating tumour lymphangiogenesis with MRI in vivo.

The impact of short daily hemodialysis on anemia and the quality of life in Chinese patients.

Anemia is a frequent complication in hemodialysis patients. Compared to conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been reported to be effective in many countries except China. The aim of the present study was to determine whether sDHD could improve anemia and quality of life (QOL) for Chinese outpatients with end-stage renal disease. Twenty-seven patients (16 males/11 females) were converted from CHD to sDHD. All laboratory values were measured before conversion (baseline), at 3 months after conversion (sDHD1), and at 6 months after conversion (sDHD2). The patient's QOL was evaluated at baseline and 6 months after conversion using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Hemoglobin concentration increased significantly from 107.4 ± 7.9 g/L at baseline to 114.4 ± 6.8 g/L (P<0.05) at sDHD1, and 118.3±8.4 g/L (P<0.001) at sDHD2 (Student paired t-test). However, the dose requirement for erythropoietin decreased from 6847.8 ± 1057.3 U/week at baseline to 5869.6±1094.6 U/week (P<0.05) at sDHD2. Weekly stdKt/V increased significantly from 2.05±0.13 at baseline to 2.73±0.20 (P<0.001) at sDHD1, and 2.84±0.26 (P<0.001) at sDHD2. C-reactive protein decreased from baseline to sDHD1 and sDHD2, but without statistically significant differences. Physical and mental health survey scores increased in the 6 months following conversion to sDHD. sDHD may increase hemoglobin levels, decrease exogenous erythropoietin dose requirements, and improve QOL in Chinese hemodialysis patients compared to CHD. A possible mechanism for improvement of clinical outcomes may be optimized management of uremia associated with the higher efficiency of sDHD.