Purpose To investigate the clinicopathological features,immunophenotypes,molecular characteristics,treat-ment and prognosis of nodal follicular helper T cell lymphoma,angioimmunoblastic type(nTFHL-AI)with B cell clonal hyper-plasia.Methods The clinicopathological data of 10 nTFHL-AI patients with B cell clonal hyperplasia were collected from medi-cal records,with HE and immunohistochemical staining and gene rearrangement analysis.Related literature was also re-viewed.Results The included 10 patients were 5 males and 5 females with a median age of 73 years.The clinical manifesta-tions were mainly systemic lymphadenopathy,splenomegaly and B symptoms.8 patients were categorized as stage Ⅳ and 2 pa-tients were staged as Ⅰ+Ⅱ according to Ann Arbor staging cri-teria.Major laboratory results were increased β2 microglobulin,lactate dehydrogenase and decreased hemoglobin,erythrocytes and thrombocytes.Plasma Epstein-Barr virus(EBV)nucleic acid quantification was positive in 8 cases.Microscopically,the morphological patterns were nodular aggregation or scattered clear cells,branched high endothelial vessels and disorderly"wind-blown"like follicular dendritic cells(FDC).The num-ber of infiltrated eosinophils was 0-5/HPF in 7 cases,5-10/HPF in 2 cases,and＞50/HPF in 1 case.Plasma cell count was≤5％in 6 cases,10％in 1 case,20％in 1 case,and the rest 2 had relative higher count of 30％.The tumor cells of 7 ca-ses coexisted with marked hyperplasia of histiocytes,and in only one case Reed-Sternberg(RS)-like large cells were found 5 ca-ses showed abundant background B cells while the other 5 cases had limited background B cells.All tumor cells expressed T cell markers,6 were positive for CD10,BCL6,CXCL13 and PD-1 simultaneously and all of 10 were positive for BCL6,CXCL13 and PD-1.8 cases were positive for EBV-encoded small RNA(EBER)by in situ hybridization.Clonal TCR gene rearrange-ments and IG gene rearrangement were detected in all 10 pa-tients.After diagnosis,all patients were treated with chemother-apy,and three of them died due to disease progression.Conclu-sion B cell clonal hyperplasia,the status of EBV infection and the number of EBV-positive cells may be related with disease progression,individualized treatment and prognosis of patients with nTFHL-AI.

Long non-coding RNAs (lncRNAs) play a significant role in maintaining tissue morphology and functions, and their precise regulatory effectiveness is closely related to expression patterns. However, the spatial expression patterns of lncRNAs in humans are poorly characterized. Here, we constructed five comprehensive transcriptomic atlases of human lncRNAs covering thousands of major tissue samples in normal and disease states. The lncRNA transcriptomes exhibited high consistency within the same tissues across resources, and even higher complexity in specialized tissues. Tissue-elevated (TE) lncRNAs were identified in each resource and robust TE lncRNAs were refined by integrative analysis. We detected 1 to 4684 robust TE lncRNAs across tissues; the highest number was in testis tissue, followed by brain tissue. Functional analyses of TE lncRNAs indicated important roles in corresponding tissue-related pathways. Moreover, we found that the expression features of robust TE lncRNAs made them be effective biomarkers to distinguish tissues; TE lncRNAs also tended to be associated with cancer, and exhibited differential expression or were correlated with patient survival. In summary, spatial classification of lncRNAs is the starting point for elucidating the function of lncRNAs in both maintenance of tissue morphology and progress of tissue-constricted diseases.
Humans ; Gene Expression Profiling ; Neoplasms/genetics* ; Organ Specificity ; RNA, Long Noncoding/genetics* ; Transcriptome

Objective:To investigate the expressions of tissue inhibitor of matrix metalloproteinase-1 (TIMP1) and fibronectin 1 (FN1) in pregnancy associated breast cancer (PABC) and their correlations with expression of E-cadherin (E-cad).Methods:The clinicopathological data of 55 PABC patients in Binzhou People's Hospital Affiliated to Shandong First Medical University from January 2011 to December 2020 were retrospectively analyzed. Immunohistochemistry was used to detect expressions of TIMP1, FN1 and E-cad in cancer tissues and corresponding paracancerous tissues (>3 cm from the edge of the tumor foci). The expressions of TIMP1 and FN1 proteins in fresh intraoperative frozen cancer tissues and paracancerous tissues of 10 PABC patients were detected by Western blotting. The correlations of TIMP1 and FN1 expressions with clinicopathological characteristics of patients were analyzed by χ2 test, the correlation of TIMP1 and FN1 expressions with E-cad expression was analyzed by Spearman method, and the correlation of TIMP1 and FN1 expressions with survival was analyzed by Kaplan-Meier method. Results:The positive rates of TIMP1 and FN1 in PABC tissues were 72.7% (40/55) and 58.2% (32/55), and 25.5% (14/55) and 18.2% (10/55) in paracancerous tissues, and the differences were statistically significant ( χ2 values were 24.59 and 18.64, both P < 0.001). The results of Western blotting showed that the relative expressions of TIMP1 and FN1 proteins in the fresh cancer tissues of 10 PABC patients was higher than those in the corresponding paracancerous tissues (1.60±0.76 vs. 0.62±0.29, 1.31±0.62 vs. 0.44±0.15), and the differences were statistically significant ( t values were 5.92 and 4.86, both P < 0.001). The expressions of TIMP1 and FN1 in PABC tissues were correlated with estrogen receptor expression, Ki-67 positivity index, TNM stage and lymph node metastasis (all P < 0.05). The expressions of TIMP1 and FN1 were negatively correlated with expression of E-cad in PABC ( r values were -0.471 and -0.432, both P < 0.001). Five cases were lost to follow-up, and the remaining 50 cases had a median follow-up time of 43 months (12-90 months). Among the 50 cases, 36 cases were TMP1-positive and 29 cases were FN1-positive. The overall survival of TIMP1-negative group and FN1-negative group were better than those of the corresponding positive group ( χ2 values were 4.49 and 6.06, both P < 0.05); the median overall survival time of TIMP1-positive group and FN1-positive group were 51 months (95% CI 37-65 months) and 43 months (95% CI 32-53 months), while that of TIMP1-negative group and FN1-negative group were 89 months (95% CI 84-93 months) and 87 months (95% CI 85-92 months). Conclusions:TIMP1 and FN1 expressions are elevated in PABC tissues and negatively correlated with E-cad expression, TIMP1 and FN1 may be involved in PABC invasion through epithelial-mesenchymal transition and affect the prognosis of patients.

Objective:To investigate the effects of propofol on malignant biological behaviors of prostate cancer DU145 cells and its possible mechanism.Methods:Control group, 5-fluorouracil group (200 ng/ml) , low-dose propofol group (100 ng/ml) and high-dose propofol group (400 ng/ml) were set up. CCK-8 kit was used to measure the level of cell proliferation, Transwell method was used to measure the abilities of cell invasion and migration, flow cytometry was used to measure the level of apoptosis, and qRT-PCR and Western blotting were used to measure hepatocyte growth factor (HGF) and c-Met mRNA and protein levels.Results:The survival rates of the control group, 5-fluorouracil group, low-dose propofol group and high-dose propofol group were (83.32±3.02) %, (36.29±3.54) %, (62.01±4.69) % and (40.20±5.48) % ( F=8.65, P=0.006) ; the apoptosis rates were (2.36±0.41) %, (12.47±0.40) %, (6.28±0.39) % and (10.24±0.37) % ( F=26.73, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . The numbers of penetrating membranes of the four groups were 617.45±29.86, 125.27±24.38, 407.02±32.27 and 230.74±31.59 ( F=18.33, P=0.002) ; the migration distances were (603.85±27.74) μm, (121.69±25.85) μm, (395.59±28.37) μm and (233.52±30.42) μm ( F=27.02, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . HGF mRNA expression levels of the four groups were 6.26±0.39, 1.94±0.35, 4.15±0.37 and 2.90±0.33 ( F=25.31, P=0.001) ; c-Met mRNA expression levels were 5.85±0.30, 2.04±0.32, 3.89±0.31 and 2.94±0.32 ( F=12.12, P=0.003) ; HGF protein expression levels were 1.43±0.04, 0.34±0.08, 0.86±0.06 and 0.63±0.09 ( F=17.02, P=0.001) ; c-Met protein expression levels were 1.63±0.14, 0.39±0.15, 0.93±0.11 and 0.64±0.17 ( F=19.89, P=0.001) . Further pairwise comparison showed that there were statistically significant differences (all P<0.05) . Conclusion:Propofol has obvious inhibitory effects on the malignant biological behaviors of prostate cancer DU145 cells, and the inhibitory effect of high-dose propofol is more obvious. The mechanism may be related to the inhibition of HGF and c-Met mRNA and protein expressions of DU145 cells by propofol, which inhibits the activation of HGF/c-Met pathway.

Objective:To analyze the urine of normal healthy left-behind children under 1 year old and left-behind children with zinc deficiency under 1 year old in Zunyi area using hydrogen nuclear magnetic resonance ( 1HNMR), thus providing a new biomarker for the early diagnosis of zinc deficiency. Methods:From January to August 2018, a total of 40 normal healthy left-behind children under 1 year old in Zunyi area(healthy control group)[22 males and 18 females, average age of (7.78±3.62) months, average height of (65.01±2.67) cm and average body mass of (7.15±1.59) kg] and 40 age-matched left-behind children with zinc deficiency in the same region(zinc deficiency group)[19 males and 21 females, average age of (7.89±3.57) months, average height of (64.25±2.95) cm and average body mass of (7.02±1.68) kg] were included for a cross-sectional study by stratified sampling.The urine 1HNMR spectra of children in the 2 groups were measured, and the age, height, body mass and serum zinc content of children in the 2 groups were compared.The metabolites of the 2 groups were compared by metabono-mics technology combined with multivariate statistical analysis, and the differential metabolites of children with zinc deficiency were screened out. Results:There were no significant differences in age, height and body mass between the 2 groups (all P>0.05). The serum zinc level of healthy control group was significantly higher than that of zinc deficiency group [(54.3±3.06) mmol/L vs.(39.2±3.77) mmol/L, t=22.65, P<0.05]. Urine 1HNMR spectrogram results showed that compared with healthy controls, 4-hydroxyphenylpyruvic acid, phenyl acetyl glycine, and hippuric acid salt water were significantly lower in zinc deficiency group ( r=-0.620, -0.689, and -0.721, respectively, all | r|>0.602, all P<0.05). Conclusions:Zinc deficiency in left-behind children under 1 year old in Zunyi area is mainly manifested by decreased metabolites of 4-hydroxyphenylpyruvic acid, phenylacetyl glycine and horse-urate, suggesting metabolic disorder of intestinal flora.Differentially expressed metabolites have a potential application value in the early diagnosis of zinc deficiency.

Objective:To establish the normal reference value of lumbar bone mineral density (BMD) under quantitative CT (QCT) in Chinese healthy adult females and to explore the regional differences.Methods:Total of 35 431 healthy women who met the inclusion criteria of Chinese health quantitative CT big data program were selected in this study. The BMD of the central plane of L 1 and L 2 vertebrae was measured by Mindways′s QCT system, and the mean value was taken. One-way analysis of variance was used to compare the BMD differences of lumbar vertebrae in women of different ages and regions. The subjects were grouped by an age interval of 10 years, and the level of BMD in different regions of the same age group were compaired. Results:The peak BMD of Chinese healthy adult women appeared in the age group of 20-29 years (Northeast China(183.01±24.58) mg/cm 3, North China (188.93±24.80) mg/cm 3, East China (187.54±27.71) mg/cm 3, South China (186.22±33.72) mg/cm 3, Central China (176.33±24.91) mg/cm 3, Southwest China(182.25±28.00) mg/cm 3), and then it decreased with age. The level of BMD in different regions decreased with the age. Before the age of 70 years, BMD in Central and Southwest China was always at a low level((176.23±24.91) to (90.38±28.12) mg/cm 3, 182.25±28.00 to (88.55±25.68) mg/cm 3), lower than those in Northeast China ((183.01±24.58) to (99.69±27.85) mg/cm 3), North China ((188.93±24.80) to (95.89±26.12) mg/cm 3), East China ((187.54±27.71) to (95.65±27.86) mg/cm 3). After 70 years of age, BMD tended to be the same in different regions ( P>0.05). The BMD values in Central China and Southwest China were similar in the age group of 40-60 years ( P>0.05). The BMD values in the health adult femles in the age group of 60 years in different regions of Chinawere all lower than those of bone mass abnormality (all P<0.05). The detection rate of osteoporosis in females over 50 years was the highest in Southwest China (25.65%) and it was the lowest in North China (17.30%). Conclusions:This study establishes reference values of BMD under QCT in healthy Chinese women, which can be used as a reference basis for identifying women with low BMD who are at risk of osteoporosis. The BMD value is the lowest in Southwest China and the highest in South China.

Objective:To understand the biological characteristics, identification methods, genome structure and clinical significance of a rare strain of Aureimonas altamirensis isolated from clinical blood sample. Methods:The culture and biochemical characteristics of a strain isolated from blood culture were observed. The routine biochemical identification methods, MALDI-TOF mass spectrometer and 16S rRNA gene sequencing were used to identify the isolate. A phylogenetic tree based on the 16S rRNA gene sequences of the isolate and related strains was constructed. The genome of the isolated strain was sequenced and assembled, and gene prediction and functional annotation were made using related software. Phylogenetic analysis based on 31 house-keeping genes and genome-wide average nucleotide identity (ANI) analysis were conducted between the isolate and other Aureimonas sp. strains.Results:The isolated bacteria were gram-negative bacillus positive for catalase, urease and oxidase. It grew slowly on blood plate and could not be reliably identified by automatic bacterial biochemical identification systems or MALDI-TOF mass spectrometry. Results of the 16S rRNA gene sequencing and phylogenetic tree showed that the 16S rRNA gene sequence of the isolated strain was highly homologous to the strains of Aureimonas altamirensis NML070722 and IARI-ABL-26 (GenBank accession number: EU442518.1 and KC581669.1) in GenBank, and the gene sequence similarity was 99.93%. The total genome (National Microbiology Data Center genome accession number: NMDC60043566) length was 4 332 458 bp and GC content was 65.14%. There were 4 088 protein-coding genes and functional gene annotation showed that functional genes were mainly enriched in protein, amino acid, carbohydrate transport and metabolic functional regions. Pathogenic gene analysis predicted two high reliable virulence factor genes, but no drug resistance genes. House-keeping gene phylogenetic tree analysis showed that this strain was highly homologous to Aureimonas altamirensis strains of DSM21988 and C2P003 (GenBank accession number: GCF 001463885.1 and GCF 000800175.1), but ANI analysis showed that its genome was significantly different from those of the two strains. Conclusions:A rare strain of Aureimonas altamirensis was isolated from clinical specimen in China. As the biological and genomic characteristics of Aureimonas altamirensis had not been fully recognized, it was difficult to be correctly identified by conventional methods. The pathogenicity of Aureimonas altamirensis to immunocompromised patients and the significance of isolation in clinical specimens might need more case studies.

OBJECTIVE: To investigate the antitumor activity of decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model. METHODS: Hepatoma H22 tumor-bearing mouse models were randomized into model group, cyclophosphamide (CTX) group, and low-, moderate-, and high-dose decoction groups (JW-L, JW-M, and JW-H groups, respectively). The antitumor activity of decoction was assessed by calculating the tumor inhibition rate and pathological observation of the tumor tissues. Immunohistochemistry was used to detect the expressions of Bax, Bcl-2, Bax/Bcl-2 and caspase-3 in the tumors. The liver and kidney toxicity of decoction was analyzed by evaluating the biochemical indicators of liver and kidney functions. The immune function of the tumor-bearing mice were assessed by calculating the immune organ index, testing peripheral blood routines, and detection of serum IL-2 and TNF-α levels using enzyme-linked immunosorbent assay. RESULTS: Compared with that in the model group, the tumor mass in CTX, JW-M and JW-H groups were all significantly reduced ( < 0.05) with cell rupture and necrosis in the tumors. Immunohistochemistry revealed obviously up-regulated expressions of Bax and caspase-3 and down- regulated expression of Bcl-2 protein with an increased Bax/Bcl-2 ratio in CTX, JW-M and JW-H groups. Treatment with decoction significantly reduced Cr, BUN, AST and ALT levels, improved the immune organ index, increased peripheral blood leukocytes, erythrocytes and hemoglobin levels, and up-regulated the levels of TNF-α and IL-2 in the tumor-bearing mice. These changes were especially significant in JW-H group when compared with the parameters in the model group ( < 0.01). CONCLUSIONS decoction has a strong anti-tumor activity and can improve the liver and kidney functions of tumor-bearing mice. Its anti-tumor effect may be attributed to the up-regulation of Bax, caspase-3, TNF-α and IL-2 levels and the down-regulation of Bcl-2 expression as well as the enhancement of the non-specific immune function.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; Liver ; drug effects ; pathology ; Liver Neoplasms ; drug therapy ; immunology ; metabolism ; pathology ; Mice ; Necrosis ; Neoplasm Proteins ; metabolism ; Random Allocation ; Up-Regulation

Objective: To explore the characteristic changes in urinary metabolites in left-behind children with vitamin D deficiency under 1 year old in Zunyi area by metabolomic nuclear magnetic resonance (NMR) in order to provide new biomarkers for early diagnosis of vitamin D deficiency. Methods: From January to August 2018, blood tests and urine collection were carried out on the left-behind children under 1 year old in Fenggang county, Bozhou district and Zheng′an county under Zunyi city by stratified sampling.Forty children diagnosed as a vitamin D deficiency were selected as a vitamin D deficiency group, and 40 children with normal urine test were selected as a healthy control group.For urine sampling, SIMCA-P+ software was applied to analyze the integral value of hydrogen spectrogram by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) was used to distinguish the difference in urine metabolites between two groups of the left-behind children.Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to screen different metabolites. Results: The serum level of 25-hydroxy vitamin D[25-(OH)D][(32.0±3.6) nmol/L ] in the healthy control group was higher than that in the vitamin D deficiency group[(15.8±2.3) nmol/L], and the difference was statistically significant (P<0.05). PCA and PLS-DA analysis showed significant differences in urine metabolites between the healthy control group and the vitamin D deficiency group (P<0.05). OPLS-DA indicated R²X=0.365, Q²=0.978, which further verified the difference of metabolites.Compared with the healthy control group, the urine of methyl malonic acid, 3-hydroxy butyrate, N-acetyl glycoprotein signal, glutamic acid, dimethyl glycine, 2-ketone glutaric acid, taurine, fumaric acid salt level increased significantly in the vitamin D deficiency group, and the differences were statistically significant (|r|>0.602, all P<0.05, df=39). However, the levels of ethyl malonic acid, creatine, choline, glycerophosphalocholine and equine were significantly decreased, and the differences were statistically significant (|r|>0.602, all P<0.05, df=39). Conclusions The left-behind children under 1 year old with vitamin D deficiency in Zunyi region are mainly characterized by disorder in energy metabolism, lipid metabolism, amino acid metabolism and intestinal microbial meta-bolism disorders, and their differential metabolites have potential application value in early diagnosis and pathogenesis of vitamin D deficiency.

OBJECTIVE： To investigate the situation and problems of clinical microecological preparations in pediatrics department of China， and to provide reference for rational application of microecological preparations in children. METHODS： Outpatient/emergency prescriptions of microecological preparations during Jan.-Mar. 2019 were retrieved from information system of 5 “Third Grade Class A” children hospitals， and were investigated and analyzed in respects of the type of microecological agents， age distribution， clinical diagnosis， drug combination， off-label medication， etc. RESULTS： A total of 74 210 outpatient/emergency prescriptions were collected， involving 18 kinds of microecological preparations. Among them， Clostridium butyricum combined viable powder ranked first （31 146， accounting for 41.97％）， followed by Brucella yeast powder （14 289， accounting for 19.25％） and Compound Lactobacillus acidophilus tablets （10 281， 13.85％）. The age of children was less than 18 years old， and the proportion of children aged 1-＜3 years old was the highest （33 753， 45.48％）. The most common clinical diagnosis     was digestive tract diseases （54 009， 72.78％）， followed    by respiratory infectious diseases （11 744， 15.83％）. In combination with microecological agents， there were Chinese patent medicine for invigorating the spleen and stomach     （18 546， 24.99％）， antibacterial medicine （10 595， 14.28％） and oral rehydration salt Ⅲ （8 238， 11.10％）. Off-label drug use was found in 19 532 prescriptions （26.32％）， mainly manifesting as super-indications （15 590， 21.01％）， super-usage and dosage （8 098， 14.52％）， super crowd medication （48， 3.91％） was found in a few prescriptions. CONCLUSIONS： There is a high incidence of off-label use of microecological agents in children. Medical staff should standardize prescription behavior and promote rational use of drugs. At the same time， the improvement of the information of children’s medication in drug instructions to ensure the safety and effectiveness of children’s medication should be encouraged.