[The value of DISCO and MUSE-DWI combined with prostate specific antigen density in the diagnosis and risk stratification of prostate cancer].

Objective: To explore the value of differential subsampling with cartesian ordering (DISCO) and multiplexed sensitivity-encoding diffusion weighted-imaging (MUSE-DWI) combined with prostate specific antigen density (PSAD) in the diagnosis and risk stratification of prostate cancer (PCa). Methods: The data of 183 patients [aged from 48 to 86 (68±8) years] with prostate diseases in the General Hospital of Ningxia Medical University from July 2020 to August 2021 were retrospectively collected. Those patients were divided into non-PCa group (n=115) and PCa group (n=68) based on the disease condition. According to the risk degree, PCa group was subdivided into low risk PCa group (n=14) and medium-to-high risk PCa group (n=54). The differences of volume transfer constant (Ktrans), rate constant (Kep), extracellular volume fraction (Ve), apparent diffusion coefficient (ADC) and PSAD between groups were analyzed. Receiver operating characteristic (ROC) curves analysis were conducted for evaluating the diagnostic efficacy of quantitative parameters and PSAD in distinguishing non-PCa and PCa, low-risk PCa and medium-high risk PCa. Multivariate logistic regression model was used for screening out the predictors, which was statistically significant differences between non-PCa group and PCa group, for PCa prediction. Results: Ktrans, Kep, Ve and PSAD of PCa group all were higher than those of non-PCa group, and ADC value was lower than that of non-PCa group, and the differences all were statistically significant (all P<0.001). Ktrans, Kep and PSAD of medium-to-high risk PCa group all were higher than those of low risk PCa group, and ADC value was lower than that of low risk PCa group, and the differences were all statistically significant (all P<0.001). When distinguishing non-PCa from PCa, the area under ROC curve (AUC) of the combined model (Ktrans+Kep+Ve+ADC+PSAD) was higher than that of any single index [0.958 (95%CI: 0.918-0.982) vs 0.881 (95%CI: 0.825-0.924), 0.836 (95%CI: 0.775-0.887), 0.672 (95%CI: 0.599-0.740), 0.940(95%CI: 0.895-0.969), 0.816(95%CI:0.752-0.869), all P<0.05]. When distinguishing low-risk PCa and medium-to-high risk PCa, the AUC of the combined model (Ktrans+Kep+ADC+PSAD) were higher than those of Ktrans, Kep and PSAD[0.933 (95%CI: 0.845-0.979) vs 0.846 (95%CI:0.738-0.922), 0.782 (95%CI:0.665-0.873), 0.84 8(95%CI: 0.740-0.923), all P<0.05]. The multivariate logistic regression analysis showed that Ktrans (OR=1.005, 95%CI:1.001-1.010) and ADC values (OR=0.992, 95%CI:0.989-0.995) were predictors of PCa (P<0.05). Conclusions: DISCO and MUSE-DWI combined with PSAD can distinguish benign and malignant prostate lesions. Ktrans and ADC values were predictors of PCa; Ktrans, Kep, ADC values and PSAD are helpful in predicting the biological behavior of PCa.

[Prognostic factors for non-small cell lung cancer patients with central nervous system metastasis with positive driver genes].

Objective: To investigate the prognostic factors of patients with central nervous system (CNS) metastatic non-small cell lung cancer (NSCLC) with positive driver genes. Methods: The clinical data of 103 patients with CNS metastatic NSCLC admitted to Beijing Tongren Hospital from January 2016 to December 2020 were retrospectively analyzed, and the patients were divided into positive driver gene group (patients with driver genes mutation and receiving corresponding targeted therapy) and negative driver gene group. Cox univariate and multivariate regression analyses were performed to identify the factors affecting patients' prognosis, and the receiver operating characteristic curve (ROC) was used to compare the predictive ability of 4 scoring systems [recursive partitioning analysis (RPA) classes, diagnosis-specific graded prognostic assessment (DS-GPA) index, basic score for brain metastasesn (BS-BM) and (lung-molecular graded prognostic assessment (lung-mol GPA)]on patients' prognosis. Results: Among the 103 patients, 48 were males and 55 were females, and aged (64.6±9.7) years old. The median survival time of the 103 patients was 24.0 (95%CI: 20.0-28.0) months, the median survival time of the 59 patients in the positive driver gene group was 33.0 (95%CI: 23.4-42.6) months, the median survival time of the 44 patients in the negative driver gene group was 17.0 (95%CI: 14.4-19.6) months, and the difference was statistically significant (χ2=24.69, P<0.001). The results of Cox multivariate analysis showed that the negative driver genes (HR=3.788, 95%CI: 1.951-7.301, P=0.001), Karnofsky performance status (KPS) score<70 (HR=2.613, 95%CI: 1.185-5.761, P=0.017) and neutrophil-to-lymphocyte ratio (NLR)>3.22 (HR=2.714, 95%CI: 1.157-6.365, P=0.022) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC. KPS score<70 (HR=3.719, 95%CI: 1.165-11.876, P=0.027) and no radiotherapy (HR=2.032, 95%CI: 1.033-11.364, P=0.041) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC with positive driver genes. ROC curve analysis showed that the area under curve (AUC) value of lung-mol GPA was the highest among the 4 scoring systems (AUC=0.843, 95%CI: 0.731-0.956, P<0.001), and the AUC value of the lung-mol GPA combined scoring system (AUC=0.904, 95%CI: 0.816-0.991, P<0.001) was higher than lung-mol GPA. Conclusions: A low KPS score and no cranial radiation therapy are independent risk factors for the prognosis of patients with CNS metastatic NSCLC with positive driver genes; the lung-mol GPA joint scoring system is more conducive to the prognostic assessment of patients with CNS metastatic NSCLC with positive driver genes.

[Diagnosis of bacterial and viral infection by HNL, SAA, PCT and CRP combined test].

The value of combined detection of neutrophil apolipoprotein (HNL), serum amyloid A (SAA), procalcitonin (PCT) and C-reactive protein (CRP) in the differential diagnosis of bacterial and viral infectious diseases. A retrospective study was conducted to collect the clinical data of infected patients and healthy people in the clinical department of Shaanxi Provincial People's Hospital from September to December in 2022. 100 patients with confirmed infection were divided into bacterial infection group (n=50) and virus infection group (n=50), and 50 healthy people were selected as control group (n=50). Fasting venous blood was collected at the initial stage of admission or on the day of physical examination. HNL was detected by double antibody sandwich method, SAA and CRP were detected by nephelometry, and PCT was detected by chemiluminescence method. The efficacy of infection markers in the differential diagnosis of bacterial infection and viral infection in infected patients was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of HNL, SAA, PCT and CRP in bacterial and viral infectious diseases; Logistic regression was used to analyze the influence of each index on the diagnostic efficiency. The results showed that the levels of HNL (126.60±33.32) ng/ml, PCT (28.02±11.37) ng/ml and CRP (36.13±14.37) mg/L in bacterial infection group were significantly higher than those of HNL (47.72±15.94) ng/ml, PCT (1.27±0.40) ng/ml, CRP (18.77±10.66) mg/L in virus group and HNL (38.21±12.53) ng/ml, PCT (0.38±0.12) ng/ml and CRP (4.13±1.07) mg/L in control group. The level of HNL increased most significantly (F=89.228, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.976), HNL (0.907), PCT (0.885), CRP (0.856), SAA (0.790), SAA/CRP (0.733). The level of SAA/CRP in virus infection group (94.05±3.75) was significantly higher than that in bacteria group (17.70±3.69) and control group (3.89±1.50) (F=84.005, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.986), SAA/CRP (0.956), SAA (0.878), HNL (0.768), CRP (0.742), PCT (0.730). In conclusion, HNL has the best auxiliary diagnostic efficacy in bacterial infection, followed by PCT; SAA/CRP has the best auxiliary diagnostic efficacy in viral infection, followed by SAA; the combined detection of serum HNL, SAA, PCT and CRP may be helpful for the differential diagnosis of bacterial and viral infections.

[The value of relaxation time quantitative technique from synthetic magnetic resonance imaging in the diagnosis and invasion assessment of prostate cancer].

Objective: To investigate the application value of relaxation time quantitative technique from synthetic magnetic resonance imaging (MRI) in the diagnosis and invasion assessment of prostate cancer. Methods: A total of 119 patients with prostate diseases [122 regions of interest(ROI)] who underwent routine MRI scan and magnetic resonance image compilation (MAGiC) sequence of prostate from March 2020 to March 2021 in General Hospital of Ningxia Medical University were retrospectively collected, they were divided into prostate cancer group(58 cases, 61 ROI) and non-prostate cancer group(61 cases, 61 ROI) according to the pathological results. In the prostate cancer group, those patients with an age of 48 to 85(69.8±5.9) years, and further divided into two subgroups according to the location of occurrence: peripheral zone cancer group (43 cases, 45 ROI) and transitional zone cancer group (15 cases, 16 ROI). The non-prostate cancer group consisted of patients with benign prostatic hyperplasia or complicated with chronic prostatitis, with an age of 41 to 81(68.6±7.0) years, and they were further divided into two subgroups according to the location of occurrence: non-cancerous peripheral zone group (45 cases, 45 ROI) and transitional zone benign prostatic hyperplasia group(16 cases, 16 ROI). Prostate cancer lesions were classified as low risk (Gleason score ≤6) or intermediate/high risk (Gleason score ≥7). After the post-processing of MAGiC images, T1, T2 and proton density(PD) values of prostate cancer group and non-prostate cancer group were obtained. At the same time, relevant software were used for image post-processing to generate apparent diffusion coefficient (ADC) value, the data between the two groups were analyzed by the Independent sample t-test or Mann-Whitney U-test, and the diagnostic effectiveness of each quantitative parameter in diagnosing prostate cancer and discriminating low risk prostate cancer from intermediate/high risk prostate cancer was analyzed by using receiver operating characteristic curve (ROC) analysis, the correlation between each quantitative parameter and Gleason score were assessed by Spearman correlation analysis. Results: The T1 value and T2 value of the peripheral zone cancer group were lower than those in non-cancerous peripheral zone group [1 201.3 (1 103.5, 1 298.2) ms vs 2 274.0 (1 620.9, 2 776.5) ms; 78.0 (74.0, 83.8) ms vs (160.6±54.9) ms] (all P<0.001), there was no statistically significant in PD value between the two groups (P>0.05). The T1 value and T2 value of the transitional zone cancer group were lower than those in transitional zone benign prostatic hyperplasia group [1 073.3 (1 003.9, 1 164.9) ms vs 1 340.8 (1 208.5, 1 502.8) ms; 76.9 (74.8, 82.8) ms vs 95.1(82.8, 103.4) ms] (all P<0.001), there was no statistically significant in PD value between the two groups (P>0.05). The area under the curve (AUC) of T2 value was similar with the ADC value in discriminating peripheral zone cancer group from non-cancerous peripheral zone group(0.963 vs 0.991, P=0.105), while in discriminating transitional zone cancer group from transitional zone benign prostatic hyperplasia group, the AUC of T2 value、T1 value and ADC value were similar(0.867, 0.930 vs 0.938, all P>0.05). ADC value, T2 value all were negatively correlated with Gleason score (r=-0.747,-0.453, all P<0.001). T2 value and ADC value demonstrated equivalent diagnostic performance in discriminating low risk from intermediate/high risk prostate cancer, and there were no statistically significant (AUC: 0.787 vs 0.943, P=0.069). Conclusions: Quantitative relaxation time T1 and T2 values derived from synthetic MRI can discriminate prostate cancer from other benign pathologies, and T2 value have the equivalent diagnostic performance compared to ADC value. Synthetic MRI has high clinical application value, and T2 value can distinguish low risk prostate cancer from intermediate/high risk prostate cancer.

[The prognostic value of myocardial infarct size measured by cardiovascular magnetic resonance in patients with acute ST-segment elevation myocardial infarction].

Objective: To investigate the prognostic value of infarct size (IS) in patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Methods: A total of 104 patients with acute STEMI who underwent primary PCI treatment in Shengjing Hospital of China Medical University from February 2017 to November 2018 were included in the present study. All patients underwent cardiovascular magnetic resonance (CMR) within one week after primary PCI treatment. The subjects were followed up for two years. Major adverse cardiac events (MACE) included new onset congestive heart failure and/or recurrent nonfatal myocardial infarction and/orcardiac death. The optimal IS cutoff value for MACE was determined by receiver operating character (ROC) curve. Based on the IS cutoff value, the patients were divided into the high IS group and the low IS group. Clinical characteristics between the two groups were compared. A cox regression model was used to analyze the prognostic value of IS in acute STEMI patients treated with primary PCI for the adverse events. Results: The IS cutoff value determined by ROC curve was 13.55%. 50 patients were in the high IS group (IS≥13.55%) and 54 patients were in the low IS group (IS<13.55%). More female patients [14 cases (28.0%) vs. 6 cases (11.1%)] were in the IS group, and a higher proportion of patients in the high IS group had anterior myocardial infarction [27 cases (54.0%) vs. 16 cases (29.6%)] or microvascular obstruction [32 cases (64.0%) vs. 16 cases (29.6%)]. White blood cell counts [11.25(8.90, 13.38) ×109/L vs. 9.25(7.58, 11.00) ×109/L], troponin I levels [50.63(16.56, 76.30)µg/L vs. 16.58(2.66, 38.42)µg/L] and brain natriuretic peptide levels [178.10(79.70, 281.95)µg/L vs. 79.60(42.83, 183.90)µg/L] in the high IS group were higher than those in the low IS group (P<0.05), and left ventricular ejection fraction [(45.15±10.65)% vs. (51.95±12.91)%] in the high IS group was lower than that in the low IS group (P<0.05). Multivariate Cox regression analyses showed that IS was independently associated with the risk of cardiac death in patients with acute STEMI two years after primary PCI(P=0.033, HR=1.075, 95%CI1.006-1.148). Every 1% increase in IS was associated with a 7.5% increase in cardiac death. Conclusions: Infarct size, measured by CMR within one week after primary PCI, is strongly associated with cardiac death in patients with acute STEMI two years after primary PCI. IS could be used as an index for the prognosis of patients with acute STEMI.

[Quantitative dynamic contrast enhancement MR imaging parameters in the prediction and evaluation of the treatment response of malignant sinonasal tumors to chemotherapy:a preliminary result].

Objective: To investigate the value of quantitative dynamic contrast enhancement MR imaging (DCE-MRI) parameters in the prediction and evaluation of the response to neoadjuvant chemotherapy in patients with malignant sinonasal tumors by comparing the parameter values before and after chemotherapy. Methods: DCE-MRI was performed in 14 patients (6 male cases, 8 female cases, 16-83 years) with malignant sinonasal tumors before chemotherapy in Beijing Tongren Hospital from January 2012 to December 2013 in which DCE-MRI was performed in 8 patients on the 7th, 21st and 42nd days after chemotherapy. The values of quantitative parameter including K(trans), K(ep), and V(e) of the tumor were assessed and the change rate of these quantitative parameter values after chemotherapy was calculated. Results: Response to chemotherapy of the tumor was found in 11 patients with malignant sinonasal tumors,whereas no response to chemotherapy of the tumor was confirmed in 3 patients. K(trans) ((0.75±0.28)/min) and K(ep) ((3.23±1.48)/min) values of the tumor before chemotherapy in patients with response to chemotherapy were significantly bigger than those ((0.43±0.41)/min, (1.34±0.42)/min) in patients with no response to chemotherapy (all P<0.01).There was no significant difference in V(e) values between two groups (P=0.165). Compared with K(trans) values of the tumor before chemotherapy,the change rate of K(trans) values decreased more than 40% on the 7th,21st and 42nd days after chemotherapy in the patients with treatment response,whereas the change rate did not decrease significantly in the patients without treatment response. Conclusion: The bigger K(trans) and K(ep) values of the tumor before chemotherapy,the better the treatment response of the tumor to chemotherapy.

[The therapeutic effect of HSV1-hGM-CSF combined with doxorubicin on the mouse breast cancer model].

Objective: To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice. Methods: We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 µg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed. Results: Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro. Doxorubicin induced the G(2)/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm(3,) (216.80±57.18)mm(3,) (246.10±21.90)mm(3,) (327.50±44.24)mm(3,) (213.30±32.31)mm(3) and (495.80±75.87)mm(3) in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo (P<0.001). The median survival times were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above, respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM-CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control (P<0.05). Conclusion: Synergistic effect of sequential treatment with doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.

Succession Law of Intestinal Flora after Death in SD Rats.

OBJECTIVES: To initially explore the sequential changes in the intestinal flora of corpse for the estimation of postmortem interval （PMI）. METHODS: Rats were sacrificed by cervical dislocation, and samples were taken from their intestines using cotton swab to extract the DNA of intestinal flora. The 16S rRNA V3 universal primers were selected for PCR, and the PCR products were used for denatured gradient gel electrophoresis. The diversity and similarity analysis of intestinal flora were analyzed between groups, and the bands were cut from denaturing gradient gel electrophoresis. After purification, PCR and sequencing, the percentage of major bacteria in each group was obtained. RESULTS: The flora diversity showed a reduced tendency from 1st to 30th day after death （ P<0.05）, while the intra-group similarity showed a downward trend （ P<0.05）. The number of bands and intra-group similarity coefficient （Cs） on the first day was higher than that of other groups （ P<0.05）. The intra-group Cs of the 25th and 30th day had a significant difference compared with the 5th day （ P<0.05）. At the genus level, the intestinal flora was mainly composed of Enterococcus sp. on the 1th and 5th day after death, Bacillus thuringienssis was the dominant species on the 10th, 15th and 20th day, and Enterococcus faecalis became the dominant species on the 25th and 30th day. CONCLUSIONS: The composition and structure of intestinal flora change significantly in rats with the time after death, which indicates that the succession of intestinal flora is related to the postmortem interval.

Long noncoding RNA HOTTIP contributes to the progression of prostate cancer by regulating HOXA13.

Prostate cancer is a leading cause of cancer-related mortality in men worldwide and there is a lack of effective treatment options for advanced (metastatic) prostate cancer. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as cell growth, apoptosis and migration. However, little is known about the molecular mechanism of lncRNA-HOTTIP-mediated prostate cancer cell proliferation and apoptosis. The aim of this study was to elucidate the involvement of lncRNA HOTTIP in prostate cancer tumorigenesis and further investigate the role of HOXA13 in this process. Here, we showed that HOTTIP silencing inhibited cell survival pathway in vitro and in vivo by reducing the protein expression of Bcl-2 and enhancing Bax. We further demonstrated that knockdown of HOTTIP inhibited the expression of cell cycle regulatory protein Cyclin D1 and induced cell cycle arrest in G0/G1 phase. Additionally, depletion of HOXA13 by RNA interference (si-HOXA13) revealed that HOTTIP silencing suppressed cell growth at least partly through regulating HOXA13. In conclusion, down-regulation of HOTTIP and HOXA13 was associated with cell growth and cell cycle, and exerts tumor-suppressive functions in the genesis and progression of prostate cancer, providing a potential attractive therapeutic approach for this malignancy.

Analysis of cell cycle shortening and developmental interruption in Dictyostelium discoideum allC RNAi mutants.

Dictyostelium discoideum allC RNAi mutant cells are motile and aggregate together, but do not undergo further morphological development. The relatively quick growth rate of allC RNAi mutants compared to wild-type D. discoideum results in a shortened mutant cell cycle. However, at present, little is known about the mechanism underlying this phenomenon. Here, we used semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR, two-dimensional gel electrophoresis, and mass spectrometry/mass spectrometry to elucidate the phenomenon. We found significant downregulation of myosin II heavy chain, D. discoideum calcium-dependent cell adhesion molecule-1 (DdCAD-1) mRNA, DdCAD-1 protein, D. discoideum mRNA for 14-3-3 and 14-3-3 protein, and type A von Willebrand factor domain-containing protein mRNA in allC RNAi mutants. The results suggest that downregulation of the myosin II heavy chain could be one of key factors causing the developmental interruption and that downregulation of the 14-3-3 protein and the type A von Willebrand factor domain-containing protein mRNA plays an important role in shortening the cell cycle of allC RNAi mutants.

[Neoadjuvant chemotherapy in the treatment of locally advanced olfactory neuroblastoma in 25 cases].

Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q1, Q3)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.

Herbaceous Dominant the Changes of Normalized Difference Vegetation Index in the Transition Zone Between Desert and Typical Steppe in Inner Mongolia, China.

Asymmetric responses of aboveground net primary productivity (ANPP) to precipitation were identified as a signal to predict ecosystem state shifts at temperate grassland zones in Inner Mongolia, China. However, mechanism studies were still lacking. This study hypothesized that the enhanced growth and newly emerged herbaceous after increased precipitation resulted in the highest asymmetry at the transition zone between desert and typical steppe. We monitored the responses of the normalized difference vegetation index (NDVI) of different species to precipitation events using un-manned aerial vehicle technology to test this hypothesis. NDVI and species richness were measured twice at fixed points in July and August with a time interval of 15 days. Results showed that: (1) From July to August, NDVI in the transition zone increased significantly after precipitation (P < 0.05), but NDVI in both the desert and typical steppe showed a non-significant change (P > 0.05). (2) In the transition zone, NDVI increases from the shrub and herbaceous contributed to 37 and 63% increases of the site NDVI, respectively. (3) There was a significant difference in species richness between July and August in the transition zone (P < 0.05), mainly caused by the herbaceous (Chenopodiaceae, Composite, Convolvulaceae, Gramineae, Leguminosae, and Liliaceae), which either emerged from soil or tillers growth from surviving plants. This study demonstrated that herbaceous dominant the changes of NDVI in the transition zone, which provides a scientific basis for the mechanism studies of ANPP asymmetric response to precipitation and warrants long-term measurements.

Augmentation of organ-associated natural killer activity by biological response modifiers. Isolation and characterization of large granular lymphocytes from the liver.

Natural killer (NK) activity in the rat and human has been attributed to cells having the morphology of large granular lymphocytes (LGL). However, this association has been less clear in the mouse, largely because of difficulties in obtaining highly enriched populations of LGL from normal spleen and blood. We have previously observed that the administration of the biological response modifier (BRM) maleic anhydride divinyl ether (MVE-2) strongly augmented NK activity in lung and liver, and the augmented NK activity coincided with increased resistance to the formation of experimental metastases in these organs. The degree of NK augmentation was most striking in the liver, an unexpected and previously unreported observation. In the present study, both MVE-2 or Corynebacterium parvum induced a dramatic augmentation of liver NK activity, which reached maximum levels 3-5 d after treatment. This augmentation of NK activity in the liver coincided with a large increase in the number of lymphoid cells with the morphological characteristics of LGL that could be isolated from enzymatically digested suspensions of perfused liver. The yield of LGL per liver following BRM treatment corresponded to a 10-50-fold increase as compared to normal mice. LGL were purified from these enzymatically digested suspensions of perfused liver by depletion of adherent cells on nylon wool columns and subsequent enrichment for low-density lymphoid cells by fractionation on Percoll density gradients. The enrichment of LGL correlated with greatly increased NK activity against YAC-1. Conversely, the higher-density fractions were depleted of both LGL and NK activity. This increase in NK activity in the liver was suppressed by in vivo treatment with anti-asialo GM1 (asGM1) serum. This treatment also resulted in a corresponding reduction in both the total number and percentage of LGL. By flow cytometry analysis, the phenotype of the majority of these highly cytolytic LGL isolated from the livers of BRM-treated mice were asGM1+, Thy-1+, Ly-5+, Qa-5+, Mac-1+, and Gma-1+, whereas these LGL were Ly-1-, Lyt-2-, L3T4-, and surface Ig-. We conclude that the livers of BRM-treated mice can provide a rich source of highly active mouse LGL that could be used for further characterization of this lymphocyte subset. Further, these studies imply a potential for BRM therapy of neoplastic or viral diseases through augmentation of organ-associated immune responses.

[Outcomes and quality of life evaluation following endoscopic endonasal approach for sinonasal malignancies].

Objective: To analyse the outcomes and the prognostic factors of patients with sinonasal malignancies following endoscopic endonasal approach, and to compare the pre- and post-operative quality of life. Methods: A retrospective single-center review of 79 patients who underwent endoscopic endonasal approach for sinonasal malignancies in Beijing Tongren Hospital from October 2004 to March 2017 was performed, including 51 males and 28 females, with a median age of 48 years. Data of demography, imaging (including nasal CT and MRI before operation), histopathology and treatment strategy were collected. Recurrence and distant metastasis were diagnosed according to endoscopic examination, MRI and general check-up after surgery. Pre- and post-operative quality of life scores were obtained by sinonasal outcome test-22, visual analog scale and anterior skull base surgery questionnaire. SPSS 22 software was used for statistical analysis. Results: The study consisted of 13 pathological types with sinonasal T1-T4 stage tumors, including cervical lymph nodes and/or distant metastasis. All patients underwent endoscopic endonasal approach surgery. After 43 months of median follow-up time, the overall, disease-free, and recurrence-free survival rates at 1, 3, 5 and 10 years was 97.4%, 92.5%, 92.5% and 83.7%; 83.2%, 68.3%, 56.8% and 33.6%; 84.5%, 66.6%, 58.0% and 34.4%, respectively. Postoperative recurrence was an independent risk factor affecting the overall survival rate (HR=8.852, P=0.044), and preoperative recurrence (secondary surgery) was an independent risk factor affecting the disease-free and recurrence-free survival rate (HR value was 2.237 and 2.095 respectively, P value was 0.029 and 0.047 respectively). After surgery, the olfaction and nasal scab got worse, while the nasal obstruction and breathing were improved. Conclusions: Endoscopic endonasal approach for sinonasal malignancies can achieve satisfactory outcomes, and has obvious advantages in improving the quality of life. Postoperative recurrence and preoperative recurrence are the prognostic factors.

[A single-arm prospective study on induction chemotherapy and subsequent comprehensive therapy for advanced hypopharyngeal squamous cell carcinoma: report of 260 cases in a single center].

Objective: To study the significance of induction chemotherapy and subsequent comprehensive therapy for overall survival rate (OS) and larynx dysfunction-free survival rate (LDFS) in patients with advanced hypopharyngeal carcinoma. Methods: Patients who met the inclusion criteria with the diagnoses of advanced hypopharyngeal carcinoma between 2011 and 2017 received 2 or 3 cycles of TPF regimen induction chemotherapy. Patients who attained complete response (CR) received radical chemotherapy. Patients who attained partial response (PR) and the reduction of tumor volume was more than 70% were defined as large PR and received concurrent chemoradiotherapy. When the tumor volume reduction of PR patients was less than 70%, they were defined as small PR. (CR+large PR) group was defined as effective group. Patients who did not reach CR and large PR were defined as uneffective group and underwent radical surgery and received adjuvant radiotherapy as appropriate after the surgery. The end points of the study were OS, progression-free survival (PFS) and LDFS. Chi-square (χ(2)) test was used for correlation analysis. Survival analysis was performed by the Kaplan-Meier method with a Log-rank test. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results: A total of 260 patients were enrolled in the study. The follow-up period ranged from 5 to 83 months, with an average of 24.7 months. The 3-year and 5-year OS rate was 46.0% and 32.6%, respectively. The 3-year and 5-year PFS rate was 41.0% and 26.6%, respectively. The 3-year and 5-year LDFS rate was 37.9% and 24.8%, respectively. Poor outcome of induction chemotherapy, advanced N stage, strong positive Ki-67 immunohistochemistry (all P<0.001) were negative prognostic factors. The advanced clinical stage was positively related to the poor outcome of induction chemotherapy (P=0.015). There was no significant difference in OS and PFS between the large PR group and the small PR group (all P>0.005). Conclusion: TPF regimen induction chemotherapy and subsequent comprehensive therapy for patients with advanced hypopharyngeal carcinoma may improve the quality of life of patients, with high OS rate and LDFS rate.

[Basal squamous cell carcinoma of external auditory meatus: a case report].

Summary The patient developed repeated itching and scabbing at the mouth of the left external auditory canal 5 years ago. In the last two years, the tumor is enlarged. After admission, the left external auditory canal can be seen as a reddish mass, brittle and easy to bleed. CT of temporal bone showed that the soft tissue shadow of left external auricle and external auditory canal was thickened. Postoperative pathological findings: (left external auditory canal) basal cell squamous cell carcinoma. According to the history, physical examination and laboratory examination, the diagnosis is considered as basal squamous cell carcinoma of the external auditory meatus.

LINC00511 promotes the progression of non-small cell lung cancer through downregulating LATS2 and KLF2 by binding to EZH2 and LSD1.

OBJECTIVE: Lung cancer is a malignant tumor with extremely high morbidity and mortality. Recent studies have identified the vital role of LINC00511 (lncRNAs) in the development and progression of non-small cell lung cancer (NSCLC). In this research, we aim to explore the biological function of LINC00511 in the development and metastasis of NSCLC. PATIENTS AND METHODS: LINC00511 expression in 57 paired NSCLC patients' tissues and matched normal tissues were detected by Real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation assay, colony formation assay and transwell assay were conducted to observe the biological behavior changes of NSCLC cells through the influence of LINC00511. In addition, dual-luciferase reporter gene assay, RNA immunoprecipitation assay (RIP) and, chromatin immunoprecipitation (ChIP) were performed to discover the potential targets of LINC00511 in NSCLC cells. RESULTS: LINC00511 was highly expressed in NSCLC tissues and cell lines compared with controls. LINC00511 expression was positively correlated with tumor size, tumor stage, lymph node metastasis and distant metastasis, but negatively correlated with overall survival (OS) of NSCLC patients. Receiver Operating Characteristic (ROC) curves suggested that LINC00511 could be an effective indicator to distinguish NSCLC patients from normal people. Cell counting kit-8 (CCK-8), flow cytometry and transwell assay showed that knockdown of LINC00511 in A549 cells decreased viability, accelerated apoptosis and inhibited invasive and migratory abilities. Overexpression of LINC00511 in PC9 cells obtained the opposite biological effects. Chromatin fractionation predicted that LINC00511 was mainly distributed in the nucleus. RIP and ChIP assay showed that LINC00551 directly bound to lysine-specific demethylase 1 (LSD1) and enhancer of zeste homolog 2 (EZH2). It inhibited expressions of LATS2 and KLF2 by binding to their promoter regions. CONCLUSIONS: LINC00511 is upregulated in NSCLC tissues and cell lines. It is closely related to tumor size, tumor stage, lymph node metastasis and, distant metastasis of NSCLC patients. Knockdown of LINC00511 attenuates proliferative, migratory and invasive capacities, but induces apoptosis of NSCLC cells. LATS2 and KLF2 are target genes of LINC00511, which are regulated by LINC00511 through binding to EZH2 and LSD1, thus influencing the progression of NSCLC.

MicroRNA-15a inhibits inflammatory response and apoptosis after spinal cord injury via targeting STAT3.

OBJECTIVE: To clarify the function of microRNA-15a in the spinal cord injury (SCI) and its potential mechanism. PATIENTS AND METHODS: The plasma levels of microRNA-15a and signal transducer and activator of transcription 3 (STAT3) in SCI patients were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the expressions of microRNA-15a and STAT3 was analyzed. The in vitro SCI model was established in H2O2-induced C8-D1A and C8B4 cells, and in vivo SCI model was established in mice by hitting T10. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) were detected in the SCI model. The apoptosis was examined by flow cytometry or TUNEL staining, respectively. The motor function of mouse hindlimb was evaluated using the Basso Beattie Bresnahan (BBB) standard scale. The target gene of microRNA-15a was predicted by bioinformatics and further verified by dual-luciferase reporter gene assay. The expression changes of target genes in C8-D1A and C8B4 cells with microRNA-15a overexpression or knockdown were examined by qRT-PCR and Western blot. Finally, rescue experiments were performed to evaluate the regulatory effects of microRNA-15a and STAT3 on cell apoptosis. RESULTS: MicroRNA-15a was lowly expressed in plasma of SCI patients, while STAT3 was highly expressed with a negative correlation to microRNA-15a. Identically, microRNA-15a was lowly expressed in H2O2-induced C8-D1A and C8B4 cells, and STAT3 was highly expressed. MicroRNA-15a overexpression downregulated mRNA and protein levels of TNF-α and IL-6 in C8-D1A and C8B4 cells. BBB score was markedly low in SCI mice relative to controls. SCI mice injected with microRNA-15a mimics had higher BBB score than those injected with negative control. Besides, SCI mice with microRNA-15a overexpression had downregulated expressions of STAT3, TNF-α, and IL-6 in the impaired spinal cord tissues, as well as lower apoptotic rate. Through bioinformatics, we found binding sites between STAT3 and microRNA-15a. Their binding conditions were further verified by dual-luciferase reporter gene assay. Moreover, STAT3 expression was negatively regulated by microRNA-15a. Finally, rescue experiments showed that STAT3 overexpression could reverse the regulatory effects of microRNA-15a on expressions of TNF-α and IL-6, as well as apoptosis. CONCLUSIONS: MicroRNA-15a expression decreases in the SCI model, which participates in the process of SCI by regulating inflammatory response and cell apoptosis via targeting STAT3.

The expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice.

OBJECTIVE: Given the important functions of TP53 pathway in various biological processes, this study aimed to investigate the expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice with and without the presence of p53 inhibitor and to explore possible roles of p53 in the development of ovarian cancer. MATERIALS AND METHODS: Thirty BALB/c-nu female nude mice were randomly divided into model group, control group and p53 inhibitor group (Pftα group). There were 10 rats in each group. The nude mice were subcutaneously inoculated with human ovarian cancer cell line SKOV3, and the tumor growth was observed. Morphological changes of tumor tissue were observed by hematoxylin and eosin (HE) staining. The mRNA and protein levels of TP53 pathway related factors-p53, p21 and mouse double minute 2 homolog (MDM2) were detected by RT-PCR and Western blot. RESULTS: p53 inhibitor can increase the growth rate of subcutaneously transplanted tumor in nude mice. p53 inhibitor could decrease the expression of p53 and p21 at both mRNA and protein levels and increase the expression of MDM2 at both mRNA and protein levels in ovarian carcinoma transplanted subcutaneously in nude mice. CONCLUSIONS: TP53 pathway may play pivotal roles in the development of ovarian cancer and TP53 pathway may be a new target for the treatment of ovarian cancer.

Tuning the catalytic activity of colloidal noble metal nanocrystals by using differently charged surfactants.

The catalytic activity of metal nanocrystals is mainly tuned through the control of their shapes and sizes. However, the shapes and sizes of many metal nanocrystals are difficult to control and therefore their catalytic activity is hard to tune. Here, we demonstrate another approach, using differently charged surfactants, for tuning the catalytic activity of metal nanocrystals. Au and Pd nanocrystals capped with cationic cetyltrimethylammonium bromide (CTAB) and anionic citrate are chosen to study the effect of surfactant charges on the catalytic activity. The oxidation of o-phenylenediamine to 2,3-diaminophenazine by H2O2 is selected as a model reaction. The prepared Au and Pd nanocrystals are initially capped with CTAB, which is changed to citrate through surfactant exchange. Owing to the relatively weak electrostatic interaction of CTAB with the nanocrystals, the surfactant exchange does not induce observable changes in nanocrystal shapes and sizes. In contrast, the catalytic activity is greatly improved by the surfactant exchange. XPS analysis and theoretical calculations indicate that the adsorption of anionic citrate enriches the electrons of the nanocrystal surfaces, while the adsorption of CTAB depletes the electrons of the nanocrystal surfaces. The different catalytic activities of CTAB and citrate-capped nanocrystals arise from the different behaviors of electron transfer between the surfactants and the nanocrystal surface. Since the surfacants that electrostatically bind to the metal nanocrystals are facile to exchange into other surfactants, our findings provide an effective way to tuning the catalytic activity of metal nanocrystals.