[The cell nuclear damage probably induces chronic refractory diseases].

The cell nuclear damage is mainly caused by the radiation and various carcinogenic compounds, the essence of the damage is molecular adhesion fracture and chemical modification. After nuclear damage, the cells whose nuclei may be abnormal in morphology, structure and function, then become a kind of morbid cells or defective cells. The cell nuclear damage can affect gene expression and regulation, leading to dysfunctions or abnormalities of transcription and protein synthesis, which results in aging and induces various chronic refractory diseases, such as hypertension, atherosclerosis, diabetes, Alzheimer's disease, autoimmune diseases, and so on. The cell nuclear damage can also affect the state of cell differentiation and lead to restart of genes related to division and proliferation, thus inducing cancer. The cancer cells are derived from the cells with nuclear abnormalities, and the biological behavior or characteristics of cancer cells (shedding and metastasis, immune tolerance, uncontrolled, loss of contact inhibition, etc.) are derived from cells with nuclear abnormalities. This article reviewed the chronic refractory diseases caused by nuclear damage and their mechanisms, which provided a new idea for occupational health and toxicology research, as well as a new method and strategy for occupational disease prevention and treatment.

[Correlation analysis of age and microbial characteristics in saliva and feces of high-risk population of upper gastrointestinal cancer].

Objective: To explore the correlation between age and diversity and microbial composition in saliva and feces microbiota in high-risk population of upper gastrointestinal cancer. Methods: Based on the national project on early diagnosis and early treatment of upper gastrointestinal cancer, 38 participants were enrolled in Linzhou in Henan province in August 2019. The participant information was collected by questionnaire. Saliva and feces specimens were collected from each participant for 16S rRNA sequencing and bioinformatics analysis. Spearman rank correlation was used to analyze the correlation between age and α diversity (Observed ASVs and Shannon index) and relative abundance of microbiota (phyla, genera, and species) in saliva and feces. Results: The median age (age range) of 38 participants was 54 (43-60) years old, and there were 16 males (42.1%). The Observed ASVs of saliva was negatively correlated with age (rs=-0.35, P<0.05), but the observed ASVs of feces was not correlated with age. In saliva, the relative abundance of Treponema (rs=‒0.44, P<0.05), Alloprevotella (rs=‒0.42, P<0.05), and Porphyromonas (rs=‒0.41,P<0.05) were significantly negatively correlated with age. At the species level, the relative abundance of Porphyromonas endodontalis, Alloprevotella tannerae, Haemophilus influenza, Moraxella bovoculi, Prevotella sp.oral clone ID019, and Prevotella sp.oral clone ASCG10 in saliva were significantly negatively correlated with age, and the rs values were -0.50, -0.40, -0.38, -0.35, -0.33 and -0.33 (P<0.05), respectively. In feces, the relative abundance of Enterobacteria (rs=-0.35, P<0.05), Escherichia (rs=-0.33, P<0.05), and Bifidobacteria (rs=0.33, P<0.05) were correlated with age. At the species level, the relative abundance of Romboutsia sedimentorum, Citrobacter murliniae, and bacteroides uniformis in feces were correlated with age, and the rs values were -0.42, -0.37 and 0.36 (P<0.05), respectively. Conclusion: Age of the high-risk population of upper gastrointestinal cancer is correlated with the relative abundance of microbiota in saliva and feces.

[Safety of an inactivated 2019-nCoV vaccine (Vero) in adults aged 60 years and older].

Objective: To analyze the safety of an inactivated 2019-nCoV vaccine (Vero cell) in adults aged 60 years and older. Methods: A randomized, double-blind, placebo-controlled clinical study was conducted in May 2020 The eligible residents aged 60 and above were recruited in Renqiu city, Hebei Province. A total of 422 subjects (phase Ⅰ/Ⅱ:72/350) were enrolled. Two doses of the trial vaccine or placebo were randomly administered according to a 0 and 28-day immunization schedule. Subjects were randomly divided into two groups in Phase Ⅰ. Within each group, participants received vaccine or placebo in a ratio of 2∶1. Subjects were randomly divided into four groups in phase Ⅱ to receive low-dose, medium-dose, high-dose vaccine and placebo, respectively, in a ratio of 2∶2∶2∶1. A combination of regular follow-up and active reporting was used to observe adverse reactions within 28 days after vaccination, and compare the incidence rate of adverse reactions in the trial and control groups. Results: 422 subjects were (66.45±4.70) years old, and 48.82% were male (206/422). There were 100, 124, 124 and 74 patients enrolled into the low-dose, medium-dose, high-dose vaccine groups and the placebo group, respectively. One person without the vaccination was removed, and 421 participants who received at least one dose of vaccine were included in the safety analysis. Within 28 days after the first or second dose, a total of 20.67% (87/421) subjects had adverse reactions (both solicitation and non-solicitation). About 76 patients suffered grade 1 adverse reactions [18.05% (76/421)] and 22 patients suffered grade 2 adverse reactions [5.23% (22/421)]. No grade 3 or above adverse reactions occurred. A total of 19.71% (83/421) subjects had solicited adverse reactions. The most common grade 1 adverse reaction was injection site pain, followed by fever and fatigue. The most common grade 2 adverse reactions were fever and fatigue, followed by muscle pain and injection site redness. A total of 2.61% (11/421) subjects had unsolicited adverse reactions. A total of 1.66% (7/421) subjects had serious adverse events after vaccination, and no serious vaccine-related adverse events were reported. Conclusions: The inactivated SARS-CoV-2 vaccine is safe for people aged 60 years and above.

Whole-lesion histogram analysis of mono-exponential and bi-exponential diffusion-weighted imaging in differentiating lung cancer from benign pulmonary lesions using 3 T MRI.

AIM: To investigate whether whole-lesion histogram analysis of apparent diffusion coefficient (ADC) values derived from mono-exponential and bi-exponential diffusion-weighted imaging (DWI) can differentiate lung cancer from benign pulmonary lesions. MATERIALS AND METHODS: Thirty-two patients with lung cancer and 17 patients with benign pulmonary lesions were included retrospectively. All patients underwent DWI before surgery or biopsy. ADC histogram parameters, including mean, percentile values (10th and 90th), kurtosis, and skewness, were calculated independently by two radiologists. The histogram parameters were compared between patients with lung cancer and benign lesions. Receiver operating characteristic curves were constructed to evaluate the diagnostic performance. RESULTS: The ADCMean, ADC10th, DMean, D10th were significantly lower in lung cancer (1.187 ± 0.144 × 10-3; 0.440 ± 0.062 × 10-3; 1.068 ± 0.108 × 10-3; and 0.422 ± 0.049 × 10-3 mm/s) compared to benign lesions (1.418 ± 0.274 × 10-3; 0.555 ± 0.113 × 10-3; 1.216 ± 0.149 × 10-3; and 0.490 ± 0.044 × 10-3 mm/s; p<0.05). The ADCSkewness and DSkewness were significantly different between lung cancer (2.35 ± 0.72; 2.58 ± 1.14) and benign lesions (1.85 ± 0.54; 1.59 ± 1.47; p<0.05). D10th was robust in differentiating lung cancer from benign lesions. Using 0.453 × 10-3 mm/s as the optimal threshold, the sensitivity, specificity, and accuracy of D10th were 78.12%, 82.35%, and 79.6%, respectively. CONCLUSION: Whole-lesion histogram analysis of ADC values derived by mono-exponential and bi-exponential DWI using 3 T magnetic resonance imaging helps distinguish lung cancer from benign pulmonary lesions.

Age-Related Changes of Material Mechanics and Bone Material Parameters of Rat Skulls.

ABSTRACT: Objective To study the relationship between material mechanics and bone material parameters of rat skulls and their correlation with age by examination of the parameters. Methods Forty-eight healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52 and 104 week groups according to their age. Each group had six rats. The right cranium was compressed by KD Ⅱ-0.2 microcomputer controlled electronic universal testing machine, and material mechanics parameters （ultimate load, compression strength and compression modulus） were measured, then the skull slices were cut off and scanned by Micro-CT system to detect bone material parameters （skull thickness, bone mineral density, bone volume, and trabecular thickness）. Results The differences in ultimate load, compression strength and compression modulus among all groups had statistical significance （P<0.05）, and were positively correlated with age within 26 weeks （P<0.05）. The differences in skull thickness, bone mineral density, bone volume and trabecular thickness among all groups had statistical significance （P<0.05）, and were positively correlated with age within 52 weeks （P<0.05）. All material mechanics parameters were positively correlated with bone material parameters （P<0.05）. Conclusion There is a positive correlation between bone material parameters （skull thickness, bone mineral density, bone volume, trabecular thickness）, material mechanics parameter （skull ultimate load, compression strength, compression modulus） and age in a certain range, which can be used to infer age.

[Comparative imaging study of mediastinal lymph node from pre-surgery dual energy CT versus post-surgeron verifications in non-small cell lung cancer patients].

OBJECTIVE: To validate the value of dual energy CT (DECT) in the differentiation of mediastinal metastatic lymph nodes from non-metastatic lymph nodes in non-small cell lung cancer (NSCLC). METHODS: In the study, 57 surgically confirmed NSCLC patients who underwent enhanced DECT scan within 2 weeks before operation were enrolled. Two radiologists analyzed the CT images before operation. All mediastinal lymph nodes with short diameter≥5 mm on axial images were included in this study. The morphological parameters [long-axis diameter (L), short-axis diameter (S) and S/L of lymph nodes] and the DECT parameters [iodine concentration (IC), normalized iodine concentration (NIC), slope of spectral hounsfield unit curve (λHU) and effective atomic number (Zeff) in arterial and venous phase] were measured. The differences of morphological parameters and DECT parameters between metastatic and non-metastatic lymph nodes were compared. The parameters with significant difference were analyzed by the Logistic regression model, then a new predictive variable was established. Receiver operator characteristic (ROC) analyses were performed for S, NIC in venous phase and the new predictive variable. RESULTS: In 57 patients, 49 metastatic lymph nodes and 938 non-metastatic lymph nodes were confirmed by surgical pathology. A total of 163 mediastinal lymph nodes (49 metastatic, 114 non-metastatic) with S≥5 mm were detected on axial CT images. The S, L and S/L of metastatic lymph nodes were significantly higher than those of non-metastatic lymph nodes (P < 0.05). The DECT parameters of metastatic lymph nodes were significantly lower than those of non-metastatic lymph nodes (P < 0.05). The best single morphological parameter for differentiation between metastatic and nonmetastatic lymph nodes was S (AUC, 0.752; threshold, 8.5 mm; sensitivity, 67.4%; specificity, 73.7%; accuracy, 71.8%). The best single DECT parameter for differentiation between metastatic and nonmetastatic lymph nodes was NIC in venous phase (AUC, 0.861; threshold, 0.53; sensitivity, 95.9%; specificity, 70.2%; accuracy, 77.9%). Multivariate analysis showed that S and NIC were independent predictors of lymph node metastasis. The AUC of combined S and NIC in the venous phase was 0.895(sensitivity, 79.6%; specificity, 87.7%; accuracy, 85.3%), which were significantly higher than that of S (P < 0.001) and NIC (P=0.037). CONCLUSIONS: The ability of quantitative DECT parameters to distinguish mediastinal lymph node metastasis in NSCLC patients is better than that of morphological parameters. Combined S and NIC in venous phase can be used to improve preoperative diagnostic accuracy of metastatic lymph nodes.

[The clinical decision-making value of prostate specific antigen and its derived indicators in prostate imaging reporting and data system version 2 3 lesions].

Objective: To explore the decision-making value of clinical data in prostate imaging reporting and data system version 2 (PI-RADS V2) 3 lesions, and to compare the diagnostic value of related data for prostate cancer (PCa) and clinically PCa(csPCa). Methods: From March 2016 to October 2018,a subset of 121 men with 121 PI-RADS 3 index lesions were retrospectively analyzed. There were 31 PCa lesions and 14 csPCa lesions, aged from 46 to 91 years with a mean age of (71±9) years. The clinical data of the age, prostate specific antigen (PSA), free PSA (fPSA), f/tPSA, PSA density (PSAD) and prostate volume (PV) were compared between PCa group and non-PCa group, csPCa group and non-csPCa group using univariate analysis, respectively.The receiver operating characteristic (ROC) curve was used to evaluate the efficiency of statistically data in detecting PCa and csPCa in men with PI-RADS 3 index lesions. Results: The differences of PSA, f/tPSA and PSAD were all statistically significant (Z=-2.004, -2.527, -2.623, all P<0.05) between PCa group and non-PCa group, and they were all also statistically significant(Z=-2.415, -2.158, -2.870, all P<0.05) between csPCa group and non-csPCa group. Both PSAD had the best diagnostic efficiency, the ROC curve of detecting PCa and csPCa was 0.658 and 0.736, respectively. If used PSAD>0.20 µg·L(-1)·ml(-1) as the biopsy threshold, the sensitivity, specificity, positive predictive value and negative predictive value of csPCa were 78.6%, 58.9%, 20.0%, 95.4%, and 54.5% (66/121) of the enrolled men can avoid biopsy, resulting only 3 cases of csPCa missed. Conclusion: PSA, f/tPSA, PSAD, especially PSAD can improve the detection efficiency of PCa,especially csPCa in PI-RADS 3 lesions, assisting clinical decision-making.

[Performance of high-risk HPV typing test in early diagnosis of cervical cancer].

Objective: To evaluate the performance of High-risk HPV typing detection in cervical cancer screening. Methods: A total of 3 231 women were recruited as the subjects of cervical cancer screening from Jiyuan city of Henan provinces from June to July 2017. All women underwent HPV DNA test. The women with cytological examination ≥ASCUS or cytological examination negative and HPV 16/18 positive underwent colposcopy biopsy and pathological examination. Pathological diagnosis was used as the gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value(NPV) as well as corresponding 95% confidence interval (CI) of HR-HPV and HPV 16/18 were calculated. Results: The mean age of 3 231 subjects selected in this study was 46.84±10.00 (21-64) years old. 524 subjects had the positive results of HR-HPV, including 91 of HPV16 and 15 of HPV18. Pathological test result CIN2+ was the gold standard. The sensitivity and specificity of HR-HPV for cervical precancer lesions screening were 93.75 (95%CI: 79.85-98.27) and 84.56% (95%CI: 83.26-85.77), respectively. To compared with HR-HPV, HPV16/18 had low sensitivity (65.63%, 95%CI: 48.31-79.59)and higher specificity (97.44%, 95%CI: 96.83-97.93). After age stratification by age 30 and 45, the sensitivity of HPV 16/18 was same with HR-HPV (100%, 95%CI: 34.24-100.00), the specificity of HPV 16/18 was higher than HR-HPV (98.71%, 95%CI: 96.27-99.56 vs 84.48%, 95%CI: 79.27-88.58) in<30 age group.The sensitivity of HR-HPVin 30-45 and ≥45 age group were higher than HPV16/18 (85.71%, 95%CI: 48.69-97.43 vs 71.43%, 95%CI: 35.89-91.78, 95.65%, 95%CI: 79.01-99.23 vs 60.87%, 95%CI: 40.79-77.84), but the specificity werelower than HPV16/18 (86.89%, 95%CI: 84.58-88.90 vs 98.51%, 95%CI: 97.51-99.11、83.49%, 95%CI: 81.81-85.04 vs 96.80%, 95%CI: 95.94-97.48). Conclusions: HR-HPV detection has relatively high sensitivity and specificity in cervical cancer screening. For >30 years old women, HR-HPV is more recommended in cervical cancer screening. Therefore, HR-HPV detection is an effective method for cervical cancer screening.

[The effect of booster dose vaccination 21- to 32-years after primary vaccination with hepatitis B vaccine in the population born from 1986 to 1996 in Zhengding County of Hebei Province].

Objective: Aanalysis the effect of booster one dose of hepatitis B vaccine after 21-32 years of primary immunization in Zhengding Country of Hebei Province. Methods: A total of 322 participants who were born between 1986 and 1996, received a full course of primary vaccination with plasma-derived hepatitis B vaccine (HepB), had no experience with booster vaccination, were HBsAg, anti-HBcnegative, had anti-HBs<10 mIU/ml, completed the booster and had laboratory results were enrolled between August 2017 to February 2018. A simple random method was uesd to randomly assigned 322 subjects to two groups, receiving a booster dose of HepB derived from either Saccharomyces cerevisiae ï¼»HepB (SC), (151 cases)ï¼½ or Chinese hamster ovary-derived HepB ï¼»HepB (CHO), (171 cases)ï¼½, the dose was 20 µg. Blood samples were collected 30 days after boosting and quantitatively tested for the geometric mean concentration (GMC) of anti-HBs to assess immunological effect. The related influencing factors of GMC and seroconversion rates of anti-HBs were analyzed by multiple linear regression and multivariate logistic regression models. Results: The 266 subjects (82.61%) had anti-HBs≥ 10 mIU/ml, and GMC was (131.63±12.94) mIU/ml.The seroconversion rates of anti-HBs in the anti-HBs<2.5 mIU/ml group and 2.5-10 mIU/ml group were 74.54% (161 cases) and 99.06% (105 cases), respectively (P<0.001).The seroconversion rates of anti-HBs after one dose of HepB (CHO) was higher than that of one dose of HepB (SC), the seroconversion rates were 87.13% (149 cases) and 77.48% (117 cases), respectively (P=0.023). Participants boostered with HepB (CHO) was the factor influencing the effect of strengthening immunization compared with boostered with HepB (SC), and OR (95%CI) was 1.91 (1.02-3.56) (P=0.042).Compared with anti-HBs<2.5 mIU/ml, prebooster anti-HBs was between 2.5 mIU/ml and 10 mIU/ml was the related factor of seroconversion rates of anti-HBs after booster immunization, and OR (95%CI) was 36.15 (4.91-266.02) (P<0.001). Conclusion: Participants boostered withone dose of HepB had a good immune response. Pre-booster anti-HBs concentration and a variety of vaccine were related factors of immune response.

Application of Sequential Changes of Dural Thickness and Biomechanical Parameters in Postmortem Interval Estimation.

ABSTRACT: Objective To study the relations of the dural thickness and the biomechanical parameters with postmortem interval （PMI） of human cadavers, and to explore the feasibility of the two indexes used for PMI estimation. Methods Dural samples were collected at different postmortem intervals of 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 48 h, 60 h, 72 h, 84 h and 96 h, then fabricated into 4.0 cm×1.0 cm A and B test specimens. The thickness of the A test specimen was measured, and the biomechanical parameters, such as ultimate load, maximum force deformation, tensile strength, elastic modulus and fracture force, were measured. The regression equations of thickness, biomechanical parameters and PMI were fitted respectively, and the difference between the predicted value and actual measured value of PMI was verified by the verification group. The B test specimen was fixed with 10% neutral formaldehyde solution, then tissue sections were prepared to observe its morphological changes. Results From 6 h to 96 h after death, the dural thickness decreased gradually, the collagen fibers gradually changed from clear arrangement to mutual fusion, and the number of nuclei decreased gradually. The dural thickness, ultimate load, tensile strength, elastic modulus and fracture force decreased sequentially, among which the dural thickness, ultimate load, elastic modulus and fracture force had a correlation with PMI （P<0.05）. In the return test, the difference between the predicted value and actual measured value of PMI in the verification group had no statistical significance （P>0.05）. Conclusion The dural thickness, ultimate load, elastic modulus and fracture force change sequentially from 6 h to 96 h after death. The regression equation established by the relationship between the changes and PMI can be used for PMI estimation.

[Discussion of correlation between histogram analysis of quantitative diffusion weighted imaging and Gleason score of prostate cancer].

Objective: To discuss the correlation between histogram analysis of quantitative mono-exponential, bi-exponential and diffusion kurtosis models in diffusion weighted imaging and the Gleason score of prostate cancer, and evaluate the application value and diagnostic efficiency in identifying low and high grade prostate cancer. Methods: A total of 50 patients with histologically confirmed as prostate cancer were examined from May 2015 to May 2016 in the Second Affiliated Hospital of Soochow University using DWI performed at 3.0 T with an extended b-value range from 0 to 2 000 s/mm(2). Data were post-processed by whole tumor histogram analysis,the ROI was manually drown in DWI (b=1 000 s/mm(2)) step by step along the outline of cancer, and quantitative analysis were performed respectively by mono-exponential, bi-exponential and diffusion kurtosis models for quantification of apparent diffusion coefficients (ADCs), diffusivity D, pseudo-diffusivity D(*), perfusion fraction f, diffusion coefficients by non-Gaussian distribution (D(k)) and kurtosis coefficient (K).Then the histogram analysis was performed to get the mean, median, 25th percentile, 75th percentile, skewness and kurtosis. The correlation between histogram analysis results of these quantitative parameters and Gleason score of prostate cancer were evaluated by Spearman correlation coefficient. The diagnostic performance of histogram analysis results of each quantitative parameters in identifying low (Gleason score≤6) and high (Gleason score>6) grade prostate cancer was performed by comparing the area under the ROC curve and the curve values. Results: The values of ADC, D and D(k) (mean, median, 25th, 75th) were negatively correlated with Gleason score of prostate cancer (r value was -0.388--0.624, P<0.05). The values of D (skewness and kurtosis) had a certain correlation with Gleason score of prostate cancer (r value were 0.413 and 0.402, P<0.05). The histogram analysis results of D(*) and f had no statistically significant correlation with Gleason score of prostate cancer (P>0.05). The values of K (mean, median, 25th, kurtosis) were positively correlated with Gleason score of prostate cancer (r value was 0.423-0.699,P<0.05). The diagnostic efficiency of histogram analysis results of these quantitative parameter values in identifying low and high grade prostate cancer showed that the ADC (median), D (25th), D(k) (mean) and K (25th) had a larger area under the curve, and were 0.844, 0.873, 0.815, and 0.919 respectively, the differences of area under the curve between any two of these parameters above were not statistically significant (all P>0.05). Conclusions: The quantitative parameters of three diffusion models (ADC, D, D(k), K) in DWI are all related to the Gleason score of prostate cancer, but in the differential diagnosis of low and high grade prostate cancer, the diagnostic efficacy of mono-exponential model is sufficient. The more complex model such as bi-exponential and diffusion kurtosis may complement it in other ways.

[Efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio in patients with diffuse large B-cell lymphoma].

Objective: To investigate the efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio (LMR) in patients with diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of 261 patients with DLBCL in the Affiliated Cancer Hospital of Zhengzhou University between March 2012 to March 2018, were analyzed retrospectively. The optimal cut-off values of LMR was determined using the receiver operating characteristic curve (ROC) method. Patients were divided into low LMR group and high LMR group according to the optimal cut-off value. The changes of LMR before and after treatment in two groups were dynamically monitored, and the relationship between LMR and efficacy and survival were analyzed. Results: Complete remission (CR) rate in patients with high LMR (64.7%) before treatment was significantly higher than that in patients with low LMR (33.3%) (P<0.05). Compared with the 5-year overall survival(OS) and progress free survival(PFS) (56.96% and 43.55%, respectively) in the low LMR group, the 5-year OS and PFS (82.92% and 66.25%, respectively) in the high LMR group were higher, and the difference was statistically significant (all P<0.05). Patients with elevated LMR after treatment in the high or low LMR group had a significant higher 5-year OS and PFS compared with patients with LMR reduction(P<0.05). LMR in both high and low LMR group were significantly lower at the last follow-up than those at the disease recurrence (all P<0.05). Both single and multivariate analyses showed that low LMR was an independent prognostic factor in patients with DLBCL (all P<0.05). Conclusions: LMR can be used as an indicator of risk stratification, efficacy, disease replase and prognosis in patients with DLBCL. Low LMR before and after treatment were poor prognostic factors in patients with DLBCL.

[Status of non-steroidal anti-inflammatory drugs use in areas with a high incidence of upper gastrointestinal cancer in China: a multi-center cross-sectional survey].

Objective: To describe the status of non-steroidal anti-inflammatory drugs (NSAIDs) use in areas with a high incidence of upper gastrointestinal cancer in China. Methods: This study was based on the National Key Research and Development Program of "National Precision Medicine Cohort of Esophageal Cancer" and "Study on Identification and Prevention of High-risk Populations of Gastrointestinal Malignancies (Esophageal cancer, Gastric cancer and Colorectal cancer)" . From January 2017 to August 2018, 212 villages or communities with a high incidence of esophageal cancer or gastric cancer were selected from 12 regions in 6 provinces. A total of 35 910 residents aged between 40 and 69 years old who met the inclusion criteria and signed the informed consent were investigated and enrolled in this study. The use of NSAIDs, demographic characteristics, health-related habits, height, weight, and blood pressure were collected by the questionnaire and physical examination. The status of main NSAIDs (aspirin, acetaminophen and ibuprofen) use with the difference varying in genders, age groups and regions were analyzed by using χ(2) test and Cochran-Armitage trend analysis method. Results: Of 35 910 subjects, the mean age was (54.6±7.1) years old and males accounted for 43.42% (15 591). The overall prevalence of NSAIDs intake was 4.56% (1 638), but it significantly varied in different provinces (P<0.001). The overall prevalence of NSAIDs intake was 4.87% (1 750) in females, which was significantly higher than that in males 4.24% (1 524) (P<0.001). The prevalence of NSAIDs intake increased with age (P for trend <0.001). As the frequency of NSAIDs intake increased, the incidence of gastrointestinal symptoms, gastrointestinal ulcers and black stools increased (P for trend <0.05 for all). Conclusion: The use of NSAIDs is prevalent in some areas with a high incidence of upper gastrointestinal cancer in China. The increased use of NSAIDs may lead to more adverse effects related to the gastrointestinal tract.

[Diffuse pulmonary meningotheliomatosis: a case report and literature review].

Objective: To analyze the clinical features, diagnosis and differential diagnosis of diffuse pulmonary meningotheliomatosis (DPM), a rare subtype of minute pulmonary meningothelial-like nodules (MPMN), so as to improve the understanding of this disorder. Methods: The clinical data of a patient diagnosed as DPM admitted in department of Respiratory Medicine, Peking University Third Hospital in August 2016 were reported and the related literatures were reviewed. With "pulmonary meningothelial-like nodules" , "minute pulmonary meningothelial-like nodules" or "diffuse pulmonary meningotheliomatosis" as the search terms, and the search time before November 1st 2017 for Wanfangdata, China National Knowledge Infrastructure (CNKI), and PubMed.Twenty-five articles were retrieved, among which 6 English (all case reports) articles were found with the search term "diffuse pulmonary meningotheliomatosis" involving 10 cases, and the other 19 articles (1 Chinese, 18 English) about MPMN mainly discussed non-DPM cases,including 13 case reports and 6 pathological/genetic studies. Results: A 68-year old female was admitted to the hospital because of intermittent cough and expectoration for more than 3 years and aggravation for 3 weeks. Her pulmonary CT showed diffuse minute nodules distributed randomly throughout both lungs, and did not improve after treatment with oral Moxifloxacin for 2 weeks. A video-assisted thoracoscopic biopsy was performed. The specimens showed MPMN and no other lesions, which confirmed the final diagnosis of DPM. She was followed without any medication therapy and her pulmonary CT showed stabilization of the lesions one year later. DPM was considered as a rare type of MPMN. A total of 11 cases were analyzed, including 10 cases reported in the literature. The patients included 1man and 10 women, aged 51 to 75 years, with an average age of (64±8) years. Among the 11 patients, 8 denied a history of smoking or of occupational exposure, 7 presented with dyspnea, shortness of breath, or fatigue, and 8 had mild abnormalities of pulmonary function test. The pulmonary CT of all the patients showed randomly distributed, diffuse bilateral small solid or ground-glass nodules, with the diameters less than 5 millimeters, some of which were cavitated. Only 1 patient had pulmonary thromboembolism, while the other 10 did not have any other lung diseases. All the patients were histologically diagnosed, 8 by open lung biopsies, 2 by transbronchial lung biopsy, and 1 by CT-guided fine needle aspiration. Three patients were followed for 12-92 months and the lung lesions were all stable. Conclusions: As a rare subtype of MPMN, DPM lacks specificity of clinical manifestations, and presents with diffuse bilateral small solid or ground-glass nodules, distributed randomly throughout both lungs. An early correct diagnosis depends on biopsy.

[Airway inflammation and small airway wall remodeling in neutrophilic asthma].

OBJECTIVE: To investigate the distribution of airway inflammation phenotype in patients with bronchial asthma (asthma), and to analyze clinical characteristics, inflammatory cytokines, pulmonary small vessels remodeling and small airway wall remodeling in patients with neutrophilic asthma. METHODS: Sixty-three patients with asthma were enrolled from January 2015 to December 2015 in Peking University Third Hospital. Clinical data including gender, age, body mass index (BMI), pulmonary function tests (PFTs), asthma control test (ACT) were recorded. All the patients underwent sputum induction. The cellular composition of the sputum was evaluatedand the concentration of active MMP-9 in the sputum tested. Blood routine tests were done and the concentration of IgE, periostin, and TGF-beta1 levels were measured in serum by enzyme-linked immunosorbent assay (ELISA). Small airway wall remodeling was measured in computed tomography (CT) scans, as the luminal diameter, luminal area, wall thickness and wall area % adjusted by body surface area (BSA) at the end of the 6th generation airway, in which the inner diameter was less than 2 mm. Small vascular alterations were measured by cross-sectional area (CSA), and the total vessel CSA < 5 mm2 was calculated using imaging software. RESULTS: The distributions of airway inflammatory phenotypes of the asthmatic patients were as follows: neutrophilic asthma (34.9%, 22/63), eosinophilic asthma (34.9%, 22/63), mixed granulocytic asthma (23.8%, 15/63), and paucigranulocytic asthma (6.3%, 4/63). The neutrophilic subtype patients had a significantly higher active MMP-9 level in sputum compared with the eosinophilic phenotypepatuents, as 179.1 (74.3, 395.5) vs. 50.5 (9.7, 225.8), P<0.05. Sputum neutrophil count was negatively correlated with FEV1%pred (r=-0.304,P<0.05), and positively correlated with active MMP-9 level in sputum (r=-0.304, P<0.05), and positive correlation trend with airway wall thickness (r=0.533, P=0.06). There was a significantly negative correlation of active MMP-9 level in sputum with FEV1%pred (r=-0.281, P<0.05), in positive correlation with small airway wall area (%)(r=0.612, P<0.05), and inpositive correlation trend with airway wall thickness (r=0.612, P=0.06). Neutrophils count in peripheral blood was positively correlated with neutrophil counts in sputum. CONCLUSION: Neutrophil count in airway is related to lung function in asthmatic patients. Neutrophils may accelerate small airway wall remodeling through the release of active MMP-9. Neutrophil count in peripheral blood is related to neutrophils count in sputum, which may be used as a substitute for evaluating inflammatory phenotype.

[Correlation of CT small airway measurement with clinical and inflammation factors in asthma patients].

Objective: To evaluate the correlation of CT small airway measurement with clinical and inflammatory factors in asthma patients. Methods: From November 2014 to December 2015, a total of 20 patients with asthma were recruited in outpatient department of Peking University Third Hospital. All underwent asthma control test (ACT), CT and pulmonary function test. Serum leptin, immunoglobulin E(IgE) and transforming growth factor-ß1(TGF-ß1), induced sputum eosinophil percentage(Eos%) and matrix metalloproteinase(MMP-9) results were collected.Using GE airway analysis software and adjusted by body surface area, luminal diameter(LD(adjusted)), luminal area(Ai(adjusted)), wall thickness(WT(adjusted)) and wall area%(WA%)at the end of 6th generation airway were recorded. Results: In asthma patients with smoking history, both LD(adjusted) and Ai(adjusted) were significantly lower than patients without smoking history(LD(adjutsed) (1.19±0.14)vs(1.34±0.11) mm, Ai(adjusted) (1.13±0.32) vs (1.43±0.24) mm(2,) t=-2.459, -2.267, all P<0.05); in asthma patients with induced sputum Eos%≥3%, both LD(adjusted) and Ai(adjusted) were significantly lower but WA% significantly higher than patients with induced sputum Eos%<3% (LD(adjutsed) (1.26±0.05) vs (1.44±0.09) mm, Ai(adjusted)(1.27±0.11) vs (1.66±0.17) mm(2,) WA%(83.96%±1.26%) vs (81.20%±2.26%), t=-3.935, -4.492, 2.448, all P<0.05). LD(adjutsed) and Ai(adjusted) had negative correlation with course of disease and induced sputum Eos%(LD(adjutsed) r=-0.512, -0.841, Ai(adjusted) r=-0.489, -0.841, all P<0.05), and positive correlation with FEV(1)/FVC and serum leptin(LD(adjutsed) r=0.669, 0.533, Ai(adjusted) r=0.681, 0.552, all P<0.05). Ai(adjusted) also showed positive correlation with FEV(1)%(r=0.452, P<0.05). WT(adjusted) and WA% were significantly negative correlated with FEV(1)/FVC and FEV(1)%(WT(adjusted) r=-0.621, -0.483, WA% r=-0.729, -0.548, all P<0.05). WA% also showed positive correlation with serum IgE and induced sputum MMP-9(r=0.509, 0.636, all P<0.05). CT airway indexes showed no significantly correlation with age, ACT scores and serum TGF-ß1. Conclusions: CT airway indexes are found partially associated with course of disease, smoking history, serum leptin and IgE, induced sputum Eos% and MMP-9. CT airway indexes show correlation with FEV(1)/FVC and FEV(1)%.

[Preliminary applicability evaluation of Prostate Imaging Reporting and Data System version 2 diagnostic score in 3.0T multi-parameters magnetic resonance imaging combined with prostate specific antigen density for prostate cancer].

Objective: To investigate the preliminary applicability of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score in the condition of 3.0T multi-parametric magnetic resonance imaging (Mp-MRI) combined with clinical classic indicators for the diagnosis of prostate cancer (PCa). Methods: The clinical and MRI materials of 247 patients of suspicious prostate disease treated in Second Affiliated Hospital of Soochow University from June 2015 to November 2016 were analyzed retrospectively, including 110 cases with PCa and 137 cases without cancer.All cases underwent the high-resolution axial T(2)-weighted imaging (T(2)WI), diffusion weighted imaging (DWI) and dynamic contrast enhancement-magnetic resonance imaging (DCE-MRI) and were confirmed pathologically by puncture biopsies.The Mp-MRI materials of all cases were scored according to PI-RADS v2.The prostate volume and prostate specific antigen (PSA) density (PSAD) value were calculated according to the formulas.The univariate and multivariate analysis were performed for the observed indicators (age, prostate volume, PSA, PSAD and PI-RADS v2 score) to determine the independent predictors for PCa.Then, a Logistic regression model (combined prediction model) was established by the independent predictors for combined diagnosis of PCa.The receiver operating characteristic curve (ROC) curve analysis was performed to get the sensitivity and specificity of each independent predictor and the model to diagnose PCa.The differences of AUC values of each independent predictor and the model were compared with each other to evaluate the diagnostic performance for PCa. Results: The differences in the age, prostate volume, PSA, PSAD and the PI-RADS v2 score between patients with PCa and non-cancer group were all statistically significant (t=2.870, Z=-4.230, -7.787, -9.477, -10.826, all P<0.05). The PSAD and PI-RADS v2 score were independent predictors for PCa (OR=3.331, 10.546, both P<0.05). The Logistic regression combined prediction model by PI-RADS v2 score and PSAD to forecast PCa was Logit(P)=-5.097+ 2.309×PSAD+ 1.214×PI-RADS v2 score.The area under the curve (AUC) of ROC in the combined model (0.911) was higher than that in the PI-RADS v2 score (0.886) and PSAD (0.851) and the differences were all statistically significant (Z=2.416, 2.716, both P<0.05); but the difference in the AUC value between PI-RADS v2 score and PSAD was not statistically significant (Z=1.191, P=0.234). The diagnostic sensitivity of PSAD, PI-RADS v2 score and the model were: 0.891, 0.782 and 0.855, respectively; the specificity were 0.449, 0.912 and 0.847, respectively on their positive thresholds (0.15 µg·L(-1)·ml(-1,) 4 and -0.82). Conclusion: PI-RADS v2 score combined with PSAD in diagnosing PCa is superior to the single application of them and it can lead to high diagnostic sensitivity and specificity for PCa.

[Clinical significance of targeting drug-based molecular biomarkers expression in ovarian clear cell carcinoma].

Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues. Results: The positive rates of EGFR, HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs 35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40) vs 17% (4/23) , and there were no significant differences between primary and recurrent OCCC (all P>0.05). χ(2)-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance (P<0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC (4 months vs 10 months, log-rank test, P<0.05 for HER2; and 4 months vs 10 months, P<0.05 for AURKA); and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P<0.05 for HER2; and 13 months vs 43 months, P<0.05 for AURKA). However, multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC (P>0.05). Conclusion: HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

Oxaliplatin-rapamycin combination was superior to mono-drug in treatment of hepatocellular carcinoma both in vitro and in vivo.

The presented study aimed to investigate the antitumor efficacy of combination of oxaliplatin with rapamycin, an mTOR inhibitor, in hepatocellular carcinoma (HCC). The activation status of mTOR pathway was first examined in HCC cell lines HepG2, BEL7402, and HuH7 using Western blotting. Effects of rapamycin, oxaliplatin, and their combination on the proliferation of HCC cells were determined in vitro using MTT assay and in vivo using a nude mice model bearing HepG2 xenografts. Drug-induced cell apoptosis was examined by flow cytometry. Expression of apoptosis-related protein was determined by Western blotting. We observed that mTOR pathway was activated in all three cell lines used in the current study. MTT assay demonstrated that oxaliplatin in combination with rapamycin synergistically inhibited the proliferation of HCC cells. The combination regimen reduced terminal tumor burden more efficiently than the corresponding monotherapy. The percentages of apoptotic cells and the expression levels of apoptosis-related proteins including cleaved caspase-9, -3, and PARP were significantly higher in combination-treatment groups than those in mono-drug-treatment groups. The ratios of Bax/Bcl-2 in cells exposed to both oxaliplatin and rapamycin were significantly increased compared to those in cells subjected to oxaliplatin or rapamycin alone treatment. Results obtained in the presented study suggested that combination of oxaliplatin and rapamycin was superior to mono-drug and may have a potential value in treatment of HCC.

Study on quality standards for Chimonanthus nitens.

Chimonanthus nitens Oliv. is a commonly used traditional Chinese medicine. Terpenoids, flavonoids, and coumarins are usually considered its main bioactive ingredients. Thus, qualitative and quantitative analyses of these compounds are crucial in quality control studies of Chimonanthus nitens. In this study, five compounds were identified by double-development thin layer chromatography (TLC) and the content of four compounds was determined by high performance liquid chromatography; the detection wavelength was set to 344 nm and the column temperature was 40°C. All calibration curves showed good linear regression (R2 > 0.9995). The average recoveries ranged from 97.06 to 104.44%. The RSD was below 4.2%. Four compounds remained stable over 24 h and the relative standard deviation (RSD) of the precision of their measurement was less than 1.5%. The developed method was reproducible, sensitive, and simple, and could be used for quality control of Chimonanthus nitens.