Effect and mechanism of recombinant human fibroblast growth factor 18 on osteoporosis in OVX mice.

OBJECTIVES: This study aimed to investigate the effect and the mechanism of recombinant human fibroblast growth factor 18 (rhFGF18) on postmenopausal osteoporosis. METHODS: The effect of rhFGF18 on the proliferation and apoptosis of osteoblasts and the mechanism underlying such an effect was evaluated using an oxidative stress model of the MC3T3-E1 cell line. Furthermore, ovariectomy was performed on ICR mice to imitate estrogen-deficiency postmenopausal osteoporosis. Bone metabolism and bone morphological parameters in the ovariectomized (OVX) mice were evaluated. RESULTS: The results obtained from the cell model showed that FGF18 promoted MC3T3-E1 cell proliferation by activating the extracellular signal-regulated kinase (ERK) and p38 instead of c-Jun N-terminal kinase (JNK). FGF18 also prevented cells from damage inflicted by oxidative stress via inhibition of apoptosis. After FGF18 administration, the expression level of anti-apoptotic protein Bcl-2 in the mice was upregulated, whereas those of the pro-apoptotic proteins Bax and caspase-3 were downregulated. Administering FGF18 also improved bone metabolism and bone morphological parameters in OVX mice. CONCLUSIONS: FGF18 could effectively prevent bone loss in OVX mice by enhancing osteoblastogenesis and protecting osteoblasts from oxidative stress-induced apoptosis.

[Value of (18)F-FDG PET-CT imaging to predict epidermal growth factor receptor mutations in patients with lung squamous cell carcinoma].

Objective: To investigate the value of (18)F-fluorodeoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT) in predicting the epidermal growth factor receptor (EGFR) mutations in patients with lung squamous cell carcinoma. Methods: We retrospectively analyzed the clinical data and (18)F-FDG PET-CT imaging data of 206 patients with lung squamous cell carcinoma confirmed by pathology and underwent EGFR mutation test in the First Affiliated Hospital of Nanjing Medical University from June 2013 to October 2018. Receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of maximum standard uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG). The Chi-squared test was used to assess the difference in PET parameters. A multivariate Logistic regression analysis was performed to yield the parameters with statistic difference. Results: All of 206 patients with lung squamous cell carcinoma showed a high (18)F-FDG uptake. The median of SUV(max), MTV and TLG were 19.14, 37.69 cm(3) and 291.73, respectively. Among the 206 patients, EGFR mutations were identified in 14 cases, including 7 with exon 21 (L858R) mutation, 6 with exon 19 mutation and 1 with exon 20 mutation. ROC curve showed that the AUC of SUV(max), MTV and TLG were 0.624 (95% CI=0.454-0.794, P=0.122), 0.892 (95% CI=0.811-0.973, P<0.001) and 0.860 (95% CI=0.768-0.952, P<0.001), respectively. The median SUV(max) (19.14) was used as the cutoff points due to the small value of AUC. The cutoff point of MTV was 20.09 cm(3), the cutoff point of TLG was 211.07. Univariate analysis showed that the sex, smoking history, M stage, MTV and TLG were associated with EGFR mutations (all P<0.05). Logistic multivariate analysis showed that the sex, smoking history and TLG were the independent predictors of EGFR mutation (all P<0.05). Conclusion: TLG detected by (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung squamous cell carcinoma, and has certain reference value for predicting EGFR mutation.

[Prognostic value of bone marrow (18)F-FDG uptake pattern of pretreatment PET-CT in extranodal NK/T cell lymphoma].

Objective: To investigate the prognostic value of bone marrow (BM) (18)F-fluorodeoxyglucose ((18)F-FDG) uptake pattern of pretreatment positron emission tomography/computed tomography (PET-CT) in extranodal NK/T cell lymphoma (ENKTL) patients. Methods: We retrospectively collected clinical data from a series of 63 ENKTL patients with stageⅡ~Ⅳ, who have received both (18)F-FDG PET-CT and bone marrow biopsy (BMB) prior to treatment. According the BM (18)F-FDG uptake pattern of PET-CT, the patients were divided into three groups: focal BM FDG uptake higher than liver (fPET+ ), diffuse BM uptake higher than liver (dPET+ ) and normal BM uptake (lower than liver) (nPET). The Kaplan-Meier method and Log-rank test were respectively used for survival analysis and univariate analysis, and COX proportional hazards model for multivariate analysis. Results: Among the 63 patients, 22 patients had nPET, 24 patients showed dPET+ , and 17 patients had fPET+ . BMB positive was found in 8 patients, and negative in 55 patients. Thirty-seven patients had disease progression or relapse, and 31 patients died. The 3-years progression free survival (3y-PFS) rates of fPET+ patients and nPET patients were 14.7% and 63.6% (P=0.006). The 3-years overall survival (3y-OS) rates were 18.8% and 64.8% (P=0.005). The 3y-PFS of dPET+ patients and nPET patients were 35.6% and 63.6% (P=0.161), 3y-OS were 47.9% and 64.8% (P=0.280). Univariate analysis showed that lactate dehydrogenase (LDH) level, Epstein-Barr virus DNA (EBV-DNA), Korean prognostic index (KPI) and BM (18)F-FDG were related with PFS and OS (all P<0.05). Multivariate analysis showed EBV-DNA and BM (18)F-FDG were independent predictors for PFS (P<0.05). EBV-DNA was also an independently predictor for OS (P<0.05). Conclusions: PET/CT-directed BM patterns are meaningful in predicting prognosis of newly diagnosed ENKTL patients. Focal BM (18)F-FDG uptake pattern is an independent predictor for PFS.

[(18)F-fluorodeoxy glucose positron emission tomography/computed tomography manifestation and clinical characteristics of primary salivary gland-type lung cancer].

Objective: To explore the imaging manifestation and clinical characteristics of primary salivary gland-type lung cancer using (18)F-fluorodeoxy glucose ((18)F-FDG) positron emission tomography/computed tomography (PET-CT). Methods: From March 2009 to January 2017, 12 patients with pathologically confirmed primary salivary gland-type lung cancer were enrolled in First Affiliated Hospital of Nanjing Medical University. Their images and clinicopathological data were retrospectively analyzed. Results: Six out of 12 patients had mucoepidermoid carcinoma (MEC), and the other six patients had adenoid cystic carcinoma (ACC). Five MEC were located in the main bronchus, and the other one was in segmental bronchus. Intrabronchial nodule or mass with smooth or lobulated margin and calcification(n=3) was the main (18)F-FDG PET-CT features of MEC. Two ACC involved trachea, two involved the main bronchi, and the other two involved lobular bronchi. The main (18)F-FDG PET-CT features of ACC were diffuse or circumferential irregular thickness of the bronchial wall, distorted lumen, and the longitudinal extent of the tumor was greater than its transverse axis. The (18)F-FDG uptake of all lesions was increased in varying degree. The median (25th percentile, 75th percentile) value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were 5.1(3.1, 8.1), 5.7(1.2, 21.4)cm(3) and 18.6(0.6, 93.7), respectively. All of them were related to pathological grading and nodal tumor involvement( all P<0.05), but not associated with tumor location or pathological type( all P>0.05). MTV and TLG were also related to clinical stage( all P<0.05). Tumor size was correlated with MTV, TLG of primary lesions(r=0.607, P=0.036; r=0.579, P=0.049), but not with SUVmax(r=0.568, P=0.054). Conclusions: Primary salivary gland-type lung cancer mainly occurs in segmental bronchus. The MTV and TLG of the tumor calculated by (18)F-FDG PET-CT are correlated with clinicopathological characteristics, and are helpful for clinical diagnosis and treatment.

[Prognostic value of pretreatment (18)F-FDG PET-CT metabolic parameters in patients with advanced extranodal NK/T cell lymphoma].

Objective: To investigate the prognostic values of the maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) calculated from pretreatment (18)F-fluorodeoxy glucose ((18)F-FDG) PET-CT results of patients with advanced extranodal NK/T cell lymphoma (ENKTL). Methods: The clinic data, follow-up data and pretreatment (18)F-FDG PET-CT data of 45 patients with ENKTL of stage Ⅳ were collected. The optimal cutoff value of progression-free survival (PFS) of SUV(max), MTV and TLG were analyzed by using receiver-operating characteristic (ROC) curve. The Kaplan-Meier method, Log-rank test and COX proportional hazards model were used for survival analysis, univariate analysis and multivariate analysis, respectively. Results: The median SUV(max), MTV and TLG of 45 ENKTL patients were 17.98, 70.18 and 755.42, respectively. ROC curve showed that the area under the curve (AUC) of SUV(max), MTV and TLG were 0.504 (P=0.970), 0.868 (P<0.001) and 0.848 (P=0.001), respectively. The value of SUV(max) was too small to fit for calculating the cutoff value of AUC. The cutoff value of MTV was 42.54 (sensitivity =78.1% and specificity =84.6%), and the cutoff value of TLG was 435.15 (sensitivity=75.0% and specificity =76.9%). Univariate analysis showed that lactate dehydrogenase (LDH) level, epstein-barr virus (EBV)-DNA, Eastern Cooperative Oncology Group (ECOG) score, bone marrow, Korean prognostic index (KPI), MTV, TLG were significantly related with PFS (all P<0.05), and lactate dehydrogenase (LDH) level, EBV-DNA, ECOG score, primary tumor location, KPI, MTV, TLG were significantly related with overall survival (OS) (all P<0.05). Multivariate analysis showed that KPI, MTV and TLG were independent prognostic predictors of PFS and OS (all P<0.05). Conclusions: MTV and TLG of pretreatment (18)F-FDG PET-CT are independent prognostic factors for PFS and OS of patients with advanced ENKTL. MTV and TLG may be more fit for evaluating the prognosis of ENKTL patients than SUV(max).

[Prognostic value of pretreatment (18)F-FDG PET-CT for patients with advanced diffuse large B-cell lymphoma].

Objective: To investigate the prognostic value of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by pretreatment (18)F-FDG PET-CT in patients with stage Ⅲ~Ⅳ diffuse large B-cell lymphoma (DLBCL). Methods: Clinical data of 72 DLBCL patients with stage Ⅲ~Ⅳ disease undergoing a pretreatment PET-CT scan were retrospectively analyzed. SUVmax, MTV and TLG values of whole-body tumor were calculated from PET-CT images with a threshold of SUVmax 40% of tumor tissues. The optimal cutoff lines of SUVmax, MTV and TLG were obtained by ROC curve analysis. The Kaplan-Meier method and Log-rank test were used to perform univariate survival analysis, while Cox proportional hazards model was done for multivariate analysis. Results: The SUVmax, MTV and TLG of 72 patients were 21.64, 139.48 cm(3) and 1 413.77, respectively. The areas under the ROC curve (AUC) of SUVmax, MTV and TLG were 0.411 (95%CI=0.279~0.544, P=0.195), 0.688 (95%CI=0.566~0.811, P=0.006) and 0.526 (95%CI= 0.469~0.672, P=0.123), respectively. The median SUVmax (21.64) and TLG(1 413.77) were used as the cutoff lines due to smaller AUC. The cutoff point of MTV was 69.71 cm(3). For DLBCL patients of stage Ⅲ~Ⅳ disease, univariate analysis showed that SUVmax and TLG were not associated with the progression-free survival (PFS) and overall survival (OS) (P>0.05 for all). Multivariate analysis showed that National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) but not MTV was the independent prognostic predictor of PFS and OS (P<0.05 for all). And MTV was not the independent prognostic factor of PFS and OS for stage Ⅲ DLBCL (P>0.05 for all). Conclusions: For DLBCL patients with stage Ⅲ~Ⅳ disease, the prognostic value of SUVmax, MTV and TLG before treatment initiation are undetermined, and these indices cannot be used to predict the prognosis.

[Prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in extensive-stage small cell lung cancer].

Objective: To investigated the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in extensive-stage small cell lung cancer (ES -SCLC). Methods: Fifty-five patients with ES-SCLC who underwent pretreatment (18)F-FDG PET-CT were retrospectively recruited in this study. The correlations of maximum standardized uptake value (SUVmax) of primary lesion, metabolic tumor volume (MTV) of primary lesion (MTVp), total lesion glycolysis (TLG) of primary lesion (TLGp), the highest SUVmax of all lesions, the sum of metabolic volume (MTV sum), the sum of total lesions glycolysis (TLGsum) and clinical factors were analyzed. Results: The SUVmax, MTVp, TLGp, the highest SUVmax, MTVsum and TLGsum of 55 patients were 11.34±7.02, 29.61 cm(3,) 207.72, 13.61±7.10, 123.57 cm(3) and 988.48, respectively. The SUVmax of primary lesion, MTVp and TLGp were correlated with tumor type and the maximal tumor length, respectively(all P<0.05). The correlations were also found between MTVp, TLGp and hydrothorax, respectively(both P<0.05). MTVsum and TLGsum were correlated with number of lesions, hydrothorax, LDH, hemoglobin and ECOG, respectively(all P<0.05). The association was also found between TLGsum and the maximal tumor length (P=0.039). 51 patients were progressive or recurrent with the median 6.9 months of progression free survival (PFS); and 50 patients were died with the median 11.7 months of overall survival (OS). Univariate analysis showed that MTVsum, TLGsum, number of lesions, ECOG, live metastasis, bone metastasis, the cycle of chemotherapy and thoracic radiation therapy were all associated with PFS and OS (all P<0.05); LDH and hemoglobin were only associated with PFS(both P<0.05). Multivariate analysis demonstrated that LDH, ECOG, live metastasis, the cycle of chemotherapy, MTVsum, TLGsum were the independent predictors of PFS (all P<0.05); and ECOG and TLG sum were the independent predictors of OS (all P<0.05). Conclusions: (18)F-FDG PET-CT has certain prognostic value of patients with ES-SCLC. MTVsum and TLGsum are the independent predictors of PFS, and TLGsum is also an independent predictor of OS.

[The relationship between (18)F-FDG PET/CT metabolic parameters and clinicopathological features of breast cancer].

Objective: To investigate the relationship between metabolic parameters of primary lesion and clinicopathological features of patients with breast cancer. Methods: Clinical data of 78 patients with breast cancer undergone (18)F-FDG PET/CT before surgery was retrospectively analyzed. SUVmax, SUVmean and metabolic tumor volume (MTV) of primary lesions were measured by horizontal, sagittal and coronal position volume section with a threshold of 40% SUVmax. TLG was calculated and the highest SUVmax among metastatic lymph nodes was measured. Results: SUVmax, SUVmean, MTV, TLG and the maximum diameter of 78 primary lesions were 6.64(1.85, 22.79), 3.88(1.30, 11.42), 13.36(1.66, 129.08)cm(3,) 47.92(2.85, 443.28)g and 2.35(1.23, 9.80)cm, respectively. SUVmax of metastatic lymph node was 5.12(2.38, 14.32). There were statistically significant differences of primary lesion metabolic parameters (SUVmax, MTV, TLG) in different pathological stages, T stages, with or without lymph node invasion (all P<0.05). Only TLG of ER negative patients was higher than that of ER positive patients (P<0.05). TLG, MTV of PR negative patients were higher than that of PR positive patients (both P<0.05). No significant differences of metabolic parameters were found between HER-2 negative and positive patients (all P>0.05). SUVmax, MTV, TLG of primary lesion were positively associated with Ki-67 and the maximum diameter (all P<0.05), and the correlation coefficient of TLG was the highest. SUVmax, SUVmean, MTV and TLG were all positively associated with T stage (all P<0.05), and the correlation coefficient of TLG was the highest. None of the parameters had correlation with N stage(all P>0.05). Only TLG had positive correlation with clinical stage (P<0.05). SUVmax of metastatic lymph node was positively associated with metabolic parameters of primary lesion, T stage and clinical stage, respectively (all P<0.05). Conclusions: (18)F-FDG PET/CT metabolic parameters, especially TLG has the highest correlation with clinicopathological features of breast cancer. SUVmax of metastatic lymph node was positively associated with metabolic parameters of primary lesion and clinical stage.

[Evaluate the value of (18)F-FDG PET-CT imaging in predicting the mutationsin epidermal growth factor receptor in lung adenocarcinoma].

Objective: To investigate the value of maximum Standardized Uptake Value(SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) calculated from (18)F-FDG PET-CT in predicting the presence of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. Methods: We retrospectively reviewed 137 lung adenocarcinoma patients with EGFR mutations testing and pretreatment (18)F-FDG PET-CT. Receiver Operating Characteristic (ROC) curve analysis was performed to quantify the predictive value of SUVmax、MTV、TLG. A multivariate logistic regression analysis was used to evaluate the predictive value of EGFR mutation. Results: Among 137 lung adenocarcinoma patients, 86(62.8%, 86/137) were identified with EGFR mutations. The SUVmax, MTV and TLG were 7.4, 5.28 cm(3,) 20.20, respectively. The optimal cut-off values of SUVmax, MTV and TLG were 7.99(AUC=0.658, 95% CI=0.566~0.752, P=0.002), 6.09 cm(3)(AUC=0.644, 95% CI=0.550~0.737, P=0.005), 35.08(AUC=0.650, 95% CI= 0.557~0.744, P=0.003), respectively. Multivariate analysis showed that TLG and smoking status were the most significant predictors of EGFR mutation(all P<0.05). Conclusion: TLG in (18)F-FDG PET/CT is an independent factor for predicting EGFR mutation in patients with lung adenocarcinoma, and has certain reference value for predicting EGFR mutation.

[Investigation of the cognition and behavior on drug safety in Beijing middle school students].

OBJECTIVE: To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. METHODS: A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. RESULTS: Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, P<0.001). Both the awareness rates and the drug safety behavior scores were statistically different among the students in different regions, different school types and different residence types (P<0.001). Multiple factors analysis demonstrated the correlation between the cognition degrees of both drug safety knowledge, behavior and the above factors. Of all the students, 80.4% agreed that any drug could have adverse drug reactions; 40.5% were aware that antibiotics couldn't kill viruses; as many as 49.6% mistook aspirin as antibiotic; 97.4% would read drug instructions before taking them; Only 42.4% put expired drugs into special recycling bins; 49.8% would deviate from the suggested dosage and frequency of their medication when they were sick with common diseases. CONCLUSION: Overall, the cognition of drug safety in Beijing middle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.

[Developing process of guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019)].

Pharmacoepidemiology refers to the use of epidemiological research methods in studying the application and use of drugs in large populations to evaluate the safety and efficacy of medical products. Therefore, standardized pharmacoepidemiology research is the basis of the above work. Based on systematic reviews of national and international pharmacoepidemiological methodological standards and guidelines, and in combination with Chinese medical and health practice and experts' opinions, the Professional Committee of Pharmacoepidemiology of Chinese Pharmaceutical Association developed the group standard, guide on methodological standards in pharmacoepidemiology (T/CPHARMA 002-2019), to better guide the work of pharmacoepidemiology. The guideline was designed to provide advice and reference for pharmacoepidemiology research by government, regulatory agencies, research institutions, and pharmaceutical manufacturers in China.

[How to write high-quality epidemiological research paper â ¥. Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut)].

Concerns have been raised about the reporting quality in nutritional epidemiology. Therefore, strengthening the reporting of observational studies in epidemiology-nutritional epidemiology (STROBE-nut) has been proposed by extending the STROBE statement to include additional recommendations on issues related to nutritional epidemiology and dietary assessment, aiming to provide more specific guidelines on how to report observational research in the field. This paper presents a brief introduction to STROBE-nut and also an explanation of the key points in the additional items, with an example illustrating the application of the checklist.

Mortality among benzene-exposed workers in China.

A large cohort of 74,828 benzene-exposed and 35,805 nonexposed workers employed between 1972 and 1987 in 12 cities in China was followed to determine mortality from all causes. Benzene-exposed study subjects were employed in a variety of occupations including coating applications, and rubber, chemical, and shoe production. Mortality was slightly increased among workers with greater cumulative exposure to benzene (ptrend < 0.05), but this excess was largely due to cancer deaths (ptrend < 0.01). Deaths due to lymphatic and hematopoietic malignancies (ptrend = 0.01) and lung cancer (ptrend = 0.01) increased with increasing cumulative exposure to benzene. Investigations continue to relate benzene exposure to specific lymphatic and hematopoietic malignancies and other causes of death.

A cohort study of cancer among benzene-exposed workers in China: overall results.

A large cohort study of 74,828 benzene-exposed and 35,805 unexposed workers employed between 1972 and 1987 in 12 cities in China were followed to determine mortality from all causes and the incidence of lymphohematopoietic malignancies and other hematologic disorders. Benzene-exposed study subjects were employed in a variety of occupations, including painting, printing, and the manufacture of footwear, paint, and other chemicals. All-cause mortality was similar in the benzene-exposed and unexposed comparison group. Statistically significant excess deaths were noted among benzene-exposed subjects for leukemia (RR = 2.3, 95% CP 1.1-5.0), malignant lymphoma (RR = 4.5, 95% CI: 1.3-28.4), and nonneoplastic diseases of the blood (RR = 95% CP 2.5-infinity), and a marginally significant excess was noted for lung cancer (RR = 1.4, 95% CI: 1.0-2.0). Risk was significantly elevated for the incidence of all lymphohematopoietic malignancies (RR = 2.6, 95% CI: 1.5-5.0), malignant lymphoma (RR = 3.5, 95% CI: 1.2-14.9), and leukemia (RR = 2.6, 95% CI.. 1.3-5.7). Among the leukemia subtypes, only acute myelogenous leukemia (AML) incidence was significantly elevated (RR = 3.1, 95% CI: 1.2-10.7), although nonsignificant excesses were also noted for chronic myelogenous leukemia (CML) (RR = 2.6, 95% CI: 0.7-16.9) and lymphocytic leukemias (RR = 2.8, 95% CI.. 0.5-54.5). Significant excesses were found for aplastic anemia (RR = infinity, 95% CI: 2.2-co) and myelodysplastic syndrome (RR = infinity, 95% CI: 1.7-infinity). Employment in benzene-associated occupations in China is associated with a wide spectrum of myelogenous and lymphocytic malignant diseases and related disorders. Investigations continue to assess the nature of these associations.