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Abstract Background Studies had suggested increased risk of death of residents was associated with typhoons, particularly coastal regions. However, these findings ignored the impact of inland typhoons on the health of residents, especially the indirect death risk caused by typhoons. This study aimed to investigate the acute death risk of residents during inland typhoon Lekima in Jinan, further identify vulnerable populations and areas. Methods We selected the daily death from 11 to 27th August 2019 in Jinan as case period, and conducted a time-stratified case-crossover design to match the contemporaneous data from 2016 to 2018 as control period. We used the generalized linear Poisson models to estimate the related effects of death risk during typhoon Lekima and lag days. Results During the Lekima typhoon month, there were 3,366 deaths occurred in Jinan. Compared to unexposed periods, the acute death risk of non-accidental diseases (especially circulatory diseases), female and the older adults increased significantly in the second week after the typhoon. The maximum significant effect of circulatory disease deaths, female and older adult deaths were appeared on lag9, lag9, and lag13 respectively. And the typhoon-associated RR were 1.19 (95%CI:1.05,1.34), 1.28 (95%CI:1.08,1.52), and 1.22 (95%CI:1.06,1.42) respectively. The acute death risk of residents living in TQ and CQ increased significantly on Lag2 and Lag6 after the typhoon, respectively, while those living in LX, LC, HY, JY, and SH occurred from Lag 8 to Lag 13 after the typhoon. LC lasted the longest days. Conclusions Typhoons would increase the vulnerability of residents living in Jinan which mainly occurred from the seventh day after the typhoon. Residents suffering from non-accidental diseases (circulatory diseases), female and the older adults were more vulnerable. The vulnerability of TQ and CQ occurred on Lag2 and Lag6 after typhoon Lekima, respectively, and the other areas except ZQ and PY occurred from Lag 8 to Lag 13. LC lasted the longest duration. Our findings emphasized the importance of the emergency response, which would help policymakers to identify vulnerable regions and populations accurately during typhoons and formulate the emergency response plan.

AbstractFargesia angustissima T. P. Yi, categorized into Arundinarieae (Poaceae: Bambusoideae), is a critical species endemic to Minshan Mountain, China. F. angustissima provides shelter and food sources for the giant panda and other endangered animals (e.g. red panda and snub-nosed monkey). This study assembled the complete chloroplast (cp) genome of F. angustissima using the high-throughput sequencing technique. The total cp length was 139,706 bp, containing 130 annotated genes with predicted GC content at 38.87%. The cp genome comprises two single-copy (LSC and SSC) regions, harboring 83,282 bp and 12,830 bp, respectively. The SSC regions were located between two inverted repeats (IR) regions (21,797 bp). Reconstruction of the phylogenetic tree illustrated that F. angustissima clustered F. canaliculata in Fargesia II. The study provides theoretical clues to explore the geographical distribution and species-level identification of the Fargesia genus.

Abstract 2D cell culture occupies an important place in cancer progression and drug discovery research. However, it limitedly models the “true biology” of tumors in vivo. 3D tumor culture systems can better mimic tumor characteristics for anticancer drug discovery but still maintain great challenges. Herein, polydopamine (PDA)‐modified decellularized lung scaffolds are designed and can serve as a functional biosystem to study tumor progression and anticancer drug screening, as well as mimic the tumor microenvironment. PDA‐modified scaffolds with strong hydrophilicity and excellent cell compatibility can promote cell growth and proliferation. After 96 h treatment with 5‐FU, cisplatin, and DOX, higher survival rates in PDA‐modified scaffolds are observed compared to nonmodified scaffolds and 2D systems. The E‐cadhesion formation, HIF‐1α‐mediated senescence decrease, and tumor stemness enhancement can drive drug resistance and antitumor drug screening of breast cancer cells. Moreover, there is a higher survival rate of CD45+/CD3+/CD4+/CD8+ T cells in PDA‐modified scaffolds for potential cancer immunotherapy drug screening. This PDA‐modified tumor bioplatform will supply some promising information for studying tumor progression, overcoming tumor resistance, and screening tumor immunotherapy drugs.

Automatic Identification System (AIS) can obtain a large amount of data on ship trajectories and movement characteristics, which provides data support for ship route planning, navigation safety, and maritime traffic control. Therefore, it is of great importance to analyze and cluster the AIS data to obtain an understanding of the movement behavior of ships. The Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm is capable of discovering arbitrarily shaped clusters and is suitable for clustering ship trajectories. However, the traditional DBSCAN algorithm suffers from the following shortcomings. First, the DBSCAN algorithm requires the input of a similarity matrix between the trajectories, and the similarity matrix obtained from the traditional Hausdorff distances does not identify the trajectory directions. Second, the DBSCAN algorithm is sensitive to the input parameters, and the clustering results obtained from different datasets with the same parameters vary widely. Finally, the DBSCAN algorithm is poor at clustering multi-density distribution datasets. To address these shortcomings, this study proposes a multi-density adaptive trajectory clustering (MDA-Traclus) algorithm, which considers the multi-density distribution trajectory dataset, adaptively determines the input parameters, and adds a trajectory direction identification mechanism to realize the clustering of trajectory clusters with different directions and different densities. Here, the classical DBSCAN algorithm, KANN-DBSCAN algorithm, and MDA-Traclus algorithm are compared and analyzed using four manually labeled trajectory datasets and a real trajectory dataset. The results show that the MDA-Traclus algorithm and KANN-DBSCAN algorithm are able to automatically determine the input parameters when clustering trajectory datasets with uniformly distributed densities and achieve the same clustering effect as the DBSCAN algorithm. When the trajectory density distribution is not uniform and the directions of the trajectory clusters are not consistent, the MDA-Traclus algorithm can effectively identify the low-density regions, differentiate the different directions of trajectories, and improve the clustering of the trajectories.

The automatic identification system (AIS) provides a massive database for ocean science. The original AIS data are redundant. Direct use will cause a waste of data storage space and computation costs; hence, data compression must be performed. The Douglas–Peucker algorithm (DP) is an effective trajectory compression algorithm that can well preserve the spatial characteristics of a trajectory but has the following shortcomings: first, it has poor track recovery when compressing multi-turn routes; second, it does not consider the ship speed and heading; and third, it may have the wrong result of the compressed trajectory crossing the obstacle. To address these situations, this study proposes a multi-objective peak DP algorithm (MPDP) that adopts a peak sampling strategy, considers three optimization objectives (spatial characteristics, heading and speed) of trajectory and adds an obstacle detection mechanism to realize a compression algorithm more suitable for curved trajectories. The classical DP algorithm is compared with the MPDP algorithm by simulating trajectory and real trajectory experiments. The results show that the MPDP algorithm optimizes the length loss rate, simultaneous Euclidean distance, and average deviations of the speed and the heading while maintaining a high compression rate similar to that of the DP algorithm. Moreover, it can also successfully avoid obstacles. The optimization effect is most obvious for the multi-turn or hovering trajectory. The optimization rate of length loss, synchronous Euclidean distance, and average deviation of the heading can reach 40%.

BackgroundThe misuse of animal-derived stimulants in food is becoming increasingly common, and mass spectrometry (MS) is used extensively for their detection and analysis. There is a growing demand for abused-substances detection, highlighting the need for systematic studies on the advantages of MS-based methods in detecting animal-derived stimulants.ObjectiveWe reviewed the application of chromatography-mass spectrometry to the screening and detection of food stimulants of animal origin. Specifically, we analyzed four common animal sources of synthetic steroids, β-receptor agonists, zearalenol (ZAL), and glucocorticoids. We also explored the potential of using chromatography-mass spectrometry to detect and analyze animal-derived foods.MethodsWe searched and screened the Web of Science and Google Scholar databases until April 2023. Our inclusion criteria included a publication year within the last 5 years, publication language of English, and the research fields of food analysis, environmental chemistry, and polymer science. Our keywords were “mass spectrometry,” “anabolic androgenic steroids,” “β-2agonists,” “glucocorticoids,” “zearalenone,” and “doping.”ResultsAlthough traditional techniques such as thin-layer chromatography and enzyme-linked immunoassays are simple, fast, and suitable for the initial screening of bulk products, they are limited by their relatively high detection limits. Among the methods based on MS, gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry are the most widely used for detecting food doping agents of animal origin. However, a sensitive method with high repeatability and a short analysis time for a large number of samples is still required. Advances in MS have enabled the detection of extremely low concentrations of these substances. Combining different techniques, such as high-resolution mass spectrometry, ultra-high performance liquid chromatography–tandem mass spectrometry, gas chromatography-combustion-isotope ratio mass spectrometry, ultra-high performance liquid chromatography-high resolution mass spectrometry, and two-dimensional chromatography, offers significant advantages for detecting trace illicit drugs in animal-derived foods. Due to advances in assay technology and sample preparation methods, sample collection and storage methods such as dried blood spots, dried urine spots, and volumetric absorptive microsampling are increasingly accepted because of their increased stability and cost-effectiveness.SignificanceMS significantly improves the efficiency of detecting doping agents of animal origin. With the continuous development of MS technology, its application in the fields of doping detection and the analysis of doping agents of animal origin is expected to become more extensive.

BackgroundPrevious studies have shown that carbon monoxide (CO) poisoning occurs mostly in winter and is associated with severe cold weather (e.g., ice storms, temperature drops). However, according to previous studies, the impact of low temperature on health has a delayed effect, and the existing research cannot fully reveal the delayed effect of cold waves on CO poisoning.ObjectivesThe purpose of this study is to analyze the temporal distribution of CO poisoning in Jinan and to explore the acute effect of cold waves on CO poisoning.MethodsWe collected emergency call data for CO poisoning in Jinan from 2013 to 2020 and used a time-stratified case-crossover design combined with a conditional logistic regression model to evaluate the impact of the cold wave day and lag 0–8 days on CO poisoning. In addition, 10 definitions of a cold wave were considered to evaluate the impact of different temperature thresholds and durations.ResultsDuring the study period, a total of 1,387 cases of CO poisoning in Jinan used the emergency call system, and more than 85% occurred in cold months. Our findings suggest that cold waves are associated with an increased risk of CO poisoning in Jinan. When P01, P05, and P10 (P01, P05, and P10 refer to the 1st, 5th, and 10th percentiles of the lowest temperature, respectively) were used as temperature thresholds for cold waves, the most significant effects (the maximum OR value, which refers to the risk of CO poisoning on cold wave days compared to other days) were 2.53 (95% CI:1.54, 4.16), 2.06 (95% CI:1.57, 2.7), and 1.49 (95% CI:1.27, 1.74), respectively.ConclusionCold waves are associated with an increased risk of CO poisoning, and the risk increases with lower temperature thresholds and longer cold wave durations. Cold wave warnings should be issued and corresponding protective policies should be formulated to reduce the potential risk of CO poisoning.

Abstract Background The number of Parkinson’s patients (PD) undergoing total knee arthroplasty (TKA) is increasing. The purpose of the study was to characterize quality of life (QOL) outcomes for patients with coexisting PD and knee osteoarthritis (KOA) following TKA. Methods Patients with coexisting PD and KOA undergoing TKA between June 2014 and June 2020 were included. These patients were matched to controls with KOA alone by age, gender, basic social background information and Knee society score (KSS). The primary measure was to assess the QOL by the absolute changes in the EuroQOL5-Dimensions (EQ-5D), Pain and Disability Questionnaire (PDQ), and Patient Health Questionnaire-9(PHQ-9) at the last follow-up (LFU). Secondary measures were changes in QOL that exceeded the minimum clinically important difference value (MCID). Data on the health status and QOL of all patients were collected. Simple and multivariate regression analysis was used to evaluate the impact of PD on their QOL. Results Twelve KOA patients with PD were compared with 48 controls. Control patients experienced QOL improvement across all three measures:EQ-5D index (0.545–0.717, P

Summary: Recent studies have shown that PM2.5 may activate the hypothalamus-pituitary-adrenal (HPA) axis by inducing hormonal changes, potentially explaining the increase in neurological and cardiovascular risks. In addition, an association between PM2.5 and gut microbiota and metabolites was established. The above evidence represents crucial parts of the gut-brain axis (GBA). In view of this evidence, we proposed a hypothesis that PM2.5 exposure may affect the HPA axis through the gastrointestinal tract microbiota pathway (GBA mechanism), leading to an increased risk of neurological and cardiovascular diseases. We conducted a real-world prospective repeated panel study in Jinan, China. At each visit, we measured real-time personal PM2.5 and collected fecal and blood samples. A linear mixed-effects model was used to analyze the association between PM2.5 and serum biomarkers, gut microbiota, and metabolites. We found that PM2.5 was associated with increased serum levels of hormones, especially the adrenocorticotropic hormone (ACTH) and cortisol, which are reliable hormones of the HPA axis. Gut microbiota and tryptophan metabolites and inflammation, which are important components of the GBA, were significantly associated with PM2.5. We also found links between PM2.5 and changes in the nervous and cardiovascular outcomes, e.g., increases of 19.77% (95% CI: −36.44, 125.69) in anxiety, 1.19% (95% CI: 0.65, 1.74) in fasting blood glucose (FBG), 2.09% (95% CI: 1.48, 2.70) in total cholesterol (TCHOL), and 0.93% (95% CI: 0.14, 1.72) in triglycerides (TG), were associated with 10 μg/m3 increase in PM2.5 at the lag 0–72 h, which represent the main effects of GBA. This study indicated the link between PM2.5 and the microbiota GBA for the first time, providing evidence of the potential mechanism for PM2.5 with neurological and cardiovascular system dysfunction.

Abstract Background Sentinel lymph node is the first stop of lymphatic spreading of cancer with known primary. The lymph node metastasis pattern of cancer of unknown primary (CUP) is unclear and has been presumed to follow the same pathway. To test this hypothesis, data of all 716 patients clinically diagnosed as CUP in our center were collected. Methods Diagnoses of lymph node metastasis were established by 18F-FDG PET-CT and/or biopsy pathology. Three hundred and forty-seven cases meeting the criteria were divided into three groups: pathology-confirmed primary with invasive biopsy or surgery of the suspicious lesion (group A, n = 64), primary still unknown even with invasive biopsy or surgery of the suspicious lesion (group B, n = 204), and others with no suspicious lesion or lesions who had not been sampled due to medical or other reasons (group C, n = 79). We assessed the clinicopathological features between these groups, and the relationship between lymph node metastasis pattern and confirmed primary site. Results In group A, the primary sites of 61 cases were compatible with sentinel node theory, resulting in a positive predictive value of 95%. No significant differences in age, sex, bone metastasis, or visceral metastasis observed between group A and group B, except that group A had a higher ratio of differentiated carcinoma (94% vs. 77%, P = 0.003). Conclusion To our knowledge, this is the first evidence indicating that the majority of clinical CUP cases follow the sentinel node theory to spread in lymph nodes, which helps tracking the primary, especially for differentiated carcinoma.

Abstract To investigate the feasibility and effectiveness of prostate‐specific membrane antigen (PSMA) imaging to make response assessment regarding novel hormone treatment and to predict the outcomes for metastatic castration‐resistant prostate cancer (mCRPC) patients. This retrospective study enrolled 68 mCRPC patients who had daily received a novel hormone agent named abiraterone. Tc‐99m PSMA single‐photon emission computed tomography (SPECT/CT) was performed at the baseline (SPECT/CT1) and after 3‐6 months of treatment (SPECT/CT2). The treatment response was determined by visual analysis based on molecular imaging PSMA (miPSMA) scores framework and was compared with conventional biochemical analysis. We chose either the hottest lesion (target A) or five of the hottest lesions (target B) to calculate the tumor/background ratio (TBR) and the maximum standardized uptake value (SUVmax) and compared their performances in predicting progression‐free survival (PFS). Changes in PSMA expression between SPECT/CT1 and SPECT/CT2 were well associated with the results of the visual analysis. The TBR and the SUVmax of both targets were significantly associated with the baseline serum PSA level (P

Abstract Background Intratumoral heterogeneity has an enormous effect on patient treatment and outcome. The purpose of the current study was to establish and validate a nomogram with intratumoral heterogeneity derived from 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for prognosis of 5-Year progression-free survival (PFS) of patients with nasopharyngeal carcinoma (NPC). Methods A total of 171 NPC patients who underwent pretreatment 18F-FDG PET/CT were retrospectively enrolled. Data was randomly divided into training cohort (n = 101) and validation cohort (n = 70). The clinicopathologic parameters and the following PET parameters were analyzed: maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI, SUVmax/SUVmean) for primary tumor and maximal neck lymph node. Cox analyses were performed on PFS in the training cohort. A prognostic nomogram based on this model was developed and validated. Results For the primary tumor, MTV-2.5, TLG-2.5, MTV-70%, and TLG-70% were significantly correlated with PFS. For the maximal neck lymph node, short diameter and HI were significantly correlated with PFS. Among the clinicopathologic parameters, M stage was a significant prognostic factor for recurrence. In multivariate analysis, M stage (P = 0.006), TLG-T-70% (P = 0.002), and HI-N (P = 0.018) were independent predictors. Based on this prognostic model, a nomogram was generated. The C-index of this model was 0.74 (95% CI: 0.63–0.85). For the cross validation, the C-index for the model was 0.73 (95% CI: 0.62–0.83) with the validation cohort. Patients with a risk score of ≥111 had poorer survival outcomes than those with a risk score of 0–76 and 77–110. Conclusions Intratumoral heterogeneity derived from 18F-FDG PET/CT could predict long-term outcome in patients with primary NPC. A combination of PET parameters and the TNM stage enables better stratification of patients into subgroups with different PFS rates.

Abstract Background Not a large number of previous studies have reported the normal sagittal balance of the cervical spine and physiological cervical lordosis (CL) has not been clearly defined yet. Methods This was a prospective radiological analysis of asymptomatic subjects. The following cervical sagittal parameters were measured: CL, thoracic inlet angle (TIA), T1 slope (T1S), neck tilt (NT), and C2–7 sagittal vertical axis (C2–7 SVA). The Pearson correlation test was calculated, and the stepwise multiple regression analysis was conducted by using the CL (dependent variable) and the other cervical sagittal parameters (independent variables) to determine the best sets of predictors. A paired sample t test was conducted between the predicted and measured values. Results The mean age of 307 participants was 24.54 + 3.07. The mean CL, TIA, T1S, NT, and C2–C7 SVA was 17.11° ± 6.31°, 67.87° ± 7.78°, 25.84° ± 5.36°, 42.53° ± 6.68°, and 14.60 ± 8.20 mm, respectively. The formula was established as follows: CL = 0.762 × T1S − 0.392 × C2–C7 SVA + 0.25 × TIA − 13.795 (R = 0.812, R 2 = 0.660) (stepwise multiple regression) and CL = 0.417 × TIA − 11.193 (R = 0.514, R 2 = 0.264) (simple linear regression). There was no statistical difference between the predicted CL and the measured CL (t = 0.034, P = 0.973). Conclusions There was a significant correlation between CL and other cervical sagittal parameters, including TIA, T1S, NT, and C2–C7 SVA in asymptomatic Chinese population. The results of this study may serve as a normal reference value for the study of asymptomatic population.

Coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to medical education systems and medical students. The aim of this study was to investigate the effects of COVID-19 pandemic on medical career and specialty choices among medical students. An online cross-sectional survey of Chinese medical students was conducted during the COVID-19 pandemic from February to April 2020. The students’ willingness to be a doctor before and after the COVID-19 pandemic and changed willingness to specialize in respiratory medicine and infectious diseases were investigated. Multiple linear regression and binary logistic regression was used to explore factors that were associated with changes of willingness. A total of 1,837 medical students, including 1,227 females (66.8%), with a median age of 21.0 years, were recruited. Of the participants, 10.6% and 6.9% showed increased and decreased willingness to be a doctor after the COVID-19 outbreak, respectively. Moreover, 11.7% showed increased willingness and 9.5% showed decreased willingness to major in respiratory medicine and infectious diseases. Students with younger age, lower household income, fewer depressive symptoms, less exposure to negative pandemic information and more satisfaction with their own major after the pandemic were associated with increased willingness to be a doctor. Students who engaged in regular exercise, were males and undergraduate level, were interested in medicine, paid more attention to positive information, were satisfied with their majors, and had increased willingness to be a doctor after the pandemic were more likely to choose to specialize in respiratory medicine and infectious disease. However, the severity of anxiety symptoms was associated with decreased willingness to work in the specialties of respiratory medicine and infectious diseases. Psychological problems and professional satisfaction appear to be independent factors that affect medial career and specialty choices. The impacts of the COVID-19 pandemic on medical students require further research.

ObjectiveThe purpose of this study was to employ dual tracers 16α-[18F]fluoro-17β-estradiol (18F-FES) and [18F]fluorodeoxyglucose (18F-FDG) as imaging biomarkers in predicting progression-free survival (PFS) in ER-positive metastatic breast cancer (MBC) patients receiving fulvestrant therapy.MethodsWe retrospectively analyzed 35 HR+HER2- MBC patients who underwent 18F-FES and 18F-FDG PET/CT scans prior to fulvestrant therapy in our center. The SUVmax across all metastatic lesions on the PET/CT were assessed. The heterogeneity of ER expression was assigned by the presence of any 18F-FES negative lesions for patients with entirely 18F-FES positive lesions categorized into two groups by the median ratio of FES/FDG SUVmax, low FES/FDG, and high FES/FDG. PFS were estimated by the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazard model.ResultsIn total, 12 patients had both 18F-FES negative and positive lesions, indicating the heterogeneity of ER expression in metastatic lesions. These patients had a low median PFS of 5.5 months (95% CI 2.3–8.7). Of patients with entirely 18F-FES positive lesions, 11 had a low FES/FDG, and 12 had a high FES/FDG. These groups had a median PFS of 29.4 months (95% CI 2.3–56.5) and 14.7 months (95% CI 10.9–18.5), respectively. The patients were stratified in three categories based on incorporating both 18F-FES and 18F-FDG imaging results that were significantly correlated with PFS by univariate analysis (P < 0.001) and multivariate analysis (P = 0.006).Conclusion18F-FES and 18F-FDG PET could serve as prognostic imaging biomarkers for ER-positive MBC patients treated with fulvestrant therapy.

Purpose: 99mTc-duramycin imaging enables specific visualization of cell death qualitatively and quantitatively. This study aimed to investigate the potential of 99mTc-duramycin imaging in the early prediction of the curative effect of radiotherapy in combination with or without cetuximab in a nasopharyngeal carcinoma (NPC) model. Methods: Male BALB/c mice bearing NPC xenografts were randomized into four groups (six mice each group). Group 1 received radiotherapy (RT, 15 Gy/mouse) in combination with cetuximab (CTX, 2 mg/mouse), group 2 received RT (15 Gy/mouse), group 3 was treated using CTX (2 mg/mouse), and group 4, the control group, was treated using a vehicle. 99mTc-duramycin imaging was performed before treatment and 24 h after treatment to evaluate tumor response. Tumor uptake of 99mTc-duramycin was validated ex vivo using γ-counting. Treatment response was further validated by cleaved caspase-3 (CC3) and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL). Another four groups were treated parallelly under the same conditions to observe treatment response by tumor volume changes. Results: After 24 h treatment, 99mTc-duramycin uptake in the NPC tumor models were significantly higher in group 1 than in group 2 (P < 0.05), group 3 (P < 0.05), or group 4 (P < 0.05); the uptake also increased notably in comparison with baseline values (P < 0.05). Compared with group 4, group 2 and group 3 both showed significant 99mTc-duramycin uptake in the tumors (P < 0.05). Although the 99mTc-duramycin uptake of group 2 was moderately higher than group 3, there were no significant differences between these two groups (P >0.05). There was a strong positive correlation between tumor 99mTc-duramycin uptake and CC3 (r = 0.893, p < 0.0001) and TUNEL (r = 0.918, P < 0.0001). Tumor volume decreased remarkably in the RT in combination with CTX group on day 5, in the RT alone group on day 7, and was inhibited on day 8 in the CTX alone group, whereas the tumors grew continuously in the control group. Conclusions: We demonstrated that RT in combination with CTX treatment significantly improved disease control in a NPC xenograft model compared with monotherapy with either. 99mTc-duramycin imaging might be able to reliably identify response to RT in combination with CTX as early as 24 h after therapy initiation in NPC xenograft models. This might help to isolate non-responding patients in a timely manner and avoid unnecessary side effects in the clinic in the future.

Personal exposure to air pollution is affected by its concentration in the microenvironment and individual time-activity patterns. To investigate personal black carbon (BC) exposure levels and identify their potential determinants, we conducted a panel study among 67 elderly residents aged 60–69 years in Jinan, China. Personal BC exposure was measured using portable real-time monitors, while corresponding ambient BC concentrations and meteorological conditions were also collected from the local central site. Time-activity and household characteristics were recorded. A linear mixed-effects model was used to identify potential determinants of personal BC exposure. The daily average personal BC exposure concentration was 4.1 ± 2.0 μg/m3 (±standard deviation, SD), which was significantly lower than the ambient concentration (4.6 ± 2.5 μg/m3) (p

Abstract Heterogeneity has been demonstrated to be a predictor of treatment failure and drug resistance. Our study aimed to investigate imaging parameters, including tumor heterogeneity, as prognostic factors of response to 500 mg fulvestrant using 18F-FDG PET/CT. Twenty-seven estrogen receptor (HR)-positive/HER2-negative metastatic breast cancer patients who received 500 mg fulvestrant and underwent 18F-FDG PET/CT before treatment were retrospectively included. In PET/CT scans, conventional parameters (maximum and mean standardized uptake value, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and heterogeneity parameters (intra-tumor heterogeneity index [HI] and inter-tumor heterogeneity coefficient of variation [COV]) were analyzed. Progression-free survival (PFS) was mainly assessed for efficacy. The survival analyses were performed using the Kaplan–Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard model. Univariate analysis indicated that a high SUVmax and a high tumor HI at baseline were associated with longer PFS of fulvestrant (P = 0.036 and P = 0.033, respectively). Liver metastasis, SUVmax and HI were statistically significant in multivariate analysis (P values of 0.017, 0.025 and 0.043, respectively). 18F-FDG based intra-tumor heterogeneity appears to be a potential predicator of efficacy of fulvestrant among HR+HER2− metastatic breast cancer patients.

Abstract The present explorative study was initiated to evaluate the clinical value of 18F-FES PET/CT in monitoring the change of estrogen receptor (ER) expression and potential predictive value in metastatic breast cancer patients. Twenty-two pathology-confirmed breast cancer patients were prospectively enrolled and randomly divided into two groups (T: docetaxel, n = 14 and TF: docetaxel + fulvestrant, n = 8). The percentage of patients without disease progression after 12 months (PFS > 12 months) was 62.5% in group TF compared with 21.4% in group T (P = 0.08). According to 18F-FES PET/CT scans, the SUVmax (maximum standard uptake value) of all the metastatic lesions decreased in group TF after 2 cycles of treatment (6 weeks ± 3 days). However, 6 of 9 patients in group T had at least one lesion with higher post-treatment SUVmax. There was a significant difference in the reduction of ER expression between these two groups (P = 0.028). In group TF, the patients with PFS > 12 months had significantly greater SUVmax changes of 18F-FES than those with PFS 12 months: 91.0 ± 12.0% versus PFS

Background: Bone metastasis of cancer can be a result from systemic blood spreading or vertebral venous plexus spreading. Systemic blood pathway induced bone metastasis can happen in any bone in the body since the spreading is considered to be random. However, it remains unknown whether there is any pattern of vertebral venous plexus related bone metastasis. In this study, we explored bone metastasis patterns in patients whose primary tumors had been well identified. Methods: We included 290 consecutive cancer patients with bone metastases but no visceral metastases, out of 2559 patients whose bone metastases were diagnosed by positron emission tomography/computed tomography, between Jan 2015 and Oct 2017 at the Fudan University Shanghai Cancer Center. We excluded those with visceral metastasis to ensure that our study focused on metastasis through the vertebral venous plexus. And we analyzed the distribution and pattern of skeletal metastases. Results: Of the 290 patients, 28 had head and neck tumors, 178 had thorax tumors, 49 had abdominal tumors and 35 had pelvic tumors; 102 (35%) had only one bone containing a metastasis and 188 (65%) had multiple bones containing metastases. Overall, metastases to the thoracic skeleton were more common in patients with thorax tumors than in other patients (81% vs. 67%, P = 0.007); metastases to the cervical spine or thoracic bones were more common in patients with primary tumors above the diaphragm than those below the diaphragm (82% vs. 66%, P = 0.002). Among those with only one bone containing a metastasis (n = 102), patients with head and neck tumors had a higher incidence of cervical spine metastasis than other patients (25% vs. 2%, P = 0.03), those with thorax tumors had a higher incidence of thoracic bone metastasis than other patients (56% vs. 35%, P = 0.035), and those with pelvic tumors had a higher incidence of pelvis bone metastasis than other patients (78% vs. 27%, P = 0.000054). Conclusions: In patients with only one bone containing a metastasis but no visceral metastasis, bones near the primary were more likely to be first metastasized. This may be a valuable clue to primary tumor sites in patients with cancers of unknown primaries. Keywords: Bone metastasis, Positron emission tomography/computed tomography (PET/CT), Vertebral venous plexus

The potential immune effects of titanium dioxide nanoparticles (nano-TiO2) are raising concern. Our previous study verified that nano-TiO2 induce local immune response in lung tissue followed by intratracheal instillation administration. In this study, we aim to evaluate the systemic immune effects of nano-TiO2. Sprague Dawley rats were treated by intratracheal instillation with nano-TiO2 at doses of 0.5, 4, and 32 mg/kg body weight, micro-TiO2 with 32 mg/kg body weight and 0.9% NaCl, respectively. The exposure was conducted twice a week, for four consecutive weeks. Histopathological immune organs from exposed animals showed slight congestion in spleen, generally brown particulate deposition in cervical and axillary lymph node. Furthermore, immune function response was characterized by increased proliferation of T cells and B cells following mitogen stimulation and enhanced natural killer (NK) cell killing activity in spleen, accompanying by increased number of B cells in blood. No significant changes of Th1-type cytokines (IL-2 and INF-γ) and Th2-type cytokines (TNF-α and IL-6) were observed. Intratracheal exposure to nano-TiO2 may be one of triggers to be responsible for the systemic immune response. Further study is needed to confirm long-lasting lymphocyte responses and the potential mechanisms.

There is an increasing need to characterize biological processes for early prediction and monitoring of response to endocrine therapy in breast cancer using multiple positron emission tomography (PET) imaging probes. However, use of more than two PET tracers in a single clinical trial is quite challenging. In this study we carried out a longitudinal investigation of 18F-FES, 18F-FDG, and 18F-FMISO PET imaging probes for early prediction and monitoring of response to endocrine therapy in a mouse xenograft model of estrogen receptor (ER)-positive breast cancer.ER+ human breast cancer ZR-75-1 models were established in female mice that were then randomly assigned to a treatment (fulvestrant, 5.0 mg/week for 21 days) or vehicle group. Micro-PET/CT imaging with 18F-FES, 18F-FDG, and 18F-FMISO was performed on days 0, 3, 14, and 21 after treatment. The uptake value (percentage injected dose per gram, %ID/g) for each probe in tumor (T) tissue and contralateral muscle (M) was measured for quantitative analysis and T/M calculation. Tumor volume was measured to record tumor growth at each time point. Tumor tissues were sampled for immunohistochemical staining of ER expression. Correlations for tumor volume and ERα levels with uptake data for the probe were tested.Uptake data for 18F-FES in ZR-75-1 tumor tissues corresponded well with tumor response to endocrine therapy, but not for 18F-FDG and 18F-FMISO, according to longitudinal micro-PET/CT imaging and quantitative correlation analysis. There was a significant positive correlation between 18F-FES uptake and ER levels (%ID/gmax r2 = 0.76, P< 0.05; T/M r2 = 0.82, P

To evaluate the clinical value of 16α-[18F]fluoroestradiol (18F-FES) PET/CT in assisting the individualized treatment decisions of breast cancer patients.Thirty-three breast cancer patients, who underwent both 18F-FES and 18F-FDG PET/CT from July 2010 to March 2013 in our center, were enrolled in this preliminary study. All the patients used 18F-FES PET/CT as a diagnostic tool with a clinical dilemma. We used the maximum Standardized Uptake Value (SUVmax) to quantify ER expression and a cutoff value of 1.5 to dichotomize results into ER positive and negative lesions. All patients were clinically followed up at least 6 months.In evaluating equivocal lesions on conventional work-up group (n = 4), three lung lesions and another iliac lesion were enrolled. As for three lung lesions, 18F-FES PET/CT showed one lesion with high uptake, which suggested it was an ER positive metastasis. The other two lesions were 18F-FES negative, which meant an ER negative metastasis or secondary primary tumor. Additionally, one iliac lesion was detected by MRI. 18F-FDG uptake was high at the suspected lesion, whereas 18F-FES uptake was absent; In predicting origin of metastasis group (n = 2), two breast cancer patients had secondary primary tumors were collected. They were 18F-FES negative, which showed low possibility of metastasis from breast cancer and they were all confirmed by biopsy. In detecting ER status in metastasis group (n = 27), 18F-FES PET/CT showed increased 18F-FES uptake in all metastatic lesions in 11 patients; absent in all lesions in 13 patients; and the remaining 3 patients had both 18F-FES positive and negative lesions. Totally, on the basis of the 18F-FES PET/CT results, we found changes in the treatment plans in 16 patients (48.5%, 16/33).18F-FES PET/CT could assess the entire tumor volume receptor status; therefore, it may be used to assist the individualized treatment decisions of breast cancer patients.

OBJECTIVE:To find out the most valuable parameter of 18F-Fluorodeoxyglucose positron emission tomography for predicting distant metastasis in nasopharyngeal carcinoma. METHODS:From June 2007 through December 2010, 43 non-metastatic NPC patients who underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) before radical Intensity-Modulated Radiation Therapy were enrolled and reviewed retrospectively. PET parameters including maximum standardized uptake value (SUV max), mean standardized uptake value (SUV mean), metabolic tumor volume (MTV), and total lesion glucose (TLG) of both primary tumor and cervical lymph nodes were calculated. Total SUV max were recorded as the sum of SUV max of primary tumor and cervical lymph nodes. Total SUV mean, Total MTV and Total TLG were calculated in the same way as Total SUV max. RESULTS:The median follow-up was 32 months (range, 23-68 months). Distant metastasis was the main pattern of treatment failure. Univariate analysis showed higher SUV max, SUV mean, MTV, and TLG of primary tumor, Total SUV max, Total MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p = 0.024, p = 0.033, p = 0.016, p = 0.015). In multivariate analysis, Total SUV max was the independent predictive factor for distant metastasis (p = 0.046). Spearman Rank correlation analysis showed mediate to strong correlationship between Total SUV max and SUV max-T, and between Total SUV max and SUV max-N(Spearman coefficient: 0.568 and 0.834; p = 0.000 and p = 0.000). CONCLUSIONS:Preliminary results indicated that Total SUV max was an independently predictive factor for distant metastasis in patients of nasopharyngeal carcinoma treated with Intensity-Modulated Radiation Therapy.

OBJECTIVE:To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT) (18)F-fluoroestradiol ((18)F-FES) and (18)F-fluorodeoxyglucose ((18)F-FDG) in predicting neoadjuvant chemotherapy response (NAC) of breast cancer. METHODS:Eighteen consecutive patients with newly diagnosed, non-inflammatory, stage II and III breast cancer undergoing NAC were included. Before chemotherapy, they underwent both (18)F-FES and (18)F-FDG PET/CT scans. Surgery was performed after three to six cycles of chemotherapy. Tumor response was graded and divided into two groups: the responders and non-responders. We used the maximum standardized uptake value (SUVmax) to qualify each primary lesion. RESULTS:Pathologic analysis revealed 10 patients were responders while the other 8 patients were non-responders. There was no statistical difference of SUVmax-FDG and tumor size between these two groups (P>0.05). On the contrary, SUVmax-FES was lower in responders (1.75±0.66 versus 4.42±1.14; U=5, P=0.002); and SUVmax-FES/FDG also showed great value in predicting outcome (0.16±0.06 versus 0.54±0.22; U=5, P=0.002). CONCLUSIONS:Our study showed (18)F-FES PET/CT might be feasible to predict response of NAC. However, whether the use of dual tracers (18)F-FES and (18)F-FDG has complementary value should be further studied.