Feasibility of using synthetic MRI to predict lymphatic vascular space invasion status in early-stage cervical cancer: added value to morphological MRI.

OBJECTIVES: To investigate the feasibility of synthetic magnetic resonance imaging (syMRI) in predicting the lymphatic vascular space invasion (LVSI) status of early-stage cervical cancer, and its added value to morphological MRI. MATERIALS AND METHODS: A total of 72 patients with pathology-confirmed early-stage cervical cancer were enrolled, and classified into LVSI- positive (n=41) and LVSI- negative (n=31) groups. Together with morphological parameters including gross tumor volume (GTV) and maximum tumor diameter (MTD), the T1, T2, and proton density (PD) values of the tumors were also measured and compared between two groups. Binary logistic regression analysis was used to identify the independent variable associated with LVSI. Receiver operating characteristic curve analyses and DeLong tests were used to evaluate and compare the performances of significant parameters or their combination in predicting LVSI. RESULTS: LVSI- positive group showed significantly higher GTV (P=0.008) and MTD (P=0.019), and lower T1 (P<0.001) and PD values (P=0.041) than LVSI- negative group. However, no statistical significance was observed regarding the T2 values (P=0.331). Binary logistic regression indicated that T1 value (odds ratio [OR] = 0.993; P=0.001) and MTD (OR=1.903, P=0.027) were independent variables associated with LVSI in early cervical cancer. Optimal performance could be achieved [area under ROC curve (AUC) = 0.784; cut-off value = 0.56; sensitivity = 80.5%; specificity = 71.0%] when combining T1 and MTD for predicting LVSI. Its performance was significantly better than that of MTD alone (AUC, 0.784 vs 0.662, P=0.035). CONCLUSION: syMRI might be a feasible approach, and it can provide added value to morphological MRI in predicting the LVSI status of early-stage cervical cancer.

Adherence to the EAT-Lancet diet reduces the risk of head and neck cancers in 101,755 American adults: a prospective cohort study.

OBJECTIVES: The aim of this study was to explore the relationship between the EAT-Lancet diet (ELD) and head and neck cancers (HNCs) in 101,755 Americans enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. STUDY DESIGN: Prospective cohort study. METHODS: ELD score was calculated to assess participant's adherence to ELD. Cox hazard regression models were utilised to evaluate the association of ELD and dietary components with HNC risk. Restricted cubic spline (RCS) plots were employed to explore the linearity of the relationships. Predefined subgroup analyses and sensitivity analyses were performed to identify potential effect modifiers and to assess the stability of the findings, respectively. RESULTS: After a mean follow-up of 8.84 years, 279 cases of HNCs, including 169 cases of oral cavity and pharyngeal cancers and 110 cases of laryngeal cancer were recorded. This study observed a dose-response negative correlation between ELD and HNCs (hazard ratio [HR]Q4 vs Q1: 0.52; 95% confidence interval [CI]: 0.34, 0.80; P-trend = 0.003; HRper SD increment: 0.80; 95% CI: 0.71, 0.91), and oral cavity and pharyngeal cancers (HRQ4 vs Q1: 0.52; 95% CI: 0.31, 0.88; P-trend = 0.008; HRper SD increment: 0.78; 95% CI: 0.66, 0.92). Analysis using RCS plots indicated a significant linear association between adherence to the ELD and reduced risk of HNCs and oral cavity and pharyngeal cancers (P-nonlinearity > 0.05). Subgroup analysis did not reveal significant interaction factors (P-interaction > 0.05), and sensitivity analysis confirmed the robustness of this study. Additionally, negative correlations were found between the consumption of fruits and whole grains and HNCs (fruits: HRQ4 vs Q1: 0.58; 95% CI: 0.40, 0.84; P-trend = 0.010; whole grains: HRQ4 vs Q1: 0.51; 95% CI: 0.26, 0.97; P-trend = 0.004). CONCLUSION: Adherence to ELD contributes to the prevention of HNCs.

China's prevention and control experience of echinococcosis: A 19-year retrospective.

Echinococcosis poses a significant threat to public health. The Chinese government has implemented prevention and control measures to mitigate the impact of the disease. By analyzing data from the Chinese Center for Disease Control and Prevention and the State Council of the People's Republic of China, we found that implementation of these measures has reduced the infection rate by nearly 50% between 2004 to 2022 (from 0.3975 to 0.1944 per 100,000 person-years). Nonetheless, some regions still bear a significant disease burden, and lack of detailed information limites further evaluation of the effects on both alveolar and cystic echinococcosis. Our analysis supports the continuing implementation of these measures and suggests that enhanced wildlife management, case-based strategies, and surveillance systems will facilitate disease control.

[Olfactory neuroblastoma in children: clinical analysis of five cases].

The clinical data of five patients diagnosed with olfactory neuroblastoma (ONB) who were admitted to the Department of Pediatrics, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2012 to January 2024 were retrospectively analyzed. Two males and three females aged 6.2 (5.7-15.8) years were included. The symptoms mainly covered nasal congestion, increased nasal secretions, headache, decreased vision and so on. Pathological grade Ⅱ, Ⅲ and Ⅳ was identified in two cases, one case and two cases, respectively. Modified Kadish stage B, C and D was detected in one case, two cases and two cases, respectively. All patients underwent surgery, chemotherapy, and radiation therapy. Among the five patients, four survived and one died. The follow-up time was 22.3 (10.4-56.4) months, and the recurrence rate was 0. ONB should be suspected when tumors are presented in the upper and middle parts of the nasal cavity, especially dumbbell shaped masses that grow towards the nasal cavity and intracranial area based on imaging. The multimodality therapy of ONB comprising of surgery and chemotherapy, can achieve good therapeutic effects and prognosis, but long-term follow-up is required.

[Hsa_circ_0000670 promoted the progression of gastric cancer through the miR-515-5p/SIX1 molecular axis].

Objective: To explore whether hsa_circ_0000670 promotes the progression of gastric cancer by regulating the miR-515-5p/SIX1 molecular axis. Methods: The gastric cancer and adjacent normal tissues of 35 gastric cancer patients admitted to Rugao Hospital Affiliated to Nantong University from 2014 to 2015 were collected. The expression levels of circ_0000670, miR-515-5p and Sine oculis homeobox 1 (SIX1) in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The correlations between circ_0000670 and miR-515-5p, miR-515-5p and SIX1, circ_0000670 and SIX1 were analyzed by the Pearson method. Patients were divided into low circ_0000670 expression group (17 cases) and high circ_0000670 expression group (18 cases) based on the median of circ_0000670 expression level, and Kaplan-Meier was used to analyze the 5-year survival of patients. Cell proliferation was assessed via clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. Wound healing and Transwell assays were used to detect cell migration and invasion ability. The targeting relationship between miR-515-5p and circ_0000670 or SIX1 was confirmed by the dual luciferase reporter assay. Nude mice were injected into HGC-27 cells transfected with sh-NC or sh-circ_0000670, and the volume and weight of the transplanted tumor were measured, also, the levels of circ_0000670, miR-515-5p and SIX1 in the transplanted tumor tissue were detected. Results: The expression levels of circ_0000670 and SIX1 in gastric cancer tissues and cell lines were significantly increased (P<0.05), while the expression levels of miR-515-5p were significantly decreased (P<0.05). The survival rate of patients in the low circ_0000670 expression group (82.4%) was significantly higher than that in the high circ_0000670 expression group (28.7%, P=0.034). Circ_0000670 was negatively correlated with miR-515-5p (r=-0.846, P<0.001), and miR-515-5p was negatively correlated with SIX1 (r=-0.615, P<0.001), but circ_0000670 was positively correlated with SIX1 (r=0.814, P<0.001). Transfection of si-circ_0000670 or miR-515-5p mimic could significantly reduce the number of clone-forming cells, migration distance, migration and invasion cells (P<0.05), and increase the ratio of G(0)/G(1) phase cells, apoptosis rate and the protein level of E-cadherin (P<0.05), decreased the proportion of S-phase cells and the protein level of Vimentin (P<0.05). The dual luciferase report assay confirmed that circ_0000670 could target miR-515-5p, and miR-515-5p could bind to SIX1. Co-transfection of si-circ_0000670 and miR-515-5p inhibitor could significantly attenuate the effects of si-circ_0000670 on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Co-transfection of miR-515-5p mimic and pcDNA-SIX1 could significantly reduce the effects of miR-515-5p mimic on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Compared with the sh-NC group [volume=(596.20±125.46) mm(3) and weight=(538.00±114.39) g], the volume and weight of transplanted tumors in the sh-circ_0000670 group [volume=(299.20±47.58) mm 3 and weight=(289.80±48.73 g)] were significantly reduced (P<0.05), the expression levels of circ_0000670 and SIX1 were significantly reduced (P<0.05), and the expression level of miR-515-5p was significantly increased (P<0.05). Conclusion: Knockdown of circ_0000670 could inhibit cell proliferation, migration, invasion of gastric cancer cells, induce cell cycle arrest in G(0)/G(1) phase and promote cell apoptosis by regulating the miR-515-5p/SIX1 axis.

[Effect of different respiratory motion correction methods on PET image quality in chest PET/MRI].

Objective: To investigate the effect of different respiratory motion correction methods on PET images during chest PET/MRI scans. Methods: The data of 35 patients (24 males and 11 females, aged from 29 to 84 year) of pulmonary lesions with significantly high uptake in thoracic PET/MRI scan were retrospective collected from Jingling Hospital. Four different methods were used to reconstruct the PET data. Group A was the full-time 20 min without respiratory motion correction static acquisition (Static) as a control, group B was the end-expiration static collection (Q.Static), and group C was the multi-bins respiratory gating (Gated-Respiratory). In addition, the influence of the time being considered, group D was added for reconstruction in the first 1/3 period (6 min 40 s) of group A. Then, the maximum value (L-SUVmax) and the mean value (L-SUVmean) of the SUV of the lesion, the mean value (B-SUVmean) and the standard deviation (B-SUVsd) of the SUV of the background under each reconstruction results were measured, and for each lesion the signal-to-noise ratio (L-SNR) was calculated. In order to exclude the interference of the background, the mean of the relative SUV (L-dSUVmean) of the L-SUVmean relative to the B-SUVmean was also calculated. Finally, One-Way Repeated Measures ANOVA was used, and the post-hoc pairwise comparison between groups was tested by Bonferroni's modified test. Results: There was statistically significant difference among group B or group C compared to group A and group D in L-SUVmax, L-SUVmean and L-dSUVmean [L-SUVmax:group B vs group A or group D was 8.06±3.57 vs 7.73±3.45 or 7.61±3.50, group C vs group A or group D was 8.04±3.56 vs 7.73±3.45 or 7.61±3.50 (all P<0.05); L-SUVmean: group B vs group A or group D was 4.12±1.78 vs 3.98±1.72 or 3.91±1.71, group C vs group A or group D was 4.13±1.78 vs 3.98±1.72 or 3.91±1.71 (all P<0.05); L-dSUVmean: group B vs group A or group D was 3.52±0.16 vs 3.39±0.18 or 3.31±0.18, group C vs group A or group D was 3.53±0.18 vs 3.39±0.18 or 3.31±0.18 (all P<0.05)], but there was no statistically significant difference between group B and group C (all P>0.05). There were statistically significant differences between group D and group A in B-SUVsd (0.07±0.00 vs 0.07±0.00, P=0.023) and L-SNR (69.80±44.57 vs 85.35±68.98, P=0.001). There was no statistically significant difference between group D and group A in L-SUVmax, L-SUVmean, B-SUVmean and L-dSUVmean (all P>0.05). Conclusions: There was no significant difference in PET image quality between the Q.static and Gated-Respiratory group, both of the two groups were better than the Static group which with no Gated-Respiratory motion correction. If non-respiratory gated Static is used, the PET acquisition time is recommended to be 6 min 40 s.

[Qualitative and quantitative PET/MRI in the evaluation of axillary lymph node metastasis in patients with breast cancer].

Objective: To investigate the value of qualitative and quantitative PET/MRI in the evaluation of axillary lymph node metastasis in patients with breast cancer. Methods: A total of 33 patients with breast cancer underwent preoperative PET/MRI examinations in Jingling Hospital from February to August in 2022 were retrospectively collected. All these patients were female, aged from 34 to 73 (51.4±11.3) years. Histopathological results and follow-up data were deemed as the referent standard, and the images were independently evaluated by two experienced breast imaging radiologists. The qualitative PET/MRI evaluation procedures were designed to evaluated the MRI alone to classify the axillary lymph nodes firstly, and then, the axillary lymph nodes status was reclassified by combining MRI and PET images. The net reclassification improvement index (NRI) was calculated using the R Programming Language (RStudio). The quantitative PET/MRI evaluation of the maximum standard uptake value (SUVmax) of axillary lymph nodes were measured by two radiologists, respectively, and the average value was compared with the referent standard to conduct a receiver operating characteristic (ROC) curve to select the optimal cutoff value of SUVmax. Based on the cutoff value and MRI classification results, axillary lymph nodes status was divided into quantitative PET/MRI positive or negative. The sensitivity, specificity and accuracy of MRI and quantitative PET/MRI in evaluating axillary lymph node metastasis were compared, and the area under the ROC curve (AUC) was compared. Results: There was no significant difference in sensitivity, specificity and accuracy between MRI and quantitative PET/MRI in evaluating lymph node metastasis of breast cancer (81.82% vs 95.46%; 81.82% vs 100%; 81.82% vs 96.97%) (all P>0.05). The AUC had a statistically significant difference [0.82 (0.65 to 0.93) vs 0.98 (0.85 to 1.00), P=0.026)]. According to the referent standard, in the 11 cases without ipsilateral axillary lymph node metastasis, the SUVmax was 0.83±0.18, while in the 22 cases with ipsilateral axillary lymph node metastasis, the SUVmax was [4.36 (1.77, 5.85)]. Compared with MRI alone, the NRI of qualitative PET/MRI in evaluating lymph node metastasis was 36.36% (P=0.021). Conclusion: Compared with MRI alone, quantitative PET/MRI has a higher AUC for evaluating axillary lymph node metastasis in patients with breast cancer, and qualitative PET/MRI had a better reclassification power in the evaluation of axillary lymph node metastasis.

[Establishment of a patient-derived xenograft humanized mouse model for hepatoblastoma in children].

Objective: To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor. Methods: A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children's data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by χ (2) test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. Results: After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, P = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma's PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, ß-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. Conclusion: A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.

[Comparative analysis of intestinal microbiota distribution characteristics based on metagenomics in patients with hepatitis B cirrhosis with or without ascites].

Objective: To use metagenomic sequencing to compare the differences in intestinal microbiota species and metabolic pathways in patients with hepatitis B cirrhosis with or without ascites and further explore the correlation between the differential microbiota and clinical indicators and metabolic pathways. Methods: 20 hepatitis B cirrhosis cases [10 without ascites (HBLC-WOA), 10 with ascites (HBLC-WA), and 5 healthy controls (HC)] were selected from the previously studied 16S rRNA samples. Metagenome sequencing was performed on the intestinal microbiota samples. The Kruskal-Wallis rank sum test and Spearman test were used to identify and analyse differential intestinal microbiota populations, metabolic pathways, and their correlations. Results: (1) The overall structure of the intestinal microbiota differed significantly among the three groups (R = 0.19, P = 0.018). The HC group had the largest abundance of Firmicutes and the lowest abundance of Proteobacteria at the genus level. Firmicutes abundance was significantly decreased (P(fdr) < 0.01), while Proteobacteria abundance was significantly increased (P(fdr) < 0.01) in patients with cirrhosis accompanied by ascites; (2) LEfSe analysis revealed that 29 intestinal microbiota (18 in the HBLC-WA group and 11 in the HBLC-WOA group) played a significant role in the disease group. The unclassified Enterobacteriaceae and Klebsiella species in the HBLC-WA group and Enterobacteriaceae in the HBLC-WOA group were positively correlated with the Child-Turcotte-Pugh (CTP) score, prothrombin time, and international normalized ratio score and negatively correlated with albumin and hemoglobin levels (P < 0.05). Escherichia and Shigella in the HBLC-WA group were positively correlated with CTP scores (P < 0.05); (3) The correlation analysis results between the KEGG pathway and 29 specific intestinal microbiota revealed that Enterobacteriaceae and arachidonic acid, α-linolenic acid, glycerolipid metabolism, and fatty acid degradation were positively correlated in the lipid metabolism pathway, while most Enterobacteriaceae were positively correlated with branched-chain amino acid degradation and negatively correlated with aromatic amino acid biosynthesis in the amino acid metabolic pathway. Conclusion: A significant increment of Enterobacteriaceae in the intestines of HBLC-WA patients influenced hepatic reserve function and was associated with amino acid and lipid metabolic pathways. Therefore, attention should be paid to controlling the intestinal microbiota to prevent complications and improve the prognosis in patients with hepatitis B cirrhosis, especially in those with ascites.

[A preliminary study on the tear matrix metalloproteinase 9 point-of-care assay using a domestic kit].

Objective: To compare the point-of-care assays for tear matrix metalloproteinase 9 (MMP-9) using domestic and InflammaDry kits, and to evaluate the feasibility of diagnosing dry eye with the domestic kit. Methods: It was a cross-sectional study. Thirty dry eye patients and 30 age-and sex-matched normal volunteers were continuously enrolled in this cross-sectional study from June 2022 to July 2022. Both domestic and InflammaDry kits were used to detect the tear MMP-9 levels. The positive rates were recorded for qualitative analysis, and the gray ratios of bands (the gray value of detection bands to that of control bands) were collected for quantitative analysis. The correlations of MMP-9 levels with age, ocular surface disease index, fluorescence tear break-up time, tear meniscus height, Schirmer's Ⅰ test score, corneal fluorescein staining score, and meibomian gland dropout were analyzed. The Mann-Whitney U test, paired Chi-square test, Kappa test, and Spearman's correlation coefficient were used for statistical analysis. Results: There were 14 males and 16 females (30 eyes) in the control group, and their age was (39.37±19.55) years. In the dry eye group, 11 males and 19 females (30 eyes), aged (46.87±17.85) years, had moderate to severe dry eye. The positive rates of MMP-9 in tear fluid were significantly different between dry eye patients (InflammaDry: 86.67%; domestic kit: 70.00%) and controls (InflammaDry: 16.67%, P<0.001; domestic kit: 6.67%, P<0.001). Although the sensitivity of the domestic kit was lower than that of the InflammaDry kit (70.0% vs. 86.7%, P=0.001), the specificity was higher (93.3% vs. 83.3%, P=0.001). In dry eye patients, the positive coincidence rate was 80.7% (21/26), the negative coincidence rate was 100% (4/4), and the total coincidence rate was 83.3% (25/30), with no significant difference between the two kits (McNemar test: χ2=3.20, P>0.05), and the results of both kits were consistent (Kappa=0.53, P=0.001). The Spearman's correlation coefficient showed the gray ratios using both kits were positively correlated with the corneal fluorescein staining score (InflammaDry: ρ=0.48, P<0.05; domestic kit: ρ=0.52, P=0.003). Conclusion: The performances of the domestic and InflammaDry kits are consistent in the point-of-care assay for tear MMP-9, and the domestic kit has lower sensitivity but higher specificity.

Repeat hepatic resection VS radiofrequency ablation for the treatment of recurrent hepatocellular carcinoma: an updated meta-analysis.

BACKGROUND: This paper evaluates the efficacy and safety of repeat hepatic resection and radiofrequency ablation in the treatment of recurrent hepatocellular carcinoma. MATERIAL AND METHODS: We retrieved and collected all relevant articles from the inception to 8 March 2020. After data extraction, we conducted meta-analysis and carried out the heterogeneity test, sensitivity analysis, and publication bias test to evaluate reliability. RESULTS: A total of 12 studies with 1746 patients (rHR 837, RFA 909) were included. rHR was similar to RFA in a one-year overall survival rate (OS), while rHR was superior to RFA in 3- and 5-year OS and 1-, 3-, and 5-year disease-free survival rates (DFS), but the procedure-related complications of RFA were significantly less than those of rHR. Among the subgroups with Milan criteria, rHR was similar to RFA in 1-, 3-, and 5-year OS and 1-year DFS, but superior to RFA in 3- and 5-year DFS. CONCLUSIONS: RFA is the first choice for recurrent HCC meeting Milan criteria. When it does not meet the Milan criteria, minimally invasive treatment should not be carried out at the cost of survival, and rHR should be the first choice.

[Association of body mass index and waist circumference with frailty among people aged 80 years and older in Chinese].

Objective: To examine the association of body mass index (BMI) and waist circumference (WC) with frailty among oldest-old adults in China. Methods: A total of 7 987 people aged 80 years and older (oldest-old) who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2017-2018 were included. Information on demographic characteristics, behavior pattern, diet, activities of daily living, cognitive function, health status, disease condition were collected by questionnaire and physical examination. Generalized linear mixed model and restricted cubic splines (RCS) were used to analyze the association of BMI and WC with frailty. Results: The mean age of all participants was 91.7 years, and their mean BMI and WC were (21.3±3.5) kg/m2 and (82.9±10.5) cm, respectively. The proportion of male was 42.3% (3 377/7 987), and the proportion of people with frailty was 33.7% (2 664/7 987). After controlling confounding factors, compared with T2 (19.1-22.1 kg/m2) of BMI, the OR (95%CI) of the female T1 (<19.1 kg/m2) and T3 (≥22.2 kg/m2) group was 1.39 (1.17-1.65) and 1.27 (1.07-1.52), respectively. Compared with T2 (77-85 cm) of WC, the OR (95%CI) of female T1 (<77 cm) and T3 (≥86 cm) group was 1.20 (1.01-1.42) and 1.10 (0.93-1.31), respectively. The results of multiple linear regression model with restrictive cubic spline showed that there was a non-linear association of BMI and WC with frailty in female. Conclusion: There is a U-shaped association of BMI and WC with frailty in female participants.

[Impact of composite clinical worsening events on outcome of patients with pulmonary arterial hypertension associated with congenital heart disease].

Objective: To explore the impact of composite clinical worsening (cCW) events and its components on the prognosis of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH). Methods: This is a retrospective study. Patients who were diagnosed with CHD-PAH in Beijing Anzhen Hospital between January 2007 and July 2018, were included, and their baseline clinical data including demographic, clinical manifestations and New York Heart Association (NYHA) classification were collected retrospectively. All-cause deaths and clinical worsening events were recorded, which included syncope, PAH related hospitalization, NYHA classification deterioration and ≥ 2 PAH related clinical symptoms (dyspnea, hemoptysis, edema, chest pain, palpitations, cyanosis) appearance/progress. Three kinds of cCW events were defined: cCW1 (included PAH related hospitalization, NYHA classification deterioration), cCW2 (increased syncope on the basis of cCW1) and cCW3 (increased ≥ 2 PAH related clinical symptoms appearance/progress on the basis of cCW2). The Kaplan-Meier survival curve was used to analyze the long-term survival of the included patients. Univariate and multivariate Cox regression models were used to evaluate the impact of cCW events and their components on the risk of all-cause mortality. Results: A total of 525 patients with CHD-PAH were included in this study. The median age at diagnosis was 20.7 (11.2, 30.3) years. There were 43.8% children (<18 years), and 68.8% female patients. There were 431 patients (82.1%) with NYHA classification II. A total of 180 patients had PAH symptoms at diagnosis. The median follow-up time was 4.5 (2.6, 6.7) years. Forty-seven patients (9.0%) died during the follow-up period. Survival rates at 1, 5 and 10 years after diagnosis of PAH were 98.0%, 89.9% and 84.4%, respectively. Cox multivariate analysis showed that NYHA classification deterioration (HR=3.901, 95%CI 1.863-8.169, P<0.001), ≥2 PAH symptoms appearance/progress (HR=4.458, 95%CI 1.870-10.625, P<0.001), PAH-related hospitalization (HR=4.058, 95%CI 1.851-8.896, P<0.001) and syncope (HR=11.313, 95%CI 4.860-26.332, P<0.001) were independent predictors of increased risk of death. All 3 kinds of cCW events were significantly associated with the significantly increased risk of death, and cCW2 was highly predictive to increased risk of death (HR=15.476, 95%CI 4.346-37.576, P<0.001). Conclusions: The overall long-term prognosis of CHD-PAH patients in this study is relatively good. cCW events and its components (NYHA classification deterioration, ≥2 PAH symptoms occurrence/worsening, PAH-related hospitalization and syncope) have adverse influence on all-cause death in this patient cohort.

[A cohort study on plasma uric acid levels and the risk of type 2 diabetes mellitus among the oldest old in longevity areas of China].

Objective: To investigate the effect of plasma uric acid level on the incident risk of type 2 diabetes mellitus (T2DM) among the oldest old (those aged ≥80 years). Methods: Participants were recruited from the Healthy Aging and Biomarkers Cohort Study (HABCS), which conducted a baseline survey in 2008-2009 and follow-up of 3 times in 2011-2012, 2014, and 2017-2018, respectively. A total of 2 213 oldest old were enrolled in this study. The general demographic, socioeconomic, lifestyle and disease data of the oldest old were collected, and physical measurements were made for the oldest old. Fasting venous blood was collected for uric acid and blood glucose detection. Information on the incident and death of T2DM were collected through the follow-up. Cox proportional hazard regression model was used to explore the association of hyperuricemia and plasma uric acid level with the incidence of T2DM. Restricted cubic spline (RCS) function was used to explore the dose-response relationship of plasma uric acid levels with the risk of T2DM. Results: The age of participants was (93.2±7.6) years old, and 66.7% of the participants (1 475) were female. The plasma uric acid level at baseline was (289.1±88.0)µmol/L, and the prevalence of hyperuricemia was 13.3% (294 cases). During 9 years of cumulative follow-up of 7 471 person-years (average of 3.38 years for each), 122 new cases of T2DM occurred and the incidence density was 1 632.98/105 person year. Cox proportional hazards regression analysis showed that per 10µmol/L increase in plasma uric acid level, the risk of T2DM increased by 1.1% [HR (95%CI): 1.011 (1.004, 1.017)]. Compared with the participants with the lowest quintile of plasma uric acid (Q1), the risk of diabetes increased by 20.7 % among the oldest old with uric acid in the highest quintile (Q5) [HR (95%CI):1.207 (1.029, 1.416)]. The risk of T2DM was 19.2% higher in the hyperuricemia group than that in the oldest old with normal plasma uric acid [HR (95%CI): 1.192 (1.033, 1.377)]. RCS function showed that the risk of T2DM increased with the increase in plasma uric acid levels in a nonlinear dose-response relationship (P=0.016). Conclusion: The incident risk of T2DM increases with the elevates of plasma uric acid levels in the oldest old.

[Association of blood arsenic level with hyperuricemia among elderly aged 65 years and older in 9 longevity areas of China].

Objective: To investigate the association of blood arsenic level with hyperuricemia among elderly aged 65 years and older. Methods: Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. 2 438 participants aged 65 years and older with complete information on blood arsenic and uric acid were included in this study. Information including demographics characteristic, life style and health status was collected by questionnaire and physical examination. Meanwhile, venous blood was collected to detect the levels of blood arsenic and uric acid. Subjects were stratified into three groups (low, middle and high) by tertiles of blood arsenic level. Logistic regression models were used to analyze the association of blood arsenic level with hyperuricemia. Results: The age of participants was (84.57±11.41) years, of which 1 172 (48.07%) were male and 1 525 (62.55%) were over 80 years old. The detection rate of hyperuricemia was 17.23% (420), and the detection rates of hyperuricemia were 11.77%, 19.25% and 20.62% among participants with low, middle and high blood arsenic, respectively (P<0.001). After controlling confounding factors, compared with participants who had low blood arsenic, the ORs (95%CI) of hyperuricemia for the participants with middle and high blood arsenic were 1.57 (1.12-2.23) and 2.08 (1.46-2.99), respectively. Subgroups analysis showed that compared with female, the association between blood arsenic level and hyperuricemia was more obvious in males (Pinteraction<0.05). Conclusion: Blood arsenic level is associated with the risk for hyperuricemia among the elderly aged 65 years and older in 9 longevity areas in China.

[Association of neutrophil-to-lymphocyte ratio with depressive symptoms among older adults aged 65 years and above in 9 longevity areas of China].

Objective: To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the risk of depression symptoms among older adults aged 65 and above in 9 longevity areas of China. Methods: Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted between 2017 and 2018. Finally,2018 elderly aged 65 years and above with complete information on neutrophil count, lymphocyte count and depressive symptoms were included in this study. Information on demographic characteristics, lifestyle, and health status was collected through questionnaire and physical examination. Complete blood counts which included lymphocytes and neutrophils were obtained by testing venous blood samples. Participants were divided into four groups by the quartile of NLR level, i.e. Q1, Q2, Q3, Q4. Logistic regression model was applied to analyze the association of NLR with depression symptoms. Results: Among 2 018 older adults, the mean(±SD) age was 82.6(±10.73), 1 032(51.14%) were male, 390(19.33%) were detected with depressive symptoms. Compared with participants of NLR in the 1st quartile, the OR(95%CI) of risk for depressive symptoms was 1.47 (0.99, 2.19), 1.67 (1.13, 2.47) and 1.95 (1.32, 2.89), respectively. Conclusion: Increased NLR level is significantly related to depressive symptoms among elderly aged 65 years and above in 9 longevity areas in China.

[Study on the etiological characteristics and prevention and control of adult community-acquired pneumonia in hospitalized patients in a hospital in Beijing from 2015 to 2019].

Objective: To explore the distribution characteristics of pathogens in adult patients with community-acquired pneumonia (CAP) and to provide basis for the diagnosis, treatment, prevention of CAP. Methods: 1 446 inpatients with CAP were prospectively enrolled in a third-class hospital in Beijing in recent 5 years (from January 2015 to December 2019). Respiratory tract samples were collected for smear, culture, nucleic acid, antigen and antibody detection to identify the pathogen of CAP. Mann-Whitney U test was used for continuous variables and χ2 test or Fisher's exact test was used for categorical data for statistical analysis. Results: Among the 1 446 patients, 822 (56.85%) patients were infected with a single pathogen, 231 (15.98%) patients were infected with multiple pathogens, and 393 (27.18%) patients were not clear about the pathogen. Influenza virus is the first pathogen of CAP (20.95%, 303/1 446), mainly H1N1 (8.51%, 123/1 446), followed by mycoplasma pneumoniae (7.19%, 104/1 446), Mycobacterium tuberculosis (5.33%, 77/1 446) and Streptococcus pneumoniae (5.05%, 73/1 446). The outbreak of H1N1 occurred from December 2018 to February 2019, and the epidemic of mycoplasma pneumoniae pneumonia was monitored from August to November 2019. Patients under 65 years old had high detection rates of Mycoplasma pneumoniae (14.41% vs. 2.41%, χ²=74.712,P<0.001), Streptococcus pneumoniae (8.16% vs. 2.99%, χ²=18.156, P<0.001), rhinovirus (6.08% vs. 3.56%, χ²=5.025, P<0.025), Chlamydia pneumoniae (5.90% vs. 1.15%, χ²=26.542, P<0.001) and adenovirus (3.13% vs. 0.92%, χ²=9.547, P=0.002). The severe disease rate of CAP was 14.66% (212/1 446), and the average mortality rate was 3.66% (53/1 446). The severe illness rate and mortality rate of bacterial-viral co-infection were 28.97% (31/107) and 19.63% (21/107), respectively. Conclusions: Influenza virus is the primary pathogen of adult CAP. Outbreaks of Mycoplasma pneumoniae and H1N1 were detected in 2018 and 2019, respectively. The remission rate and mortality rate of virus-bacteria co-infection were significantly higher than those of single pathogen infection. Accurate etiological basis not only plays a role in clinical diagnosis and treatment, but also provides important data support for prevention and early warning.

[Association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in 9 longevity areas of China].

Objective: To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China. Methods: A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia. Results: A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95%CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95%CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion: Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

[Association of blood lead level with cognition impairment among elderly aged 65 years and older in 9 longevity areas of China].

Objective: To investigate the association between blood lead concentrations and cognition impairment among Chinese older adults aged 65 or over. Method: Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. This study included 1 684 elderly aged 65 years and older. Information about demographic characteristics, socioeconomic factors, health status and cognitive function score of respondents were collected by questionnaire survey and physical examination. Venous blood of the subjects was collected to detect the blood lead concentration. Subjects were stratified into four groups (Q1-Q4) by quartile of blood lead concentration. Multivariate logistic regression model was used to analyze the association between blood lead concentration and cognitive impairment. The linear or non-linear association between blood lead concentration and cognitive impairment were described by restrictive cubic splines (RCS). Results: Among the 1 684 respondents, 843 (50.1%) were female and 191 (11.3%) suffered from cognition impairment. After adjusting for confounding factors, the OR value and 95%CI of cognition impairment was 1.05 (1.01-1.10) for every 10 µg/L increase in blood lead concentration in elderly; Compared with the elderly in Q1, the elderly with higher blood lead concentration had an increased risk of cognitive impairment. The OR value and 95%CI of Q2, Q3 and Q4 groups were 1.19 (0.69-2.05), 1.45 (0.84-2.51) and 1.92 (1.13-3.27), respectively. Conclusion: Higher blood lead concentration is associated with cognitive impairment among the elderly aged 65 years and older in 9 longevity areas in China.

Recognizing basal cell carcinoma on smartphone-captured digital histopathology images with a deep neural network.

BACKGROUND: Pioneering effort has been made to facilitate the recognition of pathology in malignancies based on whole-slide images (WSIs) through deep learning approaches. It remains unclear whether we can accurately detect and locate basal cell carcinoma (BCC) using smartphone-captured images. OBJECTIVES: To develop deep neural network frameworks for accurate BCC recognition and segmentation based on smartphone-captured microscopic ocular images (MOIs). METHODS: We collected a total of 8046 MOIs, 6610 of which had binary classification labels and the other 1436 had pixelwise annotations. Meanwhile, 128 WSIs were collected for comparison. Two deep learning frameworks were created. The 'cascade' framework had a classification model for identifying hard cases (images with low prediction confidence) and a segmentation model for further in-depth analysis of the hard cases. The 'segmentation' framework directly segmented and classified all images. Sensitivity, specificity and area under the curve (AUC) were used to evaluate the overall performance of BCC recognition. RESULTS: The MOI- and WSI-based models achieved comparable AUCs around 0·95. The 'cascade' framework achieved 0·93 sensitivity and 0·91 specificity. The 'segmentation' framework was more accurate but required more computational resources, achieving 0·97 sensitivity, 0·94 specificity and 0·987 AUC. The runtime of the 'segmentation' framework was 15·3 ± 3·9 s per image, whereas the 'cascade' framework took 4·1 ± 1·4 s. Additionally, the 'segmentation' framework achieved 0·863 mean intersection over union. CONCLUSIONS: Based on the accessible MOIs via smartphone photography, we developed two deep learning frameworks for recognizing BCC pathology with high sensitivity and specificity. This work opens a new avenue for automatic BCC diagnosis in different clinical scenarios. What's already known about this topic? The diagnosis of basal cell carcinoma (BCC) is labour intensive due to the large number of images to be examined, especially when consecutive slide reading is needed in Mohs surgery. Deep learning approaches have demonstrated promising results on pathological image-related diagnostic tasks. Previous studies have focused on whole-slide images (WSIs) and leveraged classification on image patches for detecting and localizing breast cancer metastases. What does this study add? Instead of WSIs, microscopic ocular images (MOIs) photographed from microscope eyepieces using smartphone cameras were used to develop neural network models for recognizing BCC automatically. The MOI- and WSI-based models achieved comparable areas under the curve around 0·95. Two deep learning frameworks for recognizing BCC pathology were developed with high sensitivity and specificity. Recognizing BCC through a smartphone could be considered a future clinical choice.