[Association between cognitive impairment and main metals among oldest old aged 80 years and over in China].

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 µg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

[The predictive value of warning scores for intensive care unit admission in coronavirus disease 2019 patients].

To evaluate the predictive value of early warning scores for intensive care unit (ICU) admission in patients with coronavirus disease 2019 (COVID-19). For COVID-19 patients who were admitted to Shijiazhuang People's Hospital from January 2021 to February 2021, national early warning score (NEWS), national early warning score 2 (NEWS2), rapid emergency medicine score (REMS), quick sepsis-related organ failure (qSOFA), altered consciousness, blood urea nitrogen, respiratory rate, blood pressure, and age-65 (CURB-65) were used to evaluate the inpatient condition and the predictive value for ICU admission. A total of 368 patients were included, and 32 patients (8.7%) were transferred to the ICU. The median age was 49.0 (34.0,61.0) years. The scores of NEWS, NEWS2, REMS, and CURB-65 were 1 (0, 2), 1 (0, 2), 4 (2, 6) and 0 (0, 1), respectively. The receiver operating characteristic (ROC) cure (AUC) was used to evaluate the predictive value in detecting patients who are at risk of being transferred to the ICU. Area under the ROC AUC of NEWS was 0.756, sensitivity 65.6%, and specificity 71.3%. ROC AUC of NEWS2 was 0.732, sensitivity 62.5%, and specificity 61.3%. ROC AUC of REMS was 0.787, sensitivity 84.4%, and specificity 64.6%. ROC AUC of CURB-65 was 0.814, sensitivity 81.3%, and specificity 76.8%. The predictive value of NEWS and NEWS2 combined with age were significantly improved. The ROC AUC of NEWS combined with age was 0.885, sensitivity 85.1%, and specificity 75.0%. The ROC AUC of NEWS2 combined with age was 0.883, sensitivity 84.2%, and specificity 75.0%. NEWS and NEWS2 combined with age can be used as a predictive tool for whether COVID-19 patients will be admitted to the ICU.

[Study on the comparison of postoperative liver injury caused by hepatic arterial perfusion chemotherapy combined with targeted immunotherapy with hepatic arterial chemoembolization combined with targeted immunotherapy for intermediate-and advanced-stage liver cancer].

Objective: To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs). Methods: Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ(2) test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results: This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ(2)=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ(2)=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ(2)=20.298, P < 0.001, 54.9% vs. 85.7%, χ(2)=17.917, P < 0.001;40.2% vs. 55.8%, χ(2)=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ(2)=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion: The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.

[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.

[Prediction of 6-year risk of activities of daily living disability in elderly aged 65 years and older in China].

Objective: To construct an easy-to-use risk prediction tool for 6-year risk of activities of daily living(ADL) disability among Chinese elderly aged 65 and above. Methods: A total of 34 349 elderly aged 65 and above were recruited from the Chinese Longitudinal Healthy Longevity Survey. Demographic characteristics, lifestyle and chronic diseases of the elderly were collected through face-to-face interviews. The functional status of the elderly was evaluated by the instrumental activities of daily living(IADL) scale. The mental health status of the elderly was evaluated by the Mini-Mental State Examination. The height, weight, blood pressure and other information of the subjects were obtained through physical examination and body mass index(BMI) was calculated. The ADL status was evaluated by Katz Scale at baseline and follow-up surveys. Taking ADL status as the dependent variable and the key predictors were selected from Lasso regression as the independent variables, a Cox proportional risk regression model was constructed and visualized by the nomogram tool. Area under the receiver operating characteristic curve(AUC) and calibration curve were used to evaluate the discrimination and calibration of the model. A total of 200 bootstrap resamples were used for internal validation of the model. Sensitivity analysis was used to evaluate the robustness of the model. Results: The M(Q1, Q3) of subjects' age as 86(75, 94) years old, of which 9 774(46.0%) were males. A total of 112 606 person-years were followed up, 4 578 cases of ADL disability occurred and the incidence density was 40.7/1 000 person-years. Cox proportional risk regression model analysis showed that older age, higher BMI, female, hypertension and history of cerebrovascular disease were associated with higher risk of ADL disability [HR(95%CI) were 1.06(1.05-1.06), 1.05(1.04-1.06), 1.17(1.10-1.25),1.07(1.01-1.13) and 1.41(1.23-1.62), respectively.]; Ethnic minorities, walking 1 km continuously, taking public transportation alone and doing housework almost every day were associated with lower risk of ADL disability [HR(95%CI): 0.71(0.62-0.80), 0.72(0.65-0.80), 0.74(0.68-0.82) and 0.69(0.64-0.74), respectively]. The AUC value of the model was 0.853, and the calibration curve showed that the predicted probability was highly consistent with the observed probability. After excluding non-intervening factors(age, sex and ethnicity), the AUC value of the model for predicting the risk of ADL disability was 0.779. The AUC values of 65-74 years old and 75 years old and above were 0.634 and 0.765, respectively. The AUC values of the model based on walking 1 km continuous and taking public transport alone in IADL and the model based on comprehensive score of IADL were 0.853 and 0.851, respectively. Conclusion: The risk prediction model of ADL disability established in this study has good performance and robustness.

[Association between urinary arsenic levels and anemia among older adults in nine longevity areas of China].

Objective: To investigate the association between urinary arsenic levels and anemia among older adults in nine longevity areas of China. Methods: A total of 1 896 subjects aged 65 years and above who participated in the Healthy Aging and Biomarkers Cohort Study (HABCS) in 2017-2018 were included. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information from the subjects. Through physical examination, data including height, weight and blood pressure were determined and body mass index (BMI) was calculated. Blood and urine samples were collected for the detection of hemoglobin (Hb), blood glucose, blood lipids, plasma vitamin B12 and urinary arsenic concentrations. The urinary arsenic levels were divided into four groups according to the quartiles of urinary arsenic concentrations (µg/g creatinine): Q1 (<18.7), Q2 (18.7-34.5), Q3 (34.6-69.5) and Q4(≥69.6). Multivariate logistic regression model and restricted cubic spline fitting logistic regression model were used to analyze the association between urinary arsenic levels and anemia. Results: The age of the 1 896 subjects (M (Q1, Q3)) was 83 (74, 92) years, including 952 females (50.21%), and the concentration of Hb (M (Q1, Q3)) was 135 (124, 147)g/L. The prevalence of anemia was 24.89% (472 cases). The geometric mean and M (Q1, Q3) of urinary arsenic concentrations were 37.5 and 34.6 (18.7, 69.6)µg/g creatinine, respectively. Multivariate logistic regression model analysis showed that after adjusting for age, gender, BMI, education level, smoking and drinking status, residence, economic level, ethnicity, the status of vitamin B12 deficiency, consumption frequency of aquatic products and meat, the prevalence of hypertension, diabetes and dyslipidemia, urinary arsenic levels were positively associated with anemia (Taking group Q1 as a reference, OR (95%CI) values in Q2, Q3 and Q4 groups were 1.73 (1.20-2.50), 2.08 (1.43-3.02) and 1.52 (1.02-2.28), respectively). The results of restricted cubic spline fitting logistic regression analysis showed a non-linear association between urinary arsenic concentrations and anemia (P<0.001). Subgroup analysis showed there was a negative multiplicative interaction between the prevalence of chronic diseases and urinary arsenic levels with OR (95%CI) was 0.55 (0.30-0.99), while no multiplicative interaction was found between age, gender, residence, smoking status, drinking status and urinary arsenic levels (P>0.05). There was a positive association between urinary arsenic levels and anemia in participants who were absence of chronic diseases,male, living in rural, smoking and drinking with OR (95%CI) values of 3.62 (1.30-10.06),2.46 (1.34-4.52), 1.70 (1.03-2.80), 2.21 (1.01-4.82) and 2.79 (1.23-6.33), respectively. Conclusion: There is a positive association between urinary arsenic levels and anemia among older adults in nine longevity areas of China.

[Analysis of the effect of microwave ablation in the treatment of small liver cancer].

Objective: To explore the clinical effect of microwave ablation in the treatment of early small liver cancer (≤3 cm). Methods: 103 cases with small liver cancer (tumor number < 3 and maximum tumor diameter < 3 cm) who underwent microwave ablation from November 2016 to November 2018 were retrospectively collected. The rate of residual lesions, recurrence rate one-year after the operation, and surgical complications were observed and grouped according to tumor size (< 2 cm and≥2 cm group) and tumor numbers (solitary and 2 ~ 3 lesion groups). The therapeutic effects of each group were compared and analyzed. Results: The tumor residual rate and one-year recurrence rate of small liver cancer after microwave ablation were 11.7% and 35.0%, respectively. The post-ablation syndrome incidence rate was 52.4%, with no serious adverse events. Compared with tumors < 2 cm, patients with≥2 cm had a higher postoperative residual rate (χ(2) = 7.651, P = 0.006), and the one-year recurrence rate of more solitary nodular tumors was lower (χ(2) = 10.125, P = 0.001). Conclusion: Microwave ablation is a safe and effective treatment for early small liver cancer, and it is more effective for small solitary nodules (< 2 cm).

[Regulatory effect of molecular targeted drugs on the immune system for liver cancer].

Molecular targeted drugs are the first choice for systemic treatment of liver cancer. In the past decade, several anti-liver cancer targeted drugs have been launched. More recently, immunotherapy has become a dazzling nova in the field of systemic treatment of liver cancer. Nivolumab and pembrolizumab have been approved as second-line treatments for patients with advanced hepatocellular carcinoma treated with sorafenib. However, the effect of single-agent treatment is always unsatisfactory in advanced liver cancer. An increasing number of evidences suggests that molecular targeted drugs have important immunomodulatory effects for liver cancer, and several targeted combined immunotherapies have also shown promising clinical effectiveness. This paper reviews the immunomodulatory effects of several molecular targeted drugs in the field of liver cancer.

[Deep learning reconstruction algorithm for coronary CT angiography in assessing obstructive coronary artery disease caused by calcified lesions: the clinical application value].

Objective: To investigate the image quality of coronary CT angiography (CCTA) subjected to deep learning-based reconstruction algorithm (DLR) method and its diagnostic performance for stenosis caused by coronary calcified lesions. Methods: We enrolled 33 consecutive patients with known or suspected coronary artery disease (CAD) who underwent CCTA and subsequently invasive coronary angiography (ICA) within 1 month in the department of radiology, Peking Union Medical College Hospital between February 2020 and February 2021. Among them, there are 26 males and 7 females, age range from 45 to 86 (61.9±9.0) years. The CCTA images were reconstructed with DLR and hybrid iterative reconstruction (HIR). Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated on the aorta root, left main artery, proximal left anterior descending, left circumflex, and right coronary artery of the CCTA images and were used to evaluate the objective image quality (IQ). Subjective IQ score was graded using Likert four-point scale (1 for excellent and 4 for poor). The diagnostic performance of obstructive coronary artery disease caused by calcified lesions on CCTA subjected to DLR and HIR methods were evaluated using ICA as the reference standard. Results: A total of 123 lesions in 33 patients were included in the analysis. Image noise of DLR image was significantly lower than that on HIR image(defined as the standard deviation of the attenuation values in the aortic root: 18.12±3.66 vs 24.19±5.71, P<0.001), CNR and SNR of DLR image in the aortic root were higher (CNR:43.83±23.73 vs 26.38±9.69, P<0.001,SNR:26.66±7.83 vs 21.23±8.65, P<0.001). Subjective scores of DLR was better than HIR image (1.12±0.41 vs 1.46±0.60,P<0.001). The sensitivity, specificity and accuracy of DLR and HIR images for diagnosing obstructive coronary artery disease caused by calcified lesions were 100.0%, 77.4%, 78.9% and 100.0%, 63.5%, 65.9%%, respectively. The number of false positive cases on DLR image decreased by 38% compared with HIR. Conclusions: Artificial intelligence based DLR can significantly reduce the image noise and improve the image quality of CCTA. DLR helps to improve the diagnostic performance of CCTA in assessing obstructive coronary artery disease caused by calcified lesions, which may have good clinical application value.

[Establishing an integrated hospital-community pyramid for screening and achieving hepatocellular carcinoma early diagnosis and treatment].

The comprehensive management of hepatocellular carcinoma (HCC) is a complete, dynamic and personalized process. Therefore, how to scientifically determine the HCC high-risk/extremely high-risk populations and develop a stratified monitoring plan is the key link to early detection, diagnosis and improvement of overall survival. In addition, accurately identifying high-risk/extremely high-risk groups based on the HCC risk prediction model, and applying it to establish an integrated hospital-community pyramid for HCC screening through the implementation of interdisciplinary scientific management and treatment may ultimately reduce HCC-related mortality rate.

[Application of aMAP score to assess the risk of hepatocarciongenesis in population of chronic liver disease in primary hospitals].

Objective: The aMAP score is a hepatocellular carcinoma (HCC) risk prediction model based on an international cooperative cohort, which can be applied to various liver diseases. The aim of this study is to use the aMAP score to stratify the risk of HCC in patients with chronic liver disease (combined or non-combined metabolic diseases) admitted to People's Hospital of Yudu County, Ganzhou City, Jiangxi Province, in order to guide personalized HCC screening. Methods: The demographic information, laboratory test results (platelets, albumin, and total bilirubin) and combined disease information of patients with chronic liver disease who were admitted to People's Hospital of Yudu from January 2016 to December 2020 were collected, and the aMAP score was calculated to stratify HCC risk in this population. Results: A total of 3629 cases with chronic liver disease were included in the analysis, including 3 452 (95.1%) cases with hepatitis B virus (HBV) infection, 177 (4.9%) cases with fatty liver, and 22 (0.6%) cases with HBV infection and fatty liver. There were 2 679 (73.8%) male and the median age was 44 (35, 54). In the overall population, low, medium and high risk of HCC accounted for 52.6%, 29.0%, and 18.4% respectively. In the HBV-infected population, the proportion of high risk of HCC was significantly higher than that of fatty liver (18.9% vs. 9.6%, P = 0.001). The proportion of chronic liver disease patients with combined hypertension or diabetes was significantly higher than that of those with non-combined metabolic diseases (combined hypertension: 32.3% vs. 17.9%, P < 0.001; combined diabetes: 36.5% vs. 18.1%, P < 0.001). Moreover, the proportion of high-risk population with two metabolic diseases was significantly higher than that with one and no metabolic diseases (40.9% vs. 31.8% vs. 17.7%, P < 0.001). Conclusion: The aMAP score can be used as a simple tool for HCC screening and management of chronic liver disease in primary hospitals, and it is helpful to improve the personalized follow-up management system of chronic liver disease population. Chronic liver disease patients with metabolic diseases have a higher risk of HCC, and people with high risk of HCC should be given special priority in follow-up visits, so as to improve the rate of HCC early diagnosis and reduce the mortality rate.

[Regulatory effect of miR-30b on migration and invasion of pancreatic cancer stem cells].

Objective: To detect the expression of micro RNA(miRNA, miR)-30bin pancreatic cancer stem cells (PCSCs) and to observe the regulatory effect of miR-30b on epithelial-mesenchymal transformation (EMT) process, migration and invasion of PCSCs. Methods: CD24, CD44 and EpCAM triple-positive PCSCs in pancreatic ductal adenocarcinoma(PDAC) cell line PANC-1 were sorted out by flow cytometry and the expression of Nanog and Oct4 were evaluated. The expression profile of miR-30 family in PCSCs and common cancer cells was analyzed, and the memberwith the most obvious differential expression was selected.miR-30b mimic was transfected into PCSCs and then RT-qPCR or Western Blot were performed to investigate the expression of EMT markers. The effect of miR-30b on the migration and invasion ability of PCSCs was detected by Transwell assay. Then, miR-30b agomir was transfected into PCSCs and inoculated in nude mice to study the effect of mir-30b on the tumorigenic ability. Results: PCSCs accounted for 4.52-8.09% of the total. The mRNA and protein levels of Oct4 and Nanog of PCSCswere significantly higher than those of PANC-1(P<0.001). The expression levels of miR-30b, c and d were significantly down-regulated, among which miR-30b was the most significant. After miR-30b overexpression in PCSCs, E-cadherin was significantly up-regulated (P<0.001), N-cadherin (P<0.001) and transcription factor Snail (P<0.001) were significantly down-regulated, while vimentin expression was not significantly changed. Transwell assay showed that both migration and invasiveness of PCSCs were significantly decreased after transfection (P<0.001). In vivo experiments, the tumor volume and weight of the nude mice injected with PCSCs overexpressing miR-30b were also significantly lower than those of the control group (P<0.01). Conclusions: CD24, CD44 and EpCAMtriple positive PCSCs in pancreatic cancer cells showed obvious stemness characteristics. miR-30b can reverse the EMT process of PCSCs, reduce their migration and invasion, and inhibit the tumorigenicity of PCSCs.

[Effects and related mechanism of overexpression of human thioredoxin on the inflammatory response in mice with viral myocarditis].

Objective: To observe the effects of recombinant adenovirus with human thioredoxin (hTRX) on the inflammatory response in mice with viral myocarditis and explore the related mechanism. Methods: Sixty Balb/c male mice were randomly divided into control group, myocarditis group, and hTRX group according to the random number table (n=20 each group). The myocarditis group and hTRX group were injected with 100 TCID(50) Coxackie virus B3 (0.1 ml) in the abdomen and control group were injected with saline. Two days before the viral injection, the hTRX group were injected with recombinant adenovirus vector coding the human thioredoxin gene by pericardial puncture and the control group and myocarditis group were injected with recombinant adenovirus vector without coding gene by pericardial puncture, all these mice were killed and hearts were removed 7 days later. The morphology of myocardial tissue in each group was detected by HE staining and the ultrastructure changes by electron microscope. The protein expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and NF-κB were detected by ELISA and Western blot. Immunohistochemical staining was performed to observe the protein expression levels of thioredoxin. Results: Necrosis of myocardial cells and a small amount of cell infiltration were found in the myocarditis group and necrosis and cell infiltration were significantly reduced in the hTRX group and no myocardial lesion was found in control group on HE stained sections. Electron microscope examination evidenced cell swelling and dissolved myofilament, vacuoles degeneration in mitochondria in the myocarditis group. These changes were significantly reduced in the hTRX group. There was no myocardial lesion in control group. The protein expression of TNF-α, IL-1ß and NF-κB were significantly upregulated in myocarditis group than in control group (all P<0.01). The protein expression of TNF-α, IL-1ß and NF-κB were significantly downregulated in hTRX group than in myocarditis group (all P<0.01). Immunohistochemical staining showed that protein expression of hTRX was higher in hTRX group than in myocarditis group (P<0.01). Conclusion: Recombinant adenovirus hTRX can attenuate cardiac injury in mice with acute myocarditis via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-1ß and NF-κB.

ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. METHODS: The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. RESULTS: The patients were well-controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. CONCLUSION: The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

[Analysis of prognostic factors on multidisciplinary team for diagnosis, treatment and prevention of hepatocellular carcinoma].

Objective: To analyze the prognostic factors on multidisciplinary team patients for diagnosis, and treatment of hepatocellular carcinoma. Methods: This retrospective study enrolled 132 HBsAg positive patients with HCC. MDT diagnostic approach was conducted at our hospital between 1 January 2015 and 31 December 2015, and all patients were followed up to 31 December 2017. Groups were arranged according to variables such as Barcelona stage, MDT compliance, and multidisciplinary combination therapy. TTP and OS were statistically analyzed. Results: The survival of the MDT compliance group was better than the non-compliance group. The difference in survival curves was statistically significant (χ(2) = 4.062, P < 0.05). The 1- and 2-year survival rates of the former group were 72.0%, 60.9%, and the latter was 64.3%, 40.3%. The survival of the combined treatment group was better than the non-combination group. The survival curves of the two groups were statistically significant (χ(2) = 9.502, P < 0.05), and they were independent influencing factors of survival (HR = 0.451, 95% CI, 0.210-0.968). The 1- and 2-year survival rates of the former group were 82.2% and 75.4%, and the latter was 63.1% and 44.6%. The median survival time of the follow-up group was 29.4 months, and the non-compliance and the uncombined group were 17.0 months. The difference was statistically significant (χ(2) = 13.336, P < 0.001). The median tumor progression time was 15.7 months in the combination group and 10.1 months in the non-compliance group (χ(2) = 7.263, P < 0.05). Conclusion: An advanced MDT compliance with implementation of multidisciplinary combination therapy may help to improve the prognosis of MDT patients with liver cancer.

Surface integrity and corrosion performance of biomedical magnesium-calcium alloy processed by hybrid dry cutting-finish burnishing.

Biodegradable magnesium-calcium (MgCa) alloy is a very attractive orthopedic biomaterial compared to permanent metallic alloys. However, the critical issue is that MgCa alloy corrodes too fast in the human organism. Compared to dry cutting, the synergistic dry cutting-finish burnishing can significantly improve corrosion performance of MgCa0.8 (wt%) alloy by producing a superior surface integrity including good surface finish, high compressive hook-shaped residual stress profile, extended strain hardening in subsurface, and little change of grain size. A FEA model was developed to understand the plastic deformation of MgCa materials during burnishing process. The measured polarization curves, surface micrographs, and element distributions of the corroded surfaces by burnishing show an increasing and uniform corrosion resistance to simulated body fluid.

In vitro cytotoxicity evaluation of nano-carbon particles with different sp2/sp3 ratios.

Graphitization occurs during the long-term service of a diamond-like carbon (DLC) modified artificial joint. Then, DLC wear debris, which are carbon particles with different sp2/sp3 ratios and sizes ranging from the nano- to micro-meter scale produced. In this paper, to promote the application of DLC coating for artificial joint modification, the cytotoxicity of DLC debris (nano-carbon particles, NCs) with different sp2/sp3 ratios was studied. The microstructure and physical characteristics of NCs with different sp2/sp3 ratios were investigated by Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS). Meanwhile, osteoblasts and macrophages were applied to characterize the cytotoxicity of the NCs. In vitro cytotoxicity assay results indicated that cells incubated with NCs of different sp2/sp3 ratios had greater osteogenic capacity, and these particles caused a weaker immune response in comparison with CoCrMo particles. Taken together, the results indicated that NCs with different sp2/sp3 ratios presented a good cytocompatibility than CoCrMo particles. But no significant differences were observed among NCs with different sp2/sp3 ratios. The better cytocompatibility of NCs is mainly attributable to their surface charge.

Dose-dependent cytotoxicity evaluation of graphite nanoparticles for diamond-like carbon film application on artificial joints.

While a diamond-like carbon (DLC)-coated joint prosthesis represents the implant of choice for total hip replacement in patients, it also leads to concern due to the cytotoxicity of wear debris in the form of graphite nanoparticles (GNs), ultimately limiting its clinical use. In this study, the cytotoxicity of various GN doses was evaluated. Mouse macrophages and osteoblasts were incubated with GNs (<30 nm diameter), followed by evaluation of cytotoxicity by means of assessing inflammatory cytokines, results of alkaline phosphatase assays, and related signaling protein expression. Cytotoxicity evaluation showed that cell viability decreased in a dose-dependent manner (10-100 µg ml-1), and steeply declined at GNs concentrations greater than 30 µg ml-1. Noticeable cytotoxicity was observed as the GN dose exceeded this threshold due to upregulated receptor of activator of nuclear factor kB-ligand expression and downregulated osteoprotegerin expression. Meanwhile, activated macrophage morphology was observed as a result of the intense inflammatory response caused by the high doses of GNs (>30 µg ml-1), as observed by the increased release of TNF-α and IL-6. The results suggest that GNs had a significant dose-dependent cytotoxicity in vitro, with a lethal dose of 30 µg ml-1 leading to dramatic increases in cytotoxicity. Our GN cytotoxicity evaluation indicates a safe level for wear debris-related arthropathy and could propel the clinical application of DLC-coated total hip prostheses.

Biological responses of diamond-like carbon (DLC) films with different structures in biomedical application.

Diamond-like carbon (DLC) films are potential candidates for artificial joint surface modification in biomedical applications, and the influence of the structural features of DLC surfaces on cell functions has attracted attention in recent decades. Here, the biocompatibility of DLC films with different structures was investigated using macrophages, osteoblasts and fibroblasts. The results showed that DLC films with a low ratio of sp(2)/sp(3), which tend to have a structure similar to that of diamond, led to less inflammatory, excellent osteogenic and fibroblastic reactions, with higher cell viability, better morphology, lower release of TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6), and higher release of IL-10 (interleukin-10). The results also demonstrated that the high-density diamond structure (low ratio of sp(2)/sp(3)) of DLC films is beneficial for cell adhesion and growth because of better protein adsorption without electrostatic repulsion. These findings provide valuable insights into the mechanisms underlying inhibition of an inflammatory response and the promotion of osteoblastogenesis and fibrous propagation, and effectively build a system for evaluating the biocompatibility of DLC films.

Introducing Mg-4Zn-3Gd-1Ca/ZnO nanocomposite with compressive strengths matching/exceeding that of mild steel.

This work introduces Mg-4Zn-3Gd-1Ca/2ZnO (wt.%) nanocomposite fabricated using the technique of disintegrated melt deposition and extrusion. Addition of ZnO nanoparticles enhanced the compressive strengths of alloy by ~100 MPa. Nanocomposite samples display high strength and good ductility: 0.2% compressive yield stress of 355 MPa, ultimate compressive stress of 703 MPa, and compressive failure strain of 10.6%. The significant enhancement of compressive yield stress is mainly attributed to the grain refinement by adding nanoparticles. The strength levels exceed that of commercial magnesium alloys (i.e. WE43, WE54, ZK60, and ME21) and mild steels (i.e. S275 and S355), making Mg-4Zn-3Gd-1Ca/2ZnO a very promising material for multiple engineering and biomedical applications.