A novel Senescence-Based prognostic model unveils tumor interactions and drug resistance in colorectal cancer.

BACKGROUND: In China, CRC incidence is escalating. The main hurdles are heterogeneity and drug resistance. This research delves into cellular senescence in CRC, aiming to devise a prognostic model and pinpoint mechanisms impacting drug resistance. METHODS: Mendelian randomization (MR) analysis confirmed the association between CRC and cellular aging. The Cancer Genome Atlas (TCGA)-CRC data served as the training set, with GSE38832 and GSE39582 as validation sets. Various bioinformatics methods were employed to construct and validate a risk model. CRC cells with NADPH Oxidase 4 (NOX4) knockout were generated using CRISPR-Cas9 technology. Protein blotting and colony formation assays elucidated the role of NOX4 in CRC cell aging and drug resistance. RESULTS: A prognostic model, derived from dataset analysis, uncovered a link between high-risk groups and cancer progression. Notable differences in the tumor microenvironment were observed between risk groups. Finally, NOX4 was found to be linked with aging and drug resistance in CRC. CONCLUSION: This research presents a novel senescence-based CRC prognosis model. It identifies NOX4's role in CRC drug resistance, suggesting it is a potential treatment target.

Risk factors for hospital-acquired pneumonia in hip fracture patients: A systematic review and meta-analysis.

BACKGROUND: This study aimed to comprehensively assess the prevalence and risk factors for Hospital-acquired pneumonia (HAP) in hip fracture patients by meta-analysis. METHODS: Systematically searched 4 English databases and 4 Chinese databases from inception until October 20, 2022. All studies involving risk factors of HAP in patients with hip fractures will be considered. Newcastle-Ottawa Scale was used to evaluate the quality of the included studies. The results were presented through Review Manager 5.4 with the pooled odds ratio (OR) and 95% confidence interval. RESULTS: Of 35 articles included in this study, the incidence of HAP was 8.9%. 43 risk factors for HAP were initially included, 23 were eventually involved in the meta-analysis, and 21 risk factors were significant. Among them, the 4 most frequently mentioned risk factors were as follows: Advanced age (OR 1.07, 95% CI 1.05-1.10), chronic obstructive pulmonary disease (COPD) (OR 3.44, 95% CI 2.83-4.19), time from injury to operation (OR 1.09, 95% CI 1.07-1.12), time from injury to operation ≥ 48 hours (OR 3.59, 95% CI 2.88-4.48), and hypoalbuminemia < 3.5g/dL (OR 2.68, 95% CI 2.15-3.36). DISCUSSION: Hip fracture patients diagnosed with COPD have a 3.44 times higher risk of HAP compared to the general hip fracture patients. The risk of HAP also increases with age, with patients over 70 having a 2.34-fold higher risk and those over 80 having a 2.98-fold higher risk. These findings highlight the need for tailored preventive measures and timely interventions in vulnerable patient populations. Additionally, hip fracture patients who wait more than 48 hours for surgery have a 3.59-fold higher incidence of HAP. This emphasizes the importance of swift surgical intervention to minimize HAP risk. However, there are limitations to consider in this study, such as heterogeneity in selected studies, inclusion of only factors identified through multivariate logistic regression, and the focus on non-randomized controlled trial studies.

Deciphering alternative splicing events and their therapeutic implications in colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors with complex molecular regulatory mechanisms. Alternative splicing (AS), a fundamental regulatory process of gene expression, plays an important role in the occurrence and development of CRC. This study analyzed AS Percent Spliced In (PSI) values from 49 pairs of CRC and normal samples in the TCGA SpliceSeq database. Using Lasso and SVM, AS features that can differentiate colorectal cancer from normal were screened. Univariate COX regression analysis identified prognosis-related AS events. A risk model was constructed and validated using machine learning, Kaplan-Meier analysis, and Decision Curve Analysis. The regulatory effect of protein arginine methyltransferase 5 (PRMT5) on poly(RC) binding protein 1 (PCBP1) was verified by immunoprecipitation experiments, and the effect of PCBP1 on the AS of Obscurin (OBSCN) was verified by PCR. Five AS events, including HNF4A.59461.AP and HNF4A.59462.AP, were identified, which can distinguish CRC from normal tissue. A machine learning model using 21 key AS events accurately predicted CRC prognosis. High-risk patients had significantly shorter survival times. PRMT5 was found to regulate PCBP1 function and then influence OBSCN AS, which may drive CRC progression. The study concluded that some AS events is significantly different in CRC and normal tissues, and some of these AS events are related to the prognosis of CRC. In addition, PRMT family-driven arginine modifications play an important role in CRC-specific AS events.

Association between admission albumin levels and 30-day readmission after hip fracture surgery in geriatric patients: a propensity score-matched study.

PURPOSE: This study aimed to evaluate the correlation admission albumin levels and 30-day readmission after hip fracture surgery in geriatric patients. METHODS: In this retrospective cohort study, 1270 geriatric patients admitted for hip fractures to a level I trauma center were included. Patients were stratified by clinical thresholds and albumin level quartiles. The association between admission albumin levels and 30-day readmission risk was assessed using multivariate logistic regression and propensity score-matched analyses. The predictive accuracy of albumin levels for readmission was evaluated by ROC curves. The dose-response relationship between albumin levels and readmission risk was examined. RESULTS: The incidence of 30-day readmission was significantly higher among hypoalbuminemia patients than those with normal albumin levels (OR = 2.090, 95%CI:1.296-3.370, p = 0.003). Furthermore, propensity score-matched analyses demonstrated that patients in the Q2(35.0-37.9 g/L) (OR 0.621, 95%CI 0.370-1.041, p = 0.070), Q3(38.0-40.9 g/L) (OR 0.378, 95%CI 0.199-0.717, p < 0.001) and Q4 (≥ 41 g/L) (OR 0.465, 95%CI 0.211-0.859, p = 0.047) quartiles had a significantly lower risk of 30-day readmission compared to those in the Q1(< 35 g/L) quartile. These associations remained significant after propensity score matching (PSM) and subgroup analyses. Dose-response relationships between albumin levels and 30-day readmission were observed. CONCLUSIONS: Lower admission albumin levels were independently associated with higher 30-day readmission rates in elderly hip fracture patients. Our findings indicate that serum albumin may assist perioperative risk assessment, and prompt correction of hypoalbuminemia and malnutrition could reduce short-term readmissions after hip fracture surgery in this high-risk population.

Simultaneous determination of 28 illegal drugs in sewage by high throughput online SPE-ISTD-UHPLC-MS/MS.

This study developed an online solid-phase extraction ultra-high performance liquid chromatography-tandem mass spectrometry (Online-SPE-UHPLC-MS/MS) method for the analysis of 28 illegal drugs in sewage. To achieve this, 28 isotope internal standards (ISTDs) were added to 3 mL sewage samples, the pH was adjusted to 7-8 using hydrochloric acid or 20% ammonia water, followed by centrifugation, filtration, and analysis using UHPLC-MS/MS. The results indicated an excellent linearity of 1-300 ng L-1, and cotinine in the concentration range of 20-6000 ng L-1, linear correlation coefficient R2 > 0.995, with the limit of detection (LOD) of 0.01-6 ng L-1, and a limit of quantification (LOQ) of 0.1-20 ng L-1. The addition of three concentrates of low (2 ng L-1/40 ng L-1), medium (20 ng L-1/400 ng L-1), and high concentration (200 ng L-1/4000 ng L-1) demonstrated the matrix effect of the target compound between ± 22.0%. The extraction recovery was 70.0-119.4%, and a percent accuracy of 75.7-118.1%. Similarly, the intra- and inter-day precisions were 1.8-20.0% and 1.5-18.9%, respectively. The results cemented the sensitivity, accuracy, reliability, strong specificity, and reproducibility, which can be used to screen 28 illegal drugs in sewage for trace analysis.

The correlation between admission hyperglycemia and 30-day readmission after hip fracture surgery in geriatric patients: a propensity score-matched study.

Purpose: This study aimed to investigate the association between admission hyperglycemia and 30-day readmission after hip fracture surgery in geriatric patients. Methods: This retrospective study included 1253 geriatric hip fracture patients. Patients were categorized into normoglycemia(<6.10 mmol/L) and hyperglycemia groups(≥6.10 mmol/L) based on admission blood glucose. We performed multivariable logistic regression analyses and propensity score matching (PSM) to estimate adjusted odds ratios and 95% confidence intervals for 30-day readmission, controlling for potential confounding factors. An analysis of the dose-dependent association between admission blood glucose and the probability of 30-day readmission was performed. Additional subgroup analysis was conducted to examine the impact of other factors on the relationship between admission blood glucose and 30-day readmission. Results: Patients with hyperglycemia had higher 30-day readmission rates than normoglycemic patients before (19.1% vs 9.7%, p<0.001) and after PSM (18.1% vs 12.3%, p=0.035). Admission hyperglycemia was an independent predictor of increased 30-day readmission risk, with an adjusted odds ratio of 1.57 (95% CI 1.08-2.29, p=0.019) after multivariable regression and 1.57 (95% CI 1.03-2.39, p=0.036) after PSM. A dose-response relationship was observed between higher glucose levels and increased readmission risk. Conclusion: Admission hyperglycemia is an independent risk factor for 30-day readmission after hip fracture surgery in the elderly. Routine glucose testing upon admission and perioperative glycemic control may help reduce short-term readmissions in this vulnerable population.

Association between preoperative albumin levels and postoperative delirium in geriatric hip fracture patients.

Objective: This study aims to examine the association between preoperative serum albumin levels and postoperative delirium (POD) in geriatric patients who have undergone hip fracture surgery, with the goal of offering novel insights for clinical interventions targeting POD. Methods: A retrospective analysis was conducted on the medical records of patients who underwent hip fracture surgery in a tertiary medical institution from January 2013 to November 2023. The patients were classified based on hypoalbuminemia (defined as a serum albumin level < 35 g/L) and clinical threshold. Multivariable logistic regression and propensity score matching analysis (PSM) were employed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for POD to eliminate potential confounding factors. Additionally, subgroup analysis was performed to explore the interaction effect. Results: The retrospective cohort study included 1,440 patients, with an incidence of POD found to be 19.1%. In a multivariable logistic regression analysis, patients with hypoalbuminemia had an adjusted OR of 2.99 (95%CI: 2.14-4.18) compared to those with normal albumin levels (≥ 35 g/L). Furthermore, a significant trend was observed across different severity categories, including mild hypoalbuminemia (34.9-30.0 g/L; adjusted OR = 2.71, 95%CI: 1.84-3.99), moderate hypoalbuminemia (29.9-25.0 g/L, adjusted OR = 3.44, 95%CI: 1.88-6.28), and severe hypoalbuminemia (<25.0 g/L; adjusted OR = 3.97, 95%CI: 1.78-8.86), with a trend value of p <0.001. Similar results were observed in the PSM analysis. Additionally, treating preoperative serum albumin level as a continuous variable, the risk of POD increased by 11% (95% CI, 1.08-1.15) with each 1 g/L decrease in preoperative serum albumin level. Conclusion: Low preoperative levels of albumin are strongly associated with POD in geriatric patients with hip fractures, and a significant dose-response relationship exists between them.

Correlation between admission hypoalbuminemia and postoperative urinary tract infections in elderly hip fracture patients.

PURPOSE: This study aimed to evaluate the correlation between hypoalbuminemia upon admission and the incidence of postoperative urinary tract infections (UTIs) in elderly patients with hip fractures. METHODS: A retrospective analysis was performed on the medical records of elderly patients who underwent surgical treatment for hip fractures at a level I trauma center from 2013 to 2023. Serum albumin levels were measured upon admission, and hypoalbuminemia was defined as a total albumin level < 35 g/L. Multivariable logistic regression and propensity score matching analysis were utilized to control and reduce potential confounding factors, aiming to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CI) for UTIs to determine the strength of the association. RESULTS: This observational cohort study included 1279 patients, among whom 298 (23.3%) developed UTIs. Patients with albumin levels < 35 g/L had significantly greater odds of developing UTIs compared to those with albumin levels ≥ 35 g/L (OR 1.86, 95% CI 1.28-2.70). Further analysis, dividing albumin levels into quartiles, demonstrated that patients in the Q2 group (38.0-40.9 g/L; OR 1.38, 95% CI 0.88-2.17), Q3 group (35.0-37.9 g/L; OR 1.69, 95% CI 1.06-2.71), and Q4 group (15.3-34.9 g/L; OR 2.67, 95% CI 1.61-4.43) had notably higher odds of developing UTIs compared to those in the Q1 group (41.0-52.0 g/L). CONCLUSIONS: The presence of hypoalbuminemia upon admission in elderly patients undergoing hip fracture surgery is strongly correlated with the occurrence of postoperative UTIs. Furthermore, this association exhibits a clear dose-response relationship.

Performance of multigene testing in cytologically indeterminate thyroid nodules and molecular risk stratification.

Objective: Thyroid cancer is the third most prevalent cancer among females. Genetic testing based on next-generation sequencing may provide an auxiliary diagnosis to reduce cytologically diagnostic uncertainty. However, commercial multigene tests are not widely available and are not well-tested in the Chinese population. Methods: In this study, we designed a multigene testing panel and evaluated its performance in 529 cytologically indeterminate thyroid nodules (Bethesda III, IV and V). The molecular data of the DNA mutations and RNA fusions of fine needle aspiration samples were reviewed in conjunction with a clinical diagnosis, pathological reports, and definitive surgery for retrospective analysis. Then, the molecular risk stratification was investigated for its accuracy in malignant risk prediction. Results: The overall combined consistency revealed substantial agreement (Kappa = 0.726) with the sensitivity, specificity, positive predictive value, and negative predictive values of 97.80%, 82.14%, 98.99%, and 67.65%, respectively. The most common aberration was BRAFV600E (82.59%), followed by NRAS mutants (4.07%), RET fusions (3.70%), and KRAS mutants (3.15%). Two cases (0.44%) were categorized into a high-risk group, 426 cases (94.67%) were categorized into a BRAF-like group with totally histopathologic papillary patterned tumors, and 22 cases (4.89%) were categorized into a RAS-like group with 14 papillary and eight follicular patterned tumors when the cohort concurrent aberrations were excluded. Potentially aggressive features may be related to concurrent molecular alterations of BRAFV600E with TERTQ302R, and AKT1L52R, NRASG12C, NRASQ61R, and CCDC6-RET fusions. Conclusions: This study provided a multigene panel for identifying benign nodules from cytologically indeterminate thyroid nodules to avoid unnecessary surgery. We provide further evidence for using molecular risk stratification as a promising predictor of disease outcomes. The results of this study may be limited by the extremely high prevalence of cancer in the cohort for clinical reference.

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) to predict postoperative pneumonia in elderly hip fracture patients.

PURPOSE: Investigate the association between the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) about the presence of postoperative pneumonia (POP) in geriatric patients with hip fractures. Compare the predictive value of these biomarkers for POP and assess their potential for early detection of POP. METHODS: We retrospectively included elderly patients with hip fractures who underwent surgical treatment at our institution. POP was diagnosed according to the guidelines provided by the American Thoracic Society. We collected neutrophil, lymphocyte, and platelet counts upon admission to calculate the NLR, PLR, and SII. Receiver operating characteristic curves were utilized to establish the optimal cutoff values for each index. Multivariate logistic regression analysis and propensity score matching analysis were utilized to assess the independent association between each index and POP after adjusting for demographic, comorbidity, and surgery-related variables. RESULTS: The study included a total of 1199 patients, among whom 111 cases (9.26%) developed POP. NLR exhibited the highest predictive value for POP in elderly patients with hip fractures compared to PLR and SII (AUC = 0.648, 95% CI 0.594-0.701). A high NLR, using the optimal cutoff value of 5.84, was significantly associated with an increased incidence of POP (OR = 2.24, 95% CI 1.43-3.51). This finding remained statistically significant even after propensity score matching (OR = 2.04, 95% CI 1.31-3.20). CONCLUSIONS: Among the three inflammatory/immune markers considered, the NLR demonstrates the highest reliability as a predictor for POP in elderly patients with hip fractures. Therefore, it serves as a valuable tool for early identification.

D-dimer-albumin ratio (DAR) as a new biomarker for predicting preoperative deep vein thrombosis after geriatric hip fracture patients.

PURPOSE: Hip fractures in the elderly are complicated by preoperative deep vein thrombosis (DVT). The objective of this study is to determine the usefulness of blood-based biomarkers, particularly the D-dimer-albumin ratio (DAR), in predicting preoperative DVT. METHODS: A retrospective observational study was carried out on 1149 patients from a single hospital, and subsequently validated on an additional 626 patients from a separate hospital. The aim was to evaluate the prognostic and predictive value of 10 biomarkers, with a specific emphasis on DAR, in both cohorts. The primary measure of interest was the occurrence of preoperative DVT. RESULTS: The ratio of D-dimer to albumin demonstrated superior predictive capability for preoperative DVT in older patients with hip fractures compared to other biomarkers (AUC = 0.677). Using the optimal cutoff point of 0.24, high DAR was significantly associated with preoperative DVT (OR 3.45, 95% CI 2.00-5.95). Notably, all the DAR definitions detailed above were successfully validated in an external, independent cohort. CONCLUSIONS: DAR may be a valuable biomarker for predicting preoperative DVT in elderly patients with hip fractures.

A novel prognostic signatures based on metastasis- and immune-related gene pairs for colorectal cancer.

Background: Metastasis remains the leading cause of mortality in patients diagnosed with colorectal cancer (CRC). The pivotal contribution of the immune microenvironment in the initiation and progression of CRC metastasis has gained significant attention. Methods: A total of 453 CRC patients from The Cancer Genome Atlas (TCGA) were included as the training set, and GSE39582, GSE17536, GSE29621, GSE71187 were included as the validation set. The single-sample gene set enrichment analysis (ssGSEA) was performed to assess the immune infiltration of patients. Least absolute shrinkage and selection operator (LASSO) regression analysis, Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier analysis were used to construct and validate risk models based on R package. CTSW and FABP4-knockout CRC cells were constructed via CRISPR-Cas9 system. Western-blot and Transwell assay were utilized to explore the role of fatty acid binding protein 4 (FABP4) / cathepsin W (CTSW) in CRC metastasis and immunity. Results: Based on the normal/tumor, high-/low-immune cell infiltration, and metastatic/non-metastatic group, we identified 161 differentially expressed genes. After random assignment and LASSO regression analysis, a prognostic model containing 3 metastasis- and immune-related gene pairs was constructed and represented good prognostic prediction efficiency in the training set and 4 independent CRC cohorts. According to this model, we clustered patients and found that the high-risk group was associated with stage, T and M stage. In addition, the high-risk group also shown higher immune infiltration and high sensitivity to PARP inhibitors. Further, FABP4 and CTSW derived from the constitutive model were identified to be involved in metastasis and immunity of CRC. Conclusion: In conclusion, a validated prognosis predictive model for CRC was constructed. CTSW and FABP4 are potential targets for CRC treatment.

Diagnostic performance of six ultrasound-based risk stratification systems in thyroid follicular neoplasm: A retrospective multi-center study.

This study aimed to compare the diagnostic performances of six commonly used ultrasound-based risk stratification systems for distinguishing follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), including the American Thyroid Association Sonographic Pattern System (ATASPS), ultrasound classification systems proposed by American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinology (AACE/ACE/AME), Korean thyroid imaging reporting and data system (K-TIRADS), European Thyroid Association for the imaging reporting and data system (EU-TIRADS), American College of Radiology for the imaging reporting and data system (ACR-TIRADS), and 2020 Chinese Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules (C-TIRADS). A total of 225 FTA or FTC patients were retrospectively analyzed, involving 251 thyroid nodules diagnosed by postoperative pathological examinations in three centers from January 2013 to October 2021. The diagnostic performances of six ultrasound-based risk stratification systems for distinguishing FTA from FTC were assessed by plotting the receiver operating characteristic (ROC) curves and compared at different cut-off values. A total of 205 (81.67%) cases of FTA and 46 (18.33%) cases of FTC were involved in the present study. Compared with those of FTA, FTC presented more typical ultrasound features of solid component, hypoechoic, irregular margin and sonographic halo (all P<0.001). There were no significant differences in ultrasound features of calcification, shape and comet-tail artifacts between cases of FTA and FTC. There was a significant difference in the category of thyroid nodules assessed by the six ultrasound-based risk stratification systems (P<0.001). The areas under the curve (AUCs) of ATASPS, AACE/ACE/AME, K-TIRADS, EU-TIRADS, ACR-TIRADS and C-TIRADS in distinguishing FTA from FTC were 0.645, 0.729, 0.766, 0.635, 0.783 and 0.798, respectively. Our study demonstrated that all the six ultrasound-based risk stratification systems present potential in the differential diagnosis of FTA and FTC. Specifically, C-TIRADS exerts the best diagnostic performance among the Chinese patients. ATASPS possesses a high sensitivity, while K-TIRADS possesses a high specificity in distinguishing FTA from FTC.

Ultrasound Radiomics Nomogram to Diagnose Sub-Centimeter Thyroid Nodules Based on ACR TI-RADS.

The aim of the present study was to develop a radiomics nomogram to assess whether thyroid nodules (TNs) < 1 cm are benign or malignant. From March 2021 to March 2022, 156 patients were admitted to the Affiliated Hospital of Nantong University, and from September 2017 to March 2022, 116 patients were retrospectively collected from the Jiangsu Provincial Hospital of Integrated Traditional Chinese and Western Medicine. These patients were divided into a training group and an external test group. A radiomics nomogram was established using multivariate logistics regression analysis using the radiomics score and clinical data, including the ultrasound feature scoring terms from the thyroid imaging reporting and data system (TI-RADS). The radiomics nomogram incorporated the correlated predictors, and compared with the clinical model (training set AUC: 0.795; test set AUC: 0.783) and radiomics model (training set AUC: 0.774; test set AUC: 0.740), had better discrimination performance and correction effects in both the training set (AUC: 0.866) and the test set (AUC: 0.866). Both the decision curve analysis and clinical impact curve showed that the nomogram had a high clinical application value. The nomogram constructed based on TI-RADS and radiomics features had good results in predicting and distinguishing benign and malignant TNs < 1 cm.

Combination of ShuangDan Capsule and Sorafenib Inhibits Tumor Growth and Angiogenesis in Hepatocellular Carcinoma Via PI3K/Akt/mTORC1 Pathway.

Hepatocellular carcinoma (HCC) is a high mortality liver cancer. The existing treatments (transplantation, chemotherapy, and individualized treatment) with limitations. However, drug combination provides a viable option for hepatocellular carcinoma treatment. A Chinese patent medicine, ShuangDan Capsules (SDC), has been clinically prescribed to hepatocellular carcinoma patients as adjuvant therapy and has shown good antitumor activity. The purpose of this study was to investigate whether SDC could improve the anti-cancer effect and mitigate adverse reactions of sorafenib on HCC in vivo. Magnetic resonance imaging (MRI), immunohistochemistry, and western blot were executed to reveal the potential mechanisms of the combination of SDC and sorafenib on HCC. Tumors appeared hyperintense on T2 sequence images relative to the adjacent normal liver in MRI. Combination of SDC and sorafenib inhibited the progression of DEN (Diethylnitrosamine)-induced HCC. In the HepG2 xenografts model, sorafenib plus SDC exhibited greater suppression on tumor growth than individual treatment accompanied with decreased expression of VEGF, VEGFA, Ki67, CD31 and increased expression of caspase-3. Furthermore, PI3K/Akt/mTORC1 pathway was inhibited by co-administration. Sorafenib monotherapy elicited hepatotoxicity for specific expression in the up-regulated level of aspartate transaminase (AST) and AST/glutamic-pyruvic transaminase (ALT) ratio, but the co-administration could remedy this adverse effect. These dates indicated that the combination of SDC and sorafenib might offer a potential therapy for HCC.

[Leves and health risk assessment of 10 kinds of metal/metalloid elements in drinking water in Dongcheng District of Beijing from 2018 to 2020].

OBJECTIVE: To analyze the level of metal/metalloid elements and assess the health risk in drinking water in Dongcheng District of Beijing. METHODS: From 2018 to 2020, 10 kinds of metal/metalloid elements(Fe, Mn, Cu, Zn, Al, Pb, Cd, Ni, As and Se)in drinking water were detected by inductively coupled plasma-mass spectrometry(ICP-MS). The concentration of these metals were compared with the hygiene standards of drinking water. The health risk assessment model was applied from the USEPA. RESULTS: The concentration of 10 kinds of elements met the hygiene standards in all of the drinking water samples except that the zinc concentration of one sample exceeded the limit. The concentration of Al, Fe and Zn in drinking water was tens of µg/L. The concentration of Cu, Mn, Ni and Se was 1-2 µg/L or even lower. The concentration of As, Cd and Pb was basically less than 1 µg/L. The monthly average concentration of Al in drinking water showed a trend of increasing, and then decreasing in a year. The concentration of Zn decreased year by year. The 10 kinds of elements had not shown significant difference in the two water supply modes of municipal pipe network terminal water and secondary water(P>0.05). The total carcinogenic risk of elements through drinking exposure was 3.53×10~(-5). The carcinogenic risk of As was higher than that of Cd. The total non-carcinogenic risk was 9.75×10~(-8). The order of non-carcinogenic risk was: As>Se>Ni>Zn>Al>Pb>Fe>Cu>Mn>Cd. The total health risk was 3.54×10~(-5). CONCLUSION: The 10 kinds of metal/metalloid parameters of drinking water in Dongcheng District of Beijing met the hygiene standards. According to USEPA evaluation standard, the health risk assessment of elements in drinking water was acceptable.

Anticancer effect of caudatin in diethylnitrosamine­induced hepatocarcinogenesis in rats.

An overwhelming endoplasmic reticulum stress (ERS) and the following unfolded protein response (UPR) can induce hepatic inflammation, fibrosis and hepatocellular carcinoma (HCC). Caudatin, one of the species of C­21 steroidal glycosides mainly isolated from the roots of Cynanchum bungei Decne, exhibits potent anticancer activities in vivo. However, the effect of caudatin on HCC remains unclear. In the present study, a diethylnitrosamine (DEN)­induced HCC model was established. Nodules and tumors in rat livers were monitored by T2­/T1­weighted­magnetic resonance imaging (MRI) using a 1.5 T scanner. Caudatin reduced the number and size of nodules and alleviated the inflammatory foci in the liver. In addition, the hepatic pro­inflammatory levels of interleukin (IL) 6, monocyte chemoattractant protein 1 and IL­1ß were decreased in caudatin­treated rats. The DEN­induced surge in malondialdehyde, aspartate aminotransferase, alanine transaminase and TBIL were alleviated following caudatin treatment. The expression of ERS chaperones glucose­regulated protein, 94 kDa, glucose­regulated protein, 78 kDa and protein disulfide­isomerase A4 and the proliferation marker Ki­67 in liver nodules were all downregulated by caudatin as demonstrated by immunohistochemistry, reverse transcription­quantitative PCR and western blot analysis. Caudatin reduced the cytoprotective ERS sensor activating transcription factor 6­mediated signal transduction and inhibited the PKR­like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4 pathway. However, the effect of caudatin on inositol requiring enzyme 1 signaling was negligible. In conclusion, restoration of the dysregulated UPR program was involved in the antitumor efficacy of caudatin without inducing cumulative hepatotoxicity.

[Study on synergistic anti-tumor effect of Shuangdan Capsules combined with 5-FU on hepatocellular carcinoma cells Huh-7 and xenograft mice].

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 µmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.

Nodules with nonspecific ultrasound pattern according to the 2015 American Thyroid Association malignancy risk stratification system: A comparison to the Thyroid Imaging Reporting and Data System (TIRADS-Na).

New sonographic patterns have been recommended by the 2015 American Thyroid Association (ATA) to stratify nodules in terms of malignancy risk and help guide biopsy decision. This study aimed to compare the ultrasound part of the ATA guidelines and the Thyroid Imaging Reporting and Data System (TIRADS-Na).In 2013 to 2016, 708 thyroid nodules in 505 patients were confirmed by postoperative histopathology. Hypoechogenicity, solidity, microcalcification, irregular margin, and a taller-than-wide shape were considered features suggesting malignancy. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were obtained for the TIRADS and ATA guidelines.Of the 708 nodules, 341(48.2%) and 367(51.8%) were benign and malignant, respectively. Based on the ultrasound 2015 ATA guidelines, 62 nodules had nonspecific pattern (both malignant and benign features); malignancy rates of nodules with very low, low, intermediate, and high suspicion, and nonspecific pattern were 0, 17.7%, 57.9%, 90.0%, and 69.4%, respectively (P < .001). Malignancy rates of categories 2/3/4/5 nodules by TIRADS were 0, 8.1%, 67.0%, and 90.1%, respectively (P < .001). Based on pathological results, the AUC, sensitivity, specificity, NPV, and PPV were 0.926, 96.7%, 81.5%, 84.9%, and 95.9% for TIRADS, and 0.920, 93.5%, 82.4%, 85.1%, and 92.1% for ATA patterns, respectively. The TIRADS was generally more efficient than the 2015 ATA guidelines, especially for nodules >2 cm in diameter or those with nonspecific pattern.The TIRADS show a relative superiority over the ultrasound 2015 ATA guidelines, especially for nodules with >2 cm diameter or nonspecific pattern.

A multivariable model of BRAFV600E and ultrasonographic features for predicting the risk of central lymph node metastasis in cN0 papillary thyroid microcarcinoma.

Background: Prophylactic central lymph node dissection (CLND) in papillary thyroid microcarcinoma (PTMC) patients without clinical evidence of central lymph node metastasis (CLNM) remains controversial. The purpose of our study is to identify preoperative predictive factors for finding CLNM in Chinese PTMC patients, which may allow tailored CLND. Methods: We retrospectively reviewed 182 consecutive Chinese PMTC patients with negative central lymph nodes who underwent total thyroidectomy plus central neck dissection from October 2015 to December 2017. Chi-squared and multivariate analysis were performed to evaluate the association of CLNM with ultrasonographic and clinicopathologic characteristics. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the utility of markers in predicting CLNM. Results: The CLNM was found in 39.0% (71 of 182) of cN0 PTMC patients. In multivariate analysis, tumor size>7 mm (OR: 3.636, 95% CI: 1.671-7.914), marked hypoechogenicity (OR: 2.686, 95% CI: 1.080-6.678), multifocality (OR: 4.184, 95% CI: 1.707-10.258) and BRAFV600E mutation (OR: 5.339, 95% CI: 2.529-11.272) were independent predictors of CLNM. In ROC analysis integrating these predictors, the sensitivity was 63.4% and specificity was 80.2%, and the area under the ROC (AUC) was 0.755. Conclusion: In conclusion, we found tumor size>7 mm, marked hypoechogenicity, multifocality, and BRAFV600E mutation were risk factors for CLNM. In term of these preoperative risk factors for CLNM, prophylactic CLND should be cautiously performed in cN0 PTMC patients.