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Mei Xiao,1 Guangwen Luo,1 Zhaowei Zhang,1 Yanfen Liu,2 Rui Gong,3 Jianghuan Ke1 1Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 2Department of Endocrinology and Metabolism, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Guangwen Luo, Department of pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel +86-0579-82552760, Email lgw2018@126.comPurpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients.Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR.Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, thyroid-stimulating hormone, free triiodothyronine, glucose and lipid metabolism

Xueyao Su,1,&ast; Yanyan Huang,1,&ast; Wei Dai,2 Yubo Zhang,3 Lijun Zhang,1 Jiayuan Zhang,3 Ruoyan Gong,1 Jingwen Yu,3 Dan Kang,1 Rumei Xiang,1 Jiaojiao Chen,1 Qiuling Shi1– 3 1School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 3State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuling Shi, School of Public Health, Chongqing Medical University, No. 1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-18290585397, Fax +86-28-85420116, Email qshi@cqmu.edu.cnPurpose: This study aimed to evaluate the presence of recall bias when patients retrospectively report cough scores.Patients and Methods: Patients who underwent lung surgery between July 2021 and November 2021 were recruited for this study. We retrospectively assessed the severity of cough within the past 24 hours and the past 7 days using a 0– 10 numerical rating scale. Recall bias was defined as the difference between the scores reported on the two assessments. Patients were grouped based on the longitudinal change in cough scores from pre-operation to 4 weeks after discharge using group-based trajectory models. Using generalized estimating equation to explore the factors influencing recall bias.Results: Overall, 199 patients were analyzed and demonstrated the three distinct trajectories of post-discharge cough: high (21.1%), medium (58.3%), and low (20.6%). Significant recall bias was found in week 2 for the high-trajectory patients (6.26 vs 5.10, P< 0.01) and in week 3 for the medium-trajectory patients (2.88 vs 2.60, P=0.01). Among all recall bias, 41.8% were of underestimation, and 21.7% of overestimation. The high trajectory group (β=1.14, P< 0.01) and measurement interval (β=0.36, P< 0.01) were risk factors for underestimation, while post-discharge time (β=− 0.57, P< 0.01) and measurement interval (β=− 0.13, P=0.02) were protective factors for overestimation.Conclusion: Retrospective assessment of post-discharge cough in patients who underwent lung surgery will introduce recall bias, with a tendency of underestimation. The high-trajectory group, interval time and post-discharge time are influencing factors of recall bias. For patients with severe cough at discharge, a shorter recall periods should be employed for monitoring, due to the large bias that results from a longer recall period.Keywords: patient-reported outcome, lung surgery, cough measurement, recall bias

Jingyu Zhang,1,&ast; Yinxia Zhan,2,&ast; Jiaojiao Chen,2 Dan Kang,2 Rumei Xiang,2 Ruoyi Zhang,2 Yubo Zhang,1 Yang Pu,2 Jiayuan Zhang,1 Lijun Zhang,2 Yanyan Huang,2 Ruoyan Gong,2 Xueyao Su,2 Yuxian Nie,1 Qiuling Shi1,2 1State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China; 2School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuling Shi, State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-18290585397, Email qshi@cqmu.edu.cnBackground: Patients with hepatobiliary or pancreatic cancers often experience severe symptoms, resulting in a sharp decline in functioning, poor quality of life, and increased mortality risk. Early and effective management of symptoms allows a better quality of life and reduced mortality, depending on the selection of appropriate assessment of specific symptoms for a defined purpose. We aimed to develop a symptom measurement item bank for hepatobiliary or pancreatic cancers.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was applied to organize this systematic review. The articles validated patient-reported outcome measures (PROMs) for hepatobiliary or pancreatic cancer and published before December 2021 were retrieved from the Web of Science, PubMed, Embase databases and Cochrane Library. Items from the existing PROMs were selected and classified into different patient-reported symptoms based on the concepts and specific underlying constructs of the objects measured.Results: Sixteen unique PROMs were identified across the 29 eligible studies included in our analysis. Items from the literature review (14 PROMs with 421 items for which information was obtained) were selected and classified. As a result of this study, we developed a symptom item bank with 40 patient-reported symptoms and 229 assessment items for hepatobiliary or pancreatic cancer, and fatigue, pain and nausea were the most common symptom items.Conclusion: We developed an item bank to assess the patient-reported symptoms of hepatobiliary or pancreatic cancer. This item bank could allow researchers to select appropriate measures of symptom and provide a basis for the development of a single-item symptom-measurement system.Keywords: patient-reported outcome measures, symptom, item bank, pancreatic carcinoma, hepatocellular carcinoma, cholangiocarcinoma, systematic review

Yunlei Deng,1,* Qianwen Zhao,2,* Rong Gong1 1Department of Nephrology, The Chengdu Second Affiliated Hospital of Chongqing Medical University, The Third People’s Hospital of Chengdu, Chengdu, People’s Republic of China; 2Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong GongDepartment of Nephrology, The Chengdu Second Affiliated Hospital of Chongqing Medical University, The Third People’s Hospital of Chengdu, 37# Qinglong Street, Qingyang District, Chengdu, Sichuan Province, People’s Republic of ChinaTel +86 159 8217 4685Email gongr2006@sina.comPurpose: In 2020, an international expert consensus proposed a novel concept, defined as metabolic associated fatty liver disease (MAFLD). We aimed to investigate the association between MAFLD and chronic kidney disease (CKD).Methods: A total of 4869 subjects with demographic data, laboratory tests, and ultrasound transient elastography from National Health and Nutrition Examination Surveys of the United States (NHANES) 2017– 2018 were included in the study. Statistical analysis was performed to test the independent association between the demographic data, laboratory tests, and non-invasive liver fibrosis scores in subjects with different subgroups of MAFLD.Results: A total of 4869 subjects were identified in the NHANES 2017– 2018, of which 1032 (21.2%) subjects were diagnosed with CKD. There was a higher prevalence of CKD in MAFLD subjects than in non-MALFD subjects (22.2% vs 19.1, p=0.048). After 1:1 propensity score matching by gender, age and race, we enrolled 1983 subjects with MAFLD diagnosed based on liver ultrasound transient elastography and 1983 PS-matched subjects without MAFLD. MAFLD was not independently associated with CKD after PSM. Further investigation showed that age (OR: 1.05, 95% CI: 1.03∼ 1.05, p< 0.001), hypertension (OR: 1.66, 95% CI: 1.38∼ 2.00, p< 0.001), DM (OR: 2.21, 95% CI: 1.89∼ 3.11, p< 0.001), hyperuricemia (OR: 1.91, 95% CI: 1.55∼ 2.36, p< 0.001), ALP (OR: 1.00, 95% CI: 1.00∼ 1.01, p=0.010), and FIB-4 score (OR: 1.23, 95% CI: 1.05∼ 1.01, p=0.011) were independently associated with CKD. In the subgroup analysis, the subgroups of MAFLD complicated with DM, age, hypertension, and hyperuricemia were independently related to the incidence of CKD. In the subgroup of DM without MAFLD, age, hyperuricemia, ALP, and NFS score were independently related to the incidence of CKD. In the subgroup of MAFLD without DM, age, hypertension, hyperuricemia, and ALP were independently related to the incidence of CKD.Conclusion: Based on the NHANES 2017– 2018, MAFLD was not independently associated with CKD. Thus, the link between MAFLD and CKD may be mediated by metabolic abnormalities, such as diabetes mellitus and hyperuricemia.Keywords: metabolic associated fatty liver disease, chronic kidney disease, diabetes mellitus, hyperuricemia

Jun Zuo,1,2 Ruisong Gong,1,2 Xiaowen Liu,2 Jing Zhao1,2 1Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, People’s Republic of China; 2Department of Anesthesiology, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of ChinaCorrespondence: Jing ZhaoDepartment of Anesthesiology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Beijing 100029, People’s Republic of ChinaEmail zhaojing1009@aliyun.comBackground: Local anesthetics (LAs) have been widely used throughout the healthcare settings, especially in local anesthesia and pain management. The incidence of allergic reactions to LAs remains uncertain. The danger of allergic reactions to the use of LAs in every day of clinical practice is a matter of great concern. Therefore, it is necessary to investigate the risk of true allergy to LAs.Methods: This study retrospectively evaluated the medical records of patients who were referred to an anesthesia allergy clinic in China and underwent allergy tests with LAs over a 10-year period from 2009 to 2019. The following information was collected from medical records: demographics of the patients, reasons for referral, clinical features of drug hypersensitivity reaction (DHR), and test results with LAs. Skin tests combined with an in vitro method, basophil activation test (BAT), were used to investigate allergic reactions to LAs.Results: A group of 109 patients were included in the analysis. The main reason for referral was the presence of a suspected DHR after procedures with LAs (n=68, 62%), the second most common reason for referral was a history of DHR to other drugs and the need to use LAs for upcoming procedures (n=41, 38%). Of the 68 patients with a suspected DHR to LAs, only six cases presented true allergy and showed positive results in skin tests and/or BAT. And all 41 patients who had a history of DHR to other drugs presented negative in all tests.Conclusion: Risk of true allergy to LAs may be very low. However, patients with a suspected history of DHR to LAs should be considered for allergy tests. Skin tests and BAT may be useful in the investigation and diagnosis of true allergy to LAs in clinical practice.Keywords: adverse drug reactions, local anesthetics, allergy, skin tests, BAT

Wenjie Chen,1 Tao Wei,1 Zhihui Li,1 Rixiang Gong,1 Jianyong Lei,1 Jingqiang Zhu,1 Tao Huang2 1Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Jingqiang ZhuThyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaTel/Fax +86-28-85422467Email zjqhuaxidoctor@163.comTao HuangDepartment of Breast and Thyroid Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaEmail huangtaowh@163.comBackground: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) have been reported to be prognostic biomarkers in various cancers. Our study evaluated whether the preoperative NLR, PLR and PNI predicted tumor-node-metastasis (TNM) stage and recurrence in papillary thyroid carcinoma (PTC) patients.Methods: A total of 1873 patients with PTC from 9 centers in mainland China were retrospectively assessed. Receiver operating characteristic (ROC) curves were generated, and Kaplan-Meier analyses were performed to evaluate the prognostic value of inflammation-based scores. Univariate and multivariate analyses were conducted to identify risk factors for recurrence.Results: A decreased PNI and an increased PLR were predictive of TNM stage (p=0.005 and p=0.030, respectively), while a decreased NLR was predictive of recurrence (p=0.040). Univariate and multivariate analyses indicated that N1 status (odds ratio (OR), 1.898; 95% confidence interval (CI), 1.253– 2.874; p=0.002), NLR≤ 1.6 (OR, 1.596; 95% CI, 1.207– 2.111; p=0.001) and PNI≤ 53.1 (OR, 1.511; 95% CI, 1.136– 2.009; p=0.005) were independent factors that predicted recurrence.Conclusion: The NLR, PLR and PNI have predictive value for TNM stage and recurrence in patients with PTC, but their predictive efficiency is limited. Caution should be used when considering clinical applications of inflammation-based scores.Keywords: inflammation-based scores, papillary thyroid carcinoma, lymph node metastasis, prognosis

Ke Jiang,1 Genpeng Li,1 Wenjie Chen,1 Linlin Song,1 Tao Wei,1 Zhihui Li,1 Rixiang Gong,1 Jianyong Lei,1 Hubing Shi,2 Jingqiang Zhu1 1Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 2State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, Sichuan, People’s Republic of ChinaCorrespondence: Jianyong LeiThyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaTel/Fax +86-28-85423822Email leijianyong11@163.comHubing ShiState Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, Sichuan, People’s Republic of ChinaEmail shihb@scu.edu.cnBackground: Lymph node metastasis (LNM) is associated with increased risk of recurrence and poor prognosis in papillary thyroid cancer (PTC). Novel non-invasive biomarkers for the prediction of LNM in PTC patients are still urgently needed. In this study, the relationship between the expression of plasma exosomal microRNAs (miRNAs) and LNM was analyzed. Further, we aimed to explore if exosomal miRNAs can serve as indicators of LNM in PTC patients.Methods: A total of 64 PTC patients who underwent total thyroidectomy and neck dissection from June 2018 to July 2018 in West China Hospital were enrolled in this study. Plasma exosomes were isolated by exoRNeasy Serum/Plasma Maxi Kit. The levels of selected exosomal miRNAs were detected by real-time quantitative PCR (qRT-PCR). Cox proportional hazard analyses and receiver operating characteristic (ROC) curves were conducted to evaluate the predictive efficiency. Furthermore, PTC cell lines with transfection of miRNA mimics/inhibitors were used to verify the functions of exosomal miRNAs.Results: 49 PTC patients with LNM and 15 without LNM were included in the present study. Exosomal miR-146b-5p and miR-222-3p were both significantly upregulated in patients with LNM (P values were 0.008 and 0.015, respectively). ROC analyses revealed that the areas under the curves (AUCs) of miR-146b-5p and miR-222-3p for LNM prediction were 0.811 and 0.834, respectively. Moreover, the AUC increased to 0.895 when the two miRNAs used together. Wound healing assays and transwell assays showed that miR-146b-5p and miR-222-3p significantly enhanced the migration and invasion ability of PTC cells in vitro.Conclusion: Plasma exosomal miR-146b-5p and miR-222-3p could serve as potential biomarkers for LNM in PTC.Keywords: papillary thyroid cancer, lymph node metastasis, exosomal miRNAs, biomarkers

Genpeng Li,1,* Lijuan Wang,1,* Jianyong Lei,1 Linlin Song,1 Huairong Tang,2 Zhihui Li,1 Rixiang Gong,1 Jingqiang Zhu1 1Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 2Health and Management Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huairong TangHealth and Management Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaTel +86-28-85422933Fax +86-28-85422933Email thrhuaxi11@163.comBackground: The frequency of thyroid nodules (TNs) has increased rapidly in recent decades. We established a simple, effective model to predict TN occurrence by a large-scale comparative analysis of the Chinese population.Subjects and methods: A total of 13,307 subjects were included to screen risk factors between the case group (TN+) and the control group (TN-) by univariate and multivariate analyses. A simple prediction model formed by a subset of five factors was established. The optimal index points for predicting the prevalence of TNs, the model discriminatory power and the association of the model with the size of TNs were assessed.Results: Age at diagnosis ≥45 years, female sex, body mass index (BMI) ≥24 kg/m2, hypertension, antithyroglobulin antibody (TGAB) ≥16.5 IU/mL were independently related to an increased risk of TNs. The cutoff value of 4 points was found to be the best prediction for the prevalence of TNs in the current study, and the model had better discriminatory power than other single independent predictors. In addition, a positive correlation was also found between the index points and the diameter of TNs.Conclusion: Based on our prediction model, thyroid high-resolution ultrasound and associated laboratory tests may be necessary for patients with index points ≥4 due to a higher prevalence of thyroid nodules.Keywords: thyroid nodules, large-scale, risk factors, prediction model

Linlin Song,1,2 Jingqiang Zhu,1 Zhihui Li,1,3 Tao Wei,1,3 Rixiang Gong,1,3 Jianyong Lei1 1Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of China; 2West China School of Medicine, Sichuan University, Chengdu 610065, People’s Republic of China; 3Thyroid and Breast Surgery Center, Chengdu Shang Jin Nan Fu Hospital, Chengdu 611700, People’s Republic of ChinaCorrespondence: Jianyong LeiThyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaTel +86 288 542 3822Fax +86 288 542 3822Email leijianyong11@163.comBackground and Aims: The prognosis of papillary thyroid carcinoma (PTC) is highly variable, even for high-risk cases. The predictive and prognostic role of the lymphocyte-to-monocyte ratio (LMR) has been reported in other cancers. The aim of our present study was to explore the value of LMR prognostic prediction in high-risk PTC patients.Patients and Methods: Two hundred and twenty-four PTC high-risk cases at West China Hospital were randomized into a training set (112 cases) and testing set (112 cases), while 48 cases in Shang Jin Nan Fu Hospital were included as the external validation set.Results: A lower preoperative LMR correlated with larger tumor size, advanced N and M stages, and an increased number of multiple PTC cases in the training, testing, and validation sets (all P

Ren Gong,1 Xi-Yong Li,1 Huai-Jing Chen,2 Cong-Cong Xu,1 Hai-Yang Fang,1 Jian Xiang,1 Yan-Qing Wu11Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Cardiology, Baoan Central Hospital of Shenzhen, Shenzhen, People’s Republic of ChinaObjective: The aim was to investigate the role and potential mechanism of geranylgeranylacetone (GGA) in the development of atherosclerosis, and to explore the role of heat shock protein 22 (HSP22) in mediating GGA effect.Methods: Human coronary artery endothelial cell (HCAEC) was used for in vitro study. RNA interference was applied to suppress HSP22 in the cells. Cellular apoptosis and intracellular level of reactive oxygen species (ROS) were detected by flow cytometer, and proteins of HSP22, NF-κB, eNOS, and ICAM-1 were assessed by immunoblotting. HSP22-/-//ApoE,-/- and HSP22+/+//ApoE-/- mice were used to investigate the effect of GGA in the animal model of atherosclerosis. Atherosclerotic lesion of the mice aortas was evaluated by Oil Red O staining and H&E staining.Results: GGA significantly inhibited HCAEC apoptosis in response to oxidized-LDL (ox-LDL), but stimulated HSP22 synthesis in the cells. Transfection of HSP22-siRNA in the cells resulted in complete blockage of the GGA effect on apoptosis. GGA also significantly inhibited ROS, NF-κB, and ICAM-1 in the cells transfected control siRNA, but not in the cells transfected with HSP22-siRNA. Atherosclerotic plaque in the aorta was significantly less in the wild type (WT) animals treated with GGA as stained either by Oil Red O or by H&E staining, but not in the HSP22-KO mice. GGA significantly inhibited expression of NF-κB and ICAM-1 in the WT mice, but not in the HSP22-KO mice.Conclusion: GGA-induced HSP22, and inhibited ox-LDL-induced apoptosis as well as expression of NF-κB and ICAM-1 in the HCAECs. GGA also attenuated formation of atherosclerotic plaques in mice aorta. Suppression of HSP22 by siRNA resulted in blockage of the GGA inhibition on apoptosis or stimulation on NF-κB and ICAM-1. These findings suggested that GGA protects endothelial cells from injury in response to ox-LDL and block atherosclerotic development in mice aorta through induction of HSP22.Keywords: geranylgeranylacetone (GGA), heat shock protein 22 (HSP22), endothelial cells, inflammatory response, atherosclerosis

Rui Gong,1,2 Yuan He,1,2 Xiao-Yun Liu,1,2 Hai-Yun Wang,1,2 Li-Yue Sun,1,2 Xin-Hua Yang,1,2 Bin Li,3 Xin-Kai Cao,3 Zu-Lu Ye,1,2 Ling-Heng Kong,1,4 Da-Dong Zhang,3 Yu-Hong Li,1,5 Rui-Hua Xu,1,5 Jian-Yong Shao1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 2Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China; 3Research and Development Institute of Precision Medicine, 3D Medicine Inc., Shanghai, 201114, People’s Republic of China; 4Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 5Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of ChinaBackground: Genetic factors play an important role in colorectal cancer (CRC) risk, yet the prevalence and spectrum of germline cancer susceptibility gene mutations among unselected Chinese CRC patients is largely undetermined.Methods: We performed next-generation sequencing with a 73-genes panel and analyzed the prevalence and spectrum of germline mutations in 618 unselected Chinese CRC patients. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations. Clinical characteristics were assessed by age and mutation status. Protein expressions and interactions of MLH1 missense variants were evaluated by western blot and co- immunoprecipitation.Results: Overall, 112 (18.1%) of 618 unselected Chinese CRC patients were found to carry at least one pathogenic or likely pathogenic variant (totaling 97 variants), including 70 (11.3%) Lynch syndrome (LS) mutation carriers and 42 (6.8%) non-LS mutation carriers. LS mutation carriers were significantly younger at CRC diagnosis and were more likely to have right-sided, poorly differentiated, early stage, high-frequency microsatellite instability (MSI-H) or dMMR CRC and a family history of cancer compared with noncarriers. Non-LS mutation carriers were more likely to be proficient mismatch repair (pMMR) than noncarriers (p=0.039). We found four clinical variables (gender, tumor histological stage, cancer stage and mutation status) that showed significant differences between patients younger and older than 50 years old. Higher mutation rates were found in patients under 50 years old (p=0.017). Thirty-three novel variants were discovered and evaluated as pathogenic mutations by our study.Conclusion: Given the high frequency and wide spectrum of mutations, genetic testing with a multigene panel should be considered for all Chinese CRC patients under 50 years old and is also needed to determine whether a gene is associated with CRC susceptibility and to promote clinical translation.Keywords: genetic factor, germline mutations, Lynch syndrome, next-generation sequencing

A hallmark of many unconventional superconductors is the presence of many-body interactions that give rise to broken-symmetry states intertwined with superconductivity. Recent resonant soft X-ray scattering experiments report commensurate 3a0 charge density wave order in infinite-layer nickelates, which has important implications regarding the universal interplay between charge order and superconductivity in both cuprates and nickelates. Here we present X-ray scattering and spectroscopy measurements on a series of NdNiO2+x samples, which reveal that the signatures of charge density wave order are absent in fully reduced, single-phase NdNiO2. The 3a0 superlattice peak instead originates from a partially reduced impurity phase where excess apical oxygens form ordered rows with three-unit-cell periodicity. The absence of any observable charge density wave order in NdNiO2 highlights a crucial difference between the phase diagrams of cuprate and nickelate superconductors.

Wenjie Chen,1 Jianyong Lei,1 Jiaying You,2 Yali Lei,3 Zhihui Li,1 Rixiang Gong,1 Huairong Tang,3 Jingqiang Zhu1 1Thyroid and Parathyroid Surgery Center, 2West China School of Clinical Medicine, 3Health and Management Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China Background: Recurrent laryngeal nerve (RLN) invasion in papillary thyroid carcinoma (PTC) is one of the main predictors of poor prognosis. The present study investigated the risk factors for RLN invasion in PTC patients.Methods: A total of 3,236 patients who received thyroidectomy due to PTC in Thyroid and Parathyroid Surgery Center of West China Hospital of Sichuan University were reviewed. Demographics and clinical factors, imaging examination (ultrasonography) characteristics, surgical details, postoperative pathological details, recurrence, and postoperative complications were recorded. Univariate and multivariate analyses were used to study the risk factors of RLN invasion, Kaplan–Meier method was performed to compare the outcomes of tumor recurrence.Results: Patients with RLN invasion had a higher recurrence rate than those in the control group (p

Kai Teng,1,2,* Yong Zhang,1,* Xiaoyan Hu,1 Yihui Ding,1 Rui Gong,1 Li Liu1,* 1Department of Thoracic Oncology, Cancer Center of Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Radiation Oncology, Hainan Cancer Hospital, Haikou, Hainan, People’s Republic of China *These authors contributed equally to this work Background: The epidermal growth factor receptor (EGFR) signaling pathway plays a significant role in radiation resistance. There is evidence that EGFR nuclear translocation is associated with DNA double-strand breaks (DSB) repair. Nimotuzumab has shown the effect of radiosensitization in various cancer cells, but little is known about the relationship between nimotuzumab and EGFR nuclear translocation in non-small cell lung cancer (NSCLC) cell lines. In this study, we selected two NSCLC cell lines, namely, H292 (with high EGFR expression) and H1975 (with low EGFR expression) and explored the mechanisms underlying radiation sensitivity.Methods: MTT assay, clonogenic survival assay, and flow cytometry were performed separately to test cell viability, radiation sensitivity, cell cycle distribution, and apoptosis. Protein γ-H2AX, DNA-PK/p-DNA-PK, and EGFR/p-EGFR expression were further compared both in the cytoplasm and the nucleus with the western blot.Results: Nimotuzumab reduced the viability of H292 cells and sensitized H292 cells to ionizing radiation. The radiation sensitivity enhancement ratio (SER) was 1.304 and 1.092 for H292 and H1975 cells, respectively. H292 cells after nimotuzumab administration were arrested at the G0/G1 phase in response to radiation. Apoptosis was without statistical significance in both cell lines. γ-H2AX formation in the combination group (nimotuzumab and radiation) increased both in the cytoplasm and the nucleus along with the decreased expression of nuclear EGFR/p-EGFR and p-DNA-PK in H292 cells (P

Rui Gong,1 Shengying Li2 1Pharmaceutical Department, The Second Hospital of Tianjin Medical University, 2Clinical Laboratory, Tianjin Children's Hospital, Tianjin, People's Republic of China Abstract: With the rapid development of molecular biology and the life sciences, magnetic extraction is a simple, automatic, and highly efficient method for separating biological molecules, performing immunoassays, and other applications. Human blood is an ideal source of human genomic DNA. Extracting genomic DNA by traditional methods is time-consuming, and phenol and chloroform are toxic reagents that endanger health. Therefore, it is necessary to find a more convenient and efficient method for obtaining human genomic DNA. In this study, we developed urea–formaldehyde resin magnetic microspheres and magnetic silica microspheres for extraction of human genomic DNA. First, a magnetic microsphere suspension was prepared and used to extract genomic DNA from fresh whole blood, frozen blood, dried blood, and trace blood. Second, DNA content and purity were measured by agarose electrophoresis and ultraviolet spectrophotometry. The human genomic DNA extracted from whole blood was then subjected to polymerase chain reaction analysis to further confirm its quality. The results of this study lay a good foundation for future research and development of a high-throughput and rapid extraction method for extracting genomic DNA from various types of blood samples. Keywords: magnetic separation, bioseparation, resin magnetic microspheres, human genomic DNA, extraction

This study focuses on the fabrication of fiber membranes containing different concentrations of AgNO3 via the electrospinning technique. The AgNO3 present in the fibers is subsequently reduced to silver nanoparticles (Ag NPs) through UV irradiation. The resulting nanofiber film is characterized using scanning electron microscopy, X-ray diffraction, and evaluations of its anti-UV and anti-electromagnetic radiation properties. Experimental results demonstrate that increasing the AgNO3 content initially decreases and then increases the fiber diameter and fiber diameter deviation. Under UV light, the nanofibers fuse and bond, leading to an increase in the fiber diameter. AgNO3 is effectively reduced to Ag NPs after UV irradiation for more than 60 min, as confirmed by the characteristic diffraction peaks of Ag NPs in the XRD spectrum of the irradiated AgNO3/PVB fibers. The nanofiber film containing AgNO3 exhibits superior anti-UV performance compared to the film containing AgNO3-derived Ag NPs. The anti-electromagnetic radiation performances of the nanofiber films containing AgNO3 and AgNO3-derived Ag NPs are similar, but the nanofiber film containing AgNO3-derived Ag NPs exhibits higher performance at approximately 2.5 GHZ frequency. Additionally, at an AgNO3 concentration of less than 0.5 wt%, the anti-electromagnetic radiation performance is poor, and the shielding effect of the nanofiber film on medium- and low-frequency electromagnetic waves surpasses that on high-frequency waves. This study provides guidance for the preparation of polyvinyl butyral nanofibers, Ag NPs, and functional materials with anti-ultraviolet and anti-electromagnetic radiation properties. [ABSTRACT FROM AUTHOR]

Objective To explore the effectiveness of failure mode and effect analysis (FMEA) combined with risk assessment tracking in the management of arthroscopic day surgery instruments. Methods To conduct FMEA for each link of arthroscopic day surgery instruments management process, select the failure mode of priority risk value (RPN)> 125, conduct cause analysis, and formulate improvement measures from the aspects of device information tracking, standardized equipment, fine management, and implement risk assessment tracking management. The RPN value, maintenance rate of surgery instruments, accuracy qualification rate of surgical instruments and turnover time of emergency instruments were measured for effectiveness analysis. Results Five major failure modes were determined by FMEA activity, the priority risk values of all major failure modes decreased after activity than before implementation, with a significant difference(P