LDCT screening results among eligible and ineligible screening candidates in preventive health check-ups population: a real world study in West China.

To compare the LDCT screening results between eligible and ineligible screening candidates in preventive health check-ups population. Using a real-world LDCT screening results among people who took yearly health check-up in health management center of West China Hospital between 2006 and 2017. Objects were classified according to the China National Lung Cancer Screening Guideline with Low-dose Computed Tomography (2018 version) eligibility criteria. Descriptive analysis were performed between eligible and ineligible screening candidates. The proportion of ineligible screening candidates was 64.13% (10,259), and among them there were 4005 (39.04%) subjects with positive screenings, 80 cases had a surgical lung biopsy. Pathology results from lung biopsy revealed 154 cancers (true-positive) and 26 benign results (false-positive), the surgical false-positive biopsy rate was 4.17%, and ineligible group (7.69%) was higher than eligible group (2.47%), P < 0.05. Further, in ineligible screening candidates, the proportion of current smokers was higher among males compared to females (53.85% vs. 4.88%, P < 0.05). Of the 69 lung cancer patients detected in ineligible screening candidates, lung adenocarcinoma accounts for a high proportion of lung cancers both in male (75.00%) and female (85.00%). The proportion of ineligible screening candidates and the surgical false-positive biopsy rate in ineligible candidates were both high in health check-ups population.

Case report: Effect of Hb E heterozygosity on HbA1c value by the Tosoh HLC-723G11.

Objective: We report the effect of Hb E heterozygosity on HbA1c value by the Tosoh HLC-723G11. Case report: A 45 years-old Chinese woman presented with an abnormally low HbA1c level of 3.7% (3.9%-6.1%) in a health examination. Fasting blood glucose was normal. Blood routine examination and serum bilirubin were in the normal range. HbA1c was determined by Tosoh HLC-723G11. There was an abnormal peak between A1c and A0 on the chromatogram. Hemoglobin electrophoresis indicated that the Hb E zone accounted for 25.1%. The ß-thalassemia-related genes (mutant type) were ßE M/N, and the related gene CD26 (A > G) was mutated. OGTT indicated prediabetes. Conclusion: Hb E heterozygosity may reduce HbA1c value with abnormal chromatograms, as determined by a Tosoh HLC G11 analyzer. The Tosoh HLC G11 analyzer can well identify Hb E variation. In this case, further blood glucose-related tests should be performed to avoid missed diagnoses. However, a large sample size is needed to confirm this conclusion.

Early detection and stratification of lung cancer aided by a cost-effective assay targeting circulating tumor DNA (ctDNA) methylation.

BACKGROUND: Detection of lung cancer at earlier stage can greatly improve patient survival. We aim to develop, validate, and implement a cost-effective ctDNA-methylation-based plasma test to aid lung cancer early detection. METHODS: Case-control studies were designed to select the most relevant markers to lung cancer. Patients with lung cancer or benign lung disease and healthy individuals were recruited from different clinical centers. A multi-locus qPCR assay, LunaCAM, was developed for lung cancer alertness by ctDNA methylation. Two LunaCAM models were built for screening (-S) or diagnostic aid (-D) to favor sensitivity or specificity, respectively. The performance of the models was validated for different intended uses in clinics. RESULTS: Profiling DNA methylation on 429 plasma samples including 209 lung cancer, 123 benign diseases and 97 healthy participants identified the top markers that detected lung cancer from benign diseases and healthy with an AUC of 0.85 and 0.95, respectively. The most effective methylation markers were verified individually in 40 tissues and 169 plasma samples to develop LunaCAM assay. Two models corresponding to different intended uses were trained with 513 plasma samples, and validated with an independent collection of 172 plasma samples. In validation, LunaCAM-S model achieved an AUC of 0.90 (95% CI: 0.88-0.94) between lung cancer and healthy individuals, whereas LunaCAM-D model stratified lung cancer from benign pulmonary diseases with an AUC of 0.81 (95% CI: 0.78-0.86). When implemented sequentially in the validation set, LunaCAM-S enables to identify 58 patients of lung cancer (90.6% sensitivity), followed by LunaCAM-D to remove 20 patients with no evidence of cancer (83.3% specificity). LunaCAM-D significantly outperformed the blood test of carcinoembryonic antigen (CEA), and the combined model can further improve the predictive power for lung cancer to an overall AUC of 0.86. CONCLUSIONS: We developed two different models by ctDNA methylation assay to sensitively detect early-stage lung cancer or specifically classify lung benign diseases. Implemented at different clinical settings, LunaCAM models has a potential to provide a facile and inexpensive avenue for early screening and diagnostic aids for lung cancer.

Alteration of Gut Microbiota in Individuals at High-Risk for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance.

OBJECTIVE: In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis. METHODS: Fecal samples were collected from 38 healthy individuals and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA) positivity (Pre-RA), 12 of 53 Pre-RA individuals developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the healthy controls and Pre-RA individuals or among Pre-RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice that received GM from the healthy control or Pre-RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre-RA individuals on arthritis severity in mice. RESULTS: Stool microbial diversity was lower in Pre-RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre-RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre-RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre-RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre-RA group increased intestinal permeability in FMT mice and zonula occludens-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre-RA feces compared to healthy controls. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice. CONCLUSION: Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.

Application of T-cell receptor repertoire as a novel monitor in dynamic tracking and assessment: A cohort-study based on RA patients.

T-cell receptor repertoire (TCRR) sequencing has been widely applied in many fields as a novel tool. This study explored characteristics of TCRR in detail with a cohort of 598 rheumatoid arthritis (RA) patients before and after anti-rheumatic treatments. We highlighted the abnormal TCRR distribution in RA characterized by decreased diversity and increased proportion of hyperexpanded clones (HECs), which was potentially attributed to skewed usage of global V/J segments but not a few certain ones. Enriched motifs analysis in RA community demonstrated the huge heterogeneity of CDR3 sequences, so that individual factors are strongly recommended to be taken into consideration when it comes to clinical application of TCRR. Disease-modifying antirheumatic drugs (DMARDs) can regulate immune system through recovery of TCRR richness to relieve symptoms. Remarkably, sensitive gene profile and advantageous gene profile were identified in this study as new biomarkers for different DMARDs regimens.

Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment.

Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/ .

Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome.

BACKGROUND: Primary Sjogren's syndrome (SS) is a chronic inflammatory disease with unknown aetiology. Although clonal expansion of autoreactive T cells has been identified in patients with SS, the clinical correlation of T-cell receptor (TCR) variance in SS remains unclear. METHODS: TCRß repertoire sequencing was performed on 260 SS patients with 3-6 months of follow-up in a cohort study to dynamically assess the characteristics of TCR diversity and their clinical significance. FINDINGS: We found that SS patients had lower TCR diversity, but higher frequency of public clones than healthy controls (HCs). Significant differences were identified in the usage of the variable (V) gene, joining (J) gene, and V-J pairing between SS and HCs. Eighteen SS-associated clones were identified, showing a high sensitivity and specificity for disease classification. TCR diversity was correlated with the presence of dental caries, thrombocytopenia, hepatocholangeitis, antinuclear antibody, anti-SSA/SSB, and hypergammaglobulinemia but not with disease course, number of relapses, arthritis, rheumatoid factor, hypocomplementemia or disease activity defined by SSDAI. During follow-up, the TCR abnormalities remained, represented by more altered V/J usage and higher frequencies of SS-associated clones. Among SS patients, the sensitive subgroup had increased TCR diversity after treatment. Eighty-five SS-sensitivity associated TCRs were identified and used for sensitivity classification by cross validation with high specificity and sensitivity. INTERPRETATION: These results demonstrate that the TCR repertoire could provide insights into the disease status and prognosis in SS and other autoimmune diseases. FUNDING: This study was funded by the National Key Research and Development Program of China (2016YFC0906201), Sichuan Science and Technology Program (2020YJ0223), and the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18015).

The Association Between Metabolic Syndrome and Prostate Cancer Risk: A Large-Scale Investigation and Study of Chinese.

Background: To investigate the association between metabolic syndrome (MetS) and its components and prostate cancer (PCa). Methods: This study enrolled 482 943 consecutive men who underwent routine health checkups at the Health Management Center of West China Hospital Between 2010 and 2017. For patients with elevated prostate-specific antigen (PSA) levels or color Doppler ultrasound indicating abnormal prostates, we recommended prostate puncture and follow-up. We used the chi-square test and independent t-test for categorical variables and continuous variables, respectively. We used logistic regression analysis to evaluate the effects of MetS and its components on prostate cancer risk. Results: We found that the incidence of PCa in Chinese men over 40 years of age was 0.1%. Among the 85882 participants, 31.5% (27016/85882) of the patients were diagnosed with MetS. PCa was associated with older age, higher PSA levels, lighter weight and shorter height, hypertension, elevated fasting blood glucose (FBG) and HDL cholesterol level, lower triglycerides. After excluded the interference of other factors in multivariate logistic analysis, we found that MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa. High age and PSA levels were risk factors for prostate cancer. Conclusions: High age and PSA levels were risk factors for prostate cancer. MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa.

Case Report: Abnormally Low Glycosylated Hemoglobin A1c Caused by Clinically Silent Rare ß-Thalassemia in a Tujia Chinese Woman.

Background: Glycosylated hemoglobin A1c (HbA1c) is an important means of monitoring blood glucose and diagnosing diabetes. High-performance liquid chromatography (HPLC) is the most widely used method to detect HbA1c in clinical practice. However, the results of HbA1c by HPLC are susceptible to hemoglobinopathy. Here, we report a case of discordantly low HbA1c with an abnormal chromatogram caused by rare ß-thalassemia. Case Description: A 36-year-old Tujia Chinese woman presented with an abnormally low HbA1c level of 3.4% by HPLC in a health check-up. The chromatogram of HbA1c showed an abnormal peak. Fasting blood glucose, routine blood tests and serum bilirubin were normal. Her body mass index was 27.86 kg/m2. Hemoglobin electrophoresis showed low hemoglobin A and abnormal hemoglobin ß-chain variants. The thalassemia gene test suggested a rare type of ß-thalassemia (gene sequencing HBB: c.170G>A, Hb J-Bangkok (GGC->GAC at codon 56) in a beta heterozygous mutation). Glycated albumin (GA) was slightly increased. Oral glucose tolerance tests (OGTT) and insulin release tests indicated impaired glucose tolerance and insulin resistance. The hematologist advised follow-up visits. The endocrinologist recommended that the patient adopt lifestyle intervention. Three months later, GA returned to normal, and impaired glucose tolerance and insulin resistance improved. Conclusions: Clinically silent ß-thalassemia may lead to low HbA1c values and abnormal chromatograms by HPLC. In these circumstances, differential diagnosis is important. Checking the chromatogram may be helpful in interpreting HbA1c as well as identifying hemoglobinopathy. Further tests, such as GA, OGTT, hemoglobin electrophoresis and genetic tests, are needed for differential diagnosis.

Discordantly high glycated hemoglobin might assist in diagnosing α-thalassemia, but not diabetes: A case report.

Glycated hemoglobin (HbA1c) is an important method for monitoring blood glucose and diagnosing diabetes. High-performance liquid chromatography is more commonly used in the laboratory for the detection of HbA1c. Although HbA1c detected by high-performance liquid chromatography is susceptible to abnormal hemoglobin, there are few reports that it is affected by α-thalassemia. Previous reports have generally concluded that α-thalassemia does not affect or lower HbA1c. Here, we report a case of discordantly high HbA1c inconsistent with fasting blood glucose. Finally, the patient was diagnosed with α-thalassemia and insulin resistance. α-Thalassemia might lead to a discordantly high HbA1c result, which could be attributed to elevated hemoglobin H. In this case, glycated albumin might accurately reflect the real average level of blood glucose. When finding discordant HbA1c, patients should be advised to undergo thalassemia and hemoglobinopathy screening by diabetologists/endocrinologists or primary care physicians to avoid a missed diagnosis of hematopathy.

The Hyperdense middle cerebral artery sign is associated with poor leptomeningeal collaterals in acute ischemic stroke: a retrospective study.

BACKGROUND: The hyperdense middle cerebral artery sign (HMCAS) is an early radiological marker to provide an early diagnosis and to identify ischemia. As reported, HMCAS is associated with heavy clot burden. Moreover, a heavy clot burden may cause obstruction of the orifices of arteries for leptomeningeal collateral flows and can lead to severe clinical conditions. However, the direct relationship between HMCAS and collateral flows remains unclear. Therefore, we explored the association between HMCAS and leptomeningeal collaterals in patients with acute ischemic stroke. METHODS: Consecutive ischemic stroke patients were enrolled from January 2015 to April 2021. HMCAS appearance and collateral status were detected by multimodal computed tomography at admission. Logistic regression analyses helped to identify the association between HMCAS, collateral flows and stroke severity. RESULTS: In 494 included patients, 180 (36.4%) presented with HMCAS. Ipsilateral collaterals were not seen or less prominent in patients with HMCAS (P < 0.001). The HMCAS appearance was significantly associated with less collaterals (odds ratio 5.17, 95% confidence interval 3.27-8.18, P < 0.001), internal carotid artery + M1/M1 occlusion, the initial stroke severity and follow-up outcomes. Subgroup analyses further confirmed HMCAS as an indicator of poor collaterals in ischemic stroke (all P values < 0.05). CONCLUSIONS: HMCAS is associated with poor leptomeningeal collaterals, the stroke severity and a poor neurological outcome. Therefore, the HMCAS appearance can act as an early warning sign for healthcare professionals to be alert for poor collateral flows and poor neurological outcomes in ischemic stroke patients with middle cerebral artery occlusion.

Elevated thyroid-stimulating hormone levels are associated with poor sleep: a cross-sectional and longitudinal study.

PURPOSE: Poor sleep accompanied by elevated TSH (thyroid stimulating hormone) levels is not uncommon since TSH secretion is controlled by the circadian rhythm. However, the relationship between poor sleep and TSH elevation is unclear; hence, we aimed to elucidate this relationship by conducting a cross-sectional and longitudinal study. METHODS: Participants with isolated elevated (N = 168) and normal (N = 119) TSH concentrations were recruited, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep status. Subjects with an isolated TSH elevation were followed up longitudinally. The serum TSH concentration was remeasured after sleep status improved. RESULTS: The proportions of poor sleep and occasional poor sleep in subjects with isolated TSH elevation were significantly higher than those with normal TSH levels (70.24% vs. 49.58%, p = 0.001; 9.52% vs. 1.68%, p = 0.006). Subjects with isolated TSH elevation had significantly higher PSQI scores in the subjective sleep quality, sleep latency, sleep duration, and habitual sleep efficiency dimensions than those with normal TSH levels (all p < 0.05). Poor sleep was significantly associated with isolated TSH elevation in the multiple logistic regression analysis [odds ratio (OR) = 2.396, p = 0.001]. Among subjects with an isolated TSH elevation at baseline, the percentage of TSH normalization was significantly higher in those who slept better than in those who still slept poorly (85.42% vs. 6.45%, p < 0.001). CONCLUSIONS: This study revealed that isolated elevated TSH concentrations normalize when the sleep status is improved; hence, we recommend that clinicians thoroughly assess the sleep status of patients and remeasure TSH concentrations after sleep status improves.

Systematic screening identifies a TEAD4-S100A13 axis modulating cisplatin sensitivity of oral squamous cell carcinoma cells.

BACKGROUND: This study aimed to screen prognosis-related S100 protein family members in human paxpillomaviruses (HPV)-negative oral squamous cell carcinoma (OSCC) and their molecular regulations. METHODS: Bioinformatic screening was conducted based on single-cell RNA-seq data from Puram 2017 dataset and bulk-seq data from the Cancer Genome Atlas (TCGA). HPV-negative OSCC cell lines CAL-27 and SCC-4 were used as in vitro cell models. RESULTS: Among 21 S100 protein family member genes, S100A13 upregulation was associated with unfavorable progression-free survival and disease-specific survival of OSCC patients. Gene Set Enrichment Analysis showed that the higher S100A13 expression group had elevated genes enriched in DNA repair and oxidative phosphorylation. S100A13 knockdown increased cisplatin sensitivity, while its overexpression decreased the sensitivity of CAL-27 and SCC-4 cells. S100A13 gene had complex alternative transcription patterns. ENST00000440685 is one of the major protein-coding transcripts and was the only transcript elevated in the tumor group. TEAD4 could bind to the promoter of ENST00000440685 and increase its transcription. TEAD4 overexpression alleviated the tumor-suppressive effect of cisplatin in terms of colony formation, the expression of apoptotic proteins, and DNA damage. However, S100A13 knockdown partly abrogated the protective effects of TEAD4 overexpression. CONCLUSION: This study revealed a novel TEAD4-S100A13 axis that might modulate cisplatin sensitivity of OSCC tumor cells.

Characterizing dedifferentiation of thyroid cancer by integrated analysis.

Understanding of dedifferentiation, an indicator of poo prognosis for patients with thyroid cancer, has been hampered by imprecise and incomplete characterization of its heterogeneity and its attributes. Using single-cell RNA sequencing, we explored the landscape of thyroid cancer at single-cell resolution with 46,205 cells and delineated its dedifferentiation process and suppressive immune microenvironment. The developmental trajectory indicated that anaplastic thyroid cancer (ATC) cells were derived from a small subset of papillary thyroid cancer (PTC) cells. Moreover, a potential functional role of CREB3L1 on ATC development was revealed by integrated analyses of copy number alteration and transcriptional regulatory network. Multiple genes in differentiation-related pathways (e.g., EMT) were involved as the downstream targets of CREB3L1, increased expression of which can thus predict higher relapse risk of PTC. Collectively, our study provided insights into the heterogeneity and molecular evolution of thyroid cancer and highlighted the potential driver role of CREB3L1 in its dedifferentiation process.

Associations between hepatitis B virus exposure and the risk of extrahepatic digestive system cancers: A hospital-based, case-control study (SIGES).

OBJECTIVES: This case-control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers. METHODS: The patients of gastric, small intestinal, colonic, rectal, anal, biliary tract, and pancreatic cancers were retrospectively collected between 2016.5 and 2017.12. Simultaneously, the healthy controls were collected from the health check-up registry, and cancer-free status was confirmed based on medical records. Propensity score matching was performed to reduce bias. Multinomial logit model and conditional logistic regression model were used to assess the risk of individual cancer according to HBV serological markers and classifications. RESULTS: Totally, 4748 patients involving seven cancers, and 57,499 controls were included. After matching, HBsAg was associated with increased risk of gastric cancer (aOR = 1.39, 95% CI: 1.05-1.85), and anti-HBs served as a protective factor for gastric (aOR = 0.72, 95% CI: 0.61-0.85), colonic (aOR = 0.73, 95% CI: 0.60-0.89), rectal (aOR = 0.73, 95% CI: 0.63-0.85), and pancreatic (aOR = 0.58, 95% CI: 0.42-0.82) cancers. Compared to subgroups with non-infection and vaccination status, inactive HBsAg carriers and active HBV infection subgroup were correlated with gastric carcinogenesis (aOR = 1.41, 95% CI: 1.03-1.93). However, no clear association was found between HBV infection and other cancers. CONCLUSIONS: HBV infection was potentially associated with an increased risk of gastric cancer. The development mechanism of HBV-associated gastric cancer needs to investigate further.

Nurses' core emergency competencies for COVID-19 in China: A cross-sectional study.

AIM: To investigate nurses' core emergency competencies for handling the coronavirus disease-19 (COVID-19) and analyse the factors associated with those competencies. BACKGROUND: COVID-19 has become a major global public health event. Nursing staff have played an important role in COVID-19 prevention and control. Understanding their emergency competencies for handling COVID-19, and the potential disadvantages will help governments to develop targeted training policies and improve nurses' capacities in relation to pandemics and emergency preparedness. INTRODUCTION: COVID-19 is a disastrous infectious disease, but the competencies of nurses in China to handle COVID-19 have not been well documented. METHODS: We conducted a cross-sectional survey on nurses from 22 provinces of China in February 2020. The scores of self-report questionnaires were used to analyse their competencies for core emergency care, and linear regression analysis was used to explore influential factors. RESULTS: A total of 2570 nurses participated. The study revealed that nurses had a good grasp of COVID-19 knowledge, but the majority of nurses lacked experience in isolation ward work and emergency training. We found that age, professional title, work department, major work content, total work time, disaster rescue history, emergency training and infectious disease training were associated with core emergency competencies. CONCLUSIONS: Chinese nurses were qualified for handling COVID-19 but still need to strengthen the accumulation of practical experience. IMPLICATIONS FOR NURSING: Nurses should actively participate in emergencies to strengthen their operational capacity, whether in training or actual practice. IMPLICATIONS FOR NURSING/HEALTH POLICY: Managers should improve relevant policies to ensure that nurses have more opportunities to participate in the practical training of health emergencies and explore effective training methods to improve the ability of nurses to respond to these.

Psychological Distress and Sleep Disturbance Throughout Thyroid Nodule Screening, Diagnosis, and Treatment.

CONTEXT: Many controversies exist regarding screening and treatment of thyroid cancer (TC), especially papillary thyroid microcarcinoma (PTMC). OBJECTIVE: The aim of this study was to evaluate patients' psychological distress and sleep disturbance throughout thyroid nodule (TN) screening, diagnosis, and treatment. METHODS: A total of 2834 participants (1153 participants with TNs) were enrolled during the screening phase, and 1105 individuals with TNs (87 individuals with TC) were enrolled during the diagnosis phase. Of the 87 TC patients, 66 underwent immediate operation (OP), and 21 patients with PTMC opted for active surveillance (AS). Four validated scales were applied to quantify the outcome indicators at prescreening, postscreening, postdiagnosis, and posttreatment. RESULTS: Higher psychological distress and sleep disturbance were found postscreening than prescreening in subjects with TNs, but no differences in those without nodules. Compared with postscreening, higher scores of psychological distress and sleep disturbance were identified in patients with suspicious TC treated with fine needle aspiration (FNA) or with AS. Lower psychological distress and sleep disturbance were noted for patients with benign nodules than for TC patients. OP for TC, especially PTMC, did not alleviate psychological distress or sleep disturbance compared with the same parameters in patients who underwent AS. CONCLUSION: Based on the findings of impaired psychological health and sleep quality, screening for TNs in adults who show no symptoms should be performed with caution. Psychological distress and sleep disturbance should also be taken into consideration when FNA is performed for suspected TC or OP for papillary thyroid cancer, especially PTMC.

Current lung cancer screening guidelines may miss high-risk population: a real-world study.

BACKGROUND: Despite much research published on lung cancer screening, China has had no large-scale study on the missed diagnosis of lung cancer in a health examination population. We therefore did a real-world study using the current lung cancer screening guidelines to a health examination population in China to determine the proportion of lung cancer cases that have been missed. METHODS: A real-world cohort study of screening, with the use of low-dose computed tomography, was conducted among people who took yearly health checkup in health management center of West China Hospital between 2006 and 2017. We respectively used current guidelines including lung cancer screening guidelines of the U.S. Preventive Services Task Force (USPSTF) and expert consensus on low dose spiral CT lung cancer screening in China. RESULTS: In a total of 15,996 participants with health examination who completed the baseline screening, 6779 (42.4%) subjects had at least one positive finding, and 142 (2.1%) cases of lung cancer were screened positive. The false positive rate was 97.9%. Of 142 lung cancer cases detected in our study, only 9.2% met the lung cancer screening guidelines proposed by the USPSTF, and 24.4% met that of China. The rates of missed diagnosis were as high as 90.8 and 75.6% respectively. In addition, we did an in-depth analysis by gender. We found that among male patients with lung cancer, the proportion of smokers was 75%, and the proportion of young people under 50 was 23.2%. Among female patients with lung cancer, the proportion of smokers was only 5.8%, and the proportion of young people under 50 was up to 33.3%. CONCLUSIONS: The rate of missed diagnosis was as high as 90.8% applying the current lung cancer screening guidelines to the health examination population in China. Further study to determine screening guidelines for targeted populations, is warranted.

Autophagy-related gene 7 deficiency caused by miR-154-5p overexpression suppresses the cell viability and tumorigenesis of retinoblastoma by increasing cell apoptosis.

BACKGROUND: Retinoblastoma is a rare cancer of the retina that accounts for 3% of all childhood cancers. The aim of this study was to illuminate the oncogenic role and potential molecular mechanisms of the microRNA miR-154-5p and autophagy-related gene 7 (ATG7) in retinoblastoma, and to establish a nude mouse model in order to explore new therapeutic horizons for the disease. METHODS: Quantitative reverse transcription-polymerase chain reaction and western blot were performed to detect the expression levels of miR-154-5p and ATG7. The targeting relationship between miR-154-5p and ATG7 was analyzed by employing the luciferase reporter assay. MiR-154-5p mimic and pcDNA-ATG7 were transfected, either alone or in combination, into Y79 cells. The subsequent in vitro experiments involved four groups: the control group, miR-154-5p group, ATG7 group, and miR-154-5p + ATG7 group. Orthotopic xenograft models were established by injecting BALB/c athymic nude mice with treated and untreated Y79 cells. RESULTS: Y79 cells were transfected with miR-NC or miR-154-5p. Compared to those in the control group, the mRNA expression levels of miR-154-5p were increased in the miR-154-5p mimic group; in contrast, decreases were observed in the mRNA and protein expression levels of ATG7. Y79 cells were transfected with PcDNA or pcDNA-ATG7. The mRNA expression level of ATG7 was increased in pcDNA-ATG7 group. MiR-154-5p was found to have an element complementary to the three prime untranslated region of ATG7. Overexpression of miR-154-5p inhibited Y79 cells proliferation and migration, and promoted Y79 cells apoptosis via targeting of ATG7. In the in vivo experiment, the tumors of the miR-154-5p group of mice were significantly reduced in weight. Tumor growth and the protein levels of Survivin were both suppressed when miR-154-5p was overexpressed in vivo; however, cell apoptosis and the protein levels of p21 were promoted. In the miR-154-5p group, the expression levels of miR-154-5p were upregulated compared to those in the control group, but the ATG7 expression level was downregulated. CONCLUSIONS: MiR-154-5p overexpression downregulated ATG7, which inhibited cell proliferation and apoptosis in vitro, as well as tumor formation in vivo.

Correlation between prostate-specific antigen and four renal function-associated parameters in different ethnicities in southwest China.

A limited number of studies have investigated the significance of cystatin C, creatinine, uric acid and urea in prostate cancer. The present study aimed to explore the correlation between these molecules and total prostate-specific antigen (tPSA) levels using big data from patients of different Chinese ethnicities. Patients undergoing physical examination at the Medical Examination Center of West China Hospital (Chengdu, China) between January 2010 and May 2019 were retrospectively included. A χ2 test or Fisher's test and Kruskal-Wallis rank-sum test were used to compare categorical and continuous variables. Pearson's correlation coefficients (r) with 95% CI were also determined to assess the correlation between tPSA and cystatin, uric acid, creatinine and urea in the entire patient population and in different ethnicities. A total of 253,281 male patients were included and their mean age was 47.83±14.28 years. The mean tPSA level of these patients was 1.15±1.88 ng/ml. The mean levels of the renal function-associated parameters cystatin C, uric acid, creatinine and urea were 0.91±0.19, 388.02±77.37, 83.94±55.89 and 5.23±1.23 ng/ml, respectively. In the total patient population, urea (r=0.0774, P<0.0001), creatinine (r=0.0219, P<0.0001) and cystatin (r=0.1513, P<0.0001) were slightly positively correlated with tPSA, whereas uric acid was negatively correlated with tPSA (r=-0.0307, P<0.0001). Subgroup analyses generally yielded consistent results; however, a stronger correlation was noted between cystatin C and tPSA for the Mongolian ethnicity (r=0.6572, P<0.0001) and between creatinine and tPSA for the Yi ethnicity (r=0.6125, P<0.0001). In conclusion, the present study used data from a large population to reveal a generally significant and slightly positive correlation between tPSA and cystatin C levels among the 10 most common ethnicities in China. Subgroup analyses indicated that the tPSA level was moderately positively correlated with the creatinine level for the Mongolian and Yi ethnicities and the cystatin C level was moderately positively correlated with tPSA for the Mongolian ethnicity. Future studies are required to confirm and expand the present results.