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Objective: In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. Method: Hospital employees ≥40 years old who underwent low‐dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT‐imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation‐related occupation received monitoring in hospital. Result: The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. Conclusion: The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary. [ABSTRACT FROM AUTHOR]

Anthropogenic environments such as those created by intensive farming of livestock, have been proposed to provide ideal selection pressure for the emergence of antimicrobial-resistant Escherichia coli bacteria and antimicrobial resistance genes (ARGs) and spread to humans. Here, we performed a longitudinal study in a large-scale commercial poultry farm in China, collecting E. coli isolates from both farm and slaughterhouse; targeting animals, carcasses, workers and their households and environment. By using whole-genome phylogenetic analysis and network analysis based on single nucleotide polymorphisms (SNPs), we found highly interrelated non-pathogenic and pathogenic E. coli strains with phylogenetic intermixing, and a high prevalence of shared multidrug resistance profiles amongst livestock, human and environment. Through an original data processing pipeline which combines omics, machine learning, gene sharing network and mobile genetic elements analysis, we investigated the resistance to 26 different antimicrobials and identified 361 genes associated to AR phenotypes; 58 of these were known AMR-associated genes and 35 were associated to multidrug resistance. We uncovered an extensive network of genes, correlated to AMR phenotypes, shared among livestock, humans, farm and slaughterhouse environments. We also found several human, livestock and environmental isolates sharing closely related mobile genetic elements carrying AR genes across host species and environments. In a scenario where no consensus exists on how antibiotic use in the livestock may affect antibiotic resistance in the human population, our findings provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. Moreover, our original data analysis method has the potential to uncover AR transmission pathways when applied to the study of other pathogens active in other anthropogenic environments characterised by complex interconnections between host species. Author summary: Livestock have been suggested as an important source of antimicrobial-resistant (AMR) Escherichia coli, capable of infecting humans and carrying resistance to drugs used in human medicine. China has a large intensive livestock farming industry, poultry being the second most important source of meat in the country, and is the largest user of antibiotics for food production in the world. Here we studied antimicrobial resistance gene overlap between E. coli isolates collected from humans, livestock and their shared environments in a large-scale Chinese poultry farm and associated slaughterhouse. By using a computational approach that integrates machine learning, whole-genome sequencing, gene sharing network and mobile genetic elements analysis we characterized the E. coli community structure, antimicrobial resistance phenotypes and the genetic relatedness of non-pathogenic and pathogenic E. coli strains. We uncovered the network of genes, associated with AMR, shared across host species (animals and workers) and environments (farm and slaughterhouse). Our approach opens up new avenues for the development of a fast, affordable and effective computational solutions that provide novel insights into the broader epidemiology of antimicrobial resistance in livestock farming. [ABSTRACT FROM AUTHOR]

This paper develops a political economy model to examine the implications of political selection under an authoritarian regime. We formalize the fiscal policy choice of local governments, focusing on two political selection mechanisms and their implications for public investment and welfare spending. A growth‐oriented promotion system induces local officials to increase public investment, which may increase output but crowd out welfare transfers. This mimics the recent investment‐driven growth in China and relatively low effort to tackle high inequality. Under a broader incentive structure, we show that it is possible for an authoritarian regime to attain the social welfare of a democracy. [ABSTRACT FROM AUTHOR]

Background: The relationship between alcohol consumption and Alzheimer's disease (AD) pathology is unclear. Amyloid-β (Aβ) and tau biomarkers in cerebrospinal fluid (CSF) have been proven valuable in establishing prognosis in pre-clinical AD.Objective: We sought to examine the associations between alcohol consumption and CSF AD biomarkers in cognitive intact subjects.Methods: A total of 806 cognitively intact participants who had measurements of CSF Aβ, pTau, and total Tau proteins and drinking characteristics were included from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. Linear and logistic regression analyses were utilized to explore the associations of alcohol consumption with CSF AD biomarkers. We examined the interaction effects of age, gender, and apolipoprotein epsilon (APOE) ɛ4 status on the relationships between the frequency of drinking and CSF biomarkers.Results: The multiple linear regression analyses revealed significant differences in CSF AD biomarkers between infrequent drinking (< 1 times/week) and frequent drinking groups (≥1 times/week). Participants in frequent drinking group had higher CSF p-tau/Aβ42 and tTau/Aβ42. Frequent drinking was significantly associated with greater pTau and tTau abnormalities compared to the infrequent drinking group in older (> 65 years) participants.Conclusion: The present study showed significant associations between drinking frequency and CSF AD biomarkers in cognitively intact older adults. Alcohol consumption may have an influence on AD by modulating amyloid deposition and tau phosphorylation in the preclinical stage. [ABSTRACT FROM AUTHOR]

Background and Objectives: Due to the inevitability of waiting time for surgery, this problem seems to have become more pronounced since the outbreak of COVID-19, and due to the high incidence of preoperative hydronephrosis in upper urinary tract urothelial carcinoma (UTUC) patients, it is particularly important to explore the impact of preoperative waiting time and hydronephrosis on upper urinary urothelial carcinoma. Methods: 316 patients with UTUC who underwent radical surgery at a high-volume center in China between January 2008 and December 2019 were included in this study. We retrospectively collected the clinicopathologic data from the medical records, including age, sex, smoking history, ECOG performance status (ECOG PS), body mass index (BMI), tumor location and size, number of lesions, T stage, N stage, surgical approach and occurrence of hydronephrosis, lymph node invasion, lymph node dissection, surgical margin, tumor necrosis, infiltrative tumor architecture, lymphovascular invasion and concomitant bladder cancer. Surgical wait time was defined as the interval between initial imaging diagnosis and radical surgery of UTUC. Hydronephrosis was defined as abnormal dilation of the renal pelvis and calyces due to obstruction of the urinary system. Firstly, all patients were divided into short-wait (<31 days), intermediate-wait (31-90 days) and long-wait (>90 days) groups according to the surgical wait time. The clinicopathological characteristics of each group were evaluated and the survival was compared. For patients with hydronephrosis, we subsequently divided them into two groups: short-wait (≤60 days) and long-wait (>60 days) groups according to the surgical wait time. Univariate and multivariate COX regression analysis were performed to evaluate the prognostic risk factor for patients with hydronephrosis. Results: A total of 316 patients with UTUC were included in this study with a median surgical wait time of 22 days (IQR 11-71 days). Of the 316 patients, 173 were classified into the short-wait group (54.7%), 69 into the intermediate-wait group (21.8%) and 74 into the long-wait group (23.5%). The median follow-up time for all patients was 43 months (IQR 28-67months). The median surgical wait times of the short-wait, intermediate-wait and long-wait group were12 days (IQR 8-17days), 42days (IQR 37-65days) and 191days (IQR 129-372days), respectively. The 5-year overall survival (OS) of all patients was 54.3%. The 5-year OS of short-wait, intermediate-wait and long-wait groups were 56.4%, 59.3% and 35.1%, respectively (P=0.045). The 5-year cancer-specific survival (CSS) of short-wait, intermediate-wait and long-wait groups were 65.8%, 70.9% and 39.6%, respectively (P=0.032). In the subgroup analysis, we divided 158 UTUC patients with hydronephrosis into short-wait group (≤60 days) and long-wait group (> 60 days), 120 patients were included in the short-wait group and 38 patients in the long-wait group. The median surgical wait times of the short-wait and long-wait group were 14days (IQR 8-28days) and 174days (IQR 100-369days), respectively. The 5-year OS of long-wait group was significantly lower than the OS of short-wait group (44.2% vs. 55.1%, P =0.023). The 5-year CSS of long-wait and short-wait group were 49.1% and 61.7%, respectively (P=0.041). In multivariate Cox regression analysis of UTUC patients with hydronephrosis, surgical wait time, tumor grade, pathological T stage, and tumor size were independent risk factors for OS and CSS. Lymph node involvement was also a prognostic factor for CSS. Conclusion: For patients with UTUC, the surgical wait time should be limited to less than 3 months. For UTUC patients with hydronephrosis, the OS and CSS of patients with surgical wait time of more than 60 days were relatively shorted than those of patients with surgical wait time of less than 60 days. [ABSTRACT FROM AUTHOR]

Background: Green tea has been widely recognized in ameliorating cognitive impairment and Alzheimer's disease (AD), especially the progression of cognitive dysfunction. But the underlying mechanism is still unclear.Objective: This study was designed to determine the role of green tea consumption in the association with cerebrospinal fluid (CSF) biomarkers of AD pathology and to ascertain whether specific population backgrounds showed the differences toward these relationships.Methods: Multivariate linear models analyzed the available data on CSF biomarkers and frequency of green tea consumption of 722 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database, and we additionally detected the interaction effects of tea consumption with APOEɛ4 status and gender using a two-way analysis of covariance.Results: Frequent green tea consumption was associated with a decreased level of CSF total-tau protein (t-tau) (p = 0.041) but not with the levels of CSF amyloid-β 42 (Aβ42) and CSF phosphorylated tau. The more pronounced associations of green tea consumption with CSF t-tau (p = 0.007) and CSF t-tau/Aβ42 (p = 0.039) were observed in individuals aged 65 years or younger. Additionally, males with frequent green tea consumption had a significantly low level of CSF t-tau/Aβ42 and a modest trend toward decreased CSF t-tau. There were no interaction effects of green tea consumption with APOEɛ4 and gender.Conclusion: Collectively, our findings consolidated the favorable effects of green tea on the mitigation of AD risk. The constituents of green tea may improve abnormal tau metabolism and are promising targets in interventions and drug therapies. [ABSTRACT FROM AUTHOR]

Background: The detection of the Epstein–Barr capsid antigen (VCA) immunoglobulin A (IgA) is widely used in the diagnosis of nasopharyngeal carcinoma (NPC), but a reference standard for evaluating the presence of VCA-IgA is not yet available. Therefore, a reference standard is urgently needed for a uniform and quantitative detection of VCA-IgA. Methods: A mixed reference serum from three NPC patients diluted with healthy subject serum was made as a potential first international standard for VCA-IgA. VCA-IgA was detected in twenty NPC patients by four ELISA kits and two chemiluminescent immunoassays kits using the reference as a calibration curve. The performance of these six kits was evaluated, and the quantitative results were compared. Results: Our results showed a good linearity of the reference in different kits. Without reference, the difference of the total coefficient of variation (from 3.98 to 43.11%) and Within-run coefficient of variation (from 2.47 to 19.66%) was large in the 6 kits. The positive and negative coincidence rate between the 6 kits and indirect immunofluorescence for NPC diagnosis was 75% overall agreement, but a difference among the six kits was found, ranging from 55 to 90%. The concentration of VCA-IgA in the 20 NPC samples led in the division into three categories such as negative, low, or medium/high positive, but these concentrations were significantly different within these three categories depending on the kit used of the 6 considered. However,a good correlation (R2 = 0.986) was observed between Antu and Beier ELISA kits. Conclusions: The reference serum mightbe used as a reference standard for a better comparison of the results from different kits/laboratories. However, the quantitative results of some kits are still inconsistent due to the diversity of VCA antigens. [ABSTRACT FROM AUTHOR]

Over 1,000 compounds, including ecteinascidin-743 and didemnin B, have been isolated from ascidians, with most having bioactive properties such as antimicrobial, antitumor, and enzyme-inhibiting activities. In recent years, direct and indirect evidence has shown that some bioactive compounds isolated from ascidians are not produced by ascidians themselves but by their symbiotic microorganisms. Isolated culturable bacteria associated with ascidians and investigating their potential bioactivity are an important approach for discovering novel compounds. In this study, a total of 269 bacteria were isolated from the ascidian Styela clava collected from the coast of Weihai in the north of the Yellow Sea, China. Phylogenetic relationships among 183 isolates were determined using their 16S rRNA gene sequences. Isolates were tested for antimicrobial activity against seven indicator strains, and an antiproliferative activity assay was performed to test for inhibition of human hepatocellular carcinoma Bel 7402 and human cervical carcinoma HeLa cell proliferation. Our results showed that the isolates belonged to 26 genera from 18 families in four phyla (Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes). Bacillus and Streptomyces were the most dominant genera; 146 strains had potent antimicrobial activities and inhibited at least one of the indicator strains. Crude extracts from 29 strains showed antiproliferative activity against Bel 7402 cells with IC50 values below 500 μg·mL−1, and 53 strains showed antiproliferative activity against HeLa cells, with IC50 values less than 500 μg·mL−1. Our results suggest that culturable bacteria associated with the ascidian Styela clava may be a promising source of novel bioactive compounds. [ABSTRACT FROM AUTHOR]

Background This study aims to investigate the clinical features of invasive community-acquired Staphylococcus aureus (CA-SA) infection in Chinese children and analyze its molecular features. Methods Clinical data and invasive CA-SA isolates were prospectively collected. Pediatric risk of mortality (PRISM) score was used for disease severity measurement. Molecular typing was then performed, followed by expression analysis for virulence genes. Results Among 163 invasive CA-SA infection cases, 71 (43.6%) were methicillin-resistant SA (MRSA) infections and 92 (56.4%) were methicillin-susceptible SA (MSSA). A total of 105 (64.4%) children were younger than 1 year old, and 79.7% (129/163) were under 3 years age. Thirteen kinds of diseases were observed, in which bacteremia and pneumonia accounted for 65.6% (107/163) and 52.8% (86/163), respectively. A total of 112 (68.1%) patients had two or more infective sites simultaneously, and four cases (2.5%) died. CA-MSSA more frequently caused multi-sites infections, bacteremia, and musculoskeletal infection than MRSA. A total of 25 sequence types (STs) were detected. MRSA mainly comprised ST59 (49/71, 69%), whereas the most frequent clonotypes were ST88 (15/92, 16.3%), ST25 (13/92, 14.1%), ST7 (13/92, 14.1%), ST2155 (12/92, 13%), and ST188 (9/92, 9.8%) for MSSA. Seven STs were common to both MSSA and MRSA groups. No differences in clinical presentation or PRISM score were found between the two groups or among different ST. The expression levels of the four known virulence genes varied among the six main ST clones. Conclusions Invasive CA-SA infections were characterized by high incidence and multi-site infections in young children in China. The clinical manifestations of CA-MSSA were more frequently associated with multi-site infections, bacteremia and musculoskeletal infection than those of CA-MRSA. Isolated genotypes may be relevant to the expressions of virulence genes, but not to clinical manifestations. [ABSTRACT FROM AUTHOR]

Background. Substantial progress has been made in the treatment of malignancies in the People’s Republic of China in recent years.The goal of this study was to identify the extent to which national treatment guidelines are being used to customize patient care in lung cancer and to analyze the reasons for treatment disparities. Methods. Patient characteristics and treatments were investigated retrospectively for the period from October 2004 to January 2013 using the outpatient database of the Guangdong Lung Cancer Institute (GLCI) in China. Results. A total of 2,535 outpatients with lung cancer were studied in this retrospective analysis. The treatment disparity was 45.3%. Overall, 20.6% of patients with stage I non-small cell lung cancer (NSCLC) were overtreated, and 20.1% of stage II patients were undertreated. Only 19.6% of stage IIIA patients and 30.7% of stage IIIB patients underwent the recommended combination of chemotherapy and radiotherapy, respectively. For advanced NSCLC, the greatest treatment disparity appeared in the second-line setting and beyond. Patients who were positive for epidermal growth factor receptor (EGFR) and receiving EGFR tyrosine kinase inhibitors experienced significant prolongation of survival compared with patients who were EGFR negative or whose EGFR mutation status was unknown (hazard ratio: 0.79; p 5 .037). The treatment disparities were significantly larger among patients aged younger than 65 years and in patients from developing regions compared with patients aged 65 years and older and from developed regions, respectively (p , .001, p 5 .046). The difference in treatment disparity was statistically significant between GLCI and other hospitals (p , .001). Conclusion. This retrospective study of a large number of patients from an outpatient oncology database demonstrated large disparities in the treatment of lung cancer in China. It is important to develop a new guideline for recommendations that are based on resource classification. [ABSTRACT FROM AUTHOR]

Background. Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations have mixed responses to tyrosine kinase inhibitors (TKIs). Intertumor heterogeneity in EGFR mutations is one potential explanation for this phenomenon. Methods. We performed direct sequencing to identify EGFR mutations in 180 pairs of lung adenocarcinoma samples (from 3,071 patients). The high-resolution melting method was used in discordant cases to confirm EGFR mutation status. Matching samples were divided into four groups: primary lesions detected at different times, primary tumors with matched metastatic lymph nodes, multiple pulmonary nodules, and primary tumors with matched distant metastases. Multivariate analyses were performed to evaluate correlations between heterogeneity and patient characteristics. Results. In the study population, the discordance rate was 13.9% (25 of 180). The multiple pulmonary nodules group had the highest discordance rate of 24.4% (10 of 41; odds ratio for heterogeneity in primary lesions detected at different times, 6.37; 95% confidence interval, 1.71-23.72; p = .006). Discordance rates in the metachronous and synchronous settings were 15.7% (22 of 140) and 7.5% (three of 40), respectively. In the 34 patients who developed EGFR TKI resistance, 10 (29.4%) cases exhibited heterogeneity and five (14.7%) patients exhibited a mixed response to the drug. Three (8.8%) of the patients with a mixed response also exhibited discordant EGFR mutations. Conclusions. The overall discordance rate of EGFR mutation heterogeneity in Asian patients with pulmonary adenocarcinoma is relatively low, but the rate in patients with multiple pulmonary nodules is significantly higher. This observation may explain the mixed tumor response to EGFR TKIs. [ABSTRACT FROM AUTHOR]

Background: Appropriate patient selection is needed for targeted therapies that are efficacious only in patients with specific genetic alterations. We aimed to define subgroups of patients with candidate driver genes in patients with nonsmall cell lung cancer. Methods: Patients with primary lung cancer who underwent clinical genetic tests at Guangdong General Hospital were enrolled. Driver genes were detected by sequencing, high-resolution melt analysis, qPCR, or multiple PCR and RACE methods. Results: 524 patients were enrolled in this study, and the differences in driver gene alterations among subgroups were analyzed based on histology and smoking status. In a subgroup of non-smokers with adenocarcinoma, EGFR was the most frequently altered gene, with a mutation rate of 49.8%, followed by EML4-ALK (9.3%), PTEN (9.1%), PIK3CA (5.2%), c-Met (4.8%), KRAS (4.5%), STK11 (2.7%), and BRAF (1.9%). The three most frequently altered genes in a subgroup of smokers with adenocarcinoma were EGFR (22.0%), STK11 (19.0%), and KRAS (12.0%). We only found EGFR (8.0%), c-Met (2.8%), and PIK3CA (2.6%) alterations in the non-smoker with squamous cell carcinoma (SCC) subgroup. PTEN (16.1%), STK11 (8.3%), and PIK3CA (7.2%) were the three most frequently enriched genes in smokers with SCC. DDR2 and FGFR2 only presented in smokers with SCC (4.4% and 2.2%, respectively). Among these four subgroups, the differences in EGFR, KRAS, and PTEN mutations were statistically significant. Conclusion: The distinct features of driver gene alterations in different subgroups based on histology and smoking status were helpful in defining patients for future clinical trials that target these genes. This study also suggests that we may consider patients with infrequent alterations of driver genes as having rare or orphan diseases that should be managed with special molecularly targeted therapies. [ABSTRACT FROM AUTHOR]

Background: Cross-study comparisons suggest that systemic exposure (AUC) to rosuvastatin calcium, a 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitor, may be ~2-fold higher in Asian subjects living in Asian countries than in white subjects living in Western countries. Objective: This study was conducted to determine the pharmacokinetic characteristics of rosuvastatin and its metabolites after single and multiple doses of rosuvastatin in healthy Chinese subjects living in China. Methods: This was an open-label, ascending single and multiple-dose study. Subjects were randomly assigned to receive rosuvastatin 5, 10, or 20 mg. Each subject received 1 tablet of the assigned treatment on day 1 and days 4 through 10. Plasma concentrations of rosuvastatin, N-desmethyl rosuvastatin, and rosuvastatin lactone were measured through 72 hours after administration of single doses and through 96 hours after administration of multiple doses. Blood samples were obtained within 30 minutes before dosing on days 7, 8, and 9 for the assessment of pharmacokinetic parameters at steady state. Noncompartmental pharmacokinetic analysis was performed to determine the Cmax and AUC0∓t for rosuvastatin, N-desmethyl rosuvastatin, and rosuvastatin lactone after single and multiple doses of rosuvastatin. Tolerability assessments were conducted throughout the study. Results: Of the 36 enrolled subjects, only 1 was female. The mean age of subjects in the rosuvastatin 5-, 10-, and 20-mg groups was 22.4, 21.3, and 22.4 years, respectively. Weight and height ranged from 54 to 85 kg and from 161 to 189 cm, respectively. Geometric mean Cmax values for rosuvastatin after administration of single doses of rosuvastatin 5, 10, and 20 mg were 8.33, 10.76, and 19.17 ng/mL, respectively; the corresponding geometric mean AUC0∓t values were 57.63, 88.89, and 163.87 ng · h/mL. At steady state, values for Cmax were 8.31, 8.41, and 20.73 ng/mL; the corresponding geometric mean AUC values were 64.87, 77.29, and 178.64 ng · h/mL. After administration of multiple doses of rosuvastatin 5, 10, and 20 mg, the accumulation ratios were 1.23, 0.95, and 1.23, respectively, indicating minimal accumulation of rosuvastatin. Circulating concentrations of N-desmethyl rosuvastatin and rosuvastatin lactone were well below those of rosuvastatin after administration of single and multiple doses of rosuvastatin. Conclusions: Increases in Cmax, AUC0∓t, Cmax,ss, and AUCss were observed with increasing single and multiple doses of rosuvastatin 5, 10, and 20 mg. The increase in exposure with increasing doses was lower than would be expected under conditions of strict proportionality. Rosuvastatin exhibited little accumulation on repeated administration. All rosuvastatin doses were well tolerated in these Chinese subjects. [Copyright &y& Elsevier]

[Display omitted] • Cord blood lead levels in China are higher than in most developed countries. • Passive smoking during pregnancy was a major source of cord blood lead exposure. • Not only does DHA benefit fetal brain development, but it also prevents an increase of lead levels in cord blood. • Whole grains and beverage consumption may act as a protective factor against having cord blood lead levels ≥20 μg/L. Lead exposure all over the world has gradually declined. As fetuses are more prone to lead exposure, even to low levels of lead exposure, it is important to monitor blood lead levels (BLLs) in pregnancy. We obtained data on BLLs in the third trimester of pregnancy from medical records and measured cord BLLs obtained from 121 mother-child pairs in Shenyang, China from September 2019 to February 2020. We also estimated relationships between socio-demographic, lifestyle and dietary factors during pregnancy as well as cord BLLs to identify the source of lead exposure during pregnancy. BLLs was estimated by atomic absorption spectrometry through graphite furnace ionization techniques. The data which obtained by questionnaires during pregnancy included maternal sociodemographic, lifestyle, dietary factors. We have established three multivariate logistic regression models in which the dichotomous BLLs was used as the dependent variable (cord BLLs ≥20 μg/L vs <20 μg/L). The median and geometric mean of cord BLLs were 22.90 μg/L, 21.88 μg/L and BLLs in the third trimester of pregnancy were 25.29 μg/L, 24.66 μg/L, respectively. BLLs showed significant correlations between cord and the third trimester of pregnancy (r = 0.277, P = 0.012). Pregnant women who had not been exposed to passive smoking had lower OR (95 %) [0.43(0.19–0.94)] for cord BLLs ≥20 μg/L than pregnant women who had. Intake of docosahexaenoic acid (DHA) during third trimester of pregnancy presented an OR (95 %) [0.23(0.08–0.61)] for cord BLLs ≥20 μg/L. Consuming more whole grains (>3 times/week) and beverage (≥1 times/week) showed an OR (95%CI) for cord BLLs ≥20 μg/L of 0.09(0.02–0.53) and 0.19(0.06–0.69), respectively. This study showed the cord BLLs of Chinese are still higher than most developed countries. Passive smoking is a risk factor for cord BLLs ≥20 μg/L and supplement of DHA, whole grains and beverage consumption during pregnancy may act as a beneficial factor against having cord BLLs ≥20 μg/L. [ABSTRACT FROM AUTHOR]

Whether trade wars are beneficial or hurtful for the countries involved has been widely debated, particularly with respect to the U.S. China Trade War that began in 2018 to the present. In this paper, we provide an overview of some of the theoretical literature for the expected economic and ecological effects of trade wars and provide a case study presenting the events of the U.S. China Trade War to compare theoretical views to actual net economic and sustainability effects occurring in the U.S., with a short overview of aftermath effects during the Covid19 pandemic in 2020. [ABSTRACT FROM AUTHOR]

[Display omitted] • Efficient nitrogen removal was achieved under influent nitrate and temperature variation. • Nitrate removal loading was more sensitive to temperature than other factors. • Nitrogen gas was the prominent inducement to clogging. • Using gas-venting could save 90% time and energy than conventional back-washing. • No functional instability or "treatment short-circuit" occurred in S0AD biofilter. Elemental sulfur autotrophic denitrification (S0AD) is viewed as a promising alternative to conventional heterotrophic denitrification due to lower running costs, zero carbon dioxide emission, and minimum excess sludge production. However, its scale-up capability and robustness in treating real-life wastewater have not been convincedly demonstrated. In this study, a pilot-scale S0AD packed-bed with over 1000 m3/d of actual wastewater treatment capacity was operated for 197 days. The S0AD packed-bed could effectively remove nitrate to below 12 mg-NO 3 −-N/L that is 20% stricter than China's national standard (15 mg-TN/L). The temperature effect coefficient Q 10 was calculated as 1.01, illustrating that denitrification efficiency could be doubled when the temperature increased every 10 °C. Mass balance calculations indicated that 85% of removed nitrate was contributed by S0AD process, and the rest 15% was by heterotrophic and assimilative processes. A total of 2684 kg sulfur was consumed during the course of the experiment which was attributed to 16.1% DO oxidation and 83.9% denitrification. Nitrogen gas produced through denitrification, could be trapped in the S0 packed-bed that was the primary causality of clogging. Daily gas venting instead of conventional back washing, could effectively recover the packed-bed flux and promote denitrification efficiency. In addition, a weekly thorough back washing was deemed necessary to deeply clean the trapped SS and sloughed overgrowing biofilm. The predominant S0AD bacteria belonged to the genus Thiobacillus, was enriched throughout the packed-bed providing robust and stable denitrification. Overall, we provided some guidance to the design and operation of S0AD packed bed in practical engineering. [ABSTRACT FROM AUTHOR]

Background: Early detection and screening of oesophageal squamous cell carcinoma rely on upper gastrointestinal endoscopy, which is not feasible for population-wide implementation. Tumour marker-based blood tests offer a potential alternative. However, the sensitivity of current clinical protein detection technologies is inadequate for identifying low-abundance circulating tumour biomarkers, leading to poor discrimination between individuals with and without cancer. We aimed to develop a highly sensitive blood test tool to improve detection of oesophageal squamous cell carcinoma., Methods: We designed a detection platform named SENSORS and validated its effectiveness by comparing its performance in detecting the selected serological biomarkers MMP13 and SCC against ELISA and electrochemiluminescence immunoassay (ECLIA). We then developed a SENSORS-based oesophageal squamous cell carcinoma adjunct diagnostic system (with potential applications in screening and triage under clinical supervision) to classify individuals with oesophageal squamous cell carcinoma and healthy controls in a retrospective study including participants (cohort I) from Sun Yat-sen University Cancer Center (SYSUCC; Guangzhou, China), Henan Cancer Hospital (HNCH; Zhengzhou, China), and Cancer Hospital of Shantou University Medical College (CHSUMC; Shantou, China). The inclusion criteria were age 18 years or older, pathologically confirmed primary oesophageal squamous cell carcinoma, and no cancer treatments before serum sample collection. Participants without oesophageal-related diseases were recruited from the health examination department as the control group. The SENSORS-based diagnostic system is based on a multivariable logistic regression model that uses the detection values of SENSORS as the input and outputs a risk score for the predicted likelihood of oesophageal squamous cell carcinoma. We further evaluated the clinical utility of the system in an independent prospective multicentre study with different participants selected from the same three institutions. Patients with newly diagnosed oesophageal-related diseases without previous cancer treatment were enrolled. The inclusion criteria for healthy controls were no obvious abnormalities in routine blood and tumour marker tests, no oesophageal-associated diseases, and no history of cancer. Finally, we assessed whether classification could be improved by integrating machine-learning algorithms with the system, which combined baseline clinical characteristics, epidemiological risk factors, and serological tumour marker concentrations. Retrospective SYSUCC cohort I (randomly assigned [7:3] to a training set and an internal validation set) and three prospective validation sets (SYSUCC cohort II [internal validation], HNCH cohort II [external validation], and CHSUMC cohort II [external validation]) were used in this step. Six machine-learning algorithms were compared (the least absolute shrinkage and selector operator regression, ridge regression, random forest, logistic regression, support vector machine, and neural network), and the best-performing algorithm was chosen as the final prediction model. Performance of SENSORS and the SENSORS-based diagnostic system was primarily assessed using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC)., Findings: Between Oct 1, 2017, and April 30, 2020, 1051 participants were included in the retrospective study. In the prospective diagnostic study, 924 participants were included from April 2, 2022, to Feb 2, 2023. Compared with ELISA (108·90 pg/mL) and ECLIA (41·79 pg/mL), SENSORS (243·03 fg/mL) showed 448 times and 172 times improvements, respectively. In the three retrospective validation sets, the SENSORS-based diagnostic system achieved AUCs of 0·95 (95% CI 0·90-0·99) in the SYSUCC internal validation set, 0·93 (0·89-0·97) in the HNCH external validation set, and 0·98 (0·97-1·00) in the CHSUMC external validation set, sensitivities of 87·1% (79·3-92·3), 98·6% (94·4-99·8), and 93·5% (88·1-96·7), and specificities of 88·9% (75·2-95·8), 74·6% (61·3-84·6), and 92·1% (81·7-97·0), respectively, successfully distinguishing between patients with oesophageal squamous cell carcinoma and healthy controls. Additionally, in three prospective validation cohorts, it yielded sensitivities of 90·9% (95% CI 86·1-94·2) for SYSUCC, 84·8% (76·1-90·8) for HNCH, and 95·2% (85·6-98·7) for CHSUMC. Of the six machine-learning algorithms compared, the random forest model showed the best performance. A feature selection step identified five features to have the highest performance to predictions (SCC, age, MMP13, CEA, and NSE) and a simplified random forest model using these five features further improved classification, achieving sensitivities of 98·2% (95% CI 93·2-99·7) in the internal validation set from retrospective SYSUCC cohort I, 94·1% (89·9-96·7) in SYSUCC prospective cohort II, 88·6% (80·5-93·7) in HNCH prospective cohort II, and 98·4% (90·2-99·9) in CHSUMC prospective cohort II., Interpretation: The SENSORS system facilitates highly sensitive detection of oesophageal squamous cell carcinoma tumour biomarkers, overcoming the limitations of detecting low-abundance circulating proteins, and could substantially improve oesophageal squamous cell carcinoma diagnostics. This method could act as a minimally invasive screening tool, potentially reducing the need for unnecessary endoscopies., Funding: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Enterprises Joint Fund-Key Program of Guangdong Province., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1 + rather than KMT2A-rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL., (© 2023. The Author(s).)

Background: We assessed the safety and immunogenicity of a core-shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults., Methods: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25μg (n = 20), or SW-BIC-213-45μg (n = 20). The primary study endpoint was adverse events within 30 days post-boosting. The secondary endpoint was the titers of binding antibodies and neutralizing antibodies against the wild-type (WT) of SARS-CoV-2 as well as variants of concern in serum. The exploratory endpoint was the cellular immune responses. This trial was registered with http://www.chictr.org.cn (ChiCTR2200060355)., Findings: Between Jun 6 and Jun 22, 2022, 60 participants were enrolled and randomized to receive a booster dose of SW-BIC-213 (25 μg, n = 20, or 45 μg, n = 20) or COVILO (n = 20). The baseline demographic characteristics of the participants at enrollment were similar among the treatment groups. For the primary outcome, injection site pain and fever were more common in the SW-BIC-213 groups (25 μg and 45 μg). Grade 3 fever was reported in 25% (5/20) of participants in the SW-BIC-213-45μg group but was resolved within 48 h after onset. No fatal events or adverse events leading to study discontinuation were observed. For secondary and exploratory outcomes, SW-BIC-213 elicited higher and longer humoral and cellular immune responses than that in the COVILO group., Interpretation: SW-BIC-213, a core-shell structured lipopolyplex (LPP) based mRNA vaccine, was safe, tolerable, and immunogenic as a heterologous booster in healthy Chinese adults., Funding: Shanghai Municipal Government, the Science and Technology and Economic Commission of Shanghai Pudong New Area, and mRNA Innovation and Translation Center of Shanghai., Competing Interests: Declaration of interests H-W Li, H Shen, M-Y Shen, and Y-L Yi are employees of StemiRNA Therapeutics Co., Ltd, who developed the SW-BIC-213 vaccine. All other authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Sponge-derived bacteria are considered to be a promising source of novel drugs, owing to their abundant secondary metabolites that have diverse biological activities. In this study, we explored the antimicrobial biosynthetic potential and phylogenetics of culturable bacteria associated with the sponge Ophlitaspongia sp. from the Yellow Sea, China. Using culture-dependent methods, we obtained 151 bacterial strains, which were then analysed for their antimicrobial activities against seven indicator strains. The results indicate that 94 (62.3%) of the 151 isolated strains exhibited antimicrobial activities and inhibited at least one of the indicator strains. Fifty-two strains were selected for further phylogenetic analysis using 16S rRNA gene sequencing, as well as for the presence of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes. These 52 strains belonged to 20 genera from 18 families in 4 phyla, including Actinobacteria , Bacteroidetes , Firmicutes , and Proteobacteria . Five strains with PKS genes and ten strains with NRPS genes were detected. Among them, two strains contained both PKS and NRPS genes. Notoacmeibacter sp. strain HMA008 (class Alphaproteobacteria ) exhibited potent antimicrobial activity; thus, whole genome sequencing methods were used to analyse its secondary metabolite biosynthetic gene clusters. The genome of HMA008 contained 12 biosynthetic gene clusters that potentially encode secondary metabolites belonging to compound classes such as non-ribosomal peptides, prodigiosin, terpene, β-lactones, and siderophore, among others. This study indicates that the sponge Ophlitaspongia sp. harbours diverse bacterial strains with antimicrobial properties and may serve as a potential source of bioactive compounds.

Background: Although blood lead levels (BLLs) in children are gradually decreasing, low-concentration lead exposure can still exert adverse effects. We studied the factors that affect BLLs in children in Shenyang, China., Methods: We conducted a cross-sectional study by administering structured questionnaires on family demographics and food intake. The concentrations of lead in venous blood were determined by graphite furnace atomic absorption spectrometry., Results: A total of 273 children aged 1-6 years were enrolled. The geometric mean (geometric standard deviation) of BLLs was 24.94 (12.70) μg/L in boys and 23.75 (11.34) μg/L in girls. The prevalence of BLLs of ≥35 μg/L was 22.7% and was mainly observed in children aged under 3 years. Often hand washing before meals was protective against BLLs ≥20 μg/L (adjusted OR: 0.427, 95%CI: 0.238-0.767, p = 0.004). Consumption of puffed grains and eggs had an adjusted OR (95%CI) for BLLs ≥20 μg/L of 1.714 (1.012-2.901) (p = 0.045) and 1.787 (1.000-3.192) (p = 0.050), respectively., Conclusions: BLLs of children in Shenyang are still higher than in developed countries. Consumption of puffed grains and eggs is associated with higher BLLs. Often hand washing before meals may be protective against high BLLs., (© 2022. The Author(s).)

Introduction: This study delineated the interrelationships among blood pressure (BP), cerebrospinal fluid (CSF) core biomarkers of Alzheimer's disease (AD), and cognition., Methods: The linear regression analyses were conducted in 1546 non-demented participants (mean age of 61.58 years, range 40 to 89 years; 40% female; average days of BP measurement, 9.10 days). Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects., Results: A clear age-related pattern of BP was delineated. Mid-life hypertension (especially systolic BP), late-life lower diastolic BP, as well as mid- and late-life higher pulse pressure were associated with cognitive impairment and tau-related biomarkers. BP variability was associated only with cognition but not with CSF biomarkers. Overall, the associations between BP and cognition were partially mediated (proportion: 11% to 30%) by tau pathologies, independently of amyloid pathology., Discussion: Tau pathologies might play important roles in the relationship between BP and cognition, with significant age- and BP-type dependences., (© 2021 the Alzheimer's Association.)

Objective: The aim of this study was to evaluate the relationship between lifestyle habits and health-related quality of life (HRQoL) among different ages who were initially diagnosed with breast cancer (within the first 2 weeks) and to determine the contribution of lifestyle habits factors on HRQoL. Methods: Patients with breast cancer were recruited from 22 hospitals in 11 provinces or municipalities in northern and eastern China. The Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) was used to measure HRQoL. Chi-square test, ANOVA, and multivariable generalized linear models were conducted to identify the differences in HRQoL between two age groups (age <50 years and ≥50 years) and to evaluate the contribution of lifestyle habits factors on HRQoL of patients with breast cancer. Results: About 1,199 eligible patients with breast cancer were used for analysis. Younger women (aged <50 years) appeared to show lower scores than older women (aged ≥50 years) in HRQoL subscales, including emotional well-being ( p = 0.003), functional well-being ( p = 0.006), breast cancer subscale ( p = 0.038), and FACT-B Total scores ( p = 0.028). Tea and alcohol consumption and being very satisfied with sleep and current life were the strongest predictors of higher HRQoL in younger group. Meanwhile, no coffee consumption, frequent participation in physical activities, high sleep satisfaction, and current life satisfaction were the key predictors of higher HRQoL in older women with breast cancer. Conclusion: The relationship of the nine lifestyle habit items with HRQoL differed among younger and older women. The associated variable of low HRQoL can help clinicians take intervention early in order to improve the prognosis of patients with breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Yu, Jia, Cui, Tian, Fan, Geng, Cao, Yang, Wang, Liang, Wang, Jiang, Duan, Wang, Li, Wang, Zhang, Jin, Tang, Li, Zhu, Zuo, Wang, Zhou, Xiang, Guo, Wang, Huang, Liu and Yu.)

Objective: This study aimed to investigate the relationship between the gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) C677T and left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD)., Methods: A total of 763 Chinese patients with CKD undergoing genetic testing were included in the study. The association between the gene polymorphism of MTHFR C677T and echocardiographic parameters was analyzed through univariate and multivariate analyses., Results: We found a remarkably positive association between MTHFR C677T gene polymorphism and LVH indexes, including interventricular septal thickness (F = 3.8; P = .022), left ventricular posterior wall thickness (F = 3.0; P = .052), left ventricular mass (F = 3.9; P = .022), and left ventricular mass index (F = 2.6; P = .075). After adjusting for the potential confounders linking the polymorphism,we found that the positive association between the polymorphism and LVH indexes still existed in patients with CKD in some multiple linear regression models (P <.05)., Conclusion: MTHFR C677T gene polymorphism may be a genetic susceptibility marker for the development of LVH in patients with CKD., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A -) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p < 0.001) in PSQI were positively associated with CSF sTREM2. Besides, several U-shaped relationships were revealed of sleep-time measures, such as insufficient or excessive nocturnal sleep duration, with CSF sTREM2 in A + individuals (the optimal model: bedtime 22:21 p.m., time to fall asleep 22:52 p.m., nocturnal sleep duration 7.36 h). In A - individuals, the above relationships were not found. Poor self-reported sleep characteristics and sleep indicators were associated with higher CSF sTREM2, suggesting that sleep might play an important role in the regulation of TREM2-associated microglial activity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The associations between obesity and Alzheimer's disease (AD) at different ages have been debated. Recent evidence implied the protective effects of metabolically healthy obesity on AD. We hypothesized that obesity and lipids could mitigate the detrimental impacts of AD pathological changes among metabolically healthy individuals in late life. In this study, a total of 604 metabolically healthy participants with normal cognition were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Multiple linear regression models were used to test the associations of body mass index (BMI) or lipids with cerebrospinal fluid (CSF) biomarkers after adjustment for age, gender, education, and Apolipoprotein E-ɛ4 (APOE-ɛ4). The results showed the lower CSF levels of total tau protein (t-tau: p = .0048) and phosphorylated tau protein (p-tau: p = .0035) in obese participants than in non-obese participants, even after correcting for covariates. Moreover in late life, higher BMI was associated with decreased CSF t-tau (β: -0.15, p = .0145) and p-tau (β: -0.17, p = .0052). As for lipids, higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were associated with decreased CSF t-tau (TC: β: -0.16, p = .0115; LDL-C: β: -0.16, p = .0082) and p-tau (TC: β: -0.15, p = .0177; LDL-C: β: -0.14, p = .0225) in obese participants. Furthermore, these associations were only significant in participants with late-life obesity and APOE-ɛ4 non-carriers. Overall, in a cognitively normal population, we found metabolically healthy obesity and lipids in late life might be protective factors for neurodegenerative changes., (© 2021 International Society for Neurochemistry.)

To fully decipher the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein, it is essential to assess which part is highly immunogenic in a systematic way. We generate a linear epitope landscape of the Spike protein by analyzing the serum immunoglobulin G (IgG) response of 1,051 coronavirus disease 2019 (COVID-19) patients with a peptide microarray. We reveal two regions rich in linear epitopes, i.e., C-terminal domain (CTD) and a region close to the S2' cleavage site and fusion peptide. Unexpectedly, we find that the receptor binding domain (RBD) lacks linear epitope. We reveal that the number of responsive peptides is highly variable among patients and correlates with disease severity. Some peptides are moderately associated with severity and clinical outcome. By immunizing mice, we obtain linear-epitope-specific antibodies; however, no significant neutralizing activity against the authentic virus is observed for these antibodies. This landscape will facilitate our understanding of SARS-CoV-2-specific humoral responses and might be useful for vaccine refinement., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: ADJUVANT-CTONG1104 (ClinicalTrials.gov identifier: NCT01405079), a randomized phase III trial, showed that adjuvant gefitinib treatment significantly improved disease-free survival (DFS) versus vinorelbine plus cisplatin (VP) in patients with epidermal growth factor receptor ( EGFR ) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). Here, we report the final overall survival (OS) results., Methods: From September 2011 to April 2014, 222 patients from 27 sites were randomly assigned 1:1 to adjuvant gefitinib (n = 111) or VP (n = 111). Patients with resected stage II-IIIA (N1-N2) NSCLC and EGFR -activating mutation were enrolled, receiving gefitinib for 24 months or VP every 3 weeks for four cycles. The primary end point was DFS (intention-to-treat [ITT] population). Secondary end points included OS, 3-, 5-year (y) DFS rates, and 5-year OS rate. Post hoc analysis was conducted for subsequent therapy data., Results: Median follow-up was 80.0 months. Median OS (ITT) was 75.5 and 62.8 months with gefitinib and VP, respectively (hazard ratio [HR], 0.92; 95% CI, 0.62 to 1.36; P = .674); respective 5-year OS rates were 53.2% and 51.2% ( P = .784). Subsequent therapy was administered upon progression in 68.4% and 73.6% of patients receiving gefitinib and VP, respectively. Subsequent targeted therapy contributed most to OS (HR, 0.23; 95% CI, 0.14 to 0.38) compared with no subsequent therapy. Updated 3y DFS rates were 39.6% and 32. 5% with gefitinib and VP ( P = .316) and 5y DFS rates were 22. 6% and 23.2% ( P = .928), respectively., Conclusion: Adjuvant therapy with gefitinib in patients with early-stage NSCLC and EGFR mutation demonstrated improved DFS over standard of care chemotherapy. Although this DFS advantage did not translate to a significant OS difference, OS with adjuvant gefitinib was one of the longest observed in this patient group compared with historic data.

Background: Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses., Methods: We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves., Results: Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ2 = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ2 = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006)., Conclusion: Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders., Methods: The associations between CSF α-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF α-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in the Alzheimer's disease Neuroimaging Initiative (ADNI) database., Results: The CSF α-synuclein levels correlated with AD-specific biomarkers, CSF total tau and phosphorylated tau levels, in 651 Chinese Han participants (training set). These positive correlations were replicated in the ADNI database (validation set). Using a longitudinal cohort from ADNI, the CSF α-synuclein concentrations were found to increase with disease severity. The CSF α-synuclein had high diagnostic accuracy for AD based on the "ATN" (amyloid, tau, neurodegeneration) system (A + T+ versus A - T - control) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia., Conclusions: CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.

Objective: To investigate the lead exposure levels, and the effect of blood lead level (BLL) on recurrent respiratory infections in children aged 3-7 years in Shenyang., Methods: A case-control study including 78 children with recurrent respiratory infections and 141 controls was performed. Venous blood was obtained for BLL, and a questionnaire was completed., Results: The BLL was significantly higher in children with recurrent respiratory infections than that in the control group [Median (IQR): 2.56 (1.29-6.19) vs 1.99 (0.90-5.92) µg/dL, P=0.029]. Children with BLL ≥1.95 µg/dL were more likely to be suffering from recurrent respiratory infections (OR=2.328, 95%CI=1.228-4.413) than those with BLL <1.95 µg/dL., Conclusions: High lead level can increase the risk of respiratory infections in preschool children.

It is unclear how blood glucose levels mediate the pathology of Alzheimer's disease (AD). This study aimed to investigate whether fasting blood glucose (FBG) levels are associated with cerebrospinal fluid (CSF) biomarkers preferentially affected by AD in non-diabetic cognitively normal elders. A total of 499 non-diabetic cognitively normal elders were from the Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study. We detected the associations of FBG with individual CSF measures using multiple linear regression models controlling for age, sex, educational level, and apolipoprotein E ( APOE) ε4 genotype. Fasting blood glucose level was positively correlated with CSF Aβ 42 level (β = 0.045, p = 0.010), CSF Aβ 42 /Aβ 40 ratio (β = 0.005, p < 0.001), Aβ 42 /P-tau ratio (β = 0.282, p = 0.013), and Aβ 42 /T-tau ratio (β = 0.050, p = 0.040). Interaction analysis indicated that gender affected the correlations of FBG level with CSF Aβ 40 (p < 0.001) and Aβ 42 /Aβ 40 ratio (p < 0.001). This study raises additional questions about the role of blood glucose in the predisposition to AD and supports the possibility of targeting these processes in pre-symptomatic AD trials in non-diabetic elders.

Introduction: The purpose of this study is to evaluate the diagnostic value of macrophage migration inhibitory factor in patients with nasopharyngeal carcinoma., Materials and Methods: The expression levels of macrophage migration inhibitory factor in nasopharyngeal carcinoma cell lines, tumor tissues, and plasma were measured by real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. Plasma Epstein-Barr virus viral capsid antigen was determined by immunoenzymatic techniques., Results: Both the messenger RNA and protein expression levels of macrophage migration inhibitory factor were upregulated in nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma tissues. Macrophage migration inhibitory factor in plasma was significantly elevated in patients with nasopharyngeal carcinoma compared to Epstein-Barr virus viral capsid antigen-negative and Epstein-Barr virus viral capsid antigen-positive healthy donors. The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen was better for diagnosing nasopharyngeal carcinoma (area under receiver operating characteristic curve = 0.925, 95% CI: 0.898-0.951) than macrophage migration inhibitory factor (area under receiver operating characteristic curve = 0.778, 95% CI: 0.732-0.824) and Epstein-Barr virus viral capsid antigen. Combining macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen had higher specificity (82.40% vs 69.96%) and higher positive predictive value (79.17% vs 67.44%) without an obvious reduction in sensitivity (95.25%) compared to Epstein-Barr virus viral capsid antigen alone. Macrophage migration inhibitory factor was highly expressed in nasopharyngeal carcinoma cell lines, whereas it was not associated with Epstein-Barr virus infection. The level of macrophage migration inhibitory factor in plasma was not related to the titer of Epstein-Barr virus viral capsid antigen., Conclusion: The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen increases the specificity and positive predictive value of detecting nasopharyngeal carcinoma and improves the diagnostic accuracy of nasopharyngeal carcinoma in high-risk individuals.

BACKGROUND The aim of this study was to determine the risk factors for early chronic kidney disease (CKD) (GFR 60-89 ml/min/1.73 m²; CKD stage 2) in asymptomatic Chinese individuals undergoing routine health examination. MATERIAL AND METHODS This cross-sectional study enrolled 9100 individuals who received voluntary medical examinations between 10/01/2011 and 09/30/2017. Demographic data, clinical history, clinical examination, medication, smoking, alcohol, blood biochemistry, urinalysis, and carotid ultrasound were extracted from the medical records. All laboratory analyses were performed routinely. Multivariable logistic regression for factors predicting CKD stage 2 was performed. RESULTS A total of 9100 individuals were enrolled (age of 18-65 and 65.4% male). CKD stage 2 was found in 1989/9100 individuals (21.9%). Male gender (OR=6.711, 95%CI: 5.376-8.403, P<0.001), older age (OR=1.077, 95%CI: 1.068-1.086, P<0.001), hemoglobin levels (OR=1.051, 95%CI: 1.046-1.057, P<0.001), triglycerides levels (OR=1.174, 95%CI: 1.067-1.292, P=0.001), HDL-C (OR=0.539, 95%CI: 0.380-0.763, P<0.001), Lp(a) levels (OR=1.000, 95%CI: 1.000-1.001, P=0.03), and carotid atherosclerosis (OR=1.248, 95%CI: 1.005-1.550, P=0.045) were associated with CKD stage 2 among all subjects. Serum triglycerides levels were associated with CKD stage 2 in the 18-45 and 45-65 years of age subgroups. CONCLUSIONS Factors that are routinely assessed during routine health examinations (male gender, age, hemoglobin levels, triglycerides levels, HDL-C, Lp(a) levels, and carotid atherosclerosis) can help identify individuals at higher risk of having CKD stage 2. The Chinese dyslipidemia is characterized by high triglycerides and low HDL-C and occurs in young and middle-aged individuals. Those factors could help identify individuals at higher risk for CKD stage 2 and who could benefit from preventive treatments.

Introduction: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized., Methods: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted., Results: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib., Conclusions: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

During the past decade, sustainability science has rapidly developed into a globally well-recognized and important new science of the 21st century. However, sustainability science has not received much attention from scientists and practitioners in China where sustainable development and ecological civilization have been prominent themes. To promote the development of sustainability science in China, Wu, et al. (2014) published the first in-depth review on the subject in Chinese, entitled What is sustainability science? Here, we revisit the question, and discuss the relationship between sustainability science and sustainable development research, the scientific paradigm and the core research questions of sustainability science. Our review of the recent advances in this field reveals contrasting trends for the world versus China. On the one hand, the world is witnessing sustainability science maturing with global momentum to systematically advance sustainability research and education. On the other hand, China greatly lags behind developed countries and South Africa, albeit the great deal of new passion and desire for sustainable development. To promote the science and practice of sustainability in China, we propose a trinity strategy: 1) bringing in from the global community to guide Chinese practices in sustainable development; 2) reaching out to the global community to share Chinese wisdom of sustainable development; and 3) integrating traditional Chinese philosophy with western science to lead the development of sustainability science.

Objective: Some population-based studies involving lung cancer patients have reported that inherited susceptibility is responsible for the familial aggregation observed in non-smoking lung cancer patients; however, it has been found that the false-negative rates in clinic-ascertained probands are significantly lower than population-ascertained probands. In this clinic-based study, we sought to determine the relationship between a family history of cancer and lung cancer risk in Chinese never-smokers., Methods: In this clinic-based case-control study, all 318 probands and 509 controls were Chinese. The data on demographic characteristics, age, gender, race, lung disease history, living environment, occupational exposure, and smoking history were collected from a structured questionnaire. Multiple conditional logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs after adjusting for possible confounders., Results: The risk of lung cancer was increased in individuals with a family history of lung (aOR, 3.21; p<0.001) or any other cancer (aOR, 1.79; p<0.001). Analyses were carried out using stratified relative gender; first-degree female relatives tended to have a higher risk than first-degree male relatives. Similarly, the aOR for a female developing a malignant tumor was two times greater than controls., Conclusions: Our analysis provides further evidence of the importance of genetic factors underlying lung cancer in patients who are never-smokers, especially in patients with a maternal history of cancer., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The level of total adiponectin, a mixture of different adiponectin forms, has been reported associated with breast cancer risk with inconsistent results. Whether the different forms play different roles in breast cancer risk prediction is unclear. To examine this, we measured total and high molecular weight (HMW) adiponectin in a case-control study (1167 sets). Higher circulating HMW adiponectin was negatively associated with breast cancer risk after adjusting for menopausal status and family history of breast cancer (P=0.024). We analyzed the relationship between adiponectin and breast cancer risk in 6 subgroups. Higher circulating HMW adiponectin was also negatively associated with breast cancer risk (P=0.020, 0.014, 0.035) in the subgroups of postmenopausal women, negative family history of breast cancer, BMI>=24.0. Total adiponectin was positively associated with breast cancer (P=0.028) in the subgroup of BMI<=24.0. Higher HMW/total adiponectin ratio was negatively associated with breast cancer (P=0.019) in the subgroup of postmenopausal women. Interestingly, in the subgroup of women with family history of breast cancer, higher circulating total and HMW adiponectin were positively associated with breast cancer risk (P=0.034, 0.0116). This study showed different forms of circulating adiponectin levels might play different roles in breast cancer risk. A higher circulating HMW adiponectin is associated with a decreased breast cancer risk, especially in postmenopausal, without family history of breast cancer or BMI>=24.0 subgroups, whereas higher circulating HMW adiponectin levels is a risk factor in women with a family history of breast cancer. Further investigation of different forms of adiponectin on breast cancer risk is needed.

Objective: Postoperative atrial fibrillation (POAF) is the most frequent complication arising after cardiac surgery, occurring in 30% of cases. Amiodarone is the most effective drug for prophylaxis and treatment. However, because of significant extracardiac side effects, only high-risk patients are eligible for prophylactic amiodarone therapy. We performed a randomized prospective study of 100 patients undergoing cardiac surgery with epicardial application of amiodarone-releasing hydrogel to determine the effectiveness of preventing POAF., Methods: After institutional review board approval, 100 patients, from January 2012 to July 2013, who had undergone cardiac surgery, were randomized to 2 equal groups. The study group received poly-based hydrogel with amiodarone sprayed diffusely over the epicardium. The control group underwent the procedure without the spray. Continuous telemetry monitored for POAF, and amiodarone levels in the atria, plasma, and tissue were measured postoperatively. Daily electrocardiographic parameters were measured until postoperative day 14., Results: The incidence of POAF was significantly less in the study group, with 4 of 50 patients (8%) incurring atrial fibrillation compared with 13 of 50 patients (26%) in the control group (P < .01). The mean amiodarone concentrations in the atria (12.06 ± 3.1) were significantly greater than those in the extracardiac tissues (1.32 ± 0.9; P < .01). The plasma amiodarone levels remained below the detection limit (<8 μg/mL) during the 14 days of follow-up. Bradycardia was observed less in the study group (76 ± 29) than in the control group (93 ± 18; P < .01)., Conclusions: Epicardial application of amiodarone-releasing adhesive hydrogel is a less invasive, well-tolerated, quick, and effective therapeutic option for preventing POAF at minimal risk of extracardiac adverse side effects., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background and Objectives: Ezetimibe/simvastatin combination tablet has been approved for the treatment of high low-density lipoprotein cholesterol (LDL-C) levels in patients with primary hypercholesterolaemia or mixed hypercholesterolaemia as adjunctive therapy to diet, when diet alone is insufficient in lowering cholesterol. The aims of this study were to assess the pharmacokinetics and safety of an ezetimibe/simvastatin combination tablet after oral single-dose administration in healthy Chinese subjects including sex-related differences in pharmacokinetics., Methods: This was an open-label, single-dose study. Twelve healthy subjects (six males and six females) received a single dose of an ezetimibe/simvastatin combination tablet (ezetimibe 10 mg and simvastatin 40 mg). The pharmacokinetic parameters for ezetimibe and simvastatin were assessed by determining total ezetimibe, free ezetimibe, simvastatin and simvastatin acid concentrations using a validated liquid chromatography-tandem mass spectrometry method. Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations and 12-lead electrocardiograms., Results: The pharmacokinetic parameters (mean ± SD) for total ezetimibe and free ezetimibe following a single dose were: maximum plasma drug concentration (C(max)) 81.56 ± 26.62 and 9.40 ± 6.17 ng/mL; time to reach C(max) (t(max)) 0.93 ± 0.30 and 1.25 ± 1.27 h; elimination half-life (t(½)) 24.32 ± 13.27 and 18.90 ± 9.66 h, and mean area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC(last)) 579.06 ± 241.45 and 126.01 ± 69.01 ng·h/mL, respectively. The pharmacokinetic parameters (mean ± SD) for simvastatin and simvastatin acid following a single dose were: C(max) 11.92 ± 5.50 and 3.37 ± 1.78 ng/mL, t(max) 0.98 ± 0.28 and 3.73 ± 1.68 h, t(½) 4.19 ± 1.81 and 7.65 ± 7.96 h, and mean AUC(last) 33.63 ± 20.41 and 32.50 ± 18.79 ng·h/mL. Higher AUC(last) and AUC from time zero to infinity (AUC(∞)), and lower apparent total body clearance of drug from plasma after oral administration (CL/F) for total ezetimibe and free ezetimibe were observed in female subjects compared with those in male subjects. There were no differences between the pharmacokinetic parameters of simvastatin and simvastatin acid for female and male subjects in the study., Conclusion: Ezetimibe/simvastatin combination tablet has a generally favourable safety and tolerability profile in healthy Chinese subjects. A statistically significant difference with regard to sex in the pharmacokinetics of ezetimibe was observed. Sex had no effect on the pharmacokinetics of simvastatin and simvastatin acid.

Introduction: Computed tomography screening can detect lung cancer that is curable. However, some studies demonstrated that the risk for false-positives was about 50%. To make screening more efficient, we sought to create a forecasting model for individuals with different risks for lung cancer., Methods: We used multiple logistic regression analysis to identify independent predictors and to develop a prediction model. The pathological diagnoses in Guangdong Lung Cancer Institute were consecutively chosen as probands. All first-degree relatives of probands and their spouses were included as subjects. We divided the probands and their spouses into three subgroups according to the odds ratios (ORs), and the accuracy of lung cancer predictions for patients within the subgroups increased synchronously., Results: There were 633 proband pedigrees and 565 spouse pedigrees. Independent predictors of lung cancer included sex (OR, 1.6; 95% confidence interval [CI], 1.1-2.3), smoking history (light smoker: OR, 1.1; 95% CI, 0.7-1.8; heavy smoker: OR, 4.7; 95% CI, 3.1-7.1), lung disease history (OR, 5.3; 95% CI, 2.8-10.0), occupational exposure (OR, 1.6; 95% CI, 1.1-2.2), and number of affected individuals among first-degree relatives (n = 1: OR, 2.1; 95% CI, 1.3-3.4; n ≥ 2: OR, 4.7; 95% CI, 0.5-41.2). The accuracy of the pretest probability increased for those with higher ORs: low-OR subgroup, 68.3%; mid-OR subgroup, 84.0%; and high-OR subgroup, 91.9%., Conclusions: Our prediction rule is recommended for estimating the pretest probability of lung cancer, thereby facilitating early screening.

Based on the observed data of stable isotopes in precipitation and meteorological statistics at Urümqi (1986-2003), Zhangye (1986-2003), and Hotan (1988-1992) from IAEA/WMO, the precipitation equation of arid region in Northwest China was calculated through the regression analysis, and the characteristics of stable isotopic in precipitation, as well as the correlation between stable isotopic and meteorological records, were analyzed. The water vapor source of the three sites was tracked by the HYSPLIT4. 9 model, and water vapour transmission regime of arid region in Northwest China was established, while the record of delta18O in cryosphere was discussed. Results showed that the precipitation equation of deltaD = 7.24 delta18O + 1.96 per thousand indicates intense evaporation; delta18O values at Urümqi, Zhangye and Hotan fluctuates at -20.58 per thousand- -5.4 per thousand, -18.58 per thousand- -2.46 per thousand and -20.33 per thousand- -0.01 per thousand, respectively. The delta18O value is low in winter and high in summer, but the values of d-excess is on the contrary; The spatial distribution shows that delta18O value at Zhangye is highest, followed by Hotan, and the lowest is at Urümqi; The highest of d-excess value is at Urümqi, followed by Hotan, the lowest is at Zhangye; The temperature effect of delta18O in precipitation is significant with the correlation coefficients of 0.85, 0.81 and 0.86, respectively, and the rainfall effect does not exist; The modeled trajectory of vapor source showed there are two main paths all the year, which are from the Atlantic Ocean via Westerlies and the Arctic region, respectively, influence by different vapor sources, the seasonality of delta18O values lower in winter, higher in summer; In addition, according to the cryospheric environment, the correlation between delta18O in snow pack or ice core and the corresponding meteorological station record was significant, which reflects the variation of temperature efficiently.

Objective: To investigate infections of syphilis, neisseria gonorrhoeae, chlamydia trachomatis and the related risk factors in men who have sex with men (MSM) in Jiangsu province., Methods: A total of 400 MSM were enrolled by Snowball Sampling Method from August to October in 2010 and then 328 cases were surveyed by a questionnaire and collected serum sample 5 ml per person as well as rectal swab on the spot; all of the serum samples were tested for syphilis by ELISA and TRUST, and all of the rectal swabs were tested for neisseria gonorrhoeae or chlamydia trachomatis. The influencing factors of syphilis, neisseria gonorrhoeae, chlamydia trachomatis were analyzed by logistic regression analysis., Results: The 328 MSM were (32.46 ± 9.72) years old, 59.15% (194/328) were unmarried.75.00% (246/328) MSM had rectal sex with men in the past 3 months, and condom use rate for recent sex was 56.71% (186/328), while 53.05% (174/328) MSM didn't have sex with women in the last 3 months. The syphilis infection rate among MSM was 13.41% (44/328), the neisseria gonorrhoeae infection rate was 3.66% (12/328), and the chlamydia trachomatis rate was 11.59% (38/328). The number of sex partners was the key factor that influenced syphilis infections (OR = 4.213, 95%CI: 1.133 - 15.656)., Conclusion: The prevalence of syphilis and chlamydia trachomatis was high in MSM in Jiangsu, while risk behavior rate were high in the MSM and then should be intervened.