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Biallelic pathogenic variants in TARS2 lead to combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, psychomotor developmental delay, epilepsy and brain anomalies. To date, approximately 28 individuals with COXPD21 and 28 TARS2 variants have been identified. In this study, we reported additional four individuals from three unrelated Chinese families with mitochondrial encephalomyopathy caused by pathogenic variants in TARS2, and described the novel clinical phenotypes and genotypic information. In addition to two novel variants (c.512G > A, p.Arg171Lys; c.988dup, p.Arg330Lysfs*4), one previously reported variant (c.470 C > G, p.Thr157Arg) recurred in six Chinese individuals with COXPD21 but was not present in populations of other races. Our findings expanded the mutation spectrum of TARS2 and confirmed that c.470 C > G is a Chinese-specific founder mutation. The novel phenotypes, including reduced fetal movement, eye anomalies and sleep irregularities, observed in our patients enriched the clinical characteristics of COXPD21., (© 2024. The Author(s).)

Objetive: To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c.93-21G＞A., Methods: A retrospective study was carried out on five individuals identified by the People's Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by the People's Hospital of Yangjiang (Ethics No. 20240001)., Results: Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c.93-21G＞A, one had compound heterozygous mutations of -α 3.7 and HBB: c.93-21G＞A, whilst the remaining three were heterozygous for the HBB: c.93-21G＞A mutation., Conclusion: The hematological phenotype of β-thalassemia carriers (HBB: c.93-21G＞A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

Background: Accurately distinguishing between malignant and benign thyroid nodules through fine-needle aspiration cytopathology is crucial for appropriate therapeutic intervention. However, cytopathologic diagnosis is time consuming and hindered by the shortage of experienced cytopathologists. Reliable assistive tools could improve cytopathologic diagnosis efficiency and accuracy. We aimed to develop and test an artificial intelligence (AI)-assistive system for thyroid cytopathologic diagnosis according to the Thyroid Bethesda Reporting System., Methods: 11 254 whole-slide images (WSIs) from 4037 patients were used to train deep learning models. Among the selected WSIs, cell level was manually annotated by cytopathologists according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) guidelines of the second edition (2017 version). A retrospective dataset of 5638 WSIs of 2914 patients from four medical centres was used for validation. 469 patients were recruited for the prospective study of the performance of AI models and their 537 thyroid nodule samples were used. Cohorts for training and validation were enrolled between Jan 1, 2016, and Aug 1, 2022, and the prospective dataset was recruited between Aug 1, 2022, and Jan 1, 2023. The performance of our AI models was estimated as the area under the receiver operating characteristic (AUROC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. The primary outcomes were the prediction sensitivity and specificity of the model to assist cyto-diagnosis of thyroid nodules., Findings: The AUROC of TBSRTC III+ (which distinguishes benign from TBSRTC classes III, IV, V, and VI) was 0·930 (95% CI 0·921-0·939) for Sun Yat-sen Memorial Hospital of Sun Yat-sen University (SYSMH) internal validation and 0·944 (0·929 - 0·959), 0·939 (0·924-0·955), 0·971 (0·938-1·000) for The First People's Hospital of Foshan (FPHF), Sichuan Cancer Hospital & Institute (SCHI), and The Third Affiliated Hospital of Guangzhou Medical University (TAHGMU) medical centres, respectively. The AUROC of TBSRTC V+ (which distinguishes benign from TBSRTC classes V and VI) was 0·990 (95% CI 0·986-0·995) for SYSMH internal validation and 0·988 (0·980-0·995), 0·965 (0·953-0·977), and 0·991 (0·972-1·000) for FPHF, SCHI, and TAHGMU medical centres, respectively. For the prospective study at SYSMH, the AUROC of TBSRTC III+ and TBSRTC V+ was 0·977 and 0·981, respectively. With the assistance of AI, the specificity of junior cytopathologists was boosted from 0·887 (95% CI 0·8440-0·922) to 0·993 (0·974-0·999) and the accuracy was improved from 0·877 (0·846-0·904) to 0·948 (0·926-0·965). 186 atypia of undetermined significance samples from 186 patients with BRAF mutation information were collected; 43 of them harbour the BRAF V600E mutation. 91% (39/43) of BRAF V600E -positive atypia of undetermined significance samples were identified as malignant by the AI models., Interpretation: In this study, we developed an AI-assisted model named the Thyroid Patch-Oriented WSI Ensemble Recognition (ThyroPower) system, which facilitates rapid and robust cyto-diagnosis of thyroid nodules, potentially enhancing the diagnostic capabilities of cytopathologists. Moreover, it serves as a potential solution to mitigate the scarcity of cytopathologists., Funding: Guangdong Science and Technology Department., 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 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Before (2019), during (2020), and after (2021) the COVID-19 outbreak, different response methods and measures were taken on campuses to control the spread of COVID-19 within schools. These response methods may have changed the outdoor bioaerosol characteristics, which may affect staff and student health. Therefore, we analyzed the bacterial concentrations, particle size distribution, microbial populations, exposure risks, and environmental influences of bioaerosols at a campus before, during, and after the COVID-19 outbreak. This study used eight-stage Andersen samplers to collect and analyze culturable bacteria in bioaerosols from various locations, high-throughput sequencing to analyze microbial species, principal component analysis to compare differences in samples, RDA to investigate the effects of environmental factors on bioaerosols, and hazard quotient (HQ) and BugBase to evaluate human health risks. The study findings revealed that average bacterial concentrations before, during, and after COVID-19 were 75 CFU m -3 , 136 CFU m -3 , and 78 CFU m -3 , respectively. Moreover, the average percentage of bacteria attached to PM 2.5 was 49.2%, 42.7%, and 29.9%, respectively. High-throughput sequencing revealed that species composition changed significantly during the three years of COVID-19. The proportion of Pantoea and Bacillus increased with the development of COVID-19 and these became the dominant strains after COVID-19, whereas Pseudomonas had the maximum proportion during COVID-19. Both risk assessment and BugBase phenotype prediction results indicated that the potential pathogenic risk was the highest in the outdoor environment of the campus during COVID-19 and that bioaerosol contamination was the most severe compared to the outdoor bioaerosol characteristics of the campus recovered after COVID-19.

Background: Schizothorax o'connori is an endemic fish distributed in the upper and lower reaches of the Yarlung Zangbo River in China. It has experienced a fourth round of whole gene replication events and is a good model for exploring the genetic differentiation and environmental adaptability of fish in the Qinghai-Tibet Plateau. The uplift of the Qinghai-Tibet Plateau has led to changes in the river system, thereby affecting gene exchange and population differentiation between fish populations. With the release of fish whole genome data, whole genome resequencing has been widely used in genetic evolutionary analysis and screening of selected genes in fish, which can better elucidate the genetic basis and molecular environmental adaptation mechanisms of fish. Therefore, our purpose of this study was to understand the population structure and adaptive characteristics of S. o'connori using the whole-genome resequencing method., Results: The results showed that 23,602,746 SNPs were identified from seven populations, mostly distributed on chromosomes 2 and 23. There was no significant genetic differentiation between the populations, and the genetic diversity was relatively low. However, the Zangga population could be separated from the Bomi, Linzhi, and Milin populations in the cluster analysis. Based on historical dynamics analysis of the population, the size of the ancestral population of S. o'connori was affected by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Glacial Age. The selected sites were mostly enriched in pathways related to DNA repair and energy metabolism., Conclusion: Overall, the whole-genome resequencing analysis provides valuable insights into the population structure and adaptive characteristics of S. o'connori. There was no obvious genetic differentiation at the genome level between the S. o'connori populations upstream and downstream of the Yarlung Zangbo River. The current distribution pattern and genetic diversity are influenced by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Ice Age. The selected sites of S. o'connori are enriched in the energy metabolism and DNA repair pathways to adapt to the low temperature and strong ultraviolet radiation environment at high altitude., (© 2024. The Author(s).)

The Songshan Lake Science and Technology Industrial Park is a national economic transition demonstration area, which centers at a traditional industrial region, in Dongguan, China. We were interested in the involved atmospheric particulates-bound PAHs regarding their sources, cancer risk, and related cellular toxicity for those in other areas under comparable conditions. In this study, the daily concentrations of TSP, PM 10 , and PM 2.5 were averaged 127.95, 95.91, and 67.62 μg/m 3 , and the bound PAHs were averaged 1.31, 1.22, and 0.77 ng/m 3 in summer and 12.72, 20.51 and 40.27 ng/m 3 in winter, respectively. The dominant PAHs were those with 5-6 rings, and 4-6 rings in summer and winter, respectively. The incremental lifetime cancer risk (ILCR) (90th percentile probability) of total PAHs was above 1.00E-06 in each age group, particularly high in adolescents. Sensitivity analysis indicated that slope factor and body weight had greater impact than exposure duration and inhalation rate on the ILCR. Moreover, treatment of human bronchial epithelial BEAS-2B cells with mixed five indicative PAHs increased the formation of ROS, DNA damage (elevation in γ-H2AX), and protein levels of CAR, PXR, CYP1A1, 1A2, 1B1, while reduced the AhR protein, with the winter mixture more potent than summer. For the sources of PAHs, the stable carbon isotope ratio analysis and diagnostic ratios consistently pointed to petroleum and fossil fuel combustion as major sources. In conclusion, our findings suggest that particulates-bound PAHs deserve serious concerns for a cancer risk in such environment, and the development of new power sources for reducing fossil fuel combustion is highly encouraged., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study used stable isotope (δ 15 N- NO 3 - and δ 18 O- NO 3 - ) ratios, modeled by means of a Bayesian stable isotope analysis in R (SIAR) approach, to identify nitrate sources in the Pi River, which flows through the megacity Chengdu. The goal was to determine where management resources should be applied to reduce nitrogen pollution. Results revealed that NO 3 - was the primary nitrogen species throughout the study area; that it originated in manure and sewage, as well as nitrification of fertilizer and soil nitrogen; and that the nitrogen in the main stream came primarily from the tributaries. Notably, the nitrogen concentration in the tributaries exhibited no evident seasonal variations, further demonstrating that its source was intensive anthropogenic activity. Results of Bayesian model (SIAR) estimation indicated that manure and sewage were the dominant nitrate contributors in the watershed and that the nitrate concentration decreased from 54.19% to 39.57% in response to water treatment. These results empirically demonstrate that the methodology described in this work can be used effectively in catchments affected by intensive anthropogenic activity to determine where management resources should be applied to reduce nitrogen pollution. Integr Environ Assess Manag 2022;18:1609-1620. © 2022 SETAC., (© 2022 SETAC.)

Based on the panel data of 257 prefecture-level cities in China from 2010 to 2017, this paper measured urban land green use efficiency (ULGUE), incorporating undesirable outputs, via the super efficiency slack-based model (SBM). It also explored the effect, mechanism, and heterogeneity of growth targets management and regional competition on ULGUE via the time-varying gravitational spatial weight matrix and the spatial self-lagging model. The results show that growth targets management and regional competition have significant positive effects on ULGUE, and enhance the ULGUE by promoting local investment attraction, increasing innovation inputs, optimizing environmental regulations and strengthening commercial activities. Additionally, growth targets management has a more significant effect on eastern cities, non-central cities, and mature urban agglomeration, while regional competition has a more significant effect on central cities, non-central cities, and developmental urban agglomeration. Therefore, considering development as the priority, setting relatively aggressive economic growth targets and optimizing the regional competition mechanism for growth targets management can help improve the ULGUE and promote high-quality economic development in China.

Purpose: This study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies., Patients and Methods: We included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up., Results: Baseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was -0.17% in men aged 36 to 85 years, with the fastest decrease rate -1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions., Conclusion: In men aged 36~85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Tang et al.)

Lychee is an exotic tropical fruit with a distinct flavor. The genome of cultivar 'Feizixiao' was assembled into 15 pseudochromosomes, totaling ~470 Mb. High heterozygosity (2.27%) resulted in two complete haplotypic assemblies. A total of 13,517 allelic genes (42.4%) were differentially expressed in diverse tissues. Analyses of 72 resequenced lychee accessions revealed two independent domestication events. The extremely early maturing cultivars preferentially aligned to one haplotype were domesticated from a wild population in Yunnan, whereas the late-maturing cultivars that mapped mostly to the second haplotype were domesticated independently from a wild population in Hainan. Early maturing cultivars were probably developed in Guangdong via hybridization between extremely early maturing cultivar and late-maturing cultivar individuals. Variable deletions of a 3.7 kb region encompassed by a pair of CONSTANS-like genes probably regulate fruit maturation differences among lychee cultivars. These genomic resources provide insights into the natural history of lychee domestication and will accelerate the improvement of lychee and related crops., (© 2022. The Author(s).)

Anthocyanins not only affect the quality of horticultural crops but are also vital for human health. Glutathione transferase family members (GSTs) are enzymes that help to control plant development and stress responses, and are also involved in anthocyanin accumulation. In this study, we targeted a phi (F) class glutathione S-transferase gene RsGST1 (RSG01330.t1) as a crucial gene in the accumulation of anthocyanins in radish. RsGST1 expression was closely associated with anthocyanin content in the skin and flesh of taproot from different color type radish cultivars. Furthermore, RsGST1 was able to restore anthocyanin accumulation in Arabidopsis tt19 mutants, indicating that RsGST1 has a similar function as AtTT19, a gene responsible for the transport of anthocyanins in Arabidopsis. Transient overexpression of RsGST1 together with the key anthocyanin biosynthesis regulator RsMYB1a in radish leaves significantly enhanced anthocyanin biosynthesis compared with in plants that overexpressed RsMYB1a alone. Dual-luciferase and yeast one-hybrid assays revealed that RsMYB1a binds to promotor and activates the expression of RsGST1. Altogether, these results provide molecular evidence indicating that RsGST1 and RsMYB1a coordinate radish anthocyanin accumulation., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Objective: The aim of this prospective randomized controlled clinical trial was to explore the relationship between GPX3 methylation and Pai-Neng-Da (PND) in the treatment of patients with low-risk myelodysplastic syndrome (MDS)., Methods: There were 82 low-risk MDS patients who were randomly divided into the following two groups: androl, thalidomide, and PND capsule (ATP group, n = 41); or androl and thalidomide (AT group, n = 41). Hemoglobin and neutrophil and platelet counts and changes in GPX3 methylation level were assessed., Results: The plasma hemoglobin level increased in both groups after treatment. However, the platelet count increased only in the ATP group. Patients in the ATP group had a better platelet response than the AT group, and GPX3 methylation markedly decreased after treatment with ATP but not after treatment with AT. Moreover, male patients had a significantly lower GPX3 methylation level than female patients, while platelet counts from male patients increased dramatically after the ATP regimens compared with female patients. GPX3 methylation changes were negatively correlated with platelet changes in ATP group., Conclusion: PND can improve hematological parameters and decrease the GPX3 methylation level. Decreasing GPX3 methylation is associated with the hematologic response that includes platelet in GPX3 methylation. China Clinical Trial Bureau (ChiCTR; http://www.chictr.org.cn/ ) registration number : ChiCTR-IOR-15006635.

Delay discounting describes the phenomenon whereby the subjective value of a reward declines as the time until its receipt increases. Individuals differ in the subjective value that they assign to future rewards, yet, the components feeding into this appraisal of value remain unclear. We examined whether temporal psychological distance, i.e. the closeness one feels to the past and future, is one such component. English speakers in the USA and Mandarin speakers in China completed a delay discounting task and organized past and future world events on a canvas according to their representation of the event's temporal position relative to themselves. Previous work has identified linguistic and cultural differences in time conception between these populations, thus, we hypothesized that this sample would display the variability necessary to probe whether temporal psychological distance plays a role in reward valuation. We found that English speakers employed horizontal, linear representations of world events, while Mandarin speakers used more two-dimensional, circular representations. Across cultures, individuals who represented the future as more distant discounted future rewards more strongly. Distance representations of past events, however, were associated with discounting behaviors selectively in Mandarin speakers. This suggests that temporal psychological distance plays a fundamental role in farsighted decision-making.

Background: Sarcopenia is typically defined as the loss of muscle mass, strength and low physical performance with aging. Ultrasound is a safe and easy method for evaluating muscle mass and quality by muscle thickness (MT) and pennation angle (PA), respectively. Although the positive correlations between MT and muscle mass and handgrip strength were observed, the relationship between MT, PA and physical performance remains unclear. Purpose: This study aimed to investigate the correlation of aforementioned ultrasound parameters with muscle mass, muscle strength and physical performance and explore the utility of ultrasound in predicting sarcopenia. Patients and methods: A total of 265 elderly Chinese community dwellers were included. MT of both forearm and lower leg as well as PA of gastrocnemius was assessed by ultrasound. Muscle mass was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by a Jamar hand dynamometer. Physical performance was assessed by the Short Physical Performance Battery (SPPB). Results: Anterior radial MT in men and regional MTs except posterior fibula in women were negatively correlated with the age. No significant correlation was observed between PA and the age in both genders. Posterior tibial MT and posterior fibula MT were positively correlated with the relative appendicular skeletal muscle mass in men and women, respectively. Anterior ulnar MT was positively correlated with grip strength in both genders. Moreover, gastrocnemius medialis PA showed a positive association with gait speed and SPPB in women but not in men. Conclusion: A combination of posterior fibula MT, anterior ulnar MT and gastrocnemius medialis PA measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly women. In addition, a combination of posterior tibial MT and anterior ulnar MT measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly men., Competing Interests: The authors report no conflicts of interest in this work.

Unlabelled: The trabecular bone score (TBS) was obtained from the gray levels of a dual X-ray absorptiometry (DXA) image to evaluate bone microarchitecture. Here, we established the reference plots of TBS in healthy Chinese women of Nanjing area. The TBS references are similar with French and US Caucasian women but higher than Japanese women., Purpose: The aim of the study was to establish the reference plots of the TBS in healthy Chinese women of the Nanjing area., Methods: A total of 537 healthy Chinese women of the Nanjing area were recruited, and the study was approved by the Ethics Committee of the First Affiliated Hospital with Nanjing Medical University. The TBS of the lumbar spine and the bone mineral density (BMD) of the lumbar spine and femur were measured using dual X-ray absorptiometry. The mean ± standard deviation (SD) of the TBS in women with different age groups was calculated. The correlation of TBS and age and BMD was calculated using regression analysis., Results: The reference plots of the TBS were established in healthy Chinese women of the Nanjing area between the ages of 20 and 89 years. The average TBS for total subjects was 1.32 ± 0.11 and reached the peak at the age of 20-29 years and then decreased with age thereafter. The determinant coefficient between TBS and age was 0.5065 while between TBS and BMD was 0.5191. After adjusting for lumbar total BMD, the TBS significantly correlated with age in whole subjects and only in the subgroup of ages 50-59 years., Conclusions: This study suggested that TBS decreased with age and correlated positively with BMD. The TBS reference of Chinese women is similar with those of French and US Caucasian women but higher than that of Japanese women. Furthermore, the TBS may be more significantly applied in women in menopause for less than 10 years.

Domestic pigs have evolved genetic adaptations to their local environmental conditions, such as cold and hot climates. We sequenced the genomes of 69 pigs from 15 geographically divergent locations in China and detected 41 million variants, of which 21 million were absent from the dbSNP database. In a genome-wide scan, we identified a set of loci that likely have a role in regional adaptations to high- and low-latitude environments within China. Intriguingly, we found an exceptionally large (14-Mb) region with a low recombination rate on the X chromosome that appears to have two distinct haplotypes in the high- and low-latitude populations, possibly underlying their adaptation to cold and hot environments, respectively. Surprisingly, the adaptive sweep in the high-latitude regions has acted on DNA that might have been introgressed from an extinct Sus species. Our findings provide new insights into the evolutionary history of pigs and the role of introgression in adaptation.

The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

Objective: To estimate the annual direct and indirect costs of rheumatoid arthritis (RA) in China and identify the predictors for cost of illness., Methods: A cross-sectional study of cost of illness from the societal perspective was conducted on 829 patients with RA in 21 tertiary care hospitals in China between July 2009 and December 2010. Data on demographics, clinical variables, and components of costs were collected by physician interview. Costs were represented in 2009 US dollars using purchasing power parity estimates. Univariate and multivariate linear regression analyses were performed to identify the predictors for cost of illness., Results: The mean ± SD total cost of RA in China was $3,826 ± $5,659 per patient-year, given a gross domestic product per capita of $6,798 in China in 2009. Direct costs and indirect costs comprised 90.0% and 10.0% of the total costs, respectively. Drug expense represented approximately half of the total costs, dominated by biologic agents (48.2%) and disease-modifying antirheumatic drugs (23.5%). Additionally, the cost of extracted herbal drugs and traditional Chinese medicine comprised ∼17.6% of the drug expense. Higher education level, noninsured status, longer disease duration, more extraarticular manifestations, and higher Health Assessment Questionnaire score independently predicted higher total costs., Conclusion: Our results provide the first study of costs of RA in China. This study not only demonstrates the economic burden of RA, but also identifies the predictors that could be interventional factors to reduce the societal costs of RA in China., (Copyright © 2014 by the American College of Rheumatology.)

Background: As a result of extensive use of fluroquinlones and cephalosporins, urinary tract pathogens producing extended-spectrum beta-lactamase (ESBL) pose a considerable clinical challenge in the treatment of UTIs. In the present study we retrospectively assessed the susceptibility of E. coli strains to fosfomycin trometamol and other antibiotics commonly used for the treatment of such infections., Methods: A total of 908 nonreplicate clinical E. coli urinary isolates were collected from 20 Chinese hospitals over four consecutive 1-year periods between October 2004 and June 2012. Susceptibility to antimicrobial agents fosfomycin trometamol, piperacillin-tazobactam, cefuroxime, cefotaxime, cefepime, imipenem, amikacin, levofloxacin, and nitrofurantoin was determined using the agar dilution method. A reference strain E. coli (ATCC 25922) was used as a positive control. Results were analyzed using Chi-square test or Fisher's exact tests., Results: Fosfomycin trometamol, piperacillin-tazobactam, amikacin, and imipenem were consistently the most active agents against most of the isolates. There was a decline in susceptibility to cefuroxime, cefotaxime, and cefepime between 2004 and 2010. We showed that 528 of the 908 E. coli isolates (58.1%) produced ESBLs. The ESBL-positive rates increased from 41.7% in 2004-2005 to 60.9% in 2011-2012. ESBL-producing E. coli isolates showed significantly higher resistance rates to levofloxacin than the ESBL-negative isolates. Fosfomycin trometamol, piperacillin-tazobactam, amikacin, and imipenem had good activity against both levofloxacin-susceptible and levofloxacin- nonsusceptible isolates (sensitivity rate > 90%). However susceptibility of levofloxacin-resistant isolates to cefuroxime, cefotaxime, cefepime, amikacin, and nitrofurantoin was significantly lower than that of levofloxacin-susceptible isolates., Conclusions: Owing to the increase in the bacterial resistance across the world, the European Urology Association has recommended fosfomycin trometamol as the drug of choice in its Guidelines on Urological Infections released in 2013. Our results confirm this recommendation for use in China and continued monitoring of the susceptibility of E. coli to fosfomycin trometamol is need with the widely use of the drug in China.

Objective: This study aims to determine whether baseline electrocardiography (ECG) abnormalities, the appearance of new ECG abnormalities, or other clinical characteristics are associated with increased rates of progression to chronic Keshan disease (KD) among patients with latent KD., Methods: Four hundred and fourteen new latent KD patients from a monitored population in China were diagnosed and then followed for 10 years. Baseline and 10-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict chronic KD events., Results: In 414 latent KD patients with ECG abnormalities, 220 (53.1%) had minor and 194 (46.9%) had major ECG abnormalities. During the follow-up, 92 (22.2%) patients experienced chronic KD events; 32 (14.5%) and 60 (30.9%) of these chronic KD events occurred in the minor and major ECG abnormalities groups, respectively. After adjustment for baseline potential confounders, the hazard ratios and 95% confidence intervals (CIs) for progression to chronic KD in latent KD patients with major ECG abnormalities versus those with minor ECG abnormalities was 2.43 (95% CI 1.58-3.93)., Conclusions: Major ECG abnormalities and new ventricular premature complex abnormalities that occurred during the follow-up were both associated with an increased risk of progression to chronic KD. Atrial fibrillation and right bundle branch block with left anterior hemiblock are the most strongly predictive components of major ECG abnormalities. Depending on the model, adding ECG abnormalities to traditional risk factors was associated with improved risk prediction in latent KD.

The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10(-6)). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10(-13)). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10(-13)) and -negative RA (P = 3.89×10(-5)). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.

Purpose: Overexpression of glucose transporters has been identified in a variety of human cancers. However, the expression status of Sodium dependent Glucose Transporter 1 (SGLT1) in ovarian carcinoma has not been investigated., Methods: In our study, protein expression levels of SGLT1 were explored by semiquantitative immunohistochemical staining on archival formalin-fixed paraffin-embedded pathologic specimen consisting of 178 epithelial ovarian tumors. Receiver operating characteristic curve analysis, Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were utilized to analyze the data., Results: The threshold for high expression of SGLT1 was determined to be above 40% (areas under curve = 0.683, P = 0.003) based on the area under curves. Significantly overexpression of SGLT1 was observed in 39.7% invasive carcinomas, 11.5% borderline tumors, 10% cystadenomas but in none of the normal ovaries (0%). In ovarian carcinomas, SGLT1 overexpression was positively correlated with later pT status (P = 0.029) and advanced FIGO stage (P = 0.024). By univariate survival analysis on the ovarian carcinoma cohorts, overexpression of SGLT1 was associated with shortened patient survival (mean 70.5 months in tumors with overexpression of SGLT1 versus 89.3 months in tumors with normal levels of SGLT1; P = 0.019). By multivariate analysis, SGLT1 protein expression remained as a significant and independent prognostic factor for the prediction of patient survival (P = 0.033)., Conclusions: SGLT1 overexpression, as examined by immunohistochemistry, is an independent biomarker for poor prognosis of patients with ovarian carcinoma.

Background: In rodents, zinc deficiency potentiates the effects of certain nitrosamines that act as esophageal carcinogens. Studies of the association between zinc and esophageal squamous cell carcinoma in humans have been hampered by plasma zinc homeostasis, which obscures individual differences in total zinc stores, and by the uncertainty regarding zinc bioavailability when estimating dietary zinc intake because phytate from whole grains effectively prohibits zinc absorption. By using baseline tissue biopsy specimens collected in a prospective observational study, we determined the association between incident esophageal squamous cell carcinoma and baseline element concentrations in tissue sections from residents of Linzhou, China, participating in a nutrition intervention trial., Methods: We used x-ray fluorescence spectroscopy to measure zinc, copper, iron, nickel, and sulfur concentrations in single 5-microm-thick sections from formalin-fixed, paraffin-embedded esophageal biopsy specimens collected in 1985 from 60 eventual case and 72 control subjects. Subjects were matched on baseline histology and followed for 16 years. We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between each element and risk of incident esophageal cancer. All statistical tests were two-sided., Results: The risk of developing esophageal cancer was much lower for subjects in the highest quartile of esophageal tissue zinc concentration compared with those in the lowest quartile (HR = 0.21, 95% CI = 0.065 to 0.68). The association was statistically significant across quartiles (P(trend) = .015). Individuals in the highest quartile of sulfur concentration had a lower risk of esophageal cancer than individuals in the lowest quartile (HR = 0.29, 95% CI = 0.095 to 0.85), but the association across quartiles was not statistically significant (P(trend) = .081). There was no association between copper, iron, or nickel concentrations and risk of esophageal cancer., Conclusion: High tissue zinc concentration was strongly associated with a reduced risk of developing esophageal squamous cell carcinoma. X-ray fluorescence spectroscopy can be used to assess relationships among concentrations of both nutritional and toxic elements and disease risk in banked tissue specimens.