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Background. Inflammation plays a key role in the pathophysiology and progression of acute kidney injury (AKI). Red cell distribution width (RDW) to platelet ratio (RPR) is a novel inflammatory index, and its prognostic effect on critically ill patients with AKI is rarely investigated. This work is aimed at investigating the association between RPR and in-hospital mortality in these patients. Methods. Data were extracted from the Medical Information Mart for Intensive Care III database. All-cause death during hospitalization was selected as the primary outcome. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, and the area under the curve (AUC) was applied to compare predictive ability among different indices. Cox proportional hazard models were utilized to assess the association between RPR and in-hospital mortality. Restricted cubic spline analysis for multivariate Cox model was performed to explore the shape of the relationship between RPR and mortality. Results. A total of 24,166 critically ill patients with AKI were included. The relationship of RPR and in-hospital mortality was nonlinear with a trend to rise rapidly and then gradually. For mortality prediction, RPR had the optimal cut-off value of 0.093, of which the AUC was 0.791 (95% confidence interval (CI): 0.773–0.810), which was higher than those of RDW, platelet, sequential organ failure assessment score, simplified acute physiology score II, neutrophil to lymphocyte ratio, and platelet to lymphocytes ratio. After adjustments for various confounders, high RPR showed a significant association with increased mortality with hazard ratios of 1.46 (95% CI: 1.40–1.55) for categorical variable and 1.88 (95% CI: 1.80–1.97) for continuous variables in the fully adjusted model. Conclusions. Elevated RPR on admission is substantially associated with high risk of in-hospital mortality in critically ill patients with AKI and thus may serve as a novel predictor of prognosis for these patients.

ContextHemichorea associated with nonketotic hyperglycemia (HC-NH) is a rare diabetic complication for which the pathogenesis remains unclear.ObjectiveThis study reported 16 cases of HC-NH to improve the understanding of the disease and avoid misdiagnosis and missed diagnosis.MethodsData of 16 patients with HC-NH in a single center from 2000 to 2021 were analyzed retrospectively, and the relevant literature was reviewed.ResultsThe participants (8 men and 8 women) had a mean age of 67.6 ± 16.4 years. Bilateral limbs were involved in 2 cases, and the others had hemichorea (6 in the left side and 8 in the right side). The average random blood glucose level was 17.51 ± 7.67 mmol/L, and the glycated hemoglobin A1c level was 11.9%±3.1% at admission. Eleven patients had a history of diabetes, and the other 5 patients were diagnosed with new-onset diabetes mellitus, but no remarkable differences were observed in the presentation or treatment of chorea. Ketonuria was detected in 7 patients. The basal ganglia (putamen, globus pallidus, and caudate nucleus) of 9 cases had typical hyperdensity on computed tomography and/or hyperintensity signals from magnetic resonance imaging. The chorea symptoms of 15 patients improved within 5.0 ± 1.9 days after treatment.ConclusionThis study provides additional valuable information about the clinical and neuroimaging features of HC-NH. We hypothesize that chronic ischemia of the basal ganglia due to cerebral atherosclerosis combined with hyperglycemia is associated with HC-NH.

Introduction The purpose was to quantify the health effects of tobacco using data from the 2019 Global Burden of Disease study. Aims and Methods We collected detailed information on tobacco consumption overall as well as its individual aspects (smoking, secondhand smoke, and chewing tobacco) for the deaths and disability-adjusted life years (DALYs) for all-cause disease, cardiovascular disease, neoplasms, and chronic respiratory diseases, and their age-standardized rates (ASRs). Results Tobacco was responsible for 8.71 million deaths and 229.77 million DALYs globally in 2019. The ASRs of all tobacco-related deaths and DALYs declined from 1990 to 2019, to 108.55 deaths per 100 000 population and 2791.04 DALYs per 100 000 population in 2019. During any year the ASRs of all tobacco-related deaths and DALYs were higher in males than in females. The ASRs of all tobacco-related deaths and DALYs were highest in countries with a low-middle sociodemographic index (SDI) and lowest in high-SDI countries in 2019. Cardiovascular disease, neoplasms, and chronic respiratory diseases were the three leading causes of tobacco-related mortality. Conclusions Although the ASRs of deaths and DALYs related to tobacco have declined, the absolute number remain high. Tobacco control policies need to be strengthened further in order to reduce the heavy health burden of tobacco. Implications This study provides a detailed description on the health effects of tobacco, including maps of the current global burden of tobacco-related disease. Although the ASRs of tobacco-related deaths and DALYs have declined, the absolute numbers remain high—tobacco was responsible for 8.71 million deaths and 229.77 million DALYs globally in 2019. The findings may have implications for tobacco control. Countries where progress has been slower in reducing tobacco-related disease burden should study and consider implementing policies and strategies that have been applied in countries like Singapore which show the greatest declines for recent decades.

[Objective] To analyze the QLICP-NA (V2.0) items using classical test theory and item response theory. [Methods]One hundred twenty-one nasopharyngeal carcinoma patients were investigated using QLICP-NA (V2.0). SPSS15.0 software was used to manage the data and Multilog 7.03 software was used for parameter analysis. IRT was used to calculate the discrimination, difficulty, and item information for each item in the scale. [Results] The scale covered five domains: physical (PHD); psychological (PSD); social (SOD); general symptoms and side effects (SSD); and special module (SNA). PHD contains eight items (coded GPH1-8), PSD comprises nine items (coded GPS1-9), SOD covers eight items (coded GSO1-8), SSD includes seven items (coded GSS1-7), and SNA covers eleven items (coded SNA1-11). The correlation coefficient between SNA1 and SNA8 was < 0.4, and the correlation was poor. GPS4, GOS4, SNA1, and SNA3 had low correlation with the field. The five items were deleted. SNA4 and SNA8 discrimination was poor, thus deletion was recommended. SNA2 and SNA10 discrimination was not good, thus SNA2 and SNA10 were modified and retained. The results of item information showed that the information content of the specific module, SNA1-11, was poor, but because deleting too many items had a great impact on the total table and deleting two items (SNA6 and SNA10) with < 0.2 information, 34 items were finally reserved. [Conclusion] The analysis of scale items can be evaluated from different angles and applied comprehensively.

In the process of tooth development, the interaction between genetic information, epigenetic inheritance and environment jointly affects the formation of teeth. At present, the mechanism of dental fluorosis is rarely studied from transcriptomics, and there is no report on epigenetic perspective. In the study, SD rats were divided into dental fluorosis group and control group fed with NaF (150 mg/L) or distilled water for 8 weeks. After 3.5 days of birth, the RNAs or DNA of rat mandibular molars were detected by RNA-seq or MethylTarget respectively. The rerults demonstrated that a total of 1723 differentially expressed genes (DEGs) and 2511 differential expression lncRNAs (DE-lncRNAs) were mainly involved in the changes of ion channels, calcium ion transport and immunomodulatory signaling pathways. ATP2C1 and Nr1d1, which were related to Ca2+ transport, cellular calcium homeostasis, endoplasmic reticulum stress and immunity, may be the key genes in the formation of dental fluorosis. Notably, we also found that the immune response plays an important role in the formation of dental fluorosis, and a large amount of DEGs was enriched in immune regulation and NF-κB signaling pathways. Furthermore, the methylation levels of 13 sites were increased in Ago4, Atf3, Atp2c1, Dusp1, Habp4, Mycl while methylation levels of 5 CpG sites decreased in Ago4, Atp2c1, Habp4, Traf6 and conformably the expression of these genes have been significantly changed. This study comprehensively analyzed the occurrence mechanism of dental fluorosis from transcriptomics and epigenetics, so as to provide theoretical reference for further research.

The quantitative analysis of nanoparticles (NPs) in the environment is significantly important for the exploration of the occurrence, fate, and toxicological behaviors of NPs and their subsequent environmental risks. Some protocols have been recommended for the separation and extraction of NPs that are potentially dispersed in complex environmental matrixes, e.g. sediments and soils, but they remain limited. However, certain factors that may significantly affect extraction efficiency have not been comprehensively explored. In this study, on the basis of the single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) technique, a simple standardized protocol for separating and analyzing metal-containing NPs in sediment samples was developed. On consideration of the extraction efficiencies of indigenous NPs (Ti- and Zn-NPs) and spiked NPs (Ag- and Au-NPs) in sediments, sedimentation with a settling time of 6 h is recommended for the separation of NPs and large particles, and the optimal sediment to water ratio, ultrasonication power, time, and temperature are 0.4 mg/mL, 285 W, 20 min, and 15-25 °C, respectively. On the basis of the optimized method, the recoveries of spiked Ag and Au-NPs were 71.4% and 81.1%, respectively. The applicability of the optimal protocols was verified, and TOC was proved to be an important factor controlling the separation and extraction of NPs in environmental samples. The separation and extraction of NPs in elevated TOC samples can be improved by increasing the ultrasonication power, time, and temperature.

Background Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein, whose transcript expression is restricted to the tooth germ epithelium (Epi) during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulation of tooth development. Based on this, we hypothesized that epithelium-derived SCUBE3 contributed to bio-function in dental mesenchymal cells (Mes) via epithelium-mesenchyme interactions. Methods Immunohistochemical staining and a co-culture system were performed to reveal the temporospatial expression of SCUBE3 protein during mouse tooth germ development. In addition, human dental pulp stem cells (hDPSC) were used as a Mes model to study the proliferation, migration, polarized-odontoblast capacity and mechanism of rhSCUBE3. Novel pulp-dentin-like organoid models were constructed to further confirm the polarized odontoblast-induction function of SCUBE3. Finally, semi-orthotopic animal experiments were performed to explore the clinical application of rhSCUBE3. Results The epithelium-derived SCUBE3 translocated to the mesenchyme via paracrine during mouse embryonic development, and the differentiating odontoblasts in postnatal tooth germ could subsequently secrete SCUBE3 protein via autocrine. In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling. In the semi-orthotopic animal experiments, we found that SCUBE3-pretreatment induced polarized odontoblast-like cells attached to the dental walls and better angiogenesis performance. Conclusion SCUBE3 protein expression is transferred from the epithelium to mesenchyme during embryonic development and elaborated the function of epithelium-derived SCUBE3 in Mes, including proliferation, migration, and polarized-odontoblastic differentiation, and their mechanisms. These findings shed light on exogenous SCUBE3 application in clinic dental-pulp regeneration.

Quantitative characteristics and sizes of nanoparticles (NPs) in coal fly ash (CFA) produced in coal-fired power plants as a function of coal type and plant design will help reveal the NP emission likelihood and their environmental implications. However, little is known about how combustion conditions and types of coal regulate the NP abundance in CFAs. In this study, based on single particle (SP)-ICP-MS technology, particle number concentrations (PNCs) and sizes of Fe- and Ti-containing NPs in CFAs were determined for samples collected from power plants of different designs and burning different types of coal. The PNCs of Fe- and Ti-containing NPs in all CFAs measured were in the range of 1.3 × 10

Characterization of nanoparticles (NPs) in coal fly ashes (CFAs) is critical for better understanding the potential health-related risks resulting from coal combustion. Based on single-particle (SP)-inductively coupled plasma mass spectrometry (ICP-MS) coupled with transmission electron microscopy techniques, this study is the first to determine the concentrations and sizes of metal-containing NPs in low-rank coal-derived fly ashes. Despite only comprising a minor component of the studied CFAs by mass, NPs were the dominant fraction by particle number. Fe- and Ti-containing NPs were identified as the dominant NPs with their particle number concentration ranging from 2.5 × 107 to 2.5 × 108 particles/mg. In addition, the differences of Fe-/Ti-containing NPs in various CFAs were regulated by the coalification degree of feed coals and combustion conditions of all of the low-rank CFAs tested. In the cases where these NPs in CFAs become airborne and are inhaled, they can be taken up in pulmonary interstitial fluids. This study shows that in Gamble's solution (a lung fluid simulant), 51-87% of Fe and 63-89% of Ti (ratio of the mass of Fe-/Ti-containing NPs to the total mass of Fe/Ti) exist in the NP form and remain suspended in pulmonary fluid simulants. These NPs are bioavailable and may induce lung tissue damage.

We previously reported that sputum induction was more sensitive than throat swabs for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in two convalescent coronavirus disease 2019 (COVID-19) patients; however, the value and safety of induced sputum testing require further study. We conducted a prospective multi-center cross-sectional study to compare induced sputum to throat swabs for SARS-CoV-2 detection. Confirmed COVID-19 patients from six hospitals in six cities across China who received one or more negative RT-PCR result for SARS-CoV-2 were enrolled, and paired specimens (induced sputum and throat swabs; 56 cases) were assayed. In three paired samples, both the induced sputum and throat swabs were positive for SARS-CoV-2. The positive rate for induced sputum was significantly higher than for throat swabs both overall (28.6% vs 5.4%, respectively; p

Objective: To explore the clinical effect of unilateral biportal endoscopic-assisted transforaminal lumbar interbody fusion (UBE-TLIF) in the treatment of recurrent lumbar disc herniation (RLDH). Methods: The clinical data of 44 patients with RLDH treated by UBE-TLIF in our hospital from August 2020 to December 2020 were analysed retrospectively. The study indicators included intraoperative blood loss, operation time, bed rest time, and hospital stay. The follow-up data included the visual analogue score (VAS) of low back pain, Japanese Orthopaedic Association score (JOA), Oswestry disability index (ODI) score, and the short form 36 health survey questionnaire (SF-36) score preoperatively and 1 week and 6 months postoperatively. Results: The average operation time was 179.15 ± 42.06 minutes, the average intraoperative blood loss was 132.67 ± 41.92 ml, the average bed rest time was 1.51 ± 0.42 days, and the average hospital stay was 4.82 ± 1.13 days. The VAS score of low back pain after the operation was lower than that before the operation (all P

Coal combustion is considered an important source of atmospheric nanoparticles (NPs). However, the underlying information on the emission of NPs from coal-fired power plants (CFPPs) is still lacking. Along these lines, in this study, coal fly ashes (CFAs) were collected from different multi-stage particulate emission control devices (PECDs) in three representative CFPPs in China. The particle size and particle number concentration (PNC) of typical metal-containing NPs (Fe- and Ti-containing NPs) were analyzed by using the single-particle inductively coupled plasma mass (SP-ICP-MS) technology. By increasing the stage of PECDs, the mean particle sizes of NPs gradually declined and the PNCs of Fe- and Ti-containing NPs increased significantly. Specifically, the PNC of final-stage CFA was 3 - 8 times that of the first-stage CFA. A comparison of the electrostatic precipitators (ESPs), fabric filters (FFs), and electrostatic-fabric-integrated precipitators (EFIPs) showed that the state-of-the-art EFIPs exhibited a relatively good NP-removal efficiency with the highest PNCs. In addition, NP hourly emissions in all coal combustion by-products (CCPs) were further calculated in a typical CFPP. The total emissions of Fe- and Ti-containing NPs in all CCPs were 1.87 × 10

BackgroundEating disorders (ED) have increasingly become a global topic of concern for public health. A better understanding of ED incidence is a basic requirement for improving its management. However, the temporal trend of ED incidence in China is still unknown.MethodsThe incidence rates of ED from 1990 to 2017 were collected from the Global Burden of Disease Study 2017 database according to the following: subtype, i.e. anorexia nervosa (AN) and bulimia nervosa (BN); sex; and age group. The average annual percent changes and relative risks were calculated using joinpoint regression and the age–period–cohort model, respectively.ResultsFrom 1990 to 2017, age-standardized incidence rates of ED continued to increase in males and females, and this variation trend was observed in AN and BN. Joinpoint regression analysis showed that the incidence rates increased in all age groups. Adolescents had the highest risk of developing ED, followed by young adults. Age effects were the most influential risk factor for ED incidence. Period effects showed that the risk of developing ED continuously increased with increasing time periods in BN, but not in ED and AN. Concerning the cohort effects, people born after the 1990s presented a higher risk of ED, though they presented a lower risk of BN as compared to the whole cohort.ConclusionsED incidence rates continue to increase in China, particularly among adolescents and young adults. Further etiological studies are needed to explain these increases and to facilitate the early identification of high-risk individuals.

BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas. AIM To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas. METHODS Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance, Epidemiology, and End Results database, and randomly divided into the training (n = 853) and the validation (n = 366) cohorts. Based on the Cox regression model, nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient. The performance of the nomograms was measured according to discrimination, calibration, and clinical utility. Moreover, we compared the predictive accuracy of the nomograms with that of the traditional staging system. RESULTS In the training cohort, age, marital status, histological type, T stage, N stage, M stage, and chemotherapy were selected to construct nomograms. Compared with the American Joint Committee on Cancer 7th staging system, the nomograms were generally more discriminative. The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction. Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system. With respect to decision curve analyses, the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities. CONCLUSION The nomograms show improved predictive accuracy, discrimination capability, and clinical utility, which can be used as reliable tools for risk classification and treatment recommendations.

In order to analyze the spatiotemporal characteristics and space use intensity of residents’ recreational behaviors in the public open space (POS) of communities, the Ruijin, Xincheng, and Fangsong communities, located in the city center, a suburb, and the outskirts of Shanghai, respectively, were studied. The visitor volume data were obtained through the Tencent Travel data. Points of interest of the POS were obtained by the Cat’s Eye app, and the use intensity data were analyzed by kernel density estimation. The use intensity and attraction of POS were verified by stagnation points. The classification of the stagnation points hierarchy showed that the leisure time and distribution of POS visited by residents. There were significantly different in community public spaces, which verifies the rationality of the recreational attraction of the POS. In addition, geodetectors were used to analyze the external factors affecting the characteristics and use intensity of POS. The results show that the percentage of POS area, pedestrian accessibility, population density, percentage of commercial land use, and per-capita occupancy area were important factors, influencing the use intensity of POS, which can provide suggestions for the planning and design of POS in urban communities.

Background: Human dental pulp stem cells (hDPSCs) have received widespread attention in the fields of tissue engineering and regenerative medicine. Although amphiregulin (AREG) has been shown to play a vital function in the biological processes of various cell types, its effects on DPSCs is still unknown. The aim of this study was to explore the specific role of AREG as a biologically active factor in the regeneration of dental pulp tissue.Methods: The growth of hDPSCs, together with their proliferation and apoptosis, in response to AREG was examined by CCK-8 assay and flow cytometry. We explored the effects of AREG on osteo/odontogenic differentiation in vitro and investigated the regeneration and mineralization of hDPSCs in response to AREG in vivo. The effects of AREG gain-and loss-of-function on DPSC differentiation were investigated following transfection using overexpression plasmids and shRNA, respectively. The involvement of the mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the mineralization process and expression of odontoblastic marker proteins after AREG induction was investigated by using Alizarin Red S staining and western blotting. Results: AREG (0.01-0.1µg/mL) treatment of hDPSCs from 1 to 7 days minimally increased hDPSCs growth and marginally affected apoptosis compared with negative controls. AREG exposure significantly promoted hDPSCs differentiation, shown by increased mineralized nodule formation and the expression of odontoblastic marker protein expression. In vivo micro-CT imaging and quantitative analysis showed significantly greater formation of highly mineralized tissue in the 0.1μg/mL AREG exposure group in DPSC/NF-gelatin-scaffold composites. AREG also promoted extracellular matrix production, with collagen fiber, mineralized matrix, and calcium salt deposition on the composites, as shown by H&E, Masson, and Von Kossa staining. Furthermore, AREG overexpression boosted hDPSCs differentiation while AREG silencing inhibited it. During the differentiation of DPSCs, AREG treatment led to phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and PI3K/Akt. Notably, a specific inhibitor of ERK, JNK, and PI3K/Akt signaling markedly reduced AREG-induced differentiation, as well as levels of phosphorylated ERK and JNK in hDPSCs. Conclusions: Data indicated that AREG enabled odontoblastic differentiation and facilitated the regeneration and mineralization processes in hDPSCs.

Background In China, chronic obstructive pulmonary disease (COPD) was accounted for a quarter of the global COPD population and has become a large economic burden. However, the comprehensive picture of the COPD burden, which could inform health policy, is not readily available for all of the provinces of China. Here, we aimed to describe the burden of COPD in China, providing an up-to-date and comprehensive analysis at the national and provincial levels, and time trends from 1990 to 2019.Methods Following the methodology framework and general analytical strategies used in the GBD 2019, we analyzed the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) attributable to COPD across China and the corresponding time trends from 1990 to 2019, stratified by age and province. We also presented the contribution of risk factors (e.g., smoking, ambient particulate matter, and occupational risks) to COPD-related mortality and DALYs. The association between COPD burden and socio-demographic index (SDI) were also evaluated. Results From 1990 to 2019, the incidence and prevalence of COPD increased by 61.2% and 67.8%, respectively, whereas the number of deaths and DALYs owing to COPD decreased. The age-standardized rates (ASRs) of COPD burden continuously decreased from 1990 to 2019. The crude rates of COPD burden dramatically increased with age and reached a peak in the older than 95 years age group. In 2019, the leading risk factor for COPD mortality and DALYs was tobacco use in the whole population, but ambient particulate matter pollution was the most significant risk factor in females. At the provincial level, the ASRs of COPD burden was significantly associated with the SDIs, with the highest ASRs in the western provinces with low SDIs. ConclusionsAlthough the ASRs of COPD burden in China substantially decreased at the national and provincial levels from 1990 to 2019, absolute numbers of COPD incidence and prevalence are still rising, indicating that COPD remains an important public health problem in China. Geographically targeted considerations should be developed to enhance COPD health and reduce the COPD burden throughout China and in specific provinces.

Background. Acute kidney injury (AKI) is an important complication in critically ill patients, especially in sepsis and septic shock patients. Early prediction of AKI in septic shock can provide clinicians with sufficient information for timely intervention so that improve the patients’ survival rate and quality of life. The aim of this study was to establish a nomogram that predicts the risk of AKI in patients with septic shock in the intensive care unit (ICU). Methods. The data were collected from the Medical Information Mart for Intensive Care III (MIMIC-III) database between 2001 and 2012. The primary outcome was AKI in the 48 h following ICU admission. Univariate and multivariate logistic regression analyses were used to screen the independent risk factors of AKI. The performance of the nomogram was evaluated according to the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis, and clinical impact curve. Results. A total of 2415 patients with septic shock were included in this study. In the training and validation cohort, 1091 (64.48%) of 1690 patients and 475 (65.52%) of 725 patients developed AKI, respectively. The predictive factors for nomogram construction were gender, ethnicity, congestive heart failure, diabetes, obesity, Simplified Acute Physiology Score II (SAPS II), angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs), bilirubin, creatinine, blood urea nitrogen (BUN), and mechanical ventilation. The model had a good discrimination with the area under the ROC curve of 0.756 and 0.760 in the training and validation cohorts, respectively. The calibration curve for probability of AKI in septic shock showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. Conclusion. The proposed nomogram can quickly and effectively predict the risk of AKI at an early stage in patients with septic shock in ICU, which can provide information for timely and efficient intervention in patients with septic shock in the ICU setting.

This study aimed to analyze the effect and mechanism of immunization of oral KISS1 DNA vaccine on the proliferation of goat testicular Leydig cells. Ten 8-week-old male goats were randomly divided ...

Background Human dental pulp stem cells (hDPSCs) have received widespread attention in the fields of tissue engineering and regenerative medicine. Although amphiregulin (AREG) has been shown to play a vital function in the biological processes of various cell types, its effects on DPSCs remain largely unknown. The aim of this study was to explore the specific role of AREG as a biologically active factor in the regeneration of dental pulp tissue. Methods The growth of hDPSCs, together with their proliferation and apoptosis, in response to AREG was examined by CCK-8 assay and flow cytometry. We explored the effects of AREG on osteo/odontogenic differentiation in vitro and investigated the regeneration and mineralization of hDPSCs in response to AREG in vivo. The effects of AREG gain- and loss-of-function on DPSC differentiation were investigated following transfection using overexpression plasmids and shRNA, respectively. The involvement of the mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the mineralization process and the expression of odontoblastic marker proteins after AREG induction were investigated by using Alizarin Red S staining and Western blotting, respectively. Results AREG (0.01–0.1 µg/mL) treatment of hDPSCs from 1 to 7 days increased hDPSCs growth and affected apoptosis minimally compared with negative controls. AREG exposure significantly promoted hDPSC differentiation, shown by increased mineralized nodule formation and the expression of odontoblastic marker protein expression. In vivo micro-CT imaging and quantitative analysis showed significantly greater formation of highly mineralized tissue in the 0.1 μg/mL AREG exposure group in DPSC/NF-gelatin-scaffold composites. AREG also promoted extracellular matrix production, with collagen fiber, mineralized matrix, and calcium salt deposition on the composites, as shown by H&E, Masson, and Von Kossa staining. Furthermore, AREG overexpression boosted hDPSC differentiation while AREG silencing inhibited it. During the differentiation of hDPSCs, AREG treatment led to phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and PI3K/Akt. Notably, a specific inhibitor of ERK, JNK, and PI3K/Akt signaling markedly reduced AREG-induced differentiation, as well as levels of phosphorylated ERK and JNK in hDPSCs. Conclusions The data indicated that AREG promoted odontoblastic differentiation and facilitated regeneration and mineralization processes in hDPSCs.

ObjectivesTo provide a comprehensive assessment of the estimated burden and trend of urolithiasis at the global, regional, and national levels.MethodsThe age-standardized rates (ASRs) of the incidence and disability-adjusted life years (DALYs) of urolithiasis from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 database. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in urolithiasis burden.ResultsIn 2019, the ASRs of the incidence and DALYs were 1,394.03/100,000 and 7.35/100,000, respectively. The ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019 with EAPCs of −0.83 and −1.77, respectively. Males had a higher burden of urolithiasis than females. In 2019, the highest burden of urolithiasis was observed in regions with high–middle sociodemographic index (SDI), particularly in Eastern Europe, Central Asia, and Southeast Asia. The burden of urolithiasis increased in most countries or territories. The burden of urolithiasis and SDI had a non-linear relationship, and the estimated value of urolithiasis burden was the highest when the SDI value was ~0.7.ConclusionGlobally, the ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019, but an increasing trend was observed among many countries. More effective and appropriate medical and health policies are needed to prevent and early intervene in urolithiasis.

Juanfen Mo,1 Li Zheng,1 Zhenzhen Gao,2 Jiayuan Wu,1 Yi Bao1,2 1The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 2Department of Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of ChinaCorrespondence: Yi BaoThe Key Laboratory, The Department of Oncology, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Zhejiang, 314000, People’s Republic of ChinaTel +865 738 207 3185Fax +865 738 208 2936Email ybao2011@gmail.comIntroduction: Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells, which strongly express CD161 and are involved in defending against infectious pathogens and inflammatory diseases. They are activated by inflammatory cytokines, secrete various cytokines and cytotoxic molecules, and express chemokine receptors and integrins. However, the underlying mechanisms of MAIT cells in colon cancer are still not fully understood.Methods: The phenotype and frequency of circulating MAIT cells were investigated by flow cytometry in colon cancer patients and healthy donors. CD161 was examined in cancerous and paracancerous nontumor tissues of colon cancer patients by immunohistochemistry. The serum levels of IFN-γ and IL-17A were analyzed by ELISA. Finally, MAIT cells were also detected in peripheral blood and tumor tissues in a CT26 tumor-bearing mice model.Results: The percentages of CD4+CD8− MAIT cells, CD4−CD8+ MAIT cells, and CD4−CD8− MAIT cells increased in the peripheral blood of colon cancer patients compared with healthy donors. The expression of CD161 protein in colon cancer cancerous tissues was higher than that in the paracancerous nontumor tissues. The killer cell lectin-like receptor B1 (KLRB1), a coding gene for CD161, was positively associated with the gene expressions of immune inhibitory receptors, such as CTLA4, HAVCR2, PDCD1, and CD274 in colon cancer. Furthermore, the serum levels of IFN-γ and CEA were positively correlated with CD8+ MAIT cells in the peripheral blood of colon cancer patients.Conclusion: Taken together, our data suggest that the circulating MAIT cells and the expression of CD161 protein in the tumor tissues increased in colon cancer patients, and MAIT cells may participate immune activities in colon cancer.Keywords: MAIT cells, colon cancer, KLRB1, inflammation, immune activities

Background Central venous catheter (CVC) insertion complications are a prevalent and important problem in the intensive care unit (ICU), and source control by immediate catheter removal is considered urgent in patients with septic shock suspected to be caused by catheter-related bloodstream infection (CRBSI). We sought to determine the impact of immediate reinsertion of a new catheter (IRINC) on mortality among patients after CVC removal for suspected CRBSI. Methods A propensity score-matched cohort of patients with suspected CRBSI who underwent IRINC or no IRINC in a 32-bed ICU in a university hospital in China from January 2009 through April 2021. Catheter tip culture and clinical symptoms were used to identify patients with suspected CRBSI. The Kaplan–Meier method was used to analyse 30-day mortality before and after propensity score matching, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality in the matched cohort were estimated with Cox proportional hazards models. Results In total, 1,238 patients who had a CVC removed due to suspected CRBSI were identified. Among these patients, 877 (70.8%) underwent IRINC, and 361 (29.2%) did not. Among 682 propensity score-matched patients, IRINC was associated with an increased risk of 30-day mortality (HR, 1.481; 95% CI, 1.028 to 2.134) after multivariable, multilevel adjustment. Kaplan–Meier analysis found that IRINC was associated with the risk of mortality both before matching (P = 0.00096) and after matching (P = 0.018). A competing risk analysis confirmed the results of the propensity score-matched analysis. The attributable risk associated with bloodstream infection was not significantly different (HR, 1.081; 95% CI 0.964 to 1.213) among patients with suspected CRBSI in terms of 30-day mortality compared with that associated with other infections. Conclusions In this cohort study, IRINC was associated with higher 30-day mortality compared to delayed CVC or no CVC among patients with suspected CRBSI. A large-sample randomized controlled trial is needed to define the best management for CVC in cases of suspected CRBSI because IRINC may also be associated with noninfectious complications. Trial registration This study was registered with the China Clinical Trials Registry (URL: http://www.chictr.org.cn/index.aspx) under the following registration number: ChiCTR1900022175.

The trend in mercury (Hg) content of fly ash, the primary solid Hg waste from coal-fired power plants (CFPPs), has not been well evaluated in China. This study integrated a national sampling campaign, a literature survey, and model predictions to investigate the trend in Hg content of fly ash and associated output nationwide. The results demonstrated that Hg content of fly ash from both our campaign conducted in 2020 and the literature survey met the Weibull distribution. The best estimate for the distribution of Hg content in our campaign (401.4 µg/kg) was about two-fold higher than that from the literature survey (236.6 µg/kg). The increasing trend was mainly attributed to the increasing installation of advanced air pollution control devices (APCDs) in CFPPs. The total national Hg output by fly ash was estimated to be 217.7 tons (64.1-501.8 tons) currently. Regarding the disposal of fly ash, a total of 16.1 tons and 105.8 tons of Hg were re-emitted into the air and immobilized in materials, respectively. The increasing trend in the Hg content of fly ash suggested the need for more stringent requirements for the disposal of solid Hg waste from CFPPs in China.

BACKGROUND Venous thromboembolism (VTE) after hip or knee arthroplasty has attracted increasing attention over the past few decades. However, there is no bibliometric report on the publications in this field. OBJECTIVE The purpose of this study was to analyze the global research status, hotspots, and trends in VTE after arthroplasty. METHODS All articles about VTE research after hip or knee arthroplasty from 1990 to 2021 were retrieved from the Web of Science Core Collection database. The information of each article including citation, title, author, journal, country, institution, and keywords, was extracted for bibliometric analysis. RESULTS A total of 1,245 original articles from 53 countries and 603 institutions were retrieved. The number of publications showed a rising trend, with the largest contributions made by the USA. McMaster University in Canada was the leading institution for publications. The most productive author in this field was Eriksson BI, followed by Lassen MR and Dahl OE. The journals with the highest output and highest citation were the Journal of Arthroplasty and the Thrombosis and Haemostasis, respectively. The research hotspots switched from VTE diagnosis and heparin to factor Xa inhibitors (fondaparinux, rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran etexilate, ximelagatran), and finally to aspirin, risk factor studies, which can be observed from the keyword analysis and co-cited reference cluster analysis. CONCLUSIONS Over the past few decades, the understanding of VTE after hip or knee arthroplasty has been improved significantly. VTE prophylaxis agents have attracted tremendous attention, including warfarin, low molecular weight heparin, oral direct factor Xa inhibitors, oral direct thrombin inhibitors, and aspirin. These studies exert a critical influence on decision-making and management for VTE. Additionally, individualized VTE prevention based on risk factors for each patient and the development of new safe, effective, and inexpensive oral agents will be emerging trends in the future.

Objective To determine the quality of life (QoL) of patients with nasopharyngeal carcinoma (NPC) and the clinical factors that influence QoL. Methods Multiple linear regression, simple and canonical correlation analyses were used to analyze the factors that affected QoL in patients with NPC. Results The QoL scores were as follows: physical function domain, 61.03±15.03; mental function domain, 60.95±15.35; social function domain, 59.17±14.16; specific module domain, 75.62±14.87; and total scale score, 66.10±97.18. Multiple linear regression analyses showed that family economic status and clinical stage of the disease are the factors affecting the overall QoL among NPC patients. The simple correlation analysis showed that the hemoglobin level had a positive correlation with physical function, social function, specific module domains, and the total score of the total scale. Canonical correlation analysis revealed a pair of statistically significant typical variables and the canonical correlation coefficient was 0.561 (PConclusion The indicators related to the QoL among patients with NPC included family economic status, clinical stage of the disease, red blood cell count, and albumin, total bilirubin, blood urea nitrogen, creatinine, aspartate aminotransferase, and hemoglobin levels. A focus on these indicators and implementing the corresponding treatment measures had value in improving the QoL among patients with NPC.

Background Migraine is a common disorder of the nervous system in China, imposing heavy burdens on individuals and societies. Optimal healthcare planning requires understanding the magnitude and changing trend of migraine incidence in China. However, the secular trend of migraine incidence in China remains unclear. Methods Data were collected from the Global Burden of Disease Study 2019 in China from 1990 to 2019 to investigate changes in the incidence rate of migraine. The average annual percent change and relative risk were calculated using joinpoint regression and an age–period–cohort model, respectively. Results From 1990 to 2019, the age-standardized incidence rates of migraine in China increased by 0.26% (95% CI: 0.22 to 0.31) and 0.23% (95% CI: 0.19 to 0.28) per year in males and females, respectively. The age effect exerted the most significant impact on the incidence of migraine. The period effect showed a slightly decreasing trend in the incidence of migraine. In terms of the cohort effect, people born after the 1960s presented a higher risk of migraine as compared with the total cohort, with the occurrence risk of migraine increasing with birth cohorts. Conclusion Migraine incidence shows an overall increasing trend in China, with a significant gender difference. An intensive understanding of the risk characteristics and disease pattern of migraine could allow the early detection of persons with a high risk of developing migraine and promote the development of timely intervention measures to relieve this burden effectively.

Conduct disorder is one of the least widely recognized and studied psychiatric disorders. This study aimed to comprehensively analyze the burden of conduct disorder at the global, regional, and national levels based on the Global Burden of Disease (GBD) 2019 estimates. Globally, the age-standardized prevalence rates (ASPRs) of conduct disorder slightly increased from 1990 to 2019 with an estimated annual percentage change (EAPC) at 0.147. Males had a higher burden than females, but females had a greater increment in ASPRs than males over time. In 2019, the highest ASPR of conduct disorder was observed in Western Europe, followed by Eastern Europe, with the lowest one found in East Asia, then South Asia. However, the most significant increment in ASPRs was observed in high-income North America, followed by East Asia, and South Asia. The EAPCs at the national level were negatively associated with the ASPRs in 1990. The burden of conduct disorder continues to increase globally, especially in high-income North America, East Asia, and South Asia, and should have more attention focused on it.

Background: Radiofrequency ablation (RFA) was adopted as an alternative to surgical options for sympathectomy in patients with palmar hyperhidrosis (PHH), but the RFA comparative efficacy of treatments by video-assisted thoracoscopic sympathectomy (VATS) on long-term remains uncertain.Methods: We recruited patients aged ≥14 years with diagnosed PHH from 14 centers in China. The treatment options of RFA or VATS were recruited in patient with informed consent. The primary outcome was the clinical efficacy in 1-year. Propensity scoring and multivariable models respectively were used to evaluate the clinical efficacy and inefficacy risk of treatment options.Results: A total of 807 patients were enrolled, 351 patients underwent RFA, and 456 were VATS. After propensity score matching, the rate of complete remission was lower in RFA than in VATS (79.2% [247/312] versus 91.3% [285/312], 95% confidence intervals [CI] 0.21 to 0.57, pConclusion: Performing RFA had a lower success rate than VATS for the complete remission of palmar hyperhidrosis. However, RFA may be better reasonable treatment option for palmar hyperhidrosis before surgical sympathectomy, because it more possibly accepted and generalized due to lower symptomatic burden and costs than surgical sympathectomy in patients.Trial RegistrationChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx

Background: The pediatric sequential organ dysfunction（pSOFA）score, C-reactive protein（CRP）and procalcitonin（PCT）play an important role in the prognosis assessment of children with sepsis. This study explores the value of their combined application, so as to provide a more comprehensive diagnosis method for the early diagnosis and prognosis evaluation of pediatric sepsis.Methods: A retrospective cross-sectional study method was used to collect and analyze the clinical data of 289 children who were hospitalized and diagnosed with sepsis in the Pediatric Intensive Care Unit (PICU) of the Affiliated Hospital of Guangdong Medical University from August 2018 to August 2019. The 28-day survival outcome was divided into survival group and death group. Compare the differences in various physiological and laboratory data of the two groups of children within the first 24 hours after admission to PICU; Use binary logistic regression to analyze high-risk factors that affect the prognosis of children with sepsis; The receiver operating characteristic curve (ROC) was drawn, and the area under the ROC curve (AUC) was used to evaluate the role of pSOFA score combined with CRP and PCT in the early diagnosis and prognosis evaluation of children with sepsis.Results: A total of 289 children were included in the study, 254 cases (87.9%) in the survival group and 35 cases (12.1%) in the death group; There were statistically significant differences between the two groups of children in age, whether to continuously pump vasoactive drugs, mechanical ventilation time, Glasgow coma score, gastrointestinal function, and serum PCT concentration (all PPP>0.05);Conclusions: The pSOFA score is of high value for the prognostic evaluation of children with sepsis; but the pSOFA score combined with CRP and PCT can not improve the prognostic evaluation ability of children with sepsis.

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

Quantitative characterization of nanoparticles (NPs) in marine shellfish is critical to understanding the risks of bio-accumulation. Based on single particle (sp)ICP-MS and electron microscopy, a standardized protocol was developed to extract Ag, Au, and indigenous Ti-containing NPs from mussels. The optimal parameters are: dry sample extraction with tetramethylammonium hydroxide (TMAH), 5% (v/v) final concentration of TMAH, extraction at 25 ℃ for 12 h, and separation by centrifugation (3000 rpm for 5 min). The particle number recoveries of spiked Ag and Au NPs were 88 ± 0.9% and 95 ± 1.1%, respectively, while Ti-containing NPs had a particle number concentration of 8.2 × 106 particles/mg and an average size of 70 nm in tested mussels. Furthermore, titanium oxide NPs, including rutile, anatase, and Magneli phases (TixO2x-1) were found ubiquitously in 10 shellfish based on the optimal method. The particle number concentrations and average sizes of the Ti-containing NPs were 2.1 × 106–8.4 × 106 particles/mg and 70–80 nm, respectively. These Ti-containing NPs, such as TiO2, accounted for about half of the Ti mass in shellfish, indicating that marine shellfish may be a significant sink for Ti-containing NPs.

Polydatin (PD), an active component of Chinese herbs, is reported to have many biological functions, such as cardioprotective actions, anti-inflammatory activities, and antitumor effects. In this study, we investigated the effects of PD on body weight control, glucose and lipid metabolic regulation, and anti-inflammation in a high-fat-diet- (HFD-) induced obese mice model. After treatment of PD (100 mg/kg/d for 4 weeks), HFD mice reduced body weight, retroperitoneal fat mass, and adipose cell sizes; significantly lowered serum total cholesterol triglyceride (TG) and low-density lipoprotein (LDL) levels; and increased high-density lipoprotein (HDL) levels compared with the HFD control mice. Further studies showed that PD downregulated the mRNA and protein expressions of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor involving in the regulation of adipocyte differentiation, in the retroperitoneal fat of HFD mice. Additionally, PD significantly upregulated the mRNA and protein expressions of leptin, an adipocyte-derived anorexic hormone that regulates food intake and energy expenditure, in the adipose tissues of HFD mice. Moreover, PD reduced the expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) in the retroperitoneal and epididymal tissues of HFD mice, suggesting that PD prevented adipose tissue inflammation. In conclusion, PD may serve as a pharmaceutic candidate for obesity-related lipid metabolism, anti-inflammation, and body weight loss.

Jiayuan Wu,1,* Shasha Li,2,* Yufeng Wang,2 Liren Hu2 1Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiayuan WuDepartment of Clinical Research, Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, Guangdong 524001, People’s Republic of ChinaEmail 87537665@qq.comLiren HuDepartment of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical University, No. 2, Wenmin East Road, Zhanjiang 524023, People’s Republic ChinaEmail fox833@163.comBackground: The pretreatment aspartate aminotransferase-to-alanine aminotransferase (De Ritis) ratio is reportedly valuable in prognosis prediction of various malignancies. However, its value in the prognosis of nasopharyngeal carcinoma (NPC) has not yet been reported. This study aimed to evaluate the effect of the De Ritis ratio on the survival outcomes of patients with nonmetastatic NPC.Methods: We retrospectively reviewed the medical data of 1023 patients with nonmetastatic NPC admitted between 2009 and 2013 at a single center. The Fine and Gray competing risk regression model was used to analyze the associations between the De Ritis ratio and the survival outcomes of cancer-specific survival (CSS) and progression-free survival (PFS) by using the subdistribution hazard ratio (SHR) and 95% confidence interval (CI) as size effects. The Cox proportional hazard model was used to evaluate the correlation between the De Ritis ratio and overall survival (OS) by using hazard ratio (HR) and 95% CI as size effects.Results: Patients were divided into two groups in accordance with the pretreatment De Ritis ratio by using an optimal cutoff value of 1.65. Compared with the patients with low De Ritis ratio (< 1.65), those with elevated De Ritis ratio (≥ 1.65) had poorer prognosis with regard to CSS, PFS, and OS. Notably, multivariate analyses showed that high De Ritis ratio was independently associated with poor CSS (SHR = 1.64, 95% CI: 1.25–2.16), PFS (SHR = 1.69, 95% CI: 1.30–2.19), and OS (HR = 1.81, 95% CI: 1.39–2.40).Conclusion: Pretreatment De Ritis ratio can be an independent prognostic predictor for patients with nonmetastatic NPC.Keywords: aspartate aminotransferase-to-alanine aminotransferase ratio, nasopharyngeal carcinoma, prognosis, competing risk model

Background Numerous studies have reported the association between pretreatment serum aspartate transaminase to alanine transaminase (AST/ALT) ratio and prognosis in multiple cancers. However, the results remain controversial and no consensus has been reached. Thus, we conducted this meta-analysis to quantitatively assess the prognostic value of pretreatment AST/ALT ratio in solid tumors. Methods A systematic literature search was conducted by using PubMed, EMBASE, Web of Science, Cochrane Library, and Wanfang databases, as well as several trial registry platforms, including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, up to April 5, 2019. HR and 95% CI for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were calculated to estimate the effect size. Results A total of 18 studies with 9,400 patients were included. Overall, a high level of pretreatment AST/ALT ratio was significantly associated with worse OS (pooled HR=1.70, 95% CI=1.38-2.09). The statistical significance was observed in all cancer types, including renal cell carcinoma (pooled HR=1.64, 95% CI=1.30-2.05), liver cancer (pooled HR=1.16, 95% CI=1.04-1.29), urinary tract urothelial carcinoma (pooled HR=1.96, 95% CI=1.53-2.51), bladder cancer (pooled HR =2.66, 95% CI=1.69-4.20), and other cancers (pooled HR=1.44, 95% CI=1.18-1.76). Moreover, an increased level of serum AST/ALT ratio predicted unfavorable CSS (pooled HR=2.07, 95% CI=1.74-2.46) and RFS (pooled HR=1.51, 95% CI=1.15-1.99). Conclusion Elevated level of serum AST/ALT ratio before treatment is significantly associated with poor clinical outcomes of OS, CSS, and RFS in patients with solid tumors. Pretreatment AST/ALT ratio can serve as a useful prognostic predictor for malignant patients.

Early identification of severe acute pancreatitis (SAP) is critical for clinical decision-making. The apolipoprotein B-to-apolipoprotein A1 ratio (ApoB/A1 ratio) reflects the balance between pro-inflammation and anti-inflammation in vivo. This study investigated the association between serum ApoB/A1 ratio at admission and acute pancreatitis (AP) severity. A total of 375 patients with first attack of AP were retrospectively recruited from January 2014 to December 2017. The severity of AP was assessed at admission based on the 2012 revised Atlanta Classification. Serum lipids levels were tested on the first 24 h of hospitalization, of which the correlations with clinical features or scoring systems were also measured. The ApoB/A1 ratio markedly increased across disease severity of AP. The ApoB/A1 ratio, expressed as both quartile and continuous variables, was significantly associated with a high risk of SAP, even after adjustment for other conventional SAP risk factors. The ApoB/A1 ratio positively correlated with the revised 2012 Atlanta Classification, Ranson score, Bedside Index for Severity in AP score, Modified Computed Tomography Severity Index score, and Acute Physiology and Chronic Health Evaluation II score for AP severity. The optimal cut-off value of ApoB/A1 ratio for detecting SAP was 0.88, with a sensitivity of 83.08% and a specificity of 69.03%. Serum ApoB/A1 ratio at admission is closely correlated with disease severity in patients with AP and can serve as a reliable indicator for SAP in clinical setting.

The incidence of synchronous multiple primary lung cancer (SMPLC) has been increased in recent years. Because of a variance in clinical management and outcome, it is important to distinguish SMPLC from a primary tumor with intrapulmonary metastases. Here, we reported a diagnosis and treatment procedure regarding a case of a 58-year-old woman who presented with synchronous multiple tumor lesions in separate lungs. Using a next generation sequencing technology, a discordant EGFR gene profile from the separate lungs was revealed for this patient. After standard treatment procedures, the therapeutic effects were evaluated by response evaluation criteria in solid tumors (RECIST). This case shows an essential role in the combination of molecular features, together with pathological analysis, during the management of SMPLC, but challenges still required considering during dealing the cases of SMPLC.

The aim of this study was to analyze the secular trends of conduct disorder (CD) incidence in China from 1990 to 2019 under the joinpoint analysis and the age-period-cohort framework.The sex-specific incidence rates of CD from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database according to the age group. The joinpoint regression and the age-period-cohort model were conducted using the average annual percent changes and relative risks as size effects, respectively.From 1990 to 2019, age-standardized rates (ASRs) of CD incidence showed an overall increasing trend in both sexes, and this variation trend was observed in almost all age groups. The annual sex-specific ASRs were lower in China than those worldwide but were rapidly growing. Age effects were the most significant risk factor for CD, with the highest risk in adolescents aged 10 to 14 years, followed by children aged 5 to 9 years, but a relatively lower risk in adolescents aged 15 to 19 years than in other age groups. However, period and cohort effects were not statistically significant.CD incidence rates in China have been increasing in both sexes from 1990 to 2019. Further studies are necessary to explain the etiology of these increases and promote the early identification of individuals at risk for developing CD.

Microglia-mediated neuroinflammation is tightly correlated with the etiology and progression of neurodegenerative disorders, including Parkinson's disease (PD). Nilotinib, a c-Abl inhibitor used for chronic myeloid leukemia, has been proven effective in relieving PD progression. However, whether nilotinib could affect neuroinflammation is largely unknown. In this current study, we investigated the role of nilotinib in microglia-mediated neuroinflammatory response in Parkinson's disease. Lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglial cells and mouse brains were used as models for Parkinson's disease. Our results demonstrated that nilotinib significantly suppressed LPS-induced neuroinflammation by reducing the production of pro-inflammatory factors including iNOS, COX-2, IL-1β, IL-6 and TNF-α in BV2 cells. Moreover, pretreatment of nilotinib attenuated the neurotoxicity of LPS-treated microglial conditioned medium to MES23.5 dopaminergic (DA) neurons. Mechanismly, nilotinib inhibited NF-κB signaling pathway and suppressed the nuclear translocation of p65 upon LPS stimulation. In LPS-injected mouse brains, nilotinib administration markedly suppressed the activation of microglia and down-regulated COX-2 as well as IL-1β expression. Most importantly, nilotinib effectively protected against microglial activation-mediated mouse DA neuronal loss. Taken together, our study suggests that nilotinib exerts anti-neuroinflammatory effect and protects DA neurons from activated microglia-induced inflammatory damage through suppressing NF-κB signaling pathway, indicating its potential application in further clinical trials.

Objectives Increasing life expectancy and decreasing mortality in patients with HIV infection are well documented. However, details of how many of the years of healthy life are damaged by HIV infection vs. good health have not been understood. We conducted this study to provide a comprehensive assessment of the levels and trends of the global burden, as measured by disability-adjusted life years (DALYs), of HIV infection. Methods Data on HIV-related DALY were obtained from the Global Burden of Disease Study 2019. The absolute numbers and age-standardised rates of DALYs due to HIV were reported between 1990 and 2019. Estimated annual percentage changes in age-standardised rates by sex, region and nation were calculated to quantify the temporal trends in HIV burden. Results Global HIV infection caused 47.63 million DALYs in 2019, presenting a 1.28-fold increase from 1990 to 2019. In 2019, years of life lost contributed to most of the total DALYs, but the increases in HIV-related years lived with disability have outpaced increases in years of life lost. The age-standardised rates of HIV-related DALYs in 2019 decreased as the sociodemographic indexes increased. The highest age-standardised rates were observed in sub-Saharan Africa, and the greatest increments over time were detected in Oceania. Conclusions Globally, HIV continues to cause enormous healthy life loss. The first and foremost strategy for controlling the HIV burden is still the reduction of premature deaths, and much effort needs to be exerted to mitigate the harm of comorbidities.

The imbalances between supply and demand in an urban rail transit system have received extensive attention. Addressing these imbalances by controlling the movements of passengers in the system is a real challenge. To complete the peak passenger flow control scheme, a novel discrete event simulation (DES) optimization model based on queuing theory is proposed to minimize the urban rail transit company losses and the passenger time delays considering effects of congestion propagation among facilities at busy stations. The proposed approach can generate a control scheme that consists of the controlling number of entering passengers and the controlling parameters of facilities inside the station. The first stage of the method models the subway network using queuing theory and then builds a DES model that is based on an urban rail transit queuing network. In the second stage, a service-security-economic-oriented optimization model is established and combined with a queuing network simulation model to implement the simulation optimization. We present three numerical experiments to compare the optimization results in different passenger flow scenarios. The results demonstrate that the DES optimization method in this paper can provide a reasonable and reliable control scheme in daily operations.

Background: Hyperhidrosis may affect approximately a hundred million global people; lead to they may be socially stigmatized. We hypothesized that radiofrequency ablation (RFA) and video-assisted thoracoscopic sympathectomy (VATS) would be equivalent in the treatment for primary hyperhidrosis (PH). Methods: In this multicenter cohort study, we recruited patients aged ≥14 years with diagnosed PH from 14 centers in China. The treatment options of RFA or VATS were recruited in patient with informed consent. Clinical effectiveness of treatment was assessed in patients the day of hospital discharge and on the time of study endpoint. Hyperhidrosis Disease Severity Scale (HDSS) and quality of life (QOL) were assessed in patients the day before operative and on the time of study endpoint. The primary endpoint was the rate of complete remission for hyperhidrosis. Propensity scoring and multivariable models respectively were used to assess the clinical effectiveness and the symptom recurrence risk of treatment options. Findings: Between March 4, 2015, and Sept 31, 2020, 807 patients were enrolled in our study. 351 of these patients underwent RFA, and 456 were VATS. After propensity score matching, the rate of complete remission was lower in RFA than in VATS (287/351[80.3%] versus 319/351 [90.1%], standardized mean differences, -30.4%). We did find the rate of symptom recurrence risk was higher in RFA than in VATS (HR 2.315, 95%CI 1.511-3.546, P

Aim Eating disorders have increasingly become a public health concern globally. This study aimed to reveal the burden of eating disorders at the global, regional and national levels using the Global Burden of Disease (GBD) Study 2017 data. Methods We extracted the age-standardised rates (ASRs) of prevalence and disability-adjusted life years (DALYs) and their 95% uncertainty intervals (UIs) of eating disorders, including anorexia nervosa and bulimia nervosa, between 1990 and 2017 from the GBD 2017 data. The estimated annual percentage changes (EAPCs) were calculated to quantify the secular trends of the burden of eating disorders. Results The ASRs of prevalence and the DALYs of eating disorders continuously increased worldwide from 1990 to 2017 by an average of 0.65 (95% UI: 0.59–0.71) and 0.66 (95% UI: 0.60–0.72), respectively. The burden of eating disorders was higher in females than in males, but the increment in ASRs was greater in males than in females over time. In 2017, the highest burden of eating disorders was observed in the high sociodemographic index (SDI) regions, especially Australasia (ASR of prevalence = 807.13, 95% UI: 664.20–982.30; ASR of DALYs = 170.74, 95% UI: 113.43–244.14, per 100 000 population), Western Europe and high-income North America. However, the most significant increment of the burden of eating disorders was observed in East Asia (EAPC for prevalence = 2.23, 95% UI: 2.14–2.32; EAPC for DALYs = 2.22, 95% UI: 2.13–2.31), followed by South Asia. An increasing trend in the burden of eating disorders at the national level was observed among most countries or territories. The countries with the top three highest increasing trends were Equatorial Guinea, Bosnia and Herzegovina and China. Positive associations were found between the burden estimates and the SDI levels in almost all geographic regions during the observed 28-year period. We also found that the human development indexes in 2017 were positively correlated with the EAPCs of the ASRs of prevalence (ρ = 0.222, P = 0.002) and DALYs (ρ = 0.208, P = 0.003). Conclusion The highest burden of eating disorders remains in the high-income western countries, but an increasing trend was observed globally and in all SDI-quintiles, especially in Asian regions that were highly populous. These results could help governments worldwide formulate suitable medical and health policies for the prevention and early intervention of eating disorders.