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Abstract Background In the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[18F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[18F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [18F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients. Results The automated synthesis of D6-[18F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (> 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[18F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [18F]FP-(+)-DTBZ and D6-[18F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline). Conclusions D6-[18F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain. Trial registration Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725 .

Abstract Background FANCA mutations have been detected in a variety of cancers and found to be pro-carcinogenic. However, no functional studies have been identified regarding the involvement of FANCA in the occurrence and the immune response of LUAD. Methods The mRNA expression and overall survival rates of FANCA were evaluated by the TIMER, PrognoScan and TCGA database in LUAD tissues, and FANCA expression was further validated by clinical serum samples using ELISA. The correlation between FANCA and immune infiltration level was investigated via TISIDB database and CIBERSORT algorithm. The Kaplan–Meier plotter was used to further evaluate the prognostic value based on the expression levels of FANCA in related immune cells. Then, the influence of FANCA knockout on the proliferation, migration, and invasion of A549 and H1299 cells was validated using CCK8, cloning formation, and Transwell assays. Subsequently, HLA-A2-restricted FANCA antigenic peptides were predicted and synthesized by NetMHC4.0 and SYFPEITHI, and DCs were induced and cultured in vitro. Finally, DCs loaded with HLA-A2-restricted FANCA antigenic peptides were co-cultured with autologous peripheral blood lymphocyte to generate specific CTLs. The killing effects of different CTLs on LUAD cells were studied. Results The results showed that high levels of FANCA in patients with LUAD were significantly correlated with worse OS survival, which was correlated with age, clinical stage, pathological T stage, M stage, and N stage in LUAD. Knockdown of FANCA in A549 and H1299 cells significantly inhibited proliferation, metastasis, and invasion in vitro. In addition, FANCA was significantly related to immune infiltrate, genomic alterations and TMB. FANCA expression infuenced the prognosis of LUAD patients by directly affecting immune cell infltration. Finally, HLA-A2-restricted FANCA antigenic peptides were synthesized. And FANCA 146–154 (SLLEFAQYL) antigenic peptide exhibit a stronger affinity for DCs, and induce CTLs to produce stronger targeted killing ability for LUAD cells at an effector-to-target ratio of 40:1. Conclusion These results demonstrated that the elevation of FANCA promotes malignant phenotype of LUAD, and the potential peptide P2 (SLLEFAQYL) derived from FANCA may be used as an epitope vaccine for the treatment of LUAD.

Abstract Background To explore an artificial intelligence (AI) technology employing YOLOv8 for quality control (QC) on elbow joint radiographs. Methods From January 2022 to August 2023, 2643 consecutive elbow radiographs were collected and randomly assigned to the training, validation, and test sets in a 6:2:2 ratio. We proposed the anteroposterior (AP) and lateral (LAT) models to identify target detection boxes and key points on elbow radiographs using YOLOv8. These identifications were transformed into five quality standards: (1) AP elbow positioning coordinates (XA and YA); (2) olecranon fossa positioning distance parameters (S17 and S27); (3) key points of joint space (Y3, Y4, Y5 and Y6); (4) LAT elbow positioning coordinates (X2 and Y2); and (5) flexion angle. Models were trained and validated using 2,120 radiographs. A test set of 523 radiographs was used for assessing the agreement between AI and physician and to evaluate clinical efficiency of models. Results The AP and LAT models demonstrated high precision, recall, and mean average precision for identifying boxes and points. AI and physicians showed high intraclass correlation coefficient (ICC) in evaluating: AP coordinates XA (0.987) and YA (0.991); olecranon fossa parameters S17 (0.964) and S27 (0.951); key points Y3 (0.998), Y4 (0.997), Y5 (0.998) and Y6 (0.959); LAT coordinates X2 (0.994) and Y2 (0.986); and flexion angle (0.865). Compared to manual methods, using AI, QC time was reduced by 43% for AP images and 45% for LAT images (p

Abstract Assessing the impact of past and future urban land expansion on ecosystem services (ESs) is essential for the sustainable management of urban landscapes. Despite recent progress, it remains challenging to determine the influence mechanism of different urbanization stages and areas on ESs and their trade-offs/synergies. Here, we analyzed the responses of four ESs and their trade-offs/synergies to the spatial and temporal differentiation of urbanization in the Su-Xi-Chang region of China from 1990 to 2050. The results showed that the relationship between ESs and urbanization followed a U-shaped curve from 1990 to 2050. Between 1990 and 2020, urbanization weakened trade-offs and enhanced lose-lose situations, exhibiting an S-shaped curve. From 2020 to 2050, lose-lose situations are expected to diminish, and the curve is projected to display a downward trend. Our findings suggest the implementation of compact urban development, sustainable agricultural practices, reforestation, and the conversion of farmland to lakes.

Abstract Pu'er crude tea (PCT), the initial raw material for making Pu'er tea, is favored because of unique flavor and health effects. Emotional response is helpful to explain consumers’ choice of different flavors of tea. This study aims to clarify the key floral volatiles of PCT and their emotional impact on people. Twenty‐nine compounds were identified as the key volatiles from 237 volatiles, which formed the flowery aroma of PCT. Linalool, geraniol, nonanal, and methyl salicylate were more abundant in the PCT, they evoked the top five emotions (mild, wild, aggressive, tame, bored). Methyl salicylate contributed most to the wild emotion in the two mixed samples (B10 and B14), and it may contribute positively to the health effects of tea, such as refreshing and anti‐inflammatory. This study provided a preliminary research idea for exploring the relationship between tea aroma and human emotions and its potential role in human health.

Abstract The clinical diagnosis of biliary atresia (BA) poses challenges, particularly in distinguishing it from cholestasis (CS). Moreover, the prognosis for BA is unfavorable and there is a dearth of effective non-invasive diagnostic models for detection. Therefore, the aim of this study is to elucidate the metabolic disparities among children with BA, CS, and normal controls (NC) without any hepatic abnormalities through comprehensive metabolomics analysis. Additionally, our objective is to develop an advanced diagnostic model that enables identification of BA. The plasma samples from 90 children with BA, 48 children with CS, and 47 NC without any liver abnormalities children were subjected to metabolomics analysis, revealing significant differences in metabolite profiles among the 3 groups, particularly between BA and CS. A total of 238 differential metabolites were identified in the positive mode, while 89 differential metabolites were detected in the negative mode. Enrichment analysis revealed 10 distinct metabolic pathways that differed, such as lysine degradation, bile acid biosynthesis. A total of 18 biomarkers were identified through biomarker analysis, and in combination with the exploration of 3 additional biomarkers (LysoPC(18:2(9Z,12Z)), PC (22:5(7Z,10Z,13Z,16Z,19Z)/14:0), and Biliverdin-IX-α), a diagnostic model for BA was constructed using logistic regression analysis. The resulting ROC area under the curve was determined to be 0.968. This study presents an innovative and pioneering approach that utilizes metabolomics analysis to develop a diagnostic model for BA, thereby reducing the need for unnecessary invasive examinations and contributing to advancements in diagnosis and prognosis for patients with BA.

Significant differences exist in aroma and taste of different grades of large-leaf black tea. In this study, sensory histology combined with metabolomics were used to investigate the sensory characteristics and phytochemical profiles of different grades of Huangpu black tea (HPBT). Sensory evaluation showed that high grade HPBT had high intensity of pekoe, fresh aroma and umami, with aroma and taste scores declining with decreasing grades. 173 non-volatiles were identified, of which 23 marker metabolites could be used as discrimination of different grades HPBT taste. In addition, 154 volatile compounds were identified in the different grades of HPBT, with 15 compounds as key odorants for distinguishing the aroma of different grades of HPBT. Furthermore, correlation analysis revealed that linalool, geraniol and nonanal contributed to the aroma quality score of HPBT. This study will provide a more comprehensive understanding for processing, quality evaluation and grade evaluation system of large-leaf black tea.

Background: Approximately 10%–30% of patients with Hodgkin's lymphoma (HL) experience relapse or refractory (R/R) disease after first-line standard therapy. Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) have important roles in the salvage treatment of R/R HL. However, subsequent treatment for HL refractory to BV and/or ICI treatment is challenging. Methods: We retrospectively analyzed patients in two institutions who had R/R HL, experienced BV or ICI treatment failure, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Overall, 19 patients were enrolled. First-line systemic therapy comprised doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD, 84.2%); AVD plus ICIs (10.5%); and bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP, 5.3%). After first-line therapy, 15 (78.9%) and four patients (21.1%) had refractory disease and relapsed, respectively. After R/R HL diagnosis, six (31.6%), two (10.5%), and 11 (57.9%) patients received BV and ICIs concurrently, BV monotherapy, and ICI monotherapy, respectively. All patients received intensity-modulated RT (n = 12, 63.2%) or volumetric modulated arc therapy (VMAT; n = 7, 36.8%). The ORR as well as the complete response (CR) rate was 100%; the median DOR to RT was 17.2 months (range, 7.9–46.7 months). Two patients showed progression outside the radiation field; one patient had extensive in-field, out-of-field, nodal, and extranodal relapse. With a median follow-up time of 16.2 months (range, 9.2–23.2 months), the 1-year PFS and OS were 84.4% and 100%, respectively. PFS was associated with extranodal involvement (P = 0.019) and gross tumor volume (P = 0.044). All patients tolerated RT well without adverse events of grade ≥ 3. Conclusion: RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Abstract Cancer testis antigen (CTA) Melanoma Antigen Gene A3 (MAGEA3) were overexpressed in multiple tumor types, but the expression pattern of MAGEA3 in the serum of lung adenocarcinoma (LUAD) remains unclear. Clinically derived serum and serum exosome samples were used to assess the mRNA expression of MAGEA3 and MAGEA4 by qRT-PCR, and serum MAGEA3 and MAGEA4 protein expression were evaluated by ELISA in total 133 healthy volunteers’ and 289 LUAD patients’ serum samples. An analysis of the relationship of the mRNA and protein expression of MAGEA3 and MAGEA4 with clinicopathologic parameters was performed and the diagnostic value of MAGEA3 and MAGEA4 was plotted on an ROC curve. In addition, the correlation of MAGEA3 mRNA with infiltrating immune cells was investigated through TIMER, the CIBERSORT algorithm and the TISIDB database. Expression of serum and serum exosome MAGEA3 and MAGEA4 mRNA were significantly higher in LUAD patients than in healthy donors. MAGEA3 mRNA associated with tumor diameter, TMN stage, and NSE in LUAD serum samples, and MAGEA3 mRNA correlated with N stage in serum-derived exosomes, possessing areas under the curve (AUC) of 0.721 and 0.832, respectively. Besides, serum MAGEA3 protein levels were elevated in LUAD patients, and were closely related to stage and NSE levels, possessing AUC of 0.781. Further analysis signified that the expression of MAGEA3 mRNA was positive correlation with neutrophil, macrophages M2, dendritic cells resting, and eosinophilic, but negatively correlated with B cells, plasma cells, CD8 + T cells, CD4 + T cells, Th17 cells, macrophages and dendritic cells. Collectively, our results suggested that the MAGEA3 expression in mRNA and protein were upregulated in LUAD, and MAGEA3 could be used as a diagnostic biomarker and immunotherapy target for LUAD patients.

ObjectiveThis study aimed to develop and validate a survival prediction model and nomogram to predict survival in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma undergoing treatment with anti-programmed cell death 1 receptor (PD-1). This model incorporates immune-related adverse events (irAEs) alongside common clinical characteristics as predictive factors.MethodA dataset comprising 255 adult patients diagnosed with advanced G/GEJ adenocarcinoma was assembled. The irAEs affecting overall survival (OS) to a significant degree were identified and integrated as a candidate variable, together with 12 other candidate variables. These included gender, age, Eastern cooperative oncology group performance status (ECOG PS) score, tumor stage, human epidermal growth factor receptor 2 (HER2) expression status, presence of peritoneal and liver metastases, year and line of anti-PD-1 treatment, neutrophil-to-lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and Charlson comorbidity index (CCI). To mitigate timing bias related to irAEs, landmark analysis was employed. Variable selection was performed using the least absolute shrinkage and selection operator (LASSO) regression to pinpoint significant predictors, and the variance inflation factor was applied to address multicollinearity. Subsequently, a Cox regression analysis utilizing the forward likelihood ratio method was conducted to develop a survival prediction model, excluding variables that failed to satisfy the proportional hazards (PH) assumption. The model was developed using the entire dataset, then internally validated through bootstrap resampling and externally validated with a cohort from another Hospital. Furthermore, a nomogram was created to delineate the predictive model.ResultsAfter consolidating irAEs from the skin and endocrine systems into a single protective irAE category and applying landmark analysis, variable selection was conducted for the prognostic prediction model along with other candidate variables. The finalized model comprised seven variables: ECOG PS score, tumor stage, HER2 expression status in tumor tissue, first-line anti-PD-1 treatment, peritoneal metastasis, CONUT score, and protective irAE. The overall concordance index for the model was 0.66. Calibration analysis verified the model’s accuracy in aligning predicted outcomes with actual results. Clinical decision curve analysis indicated that utilizing this model for treatment decisions could enhance the net benefit regarding 1- and 2-year survival rates for patients.ConclusionThis study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

IntroductionCyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are first-line treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. With their increasing clinical use, infection-related adverse events (AEs) associated with CDK4/6 inhibitors have been widely reported in recent years. This study aimed to analyze the occurrence of infections associated with the CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) based on the real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsData were extracted from the FAERS database between 2015Q1 and 2022Q3. The clinical characteristics of patients with primary suspected infection-related AEs were analyzed. A disproportionality analysis was performed to investigate the potential association between AEs and CDK4/6 inhibitors. The influencing factors were evaluated using Pearson’s chi-square test.ResultsReports of infection-related AEs associated with ribociclib accounted for 8.58% of the total reports of AEs associated with ribociclib, followed by palbociclib (2.72%) and abemaciclib (1.24%). Ribociclib (67.65%) was associated with more serious outcome events than palbociclib (30%) or abemaciclib (48.08%). The sex and age were not associated with outcome severity. Disproportionality analysis showed that fourteen, sixteen and two infection-related preferred terms were detected for palbociclib, ribociclib and abemaciclib, respectively.ConclusionInfection-related AEs were highly associated with three CDK4/6 inhibitors, especially palbociclib and ribociclib, based on the real-world data from the FAERS database. However, further causality assessment is required.

Abstract Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes. The development of pharmaceutics and material science provides the potential for highly effective pulmonary medicine delivery. In this review, the key factors and barriers are first introduced that affect the pulmonary delivery and bioavailability of nucleic acids. The advanced inhaled materials for nucleic acid delivery are further summarized. The recent progress of platform designs for improving the pulmonary delivery efficiency of nucleic acids and their therapeutic outcomes have been systematically analyzed, with the application and the perspectives of advanced vectors for pulmonary gene delivery.

BackgroundThe severity, symptoms, and outcome of COVID-19 is thought to be closely linked to how the virus enters host cells. This process involves the key roles of angiotensin-converting enzyme 2 (ACE2) and the Tyrosine protein kinase receptor UFO (AXL) receptors. However, there is limited research on the circulating levels of ACE2 and AXL and their implications in COVID-19.MethodsA control group of 71 uninfected individuals was also included in the study. According to the Guidance for Corona Virus Disease 2019 (10th edition), a cohort of 358 COVID-19 patients were categorized into non-severe and severe cases. Serum ACE2/AXL levels in COVID-19 patients were detected by enzyme-linked immunosorbent assay (ELISA) at different time points post-COVID-19 infection, including days 0-7, 8-15, 31-179 and >180 days. Serum SARS-CoV-2 IgG/IgM antibodies in COVID-19 patients at the same intervals were assessed by using an iFlash 3000 Chemiluminescence Immunoassay Analyzer. The receiver operating characteristic (ROC) curves were used to assess the diagnostic value of the biological markers, and the association between laboratory parameters and illness progression were explored.ResultsCompared with the uninfected group, the levels of ACE2 and AXL in the COVID-19 group were decreased, and the SARS-COV-2 IgG level was increased. AXL (AUC = 0.774) demonstrated a stronger predictive ability for COVID-19 than ACE2. In the first week after infection, only the level of AXL was statistically different between severe group and non-severe group. After first week, the levels of ACE2 and AXL were different in two groups. Moreover, in severe COVID-19 cases, the serum ACE2, AXL, and SARS-COV-2 IgM levels reached a peak during days 8–15 before declining, whereas serum SARS-COV-2 IgG levels continued to rise, reaching a peak at day 31-180 days before decreasing. In addition, the AXL level continued to decrease and the SARS-COV-2 IgG level continued to increase in the infected group after 180 days compared to the uninfected group.ConclusionsThe levels of serum ACE2 and AXL correlate with COVID-19 severity. However, AXL can also provide early warning of clinical deterioration in the first week after infection. AXL appears to be a superior potential molecular marker for predicting COVID-19 progression.

BackgroundLow-dose aspirin is one of the widely used adjuvants in assisted reproductive technologies with the hope of improving the live birth rate. However, the studies regarding its effects are conflicting. The study aimed to investigate the association between aspirin administration and live birth following frozen-thawed embryo transfer (FET) in patients with different body mass index (BMI).MethodsA retrospective cohort study was performed on 11,993 patients receiving FET treatments. 644 of which received a low-dose aspirin (100 mg/day) during endometrial preparation until 10 weeks after transfer. Propensity score matching was performed to avoid selection biases and potential confounders.ResultsThe clinical pregnancy rate and live birth rate were similar before matching (54.4% versus 55.4%, RR: 1.02, 95%CI: 0.95-1.09, and 46.3 versus 47.8, RR: 1.03, 95%CI: 0.95-1.12 respectively). A weak association in favor of aspirin administration was found in the matched cohort (49.5% versus 55.4%, RR: 1.12, 95%CI: 1.01-1.24, and 41.9% versus 47.8%, RR: 1.14, 95%CI: 1.01-1.29 respectively). However, when stratified the patients with WHO BMI criteria, a significant increase in live birth rate associated with aspirin treatment was found only in patients with low BMI (

IntroductionTriazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased. The aim of this study was to analyze the cardiac disorders associated with TAAs (fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole) based on data from the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System.MethodsData were extracted from the FAERS database between the first quarter of 2004 and third quarter of 2022. The clinical characteristics in TAA-associated cardiac AE reports were analyzed. Disproportionality analysis was performed to evaluate the potential association between AEs and TAAs using the reporting odds ratio (ROR) and proportional reporting ratio (PRR).ResultsAmong 10,178,522 AE reports, 1719 reports were TAA-associated cardiac AEs as primary suspect drug. Most reports were related to fluconazole (38.34%), voriconazole (28.56%) and itraconazole (26.76%). Itraconazole (N = 195, 42.39%) and isavuconazole (N = 2, 14.29%) had fewer serious outcome events than three other drugs including fluconazole, voriconazole, and posaconazole. 13, 11, 26, 5 and 1 signals were detected for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. The number of new signals unrecorded in the drug label was 9, 2, 13, 2 and 0 for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively.ConclusionIsavuconazole might be the safest of the five TAAs for cardiac AEs. TAA-associated cardiac disorders may result in serious adverse outcomes. Therefore, in addition to AEs on the drug label, we should pay attention to new AEs unrecorded on the drug label during the clinical use of TAAs.

Abstract Background Non-communicable diseases (NCDs) pose a major challenge to health economic cost and residents’ health status. Community health workers (CHWs) are the gatekeeper of primary health care. Objective This study aimed to conduct a situational analysis of current human resource and requirements of NCDs-related training among CHWs in Chengdu with regard to address to understand the suggestions for improvement of challenges and barriers. Methods A descriptive online cross-sectional survey was conducted among CHWs (doctors and nurses) from 23 districts and counties in Chengdu. Sociodemographic and NCDs-related variables were collected. Univariate analysis and multiple response analysis were used to describe the characteristics of these variables. Results 711 doctors and 637 nurses completely responded. There were significant differences among gender, age, educational levels, professional title, working year, type of institution, urban circle and registration in general practice between doctors and nurses (P

Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation and cytokine storm. It is essential to explore the immune response characteristics of peripheral circulation in COVID-19 patients to reveal pathogenesis and predict disease progression. In this study, the levels of total immunoglobulins (IgG, IgM, IgA), complement (C3, C4)，lymphocyte subsets (CD3+ cell，CD4+ cell，CD8+ cell, NK cell, CD19+ cell and CD45+ cell) and cytokines (IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, IL-12p, IL-1β, TNF-α, IFN-α and IFN-γ) were retrospectively analyzed in COVID-19 patients. A total of 513 patients were enrolled in this study, cases were distributed according to clinical status as mild or moderate (n = 212), severe survivors (n = 197) and severe non-survivors (n = 104). IL-6, IL-8, IL-10 and IFN-γ were increased in severe patients compared with non-severe patients, despite decreased CD45+ cell, CD3+ cell, CD4+ cell, CD8+ cell, CD19+ cell, and NK cell. Compared with severe survivors, the levels of L-6, IL-8 and IL-10 in non-survivors increased significantly, and levels of C3, CD45+ cell, CD3+ cell，CD4+ cell，CD8+ cell, and NK cell decreased. Moreover, age, IL-8, IL-10, CD8+cells and NK cell were independent risk factors for the severity of COVID-19. Multivariable regression showed increasing odds ratio of in-hospital death associated with tumor, older age, higher IL-8 level, and decreasing odds ratio of in-hospital death associated with increased levels of CD8+cell and NK cell. Finally, patients with tumor, or high IL-6 or high IL-10 expression and lower CD8+ or lower NK levels exhibited a significantly shorter survival time. In conclusion, our study provides findings of the immunological characteristics associated with disease severity to predict the progression of COVID-19. The immune inflammation factors, such as IL-6, IL-8, IL-10, CD8+ cell and NK cell, could serve as excellent biomarkers for monitoring or predicting COVID-19 progression therapeutic to COVID-19 patients.

Abstract Objective To investigate whether the application of a curved rasp on the femoral side is effective in reducing the incidence of stem malalignment in total hip replacement with direct anterior approach (DAA-THA), followed by the analysis of the independent risk factors affecting stem malalignment. Methods Retrospective analysis was carried out covering 160 patients undergoing DAA-THA from January 2019 to December 2021, with Tri-Lock (BPS, Depuy) stem applied in all 113 patients were screened according to inclusion and exclusion criteria. The data of gender, age, body mass index, preoperative diagnoses, Dorr classification, FAR ratio, pelvic morphology ratio, WOMAC scores, were analyzed to explore the independent factors influencing the malalignment of the femoral prosthesis implantation. Then data of patients were divided into group A and group B according to whether the curved rasp was taken during the operation. The chi-square test was performed to compare the incidence of femoral stem malalignment between the two groups. Results There revealed two independent risk factors: BMI and FAR ratio that affected femoral stem malalignment. The increased BMI was associated with a higher probability of femoral stem malalignment (P1(OR = 1.15, 95% CI: 1.03–1.28, P

Scholars and engineers have increasingly focused on the safety of steel-structure buildings. An accurate analysis can substantially reduce the collapse probability of these buildings. This paper proposes a novel risk analysis model to assess the safety of steel-structure buildings. The vector entropy method and weight clustering were used to improve the controlled interval and memory (CIM) model. The proposed model has the advantages of a straightforward modeling approach, strong adaptability, and logical relationships. The new strategy improves the reliability and stability of the CIM model results when the maximum membership principle is not applicable. The Jiangxi Exhibition Center in China, which has a steel truss roof, is used as a case study. The results indicate a high safety risk of the project and the need for maintenance and repair. The improved CIM model has higher stability and adaptability for analyzing the safety risks of steel structure than the standard CIM model.

Integrated project delivery (IPD) has gained significant attention as an effective alternative to traditional project delivery models. Profit distribution is a crucial aspect of IPD projects, influencing their overall success. This study aims to investigate the key factors impacting profit distribution to offer strategic guidance for project management practices. The study employs a comprehensive bibliometric analysis to establish an updated research framework in this domain. Through this analysis, 24 articles with highly relevant and extensively cited sources are identified for further examination. Grounded theory is subsequently applied to distill the findings. This process yields a foundational theoretical framework that delineates the factors influencing profit distribution in IPD projects, namely, contribution, resource-based input, effort level, and risk sharing. Additionally, a textual analysis of ten burst words is conducted to discern research trends and identify future areas of study. This research contributes to the existing literature by addressing gaps and providing a roadmap for future IPD investigations. A theoretical framework of influencing factors in profit distribution in IPD projects is developed based on the literature. The findings not only enhance understanding of profit distribution dynamics in IPD projects but also guide the implementation and optimization of IPD practices.

Vegetation Net Primary Productivity (NPP) plays a crucial role in terrestrial carbon sinks and the global carbon cycle. Investigating the spatiotemporal dynamics and influencing factors in the Yangtze River Delta (YRD) region can furnish a solid scientific foundation for green, low-carbon, and sustainable development in China, as well as a reference for other rapidly urbanizing regions. This study focuses on the YRD region as an illustration and utilizes the Carnegie–Ames–Stanford Approach (CASA model) to quantify NPP in this region from 2000 to 2018. Investigation into the spatiotemporal dynamics and influencing factors was conducted using Theil–Sen median trend analysis and scenario analysis. The results indicate that the NPP in the YRD region from 2000 to 2018 exhibited pronounced spatial differentiation characteristics, typically exhibiting a spatial distribution pattern of being high in the south and low in the north, high in the west and low in the east. Additionally, the expansion of built-up areas and the reduction in cultivated land have the potential to reduce NPP in the YRD region. Moreover, the influence of land-use and land-cover change (LULCC) is anticipated to be relatively limited compared to that of climate change. Furthermore, changes in precipitation were found to be positively correlated with changes in NPP, with the effect being relatively more pronounced. The correlation between temperature and NPP demonstrated spatial differentiation, with a mainly positive correlation in the central and southern parts of the YRD and a mainly negative correlation in the northern part. Changes in solar radiation had a negative correlation with changes in NPP. Based on these results, it is recommended that local governments strictly enforce urban development boundaries and manage the disorderly expansion of built-up areas, enhance the regional irrigation infrastructure, and address air pollution, so as to ensure the necessary conditions for the growth of vegetation, reduce greenhouse gas emissions, and control regional temperature rises. This study can provide stronger evidence for revealing the influencing mechanisms of NPP through the control of impact conditions and the exclusion of confounding factors via scenario analysis. The policy implications can offer insights into NPP enhancement and environmental management for the YRD and other rapidly urbanizing regions.

Efficient removal of extremely mobile and toxic As(III) from water is a challenging but critical task. Herein, we developed a functionalized sorbent of chitosan nanofiber with iron–manganese (Fe-Mn@CS NF) using a one-step hybrid electrospinning approach to remove trace As(III) from water. Batch adsorption studies were performed to determine the adsorption efficiency under a variety of conditions, including contact time, starting concentration of As(III), ionic strength, and the presence of competing anions. The experimental results demonstrated that the concentration of As(III) dropped from 550 to less than 1.2 µg/L when using 0.5 g/L Fe-Mn@CS NF. This demonstrates the exceptional adsorption efficiency (99.8%) of Fe-Mn@CS NF for removing As(III) at pH 6.5. The kinetic tests revealed that the adsorption equilibrium was reached in 2.6 h, indicating a quick uptake of As(III). The ionic strength effect analysis showed that the adsorbed As(III) formed inner-sphere surface complexes with Fe-Mn@CS NF. The presence of SO42− or F− had a negligible impact on As(III) uptake, while the presence of PO43− impeded As(III) absorption by competing for adsorption sites. The exhausted sorbent could be effectively regenerated with a dilute NaOH solution. Even after 10 cycles of regenerating Fe-Mn@CS NF, the adsorption efficiency of As(III) in natural groundwater was maintained over 65%. XPS and FTIR analyses show that the presence of M–OH and C–O groups on the sorbent surface is essential for removing As(III) from water. Overall, our study highlights the significant potential of Fe-Mn@CS NF for the efficient and quick elimination of As(III) from water.

The quality of jasmine tea is related to the volatiles of its infusion. In this study, the volatiles of jasmine tea infusion were extracted under the optimal conditions with a 50/30 μm DVB/CAR/PDMS fiber, tea/water ratio of 1:25 and extraction time of 5 min. A total of 204 volatiles were analyzed by comprehensive two-dimensional gas chromatography-quadrupole time-of-flight mass spectrometry (GC × GC-Q-TOF-MS). Twenty-five compounds were identified as the key volatile compounds by fold change (FC), orthogonal partial least squares discriminant analysis (OPLS-DA), and two-way orthogonal partial least squares analysis (O2PLS). Then optimal amount of flowers (80%–120%) was obtained by the equation describing key volatiles and quality of jasmine tea infusion. And 80% amount of flowers was more appropriate considering the production cost and more pleasant taste. This study laid a foundation for the extraction and research of volatiles of tea infusion and guided the reasonable amount of flowers to produce jasmine tea.

Abstract Background Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder with complex physiopathological mechanisms that have not been fully understood. Early identification is of great prognostic significance, of which the symptoms and radiological abnormalities can be completely reversed. If the diagnosis and treatment are delayed, ischemia and massive infarction may be developed in some patients. Posterior reversible encephalopathy syndrome (PRES) has been reported mainly in association with postpartum eclampsia, which have been rarely reported, while the association with hypothyroidism has not been reported at home or abroad. Case presentation Here we report on a pregnant 29-year-old with multipara and a chief complication of hypothyroidism. She presented in the emergency department with frequent attacks of severe headache symptoms resulting from reversible cerebral vasoconstriction syndrome (RCVS), accompanied with prenatal eclampsia. PRES was determined by radiological examination. Conclusion To the best of our knowledge, this is the first case of PRES complicated by hypothyroidism and prepartum eclampsia.Clinicians should be alert for the co-occurence of eclampsia, PRES, and RCVS when patients have convulsions after a typical throbbing headache. Moreover, regular monitoring of thyroid function during pregnancy should also occupy certain special attention.

BackgroundThe contracted family doctor services are the embodiment of the implementation of the new medical reform policy, and the transformation of the grass-roots health service mode. Studies have proved that the occupational stress in medical staff was at a high level. The enhancement of professional identity will contribute to strengthen team building，alleviate job burnout, and reduce turnover intention of family doctors. ObjectiveTo investigate the current situation of occupational identity among family doctor teams in Chengdu, to examine potential influencing factors of occupational identity, and to provide a reference for promoting career development and team building of family doctor teams. MethodsMulti-stage random cluster sampling was adopted to enroll study participants form 46 primary healthcare centers where family doctor contract services were implemented among 23 districts and counties in Chengdu between March 4 and 26, 2021. A total of 2 681 family doctors participated in this survey. A self-reported survey was conducted to collect participants' demographic and occupational data. The Effort-Reward Imbalance (ERI）questionnaire was implemented to assess occupational stress. The Professional Identity Scale was used to appraise occupational identity. ResultsA total of 2 327 valid questionnaires were collected, with a valid recovery rate of 86.80%, involving 1 715 females (73.7%) and 612 males (26.3%), with dominant age groups of 26−35 years (43.3%) and 36−45 years (30.4%), a high proportion of being married (82.8%), having college (36.0%) and undergraduate (47.3%) education, a high proportion of primary titles (66.0%) and informal work contract (66.1%). About 88.7% of family doctor team workers reported occupational stress. The average score of occupational identity was (3.68±0.62) points. There were significant differences in occupational identity scores among different professional title, work contract, working years in medical institutions, income, and effort/reward ratio (EER) groups (P < 0.05). ERR was negatively correlated with occupational identity (rs=−0.495, P

Copper (Cu) is an essential trace element in the brain and serves as an important cofactor for numerous enzymes involved in a wide range of biochemical processes including neurobehavioral, mitochondrial respiration, and antioxidant effects. Recent studies have demonstrated that copper dyshomeostasis is tightly associated with the development of depression by inducing oxidative stress and inflammatory responses. However, these findings have remained controversial so far. Cumulative studies have shown a positive association, while some other studies showed no association and even a negative association between serum/plasma copper level and depression. Based on these conflicted results, the association was speculated to be due to the clinical features of the population, stages of the disease, severity of copper excess, and types of specimens detected in these studies. In addition, there was an inverse association between dietary copper intake and depression. Furthermore, increasing copper intake could influence dietary zinc and iron intake to prevent and treat depression. Thus, copper supplementation may be a good measure to manage depression. This review provided a deeper understanding of the potential applicability of copper in the prevention and treatment of depression.

Abstract Background Family doctor contract services was launched in Sichuan province in 2016. The focus was mainly on developing primary health care services but paying less attention to the work stress and job satisfaction of in-service family doctors. Objective This study aims to explore the influencing factors of job satisfaction, and the relation between work stress indicators and job satisfaction among family physicians. Methods An analytical online cross-sectional survey was performed among 1,105 family doctors from 23 districts and counties in Chengdu. Self-administered questionnaire was completed. Sociodemographic factors, work stress measured by Effort-Reward Imbalance (ERI)scale, and job satisfaction assessed by the short Chinese version of the Minnesota Satisfaction Questionnaire (MSQ) were collected in this study. A statistical analysis and hierarchical linear regression analysis were performed to explore the influencing factors and the correlations among related variables. Results The overall mean MSQ score was 52.01 ± 13.23. Analysis of doctor satisfaction indicated that age, education, job rank, type of institution, years of working and monthly income were statistically significant (P

In order to promote the development of China′s fishing village tourism and the implementation of the "Rural Revitalization" strategy, the paper studied the impact mechanism of tourism experience on the image of fishing village, the role of tourists′ perceived value and tourists′ risk perception, based on the field survey data of Xunpu village in Quanzhou City, then put forward development suggestions. The results showed that tourism experience had a significant positive impact on the image of fishing village. Tourists′ perceived value played an intermediary role in the impact mechanism of tourism experience on the image of fishing village. Tourists′ risk perception played a regulatory role between tourism experience and tourists′ perceived value, as well as between tourism experience and fishing village image. When tourists′ risk perception was low, tourism experience was easier to improve the fishing village image by improving tourists′ perceived value. The development of fishing village tourism in Xunpu village should focus on improving tourism experience and tourists′ perceived value, reducing tourists′ risk perception, and building a fishing village tourism brand.

BackgroundsThe effects of various treatments on Graves’ ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking.We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs.MethodsTo identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase,Cochrane Library, CBM, CNKI,Wan-Fang and ICTRP databases.The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies.The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS),the improvement of proptosis and diplopia improvement,and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses.ResultsA total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab).TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX.TCZ was the highest probability of safety, followed by RTX and TMB.ConclusionsBased on the best available evidence,TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials,indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition,the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established,and it is encouraging that the treatment paradigm for GO may change in the future.This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA)(27).Systematic Review Registrationhttp://www.crd.york.ac.uk/prospero, identifier CRD42023398170.

IntroductionTraditional DBS is usually conducted under local anesthesia (LA) which is intolerable to some patients, DBS under general anesthesia (GA) was opted to extended surgical indication. This study aimed to compare the efficacy and safety of bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) under asleep and awake anesthesia state in 1-year postoperative follow-up.MethodsTwenty-one PD patients were assigned to asleep group and 25 patients to awake group. Patients received bilateral STN-DBS under different anesthesia state. The PD participants were interviewed and assessed preoperatively and at 1-year postoperative follow-up.ResultsAt 1-year follow-up, compared surgical coordinate in two groups, the left-side Y of asleep group showed more posterior than awake group (Y was-2.39 ± 0.23 in asleep group, −1.46 ± 0.22 in awake group, p = 0.007). Compared with preoperative OFF MED state, MDS-UPDRS III scores in OFF MED/OFF STIM state remained unchanged, while in OFF MED/ON STIM state were significantly improved in awake and asleep groups, yet without significant difference. Compared with preoperative ON MED state, MDS-UPDRS III scores in ON MED/OFF STIM, and ON MED/ON STIM state remained unchanged in both groups. In non-motor outcomes, PSQI, HAMD, and HAMA score significantly improved in asleep group compared to awake group at 1-year follow-up (PSQI, HAMD, and HAMA score in 1-year follow-up were 9.81 ± 4.43; 10.00 ± 5.80; 5.71 ± 4.75 in awake group, 6.64 ± 4.14; 5.32 ± 3.78; 3.76 ± 3.87 in asleep group, p = 0.009; 0.008; 0.015, respectively), while there was no significant difference in PDQ-39, NMSS, ESS, PDSS score, and cognitive function. Anesthesia methods was significantly associated with improvement of HAMA and HAMD score (p = 0.029; 0.002, respectively). No difference in LEDD, stimulation parameters and adverse events was observed between two groups.DiscussionAsleep STN-DBS may be considered a good alternative method for PD patients. It is largely consistent with awake STN-DBS in motor symptoms and safety. Yet, it showed higher improvement in terms of mood and sleep compared to awake group at 1-year follow-up.

Objective To explore the learning curve of total hip arthroplasty in direct anterior approach (DA‐THA) without requiring corrective osteotomy for patients with unilateral developmental dysplasia of the hip (DDH) through the evaluation of clinical and radiographic results. Method From December 2015 to January 2021, we retrospectively evaluated a surgeon's first 100 patients with unilateral hip dysplasia (Crowe I‐III) who underwent DA‐THA. All procedures were performed by a fellowship‐trained joint surgeon. Cementless hemispheric porous‐coated acetabular cups and tapered cementless stems were used in all hips. The radiographic data, including leg length, the height of the center of rotation, femoral head offset, the cup anteversion and inclination angle, were measured. The cumulative sum analysis (CUSUM) and risk‐adjusted cumulative sum analysis (RA‐CUSUM) were used to determine the learning curve of DA‐THA for each patient's operation time. By analyzing the operation time, complication rate, postoperative length of hospitalization and creatine kinase (before surgery and the third day after surgery), estimated blood loss, Harris score, radiographic data were compared between the different stages of the learning curve. Results The mean follow‐up time was 35.45 ± 16.82 months. The CUSUM method obtained the maximum turning point of the curve at 43 cases, which divided the learning curve into Learning Period and Mastery Period. The CUSUM learning curve was best modeled as a cubic curve with the equation: CUSUM (min) = 0.001x3 − 0.495x2 + 33.60x − 10.00, which had a higher R2 value of 0.967. The pre‐operative data, creatine kinase, estimated blood loss and postoperative Harris scores of the two stages were not statistically significant (P > 0.05). The mean operation time was 118 min in the Learning Period and 87 min in the Mastery Period. Statistically significant differences were detected in the operation time (P

Abstract Background Advanced models including time-lapse imaging and artificial intelligence technologies have been used to predict blastocyst formation. However, the conventional morphological evaluation of embryos is still widely used. The purpose of the present study was to evaluate the predictive power of conventional morphological evaluation regarding blastocyst formation. Methods Retrospective evaluation of data from 15,613 patients receiving blastocyst culture from January 2013 through December 2020 in our institution were reviewed. Generalized estimating equations (GEE) were used to establish the morphology-based model. To estimate whether including more features regarding patient characteristics and cycle parameters improve the predicting power, we also establish models including 27 more features with either LASSO regression or XGbosst. The predicted number of blastocyst were associated with the observed number of the blastocyst and were used to predict the blastocyst transfer cancellation either in fresh or frozen cycles. Results Based on early cleavage and routine observed morphological parameters (cell number, fragmentation, and symmetry), the GEE model predicted blastocyst formation with an AUC of 0.779(95%CI: 0.77–0.787) and an accuracy of 74.7%(95%CI: 73.9%-75.5%) in the validation set. LASSO regression model and XGboost model based on the combination of cycle characteristics and embryo morphology yielded similar predicting power with AUCs of 0.78(95%CI: 0.771–0.789) and 0.754(95%CI: 0.745–0.763), respectively. For per-cycle blastocyst yield, the predicted number of blastocysts using morphological parameters alone strongly correlated with observed blastocyst number (r = 0.897, P

Background: Male and female gametes factors might contribute to the total fertilization failure (TFF). In first in vitro fertilization (IVF) cycles, decision-making of insemination protocol was mainly based on semen quality for the contribution of female clinical characteristics to TFF remained obscure. The purpose of the study was to evaluate the role of semen quality in predicting unexpected TFF.Methods: A single-center retrospective cohort analysis was performed on 19539 cycles between 2013 and 2021. Two algorithms, a Least Absolute Shrinkage and Selection Operator (LASSO) and an Extreme Gradient Boosting (Xgboost) were used to create models with cycle characteristics parameters. By including semen parameters or not, the contribution of semen parameters to the performance of the models was evaluated. The area under the curve (AUC), the calibration, and the net reclassification index (NRI) were used to evaluate the performance of the models.Results: The prevalence of TFF were .07 (95%CI:0.07-0.08), and .08 (95%CI:0.07-0.09) respectively in the development and validation group. Including all characteristics, with the models of LASSO and Xgboost, TFF was predicted with the AUCs of .74 (95%CI:0.72-0.77) and .75 (95%CI:0.72-0.77) in the validation group. The AUCs with models of LASSO and Xgboost without semen parameters were .72 (95%CI:0.69-0.74) and .73 (95%CI:0.7-0.75). The models of LASSO and Xgboost with semen parameters only gave the AUCs of .58 (95%CI:0.55-0.61) and .57 (95%CI:0.55-0.6). For the overall validation cohort, the event NRI values were −5.20 for the LASSO model and −.71 for the Xgboost while the non-event NRI values were 10.40 for LASSO model and 0.64 for Xgboost. In the subgroup of poor responders, the prevalence was .21 (95%CI:0.18-0.24). With refitted models of LASSO and Xgboost, the AUCs were .72 (95%CI:0.67-0.77) and .69 (95%CI:0.65-0.74) respectively.Conclusion: In unselected patients, semen parameters contribute to limited value in predicting TFF. However, oocyte yield is an important predictor for TFF and the prevalence of TFF in poor responders was high. Because reasonable predicting power for TFF could be achieved in poor responders, it may warrant further study to prevent TFF in these patients.

Bougainvillea Comm. ex Juss. (Nyctaginaceae; Bougainvillea) is a popular ornamental plant with vigorous growth, luxuriant blooming, colorful bracts, and a high tolerance to the stresses of temperature, drought, and soil pollution, and thus is widely cultivated in tropical and subtropical regions. However, the paucity of information on ploidy and the genomic constitution is a significant challenge to genome research and cultivar improvement. We present a flow cytometry method for ploidy detection in bougainvillea based on evaluating different lysates and tissues, identify the ploidy level of a batch of bougainvillea accessions, and infer the genome size of horticultural species Bougainvillea glabra, Bougainvillea spectobilis, and Bougainvillea peruviana. The results show that tender leaves and woody plant buffer (WPB) were optimal for flow cytometry analysis. The 2C nuclear DNA amounts in 176 bougainvillea accessions ranged from 4.66 ± 0.04 to 12.26 ± 0.1 pg, which represents 161 diploids, 13 triploids, 1 tetraploid, and 1 di-tetraploid mixoploid. For B. glabra, B. spectobilis, and B. peruviana, the mean 1C values were 3.201, 3.066, and 2.915 pg, respectively. The genome size of B. glabra was significantly larger than that of B. peruviana (P = 0.0004), but had no significant variation with that of B. spectobilis (P = 0.1061). These results reveal fundamental cytogenetic information for bougainvillea that are beneficial to whole-genome sequencing and hybrid breeding programs.

Objective To evaluate the immunogenicity, safety and lot-to-lot consistency of an inactivated enterovirus 71 (EV71) vaccine cultured in bioreactors with different specifications after full immunization. Methods A randomized, double-blind trial was performed in 3,000 children aged 6 ~ 35 months with six vaccine batches, which were prepared in 40 L and 150 L bioreactors for three consecutive batches respectively. Children were immunized on day 0 and 28, serum samples were collected on day 0 and 56, and neutralizing antibody titers were determined by the microcytopathic method. Immediate reactions were recorded within 30 min, local and systemic symptoms were recorded within 0 ~ 28 days, and serious adverse events were recorded within 6 months. Results After immunization with two doses of the inactivated EV71 vaccine, the neutralizing antibody GMT was 825.52 ± 4.09, and the positive conversion rate was 96.18%, with no significant difference. The 95% CI of the serum neutralizing antibody GMT ratio between the two groups after immunization with the three vaccine batches produced in the 150 L and 40 L bioreactors ranged from .67 ~ 1.5. The overall incidence of adverse reactions, mainly grade 1 reactions, for all 6 batches from 0 to 28 days after vaccination was 49.62%, with no significant difference (p = .8736). The incidence of systemic adverse reactions, primarily fever and diarrhea, was 45.14%; the incidence of local adverse reactions, primarily erythema and tenderness, was 9.43%. Conclusion The EV71 vaccine was highly immunogenic and safe in children aged 6–35 months, and 6 consecutive batches produced by the two bioreactors with different specifications were consistent.

Summary: Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration. Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345). Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%–100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%–99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%–100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%–2.86%) and -0.34% (95%CI: -2.78%–2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00–3.00) and 1.00 (95%CI: 0.75–1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines. Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated. Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.

Background: The aim of this study was to explore the significance of three-dimensional double-echo steady-state (3D-DESS) sequence and multidetector computed tomography (CT) plain scan in the diagnosis of lumbar disc herniation (LDH) remaining controversial in conventional magnetic resonance imaging (MRI), and to compare the efficiency between 3D-DESS and CT in diagnosing controversial patients by conventional MRI.Methods: A total of 61 patients with controversial LDH diagnosed by conventional MRI were collected. Before operation, the disease of these patients was further confirmed by 3D-DESS sequences and continuous CT plain scan from L3 to S1. Finally, for patients whose postoperative curative effect was marked and symptoms were obviously alleviated, the sensitivity, specificity and accuracy.Results: Among, 59 patients with remarkably relieved symptoms after operation were included, and 2 patients with varying degrees of non-remission of pain and partial dysfunction after operation were excluded. The sensitivity, specificity and accuracy of 3D-DESS were 94.6, 100 and 94.9%, respectively, and those of CT were 75.0, 33.3 and 72.9%, respectively.Conclusion: 3D-DESS is a very useful diagnostic method for patients with some special types of LDH that remain controversial in conventional imaging diagnostic methods. Through 3D-DESS, the morphology of lumbosacral nerve roots can be directly observed, which is conducive to the improvement of the sensitivity, specificity and accuracy, thus further reducing the misdiagnosis rate. Moreover, 3D-DESS plays a guiding role in the formulation of operative methods.

Abstract The Jumonji domain-containing protein-3 (JMJD3) is a histone demethylase that regulates the trimethylation of histone H3 on lysine 27 (H3K27me3). H3K27me3 is an important epigenetic event associated with transcriptional silencing. JMJD3 has been studied extensively in immune diseases, cancer, and tumor development. There is a comprehensive epigenetic transformation during the transition of embryonic stem cells (ESCs) into specialized cells or the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). Recent studies have illustrated that JMJD3 plays a major role in cell fate determination of pluripotent and multipotent stem cells (MSCs). JMJD3 has been found to enhance self-renewal ability and reduce the differentiation capacity of ESCs and MSCs. In this review, we will focus on the recent advances of JMJD3 function in stem cell fate. Video Abstract

Summary: Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an established treatment for common bile duct (CBD) stones. Post- ERCP cholecystitis (PEC) is a known complication of such procedure and there are no effective models and clinical applicable tools for PEC prediction. Methods: A random forest (RF) machine learning model was developed to predict PEC. Eligible patients at The First Hospital of Lanzhou University in China with common bile duct (CBD) stones and gallbladders in-situ were enrolled from 2010 to 2019. Logistic regression analysis was used to compare the predictive discrimination and accuracy values based on receiver operation characteristics (ROC) curve and decision and clinical impact curve. The RF model was further validated by another 117 patients. This study was registered with ClinicalTrials.gov, NCT04234126. Findings: A total of 1117 patients were enrolled (90 PEC, 8.06%) to build the predictive model for PEC. The RF method identified white blood cell (WBC) count, endoscopic papillary balloon dilatation (EPBD), increase in WBC, residual CBD stones after ERCP, serum amylase levels, and mechanical lithotripsy as the top six predictive factors and has a sensitivity of 0.822, specificity of 0.853 and accuracy of 0.855, with the area under curve (AUC) value of 0.890. A separate logistic regression prediction model was built with sensitivity, specificity, and AUC of 0.811, 0.791, and 0.864, respectively. An additional 117 patients (11 PEC, 9.40%) were used to validate the RF model, with an AUC of 0.889 compared to an AUC of 0.884 with the logistic regression model. Interpretation: The results suggest that the proposed RF model based on the top six PEC risk factors could be a promising tool to predict the occurrence of PEC. Funding: This work was supported by National Natural Science Foundation of China (8187103130; 32160255); Gansu Competitive Foundation Projects for Technology Development and Innovation (1602FKDA001); Gansu Province Science and Technology Planning Project (20YF8WA085); Science and Technology Planning Project of Chengguan District in Lanzhou (2020JSCX0043). The Foundation of The First Hospital of Lanzhou University (ldyyyn-2018-16).

Background: We aimed to evaluate the therapeutic effect of additional ursodeoxycholic acid (UDCA) with mesalazine, compared to mesalazine alone in patients with ulcerative colitis (UC). The mechanism was evaluated by monitoring the changes of IL-23-IL-17 axis and the intestinal microflora. Methods: In this prospective, single center study, patients with UC were randomly assigned to the Mesalazine group (n=20) or the UDCA + Mesalazine group (n=20). Mayo score and Inflammatory Bowel Disease Questionnaire (IBDQ), and fecal samples for 16S rRNA sequencing and blood samples for IL-23 and IL-17 ELISA were collected for analysis. Results: Mayo scores and IBDQ score of the UDCA + Mesalazine group were significantly better than those of the Mesalazine group (P = 0.015 and P < 0.001, respectively). At post-treatment week 4, IL-23 and IL-17 levels were significantly lower in the UDCA + Mesalazine group compared to those in the Mesalazine group (both P < 0.038). In patients with UC after treatment, Firmicutes in the UDCA + Mesalazine group was higher than those in the Mesalazine group (P < 0.001). The UDCA + Mesalazine group showed lower percentage of Proteobacteria compared to those in the Mesalazine group (P < 0.001). Conclusion: Additional UDCA could provide better therapeutic effects than mesalazine alone, possibly due to the change of IL-23 and IL-17 and the proportional distribution of intestinal microflora.

Abstract Background Cerebral-cardiac syndrome, newly developed cardiac damage manifestations subsequent to cerebral injuries, is a common complication of stroke and leads to increased morbidity and mortality. The current study is aimed to develop a risk prediction scale to stratify high-risk population of CCS among ischemic stroke patients. Methods The study included 410 cases from four tertiary medical centers from June 2018 to April 2019. The risk prediction model was established via logistic regression from the derivation cohort including 250 cases admitted between June 2018 and December 2018. Another 160 cases admitted from January 2019 to April 2019 were included as the validation cohort for external validation. The performance of the model was determined by the area under curve of the receiver operating characteristic curve. A rating scale was developed based on the magnitude of the logistic regression coefficient. Results The prevalence of CCS was 55.2% in our study. The predictive model derived from the derivation cohort showed good calibration by Hosmer-Lemeshow test (P = 0.492), and showed sensitivity of 0.935, specificity of 0.720, and Youden index of 0.655. The C-statistic for derivation and validation cohort were 0.888 and 0.813, respectively. Our PANSCAN score (0 to 10 points) was then established, which consists of the following independent risk factors: PT(12 s–14 s = 0; otherwise = 1), APTT(30s–45s = 0, otherwise = 1), Neutrophils(50–70% = 0; otherwise = 1), Sex(female = 1), Carotid artery stenosis(normal or mild = 0; moderate to severe = 2), Age(≥65 years = 1), NIHSS score(1 to 4 = 2; ≥5 = 3). Patients scored 3 or more points were stratified as high risk. Conclusion The risk prediction model showed satisfactory prediction effects. The PANSCAN scale provides convenient reference for preventative treatment and early management for high-risk patients. Trial registration The study was retrospectively registered in Chinese Trial Registry. The date of registration is April 17, 2019. Trial registration number: ChiCTR1900022587 .

This study aims to effectively control the effects of blast vibrations and improve the safety factor for personnel and facilities in blasting engineering. Using high-precision digital electronic detonators according to the propagation and superposition principle of blasting vibration signals, a superposition prediction method based on single-hole blasting vibration waveform is proposed to determine the group-hole blasting vibration waveform. Experimental results show that the variation law of the predicted blasting vibration wave is consistent with that of the measured blasting vibration wave, and the error rate is less than 16%. Based on the proposed superposition prediction method, the variation law of particle vibration velocity peak with micro-differences in time is studied. Consequently, an optimal differential time interval (delay time) is obtained with regard to the blasting vibration reduction. The results are applied in a site leveling project, and the results show that the slight time difference between zones has an evident effect on vibration reduction. The maximum reduction achieved with the proposed method is superior (69.7%) to that obtained via other controlled blasting delay methods. This result has been successfully applied in a flat project in China.

BackgroundCilostazol is often used in Asia-Pacific countries for stroke prevention. The current systematic review and meta-analysis aimed to evaluate the effectiveness, safety, and adverse outcomes of cilostazol monotherapy compared to aspirin monotherapy for secondary stroke prevention.MethodsThe researchers conducted a comprehensive research in multiple databases (PubMed, Embase, and Cochrane library) of randomized controlled trials from conception to December 2020. The primary efficacy outcome was the occurrence of any stroke, the primary safety outcome was the bleeding risk, and the primary adverse outcome was the rate of headache and dizziness. The Mantel-Haenszel method was used to calculate a random-effects prediction. Cilostazol and aspirin were compared using a pooled risk assessment with 95% CIs.ResultsSix studies involving 5,617 patients were included in this review. Compared with aspirin monotherapy, cilostazol was associated with significantly lower rates of any strokes (RR: 0.67; 95% CI: 0.55–0.82) and significantly lower bleeding rates [risk ratio (RR): 0.53; 95% CI: 0.37–0.74]. However, compared with aspirin monotherapy, cilostazol was associated with significantly higher rates of headache (RR: 1.77; 95% CI: 1.41–2.20) and dizziness (RR: 1.28; 95% CI: 1.08–1.52).ConclusionsConsistent with previous studies, cilostazol monotherapy is superior to aspirin monotherapy in reducing the rate of any strokes and the bleeding risk after having a stroke. However, the use of cilostazol monotherapy is associated with several adverse life outcomes such as headaches and dizziness.

Purpose The direct anterior approach (DAA) for total hip arthroplasty (THA) can be performed with patients in either in the lateral decubitus or supine position. Prompted by the lack of studies addressing differences between the two positions, this investigation aimed to examine clinical and radiographic outcomes and compare the lateral decubitus versus the supine position for THA using the DAA. Methods Between January 1 and October 1, 2020, 90 patients who underwent primary unilateral THA using the DAA were recruited, with 54 (60%) undergoing THA in the supine position (SP group) and 36 (40%) in the lateral decubitus position (LP group). Technical information, clinical and radiographic outcomes, and patient-reported outcomes, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short-Form-12 (SF-12) were evaluated. All data were subjected to several statistical tests. Results There were no preoperative differences in baseline characteristics between the LP and SP groups, which were also similar in terms of operative duration, length of hospital stay, and blood loss. Radiographic assessment confirmed satisfactory positioning of the prosthesis in both groups. There were no significant differences in terms of CK-MB and hemoglobin levels, Harris Hip Score, WOMAC, UCLA, visual analog scale score, and SF-12. The incidence of complications in the LP group was lower than in the SP group. Conclusion Total hip arthroplasty performed via DAA in the LP and SP groups yielded excellent clinical outcomes, although the incidence of complications in the former was lower than in the latter.

Accumulating evidence has showed that sushi-repeat-containing protein X-linked 2 (SRPX2) is an abnormal expression in a variety of cancers and involved in cancer carcinogenesis, chemosensitivity, and prognosis, which mainly promote cancer cell metastasis, invasion, and migration by regulating the uPAR/integrins/FAK signaling pathway, epithelial-mesenchymal transition (EMT), angiogenesis, and glycosylation. Inflammation has been regarded as a key role in regulating cancer initiation, progression, EMT, and therapeutics. Furthermore, SRPX2 exhibited excellent antifibrosis effect via the TGFβR1/SMAD3/SRPX2/AP1/SMAD7 signaling pathway. Therefore, this review provides compelling evidence that SRPX2 might be a therapeutic target for inflammation and cancer-related inflammation for future cancer therapeutics.

Abstract The effects of global warming on crop production have received great attention in recent years. However, inconsistent results have been obtained with regard to major crops such as rice and wheat in rice–wheat rotation systems of China. Therefore, we undertook a comprehensive meta‐analysis of literature data. The yield response to warming differed for rice and wheat in the rice–wheat rotation system. Overall, warming significantly increased wheat yield (by 4.8%) but significantly reduced rice yield (by 14.8%). A number of factors were responsible for these observations. For example, rice yield responses varied with the temperature increase, variety and nitrogen (N) rate. Of these, N was the most important variable influencing yield responses to warming. The yield loss for rice was lower at temperature increases of 0.40–1.40°C and at a high N rate than that at temperature increases of 1.60–2.49°C and at a low N rate, respectively. The yield loss of indica rice was lower than that of japonica rice. For wheat, however, yield responses to warming varied with the warming regime, ambient temperature, temperature increases, and CO2 concentrations. Of these factors, ambient temperature was the most important variable influencing yield in response to warming. Warming increased wheat yield at a mean growth season temperature ≤10°C, temperature increases of 0.80–1.50°C, and at ambient CO2 concentrations. In addition, either daytime warming or nighttime warming significantly increased wheat yield. However, all‐day warming had no effect on wheat yields. We conclude that global warming will benefit wheat production but result in a serious loss of rice yield in rice–wheat rotations in China.

Rice growth is constantly challenged by severe environmental conditions, especially high-temperature stress, brought about by global warming. How to increase rice yields is a current issue in many countries. By analyzing the meteorological data from Anhui Province over the past 60 years, the frequency and level of high-temperature damage were comprehensively analyzed. On this basis, five indica rice varieties with strong high-temperature tolerance, relatively high yield and stable yield were selected by laboratory-simulated high-temperature and field high-temperature experiments: Longliangyou Huazan (LLYHZ), 9you-6 (9Y-6), Longliangyou-1988 (LLY-1988), Fengliangyou-4 (FLY-4) and Huanghuazan (HHZ). These are suitable for planting in the middle and lower reaches of the Yangtze River. This study provides a theoretical reference and scientific basis for the study of rice tolerance to high-temperature stress.

Rice (Oryza sativa L.) is cultivated in a wide range of climatic conditions, thereby inducing great variations in the rice growth, yield and quality. However, the comprehensive effects of temperature and solar radiation under different ecological regions on the rice growth, yield and quality are not well understood, especially in a middle rice cropping system. The rice growth, yield- and quality-related traits were investigated under different ecological regions. Among different areas, the days before the heading stage and after the heading stage of six cultivars ranged from 80 to 120 and from 30 to 50. The gaps of the grain yield, head rice rate, chalky grain rate and chalkiness level were about 1.2–52.4%, 1.0–3.0%, 2.7–12.7% and 0.3–4.5%, respectively. This study demonstrated that in these regions, temperature is a limiting factor compared with radiation. Moreover, the rice growth, yield and quality were closely associated with daily air (DT), maximum (MaT), minimum (MiT) and effective accumulated temperatures (EAT). An excellent rice growth, a high grain yield and an excellent quality could be achieved if the EAT was higher than 1592 °C·d and the MiT was lower than 23.1 °C before the heading stage, and if the DT, MiT and MaT were lower than 25.7 °C, 22.0 °C and 30 °C after the heading stage, respectively. These findings served as an important reference for optimizing cultivar selection for a specific area and determining suitable areas for a certain variety.

Coalbed gas (CBG) has been widely used as an important energy source. However, its utilization and allocation system is imperfect in mining areas. During the utilization process, a large amount of CBG is discharged into the air, causing environmental pollution. In this study, we proposed a “full spectrum-domain-time” CBG utilization model. In this model, by combining high methane concentration gas power generation, low methane concentration gas purification, and ultra-low methane concentration gas thermal storage and oxidation utilization, we were able to utilize CBG with full-spectrum of methane concentrations. In addition, by establishing CBG transportation and storage system in mining area, we were able to realize CBG supply in the entire network domain. Furthermore, based on the time series prediction algorithm, the CBG demand of different mining areas is predicted and regulatorily met by real time allocation. Through these three steps, an efficient “full spectrum-domain-time” CBG utilization system was formed and practically applied in Yangquan mining area. The application results showed that under the comprehensive control of “full spectrum-domain-time” CBG utilization model, CBG with methane concentration ≥0.2% could be used in the mining area and its utilization rate increased year by year, reaching the highest of 77.15%. Overall, our study provided a reference for the efficient CBG utilization in the mining area.