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To solve the problem of phased-array radar individual identification in the complex electromagnetic environment with wide spectrum, heterogeneous waveforms and strong energy, an unintentional modulation feature extraction method based on phase and frequency fusion was proposed for the individual features carried by phased-array radar signals. Considering that the phased array radar signal was difficult to collect, the number of transceiver components was large, and the unintentional modulation features were complex, the phased array radar unintentional modulation signal model was constructed based on the method of wave-position orchestration and isophase surface. Based on the bispectral method, the signal bispectral map was obtained and perimeter integration was performed to extract the unintentionally modulated phase features of the signal. Based on the variational modal decomposition method, the original signal was decomposed to obtain the modal components, and the energy ratio difference of the set of modal components was further computed to extract the unintentionally modulated frequency features of the signal. Finally, the local holding projection method was used to integrate the phase and frequency features, and the K nearest-neighbor classification method was adopted based on the tree retrieval method to realize the individual identification. Representative numerical results are reported, indicating that the proposed method has higher recognition accuracy and efficiency.

Background Japanese encephalitis (JE) is a severe infectious disease of the central nervous system. Vaccination with Vero cell culture-derived vaccines may effectively reduce JE incidence.Research Design and Methods In this single-center, randomized, blinded, positive-controlled clinical trial in China involving 600 healthy infants aged 6–11 months, participants were divided into experimental and control groups administered JEV-PI and JEV-LI, respectively. Antibody titers were determined after 0- and 7-day immunization schedules. A booster dose followed 12 months later.Results After primary vaccination and before booster vaccination, the positive conversion rate, geometric mean titer (GMT), and geometric mean increase (GMI) of JEV-PI-neutralizing antibodies exceeded those of JEV-LI. After booster immunization, the GMT and GMI of JEV-PI were higher than those of JEV-LI. After primary immunization, the local, systemic, and overall adverse reactions were of grades 1 and 2, with a low incidence of grade 3. After booster immunization, these differences were mainly grades 1 and 2, with no differences between JEV-PI and JEV-LI.Conclusion JEV-PI is a promising vaccine as infants acquired long-lasting and highly neutralizing immune antibodies after inoculation with JEV-PI.Trial Registration The trial was registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj = 203130; registration number: ChiCTR2300074692; registration date: 14/08/2023).

Abstract Background Delirium is one of the most common neurological complications after cardiac surgery. The purpose of our study was to assess the relationship between perioperative blood pressure variability (BPV) and postoperative delirium (POD) in the patients undergoing cardiac surgery. Methods Adult patients received cardiac surgery and stayed in Cardiovascular Intensive Care Unit (ICU) for more than 24 h after surgery during the study period between June 2019 and December 2022 were included in this study. Baseline characteristics, perioperative hemodynamic variables and postoperative laboratory results of the cardiac patients were collected and analyzed. Perioperative BPV was quantified by calculating the standard deviation (SD) and average real variability (ARV) of blood pressure. Assessment of delirium was based on the mental status of the patients and CAM-positive. The relationship between perioperative BPV and POD was analyzed by LASSO and logistic regression using R (R package, 4.3.2). Results The incidence of POD was 15.0% (324/2164) in the patients receiving cardiac surgery, and the average day for POD occurred at day 3 after surgery. Patients with POD had statistically lower levels of intraoperative mean blood pressure (P = 0.015) and blood pressure ARV (P

The paper analyzed the current state of China's grain supply chain in 2023, highlighting the continuous innovations in various aspects, including production, import and export, storage, transportation, processing, and sales. It summarized the exploration of various supply chain models in practice, such as the futures market, group enterprises, wholesale markets (National Grain Trade Centers), logistics companies, new retail enterprises, digital technology companies, production bases, fertilizer companies, exhibitions, "grain logistics channels," provincial regional brands, and the grain logistics supply chain, etc. The paper analyzed the existing problems in China's grain supply chain innovation and application, and identified seven major trends in the development of the grain supply chain, namely digitalization, greening, safety, globalization, coordination, intelligence, and standardization. It also put forward policy recommendations for China's grain supply chain innovation.

Abstract Background Primary screening for high-risk human papillomavirus (hrHPV) with cytological triage for women with non-16/18 hrHPV-positive status has become popular in China. However, cytology relies on the subjective judgment of pathologists, leading to inconsistent clinical performance. Methods A total of 657 hrHPV-positive women aged 25–64 years were enrolled in this cross-sectional study. All participants underwent colposcopic biopsy after cytology triage, with cytology residual specimens undergoing DNA methylation testing. CIN2+ and CIN3+ sensitivity and specificity were compared between the different triage strategies (n=487): PAX1 methylation (PAX1 m ) , Glycophorin C methylation (GYPC m ), cytology, and combinations between them or with HPV16/18. Results The area under the receiver operating characteristic curves (AUCs) for PAX1 m and GYPC m in detecting CIN2 or worse (CIN2+) were 0.867 (95% confidence interval [CI]: 0.796–0.937) and 0.873 (95% CI: 0.808–0.938), respectively. The sensitivities of PAX1 m and GYPC m were consistent with those of cytology for both CIN2+ and CIN3+ detection. The relative specificities of PAX1 m and GYPC m for CIN2+ detection compared to cytology were 2.83 (95% CI: 2.33–2.45) and 3.09 (95% CI: 2.40–3.98), respectively. The relative specificities of combining HPV 16/18 with PAX1 m and GYPC m for CIN2+ detection compared to cytology were 3.38 (95% CI: 2.96–3.86) and 3.67 (95% CI: 3.15–4.27), respectively. Compared to low levels of DNA methylation, high levels of PAX1 m and GYPC m resulted in odd ratios (ORs) of 57.66 (95% CI: 13.57–409.12, p < 0.001) and 23.87 (95% CI: 6.49–115.42, p < 0.001) for CIN3+, adjusted for HPV 16/18 and cytology results. Conclusions PAX1 m and GYPC m demonstrated superior ability to identify cervical precancerous lesions and cervical cancer, with AUC values exceeding 0.85. For detecting CIN2+/CIN3+ in women with hrHPV-positive status, DNA methylation (combined with HPV 16/18) showed higher specificity than cytology (combined with HPV 16/18) and is a potential molecular biomarker for detecting cervical (pre)cancer.

Abstract Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

Abstract Background Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. Methods Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. Results Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. Conclusions Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

Abstract Background The risk of cervical cancer progression in high-risk human papillomavirus (HR-HPV)-positive women is associated with cervical lesion severity and molecular heterogeneity. Classification systems based on p16 and Ki67 expression cumulative scores (0–3 each)—p16/Ki67 collectively known as an immunoscore [IS]—are an accurate and reproducible method for grading cervical intraepithelial neoplasia (CIN) lesions. Meanwhile, DNA methylation is an early event in the development of cervical cancer. Hence, this study evaluated the relationship among CIN, p16/Ki-67 IS, and PAX1/ZNF582 methylation. Methods In this study, 414 HPV-positive paraffin-embedded specimens were collected, and PAX1/ZNF582 methylation and the p16/ki67 IS were determined. A total of 43 invalid samples were excluded and 371 were included in the statistical analyses. There were 103 cervicitis, 95 CIN1, 71 CIN2, 89 CIN3, and 13 squamous cell carcinoma (SCC) cases. The association between PAX1/ZNF582 methylation and p16/Ki6 immunohistochemical staining scores was analyzed. Results The ΔCp of PAX1 m (PAX1 methylation) and ZNF582 m (ZNF582 methylation) decreased with cervical lesion severity (Cuzick trend test, all P

Abstract Background Acute kidney injury (AKI) is a major complication following cardiac surgery. We explored the clinical utility of iron metabolism indexes for identification of patients at risk for AKI after cardiac surgery. Methods This prospective observational study included patients who underwent cardiac surgery between March 2023 and June 2023. Iron metabolism indexes were measured upon admission to the intensive care unit. Multivariable logistic regression analyses were performed to explore the relationship between iron metabolism indexes and cardiac surgery-associated AKI (CSA-AKI). Receiver operating characteristic (ROC) curve was used to assess the predictive ability of iron, APACHE II score and the combination of the two indicators. Restricted cubic splines (RCS) was used to further confirm the linear relationship between iron and CSA-AKI. Results Among the 112 recruited patients, 38 (33.9%) were diagnosed with AKI. Multivariable logistic regression analysis indicated that APACHE II score (odds ratio [OR], 1.208; 95% confidence interval [CI], 1.003–1.455, P = 0.036) and iron (OR 1.069; 95% CI 1.009–1.133, P = 0.036) could be used as independent risk factors to predict CSA-AKI. ROC curve analysis showed that iron (area under curve [AUC] = 0.669, 95% CI 0.572–0.757), APACHE II score (AUC = 0.655, 95% CI 0.557–0.744) and iron and APACHE II score combination (AUC = 0.726, 95% CI 0.632–0.807) were predictive indicators for CSA-AKI. RCS further confirmed the linear relationship between iron and CSA-AKI. Conclusions Elevated iron levels were independently associated with higher risk of CSA-AKI, and there was a linear relationship between iron and CSA-AKI.

BackgroundHuman papillomavirus (HPV) infection is a worldwide reproductive system disease. Baofukang suppository, a traditional herbal preparation that includes curdione and borneol, has been reported to treat bacterial vaginosis (BV) and HPV infection in China. However, the therapeutic mechanism is still unknown. This study aims to explore the molecular mechanisms of curdione and borneol in treating HPV infection.MethodsWe conducted a retrospective cohort analysis of medical records from a single-center study involving 205 HPV patients, focusing on the correlation between HPV clearance and co-infection with other pathogens, confirming the efficacy of Baofukang suppository. Bioinformatics and network pharmacology approaches were employed to identify therapeutic targets of Baofukang suppository for BV/HPV co-infections. qRT-PCR, Western blot, immunofluorescence staining, and flow cytometry were utilized to validate the therapeutic targets of curdione and borneol, along with the associated immune molecular changes. Finally, the molecular mechanisms and therapeutic efficacy of curdione and borneol were confirmed in vivo using an LPS/TC-1 cervical orthotopic injection model.ResultsCurdione and borneol selectively inhibit the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) by macrophages. The reduction in IL-6 and IL-1β levels effectively inhibits the expression of CD274 (Programmed death ligand 1, PD-L1) in infected epithelial cells by inhibiting STAT3 phosphorylation, thereby suppressing their immune evasion capabilities. Furthermore, curdione and borneol enhance the expression of tumor necrosis factor α (TNF-α) and caspase 1 (CASP1) in macrophages, as well as the expression of interleukin 12 (IL-12) and interleukin 23 (IL-23) in dendritic cells (DCs). The expression of these inflammatory factors effectively promotes the migration and differentiation of T cells to the site of infection, completing the clearance of infected epithelial cells.ConclusionThe main components of Baofukang suppository, curdione and borneol, inhibit the progression of HPV infection and the occurrence of cervical cancer by modulating the communication between innate and adaptive immunity, promoting the recruitment and recognition of CD8+ T cells to eliminate HPV-infected epithelial cells.

BackgroundTuberculosis (TB) is a leading cause of death worldwide from a single infectious agent. In China the most common extra-pulmonary TB (EPTB) is pleural tuberculosis (PLTB). An important clinical feature of PLTB is that the lymphocytes associated with TB will accumulate in the pleural fluid. The adaptive immune repertoires play important roles in Mycobacterium tuberculosis (Mtb) infection.MethodsIn this study, 10 PLTB patients were enrolled, and their Peripheral Blood Mononuclear Cells(PBMCs) and Pleural Effusion Mononuclear Cells(PEMCs) were collected. After T cells were purified from PBMCs and PEMCs, high-throughput immunosequencing of the TCRβ chain (TRB), TCRγ chain(TRG), and B cell receptor(BCR) immunoglobulin heavy chain (IGH) were conducted on these samples.ResultsThe TRB, TRG, and BCR IGH repertoires were characterized between the pleural effusion and blood in PLTB patients, and the shared clones were analyzed and collected. The binding activity of antibodies in plasma and pleural effusion to Mtb antigens was tested which indicates that different antibodies responses to Mtb antigens in plasma and pleural effusion in PLTB patients. Moreover, GLIPH2 was used to identify the specificity groups of TRB clusters and Mtb-specific TRB sequences were analyzed and collected by VJ mapping.ConclusionWe characterize the adaptive immune repertoires and identify the shared clones and Mtb-specific clones in pleural effusion and blood in PLTB patients which can give important clues for TB diagnosis, treatment, and vaccine development.

Abstract Background Delirium is a common disorder affecting patients’ psychiatric illness, characterized by a high rate of underdiagnosis, misdiagnosis, and high risks. However, previous studies frequently excluded patients with psychiatric illness, leading to limited knowledge about risk factors and optimal assessment tools for delirium in psychiatric settings. Objectives The scoping review was carried out to (1) identify the risk factors associated with delirium in patients with psychiatric illness; (2) synthesize the performance of assessment tools for detecting delirium in patients with psychiatric illness in psychiatric settings. Design Scoping review. Data sources PubMed, Web of Science, and Embase were searched to identify primary studies on delirium in psychiatric settings from inception to Dec 2023 inclusive. Two independent reviewers screened eligible studies against inclusion criteria. A narrative synthesis of the included studies was conducted. Results A final set of 36 articles meeting the inclusion criteria, two main themes were extracted: risk factors associated with delirium in patients with psychiatric illness and assessment tools for detecting delirium in psychiatric settings. The risk factors associated with delirium primarily included advanced age, physical comorbid, types of psychiatric illness, antipsychotics, anticholinergic drug, Electroconvulsive therapy, and the combination of lithium and Electroconvulsive therapy. Delirium Rating Scale-Revised-98, Memorial Delirium Assessment Scale, and Delirium Diagnostic Tool-Provisional might be valuable for delirium assessment in patients with psychiatric illness in psychiatric settings. Conclusions Delirium diagnosis in psychiatric settings is complex due to the overlapping clinical manifestations between psychiatric illness and delirium, as well as their potential co-occurrence. It is imperative to understand the risk factors and assessment methods related to delirium in this population to address diagnostic delays, establish effective prevention and screening strategies. Future research should focus on designing, implementing, and evaluating interventions that target modifiable risk factors, to prevent and manage delirium in patients with psychiatric illness.

Abstract Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. However, the predictive value of single indictor still remains controversial. This study aimed to assess the predictive value of combining preoperative left atrial volume index (LAVI) and postoperative interleukin-6 (IL-6) for POAF in the patients receiving cardiac surgery. Methods Patients who admitted to Nanjing First Hospital during the study period between December 2022 and June 2023, and underwent open-heart surgery without a history of atrial fibrillation (AF) were enrolled. The relationships between predictors and POAF were investigated using logistic regression analysis. We determined the combined predictive value of LAVI and IL-6 for POAF by measuring the changes in the area under the receiver operating characteristic curve (AUC) and calculating the net reclassification improvements (NRIs) and integrated discrimination improvement (IDIs). Results 102 patients were enrolled in this study, and 50 participants developed POAF (49.0%). Patients who experienced POAF had higher levels of preoperative LAVI and postoperative IL-6 than those who did not. Regression analysis revealed that larger LAVI and higher level of IL-6 were independently associated with increased risk of POAF. The combined addition of LAVI and IL-6 to the predictive model resulted in an evident increase in the AUC. Incorporating both LAVI and IL-6 increased IDIs in all models. Conclusion Our results demonstrated that combined LAVI and IL-6 achieved a higher prediction performance for POAF.

【Objective】In the Low Earth Orbit (LEO) satellite Internet of Things (IoT) scenario, the time delay and power consumption requirements of Narrowband (NB) -IoT terminal in wide coverage area vary due to different business scenarios. However, the ground NB-IoT terminal with a single business scenario adopts a fixed working state timer parameter configuration method, which cannot meet the needs of time delay and power consumption for multi-scenario terminals in large geographical areas of LEO satellite IoT.【Methods】In response to the wide coverage characteristics of LEO satellite IoT, the problem of different delay and power consumption requirements for terminal multi-scenario application services in LEO satellite IoT scenarios, this article proposes a method based on a simplified interaction process and Markov chain model for terminal work state switching. The method uses system downlink delay and terminal power consumption as Non-dominated Sorting Genetic Algorithms-Ⅱobjective functions to obtain a set of Pareto optimal solutions for multiple scenario frontiers. Furthermore, it selects working state timer parameters from the Pareto frontier to configure terminals online that meet different scenario delay and power consumption requirements.【Results】The simulation results show that the multi-objective optimization method proposed in this paper can globally optimize the timing parameters of the working state timer, and overcome the shortcomings of traditional methods such as exhaustive search falling into local optima. Additionally, it has been verified that simplifying the random access interaction process can effectively reduce terminal delay and power consumption.【Conclusion】The multi-objective optimization method proposed in this paper can obtain the working state timer parameters of the terminal in various scenarios of LEO satellite IoT.

Abstract Despite the dominance of lead-based piezoelectric materials with ultrahigh electric-field-induced strain in actuating applications, seeking eco-friendly substitutes with an equivalent performance remains an urgent demand. Here, a strategy of regulating the irreversible non-180° domain via phase engineering is introduced to optimize the available strain (the difference between the maximum strain and the remnant strain in a unipolar strain curve) in the lead-free potassium–sodium niobate-based piezoelectric ceramics. In situ synchrotron X-ray diffraction and Rayleigh analysis reveal the contribution of the non-180° domain to available strain in the tetragonal–orthorhombic–rhombohedral phase boundary. The reducing orthorhombic phase and increasing rhombohedral/tetragonal phase accompanied by the reduced irreversible non-180° domain are obtained with increasing doping of Sb5+, resulting in an enlarged available strain due to the significantly lowered remnant strain. This optimization is mainly attributed to the reduced irreversible non-180° domain wall motion and the increased lattice distortion, which are beneficial to decrease extrinsic contribution and enhance intrinsic contribution. The mesoscopic structure of miniaturized nanosized domain with facilitated domain switching also contributes to the enhancement of available strain due to the improved random field and decreased energy barrier. The study will shed light on the design of lead-free high-performance piezoelectric ceramics for actuator applications.

A single crystal of potassium tantalum niobate was chosen to deposit high quality diamond thin films by microwave plasma chemical vapor deposition (MPCVD) techniques. The surface morphologies and microstructures of the as-deposited diamond films were characterized by XRD, SEM, and Raman spectroscopy. The photocatalytic properties of the samples were studied. A TaC transition layer was identified during the deposition of diamond. Additionally, it was observed that as the deposition time prolonged, the quality of the diamond film improved. All film samples showed good ability to degrade Rhodamine B, with the degradation rate of the film deposited for 12 h being 0.29 times higher, corresponding to a 1.6 times greater degrading speed of Rhodamine B compared to the film deposited for 3 h. This research introduces a novel substrate for depositing polycrystalline diamond and explores its application in photocatalysis.

Abstract Background Nursing interns often experience lots of challenges during their clinical nursing internships, which can adversely affect career decisions and result in a squandering of nursing education resources. Patient safety attitudes, professional identity and climate of caring may affect nursing interns’ clinical experience. However, more evidence is requested to validate these relationships for nursing educators to develop effective education programs and facilitate interns’ successful transition. Methods This was a cross-sectional study, which used a convenience sampling method to recruit 387 nursing interns during December 2022 to April 2023 in university affiliated hospital in Hunan province, China. Data were collected using standardized scales. Spearman correlation and multiple regression analysis were employed to examine the relationship between transition shock, patient safety attitudes, professional identity, and climate of caring. Results Nursing interns experienced transition shock at a moderate level and the highest levels of transition shock in response to overwhelming practicum workloads, with the second being related to the conflict between theory and practice. Transition shock was negatively correlated with patient safety attitudes, professional identity and climate of caring among nursing interns. Conclusions Nursing managers and educators need to value the transition shock experienced by nursing interns. Our study suggests that developing a strong sense of professional identity and a positive attitude toward patient safety can be effective in reducing the level of transition shock among nursing interns. In addition, a caring climate within the nursing unit can significantly enhance the overall experience of nursing interns. This can be achieved by enhancing the support of clinical mentors, providing patient safety-focused education, and facilitating team communication among nurses.

In this paper, we continue to build an ultra-high speed laser schlieren testing system on the self-developed mesoscale explosion pipeline to explore the flame propagation characteristics of nitrogen and carbon dioxide inhibiting gas/air premixed gas deflagration under different injection positions and pressures. The results show that: in the experiment of inert gas inhibiting gas/air premixed gas deflagration, with the gradual increase of injection pressure, the flame propagation speed shows a trend of first increasing and then decreasing, the flame shape also gradually stretches and deforms from fingertip shape, and the middle protruding part becomes smaller until it is nearly flat; the maximum flame propagation speed of CO2 injection near the ignition end is 20.79% lower than that of N2 injection far away from the ignition end, and 20.25% lower than that of N2 injection; when CO2 is injected far from the ignition end, the minimum flame speed is 9.68% lower than that of CO2 injection, and 12.86% lower than that of N2 injection; compared with the two kinds of flame retarding and explosion inhibition gases, the highest flame propagation speed of CO2 sprayed near the ignition end is 21.78% lower than that of N2, and the lowest flame propagation speed is 1.82% lower than that of N2. The highest flame velocity and the lowest flame velocity are 21.25% and 5.27% lower than N2 when CO2 is sprayed at the far ignition end.

Hypophthalmichthys nobilis are widely distributed in the Yangtze River basin and its related lakes. They are an important economic fish species and are a famous cultured species known as the “Four Famous Domestic Fishes” in China. Currently, with the fishing ban in the Yangtze River basin, fishing for H. nobilis in the natural water bodies of the Yangtze River basin has been completely prohibited. In order to identify the sources of H. nobilis appearing in the market, further control and accountability is necessary to trace the sources of H. nobilis in the Yangtze River basin and its related water bodies. Therefore, this study identified and traced different sources of H. nobilis through muscle element fingerprint analysis (EFA). The results show that H. nobilis from different stations have characteristic element compositions. The characteristic element of H. nobilis from Wuhan (WH) is Pb, which is significantly higher than that in other stations; the characteristic element from Anqing (AQ) is Hg, which is significantly higher than that in other stations; and the characteristic element from Taihu (TH) is Al, which is significantly higher than that in other water areas. Multivariate analysis selected different spatial distribution patterns in four discriminative element ratios (Pb/Ca, Cr/Ca, Na/Ca, and Al/Ca) in the muscle of H. nobilis in the Yangtze River basin and its related lakes. This study suggests that the screened discriminative elements can be used to visually distinguish different sources of H. nobilis and to quickly trace and verify the origin of newly emerging samples. Therefore, the use of selected discriminative element fingerprint features to trace the origin of new samples has been proven to be feasible. By further discriminating and verifying the muscle element fingerprints of new samples, the discrimination rate is high. Therefore, a multivariate analysis of muscle element fingerprints can be used for tracing the origins of samples of unknown origin in market supervision.

Background: There are limited population studies on the neurodevelopmental effects of bisphenol F (BPF), a substitute for bisphenol A. Furthermore, the role of placental estradiol as a potential mediator linking these two factors remains unclear. Objective: To examine the association between maternal prenatal BPF exposure and infant neurodevelopment in a prospective cohort study and to explore the mediating effects of placental estradiol between BPF exposure and neurodevelopment in a nested case-control study. Methods: The prospective cohort study included 1077 mother-neonate pairs from the Wuhu city cohort study in China. Maternal BPF was determined using the liquid/liquid extraction and Ultra-performance liquid chromatography tandem mass spectrometry method. Children's neurodevelopment was assessed at ages 3, 6, and 12 months using Ages and Stages Questionnaires. The nested case-control study included 150 neurodevelopmental delay cases and 150 healthy controls. Placental estradiol levels were measured using enzyme-linked immunosorbent assay kits. Generalized estimating equation models and robust Poisson regression models were used to examine the associations between BPF exposure and children's neurodevelopment. In the nested case-control study, causal mediation analysis was conducted to assess the role of placental estradiol as a mediator in multivariate models. Results: In the prospective cohort study, the pregnancy-average BPF concentration was positively associated with developmental delays in gross-motor, fine-motor, and problem-solving ( ORtotal ASQ: 1.14(1.05, 1.25), ORgross-motor: 1.22(1.10, 1.36), ORfine-motor: 1.19(1.07, 1.31), ORproblem-solving: 1.11(1.01, 1.23)). After sex-stratified analyses, pregnancy-average BPF concentration was associated with an increased risk of neurodevelopmental delays in the gross-motor (ORgross-motor:1.30(1.12, 1.51)) and fine-motor (ORfine-motor: 1.22(1.06, 1.40)) domains in boys. In the nested case-control study, placental estradiol mediated 16.6% (95%CI: 4.4%, 35.0%) of the effects of prenatal BPF exposure on developmental delay. Conclusions: Our study supports an inverse relationship between prenatal BPF exposure and child neurodevelopment in infancy, particularly in boys. Decreased placental estradiol may be an underlying biological pathway linking prenatal BPF exposure to neurodevelopmental delay in offspring.

Abstract Background This study used next‐generation sequencing (NGS) to investigate the genetic profiles in cerebrospinal fluid (CSF), plasma, and tumor tissue to explore alternative detection methods for anaplastic lymphoma kinase (ALK) rearrangement status and potential resistance mechanisms to ALK inhibitors. Methods From January 2016 to January 2021, 19 non‐small cell lung cancer (NSCLC) patients with brain metastases (BMs) and ALK‐positive primary tumors were enrolled at Beijing Chest Hospital. CSF, plasma, and primary tumor samples from patients with BMs of NSCLC were tested using NGS with a 168‐gene panel. The intracranial response and prognosis were also investigated. Results The study included 19 patients, seven females and 12 males, aged between 29 and 68 (median age 44). CSF cytology was negative in all cases. NGS results showed ALK fusion genes detected in 26.3% (5/19) of CSF cfDNA samples, 78.9% (15/19) of plasma samples, and 89.5% (17/19) of tumor samples from ALK‐positive patients. ALK‐positive CSF samples had significantly higher allele fractions in CSF cfDNA compared with the other two sample types. In five patients with ALK‐positive in CSF, after receiving ALK inhibitors ± local treatment, one case achieved an intracranial complete response, and two had an intracranial partial response. In CSF samples, the intracranial median progression‐free survival was 8.0 and 18.0 months for ALK‐positive (n = 5) and ALK‐negative (n = 14), respectively (p = 0.077). Conclusion CSF may serve as a liquid biopsy for ALK‐positive lung cancer with BMs by detecting cfDNA within CSF to characterize driver and resistant genes.

Abstract In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independent of tissue morphology or conventional immunohistochemistry (IHC) markers is required. We analyzed the lipid profiles of resected primary lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) specimens using liquid chromatography-tandem mass spectrometry. The specimens of 26 ADC and 18 SQCC cases were evenly assigned to the discovery and validation cohorts. Non-target screening on the discovery cohort identified 96 and 13 lipid peaks abundant in ADC and SQCC, respectively. Among these 109 lipid peaks, six and six lipid peaks in ADC and SQCC showed reproducibility in target screening on the validation cohort. Finally, we selected three and four positive lipid markers for ADC and SQCC, demonstrating high discrimination abilities. In cases difficult to diagnose by IHC staining, [cardiolipin(18:2_18:2_18:2_18:2)-H]− and [triglyceride(18:1_17:1_18:1) + NH4]+ showed the excellent diagnostic ability for ADC (sensitivity: 1.00, specificity: 0.89, accuracy: 0.93) and SQCC (sensitivity: 0.89, specificity: 0.83, accuracy: 0.87), respectively. These novel candidate lipid markers may contribute to a more accurate diagnosis and subsequent treatment strategy for unresectable NSCLC.

Skull base surgery is an important branch of neurosurgery that focuses on the surgical treatment of skull base lesions. This field requires a high degree of specialization and a high technical level. Skull base surgeons must be skilled and experienced while maintaining high ethical standards to ensure patients receive the best results. This article intends to systematically illustrate how to become an excellent skull base surgeon based on the update and progress of technology and equipment in the field of skull base surgery, combined with own experience.

Studying the adsorption behavior of Yangjiang granite to Sr2+ is very meaningful for the safety assessment of the low- and medium-level nuclear waste repository in Yangjiang. In this study, experimental samples were obtained from the granite rock formations near the low- and medium-level nuclear waste repository in Yangjiang. The static adsorption experiment was performed study the adsorption behavior of Yangjiang surrounding rocks granite on Sr2+. And the effect of contact time, initial concentration, reaction temperature, pH, as well as cation and anion on the adsorption behavior of granite was studied in detail. The physical and chemical compositions of Yangjiang granite were investigated by X-ray diffraction spectra(XRD), X-ray fluorescence spectrometer(XRF), scanning electron microscopy-energy dispersive spectroscopy(SEM-EDS), Fourier transform infrared spectra(FTIR) and Zeta potential analyzer. The characterization studies show the granite surface becomes rough after adsorption. The results of static adsorption experiments indicate that adsorption equilibrium time is about 5 days. The Sr2+ adsorption decreases with the increase of Sr2+ concentration which conforms to the Langmuir isotherm adsorption model and belongs to single-layer adsorption. Under neutral and higher temperature conditions, the adsorption effect is better. The fitting thermodynamic equation suggests that adsorption is a spontaneous endothermic reaction. The ion in groundwater such as Ca2+, Mg2+, Fe3+, NO3- all can inhibit the adsorption of Sr2+ by Yangjiang granite, while CO32- can interfere with adsorption by forming polymers with Sr2+. The results of this study can provide a certain reference for the safety evaluation of the low- and medium-level nuclear waste repository in Yangjiang.

Feature selection is a basic and important step in real applications, such as face recognition and image segmentation. In this paper, we propose a new weakly supervised multi-view feature selection method by utilizing pairwise constraints, i.e., the pairwise constraint-guided multi-view feature selection (PCFS for short) method. In this method, linear projections of all views and a consistent similarity graph with pairwise constraints are jointly optimized to learning discriminative projections. Meanwhile, the l2,0-norm-based row sparsity constraint is imposed on the concatenation of projections for discriminative feature selection. Then, an iterative algorithm with theoretically guaranteed convergence is developed for the optimization of PCFS. The performance of the proposed PCFS method was evaluated by comprehensive experiments on six benchmark datasets and applications on cancer clustering. The experimental results demonstrate that PCFS exhibited competitive performance in feature selection in comparison with related models.

ABSTRACTObjective To explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS).Methods A total of 74 de novo primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence in-situ hybridization.Results Patients were divided into two cohorts, the TP53-mutated type (TP53Mut) group (n = 19) and TP53 wild type (TP53WT) group (n = 55). Compared with the TP53WT group, patients in the TP53Mut group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, P

IntroductionMoral injury, predominantly studied in military populations, has garnered increased attention in the healthcare setting, in large part due to the psychological and emotional consequences of the COVID-19 pandemic. The measurement of moral injury with instrumentation adapted from military settings and validated by frontline healthcare personnel is essential to assess prevalence and guide intervention. This study aimed to validate the Moral Injury Outcome Scale (MIOS) in the population of acute care.MethodsA sample of 309 acute care nurses completed surveys regarding moral injury, depression, anxiety, burnout, professional fulfillment, spiritual wellbeing, and post-traumatic stress disorder symptoms. Confirmatory factor analysis was conducted as well as an assessment of reliability and validity.ResultsThe internal consistency of the 14-item MIOS was 0.89. The scale demonstrated significant convergent and discriminant validity, and the test of construct validity confirmed the two-factor structure of shame and trust violations in this clinical population. Regression analysis indicated age, race, and marital status-related differences in the experience of moral injury.DiscussionThe MIOS is valid and reliable in acute care nursing populations and demonstrates sound psychometric properties. Scores among nurses diverge from those of military personnel in areas that may inform distinctions in interventions to address moral injury in these populations.

Abstract We provide an approach for compiling quantum simulation circuits that appear in Trotter, qDRIFT and multi-product formulas to Clifford and non-Clifford operations that can reduce the number of non-Clifford operations. The total number of gates, especially CNOT, reduce in many cases. We show that it is possible to implement an exponentiated sum of commuting Paulis with at most m (controlled)-rotation gates, where m is the number of distinct non-zero eigenvalues (ignoring sign). Thus we can collect mutually commuting Hamiltonian terms into groups satisfying one of several symmetries identified in this work. This allows an inexpensive simulation of the entire group of terms. We further show that the cost can in some cases be reduced by partially allocating Hamiltonian terms to several groups and provide a polynomial time classical algorithm that can greedily allocate the terms to appropriate groupings.

Abstract Background Anxiety and depression are common psychological comorbidities in patients with chronic pancreatitis (CP). There is still a lack of epidemiological studies on anxiety and depression in Chinese CP patients. This study aimed to identify the incidence and related factor of anxiety and depression among East Chinese CP patients and explore the relationship between anxiety, depression, and coping styles. Methods This prospective observational study was conducted from June 1, 2019 to March 31, 2021 in Shanghai, China. Patient diagnosed with CP were interviewed using the sociodemographic and clinical characteristics questionnaire, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and Coping Style Questionnaire (CSQ). Multivariate logistic regression analysis was conducted to identify the related factors of anxiety and depression. Correlation test was preformed to analyze the correlation between anxiety, depression, and coping styles. Results The incidence of anxiety and depression in East Chinese CP patients was 22.64% and 38.61%, respectively. Patients’ previous health status, level of disease coping, frequency of abdominal pain episodes, and pain severity were significantly associated with anxiety and depression. Mature coping styles (Problem solving, Seeking for help) had a positive impact on anxiety and depression, while immature coping styles (Self-blame, Fantasy, Repression, Rationalization) had negative effects on anxiety and depression. Conclusion Anxiety and depression were common in patients with CP in China. The factors identified in this study may provide references for the management of anxiety and depression in CP patients.

Computational Fluid Dynamics (CFD) and Fluid-Structure Interaction (FSI) are increasingly used to predict the hemodynamic and structural behaviors of cerebral aneurysms (CAs) whilst a less-pursued method is the static structural analysis (SSA) using the finite element method. In this paper, hemodynamic parameters including the flow velocity and wall shear stress predicted by CFD and FSI are compared whilst structural parameters including the wall displacement and wall stress predicted by SSA and FSI are compared for four patient-specific CA models under different systolic/diastolic pressures. The predicted distribution patterns of the same parameters for the same CA model under different pressures are similar. However, the percentage differences of the maximum hemodynamic parameters increase with increasing pressure. Conversely, the percentage differences of the maximum structural parameters decrease from a few to less than 1.5% when the systolic/diastolic pressure changes from 120/80 to 180/110 mmHg. The ratio of the computation times for CFD, SSA and FSI is typically 75:1:165. If the maximum wall stress under either ongoing or temporary hypertension is the most critical factor for immediate rupture and, thus, clinical treatment of CAs, SSA can provide a low cost and efficient predictions close to those of FSI for assessing the rupture risk.

Abstract Background This study aimed to analyze associations between genetic variants and plasma concentrations along with clinical outcomes in dabigatran in patients with non-valvular atrial fibrillation (NVAF). Methods We conducted a prospective study and enrolled NVAF patients treated with dabigatran in the real world. A total of 86 patients treated with 110 mg DE twice daily were recruited for this study. Blood samples were obtained from each patient and used for genotyping and determination of plasma dabigatran concentration. All bleeding and thromboembolic complications were recorded during the 1.5 years of follow-up. Results Eighty-three patients provided samples at the trough plasma level of dabigatran, and 58 patients provided samples at the peak plasma level of dabigatran. There was a significant association between the CES1 SNP rs8192935 and trough plasma concentrations of dabigatran (P = 0.013). Our results showed that the CES1 SNP rs8192935 significantly influenced dabigatran trough concentrations in the Chinese population, and carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 SNP c.2482-2236G > A (rs4148738) was associated with major bleeding events in the addictive model (P = 0.046, OR = 3.29) and dominant model (P = 0.040, OR = 8.17). Additionally, the ABCB1 SNP c.3435 C > T (rs1045642) was associated with the incidence of major bleeding events in the addictive model (P = 0.043, OR = 3.34) and dominant model (P = 0.046, OR = 7.77). However, no significant associations were found between all the SNPs and the incidence of minor bleeding events. Conclusion Our results indicated that the CES1 polymorphism rs8192935 was associated with trough plasma concentrations of dabigatran. Carriers of the G allele had increased trough plasma concentrations of dabigatran compared to noncarriers. The ABCB1 polymorphisms rs4148738 and rs1045642 were associated with an increased risk for major bleeding events for the first time in a Chinese population.

BackgroundIt has been reported that inflammatory bowel disease (IBD) is associated with an increased risk of malignancies, including lymphoma. A number of large observational studies have been devoted to exploring the causal link between IBD and malignant lymphoma. However, no consensus exists on whether there is a causal relationship between IBD and malignant lymphoma.MethodsThe summary dataset of the IBD and lymphoma genome-wide association studies (GWAS) was obtained from the OPEN GWAS website. Single-nucleotide polymorphisms (SNPs) were selected as genetic instrumental variants (IVs) for fulling P < 5 × 10-8 and linkage disequilibrium (LD) of r2 = 0.001 in the IBD GWAS. The proxy SNPs with LD of r2 > 0.8 were identified. Palindromic SNPs and outlier SNPs were excluded. The assessments of sensitivity employed the Cochran’s Q test, Mendelian randomization (MR)-Egger intercept test, and leave-one-out analysis.ResultsThe MR analysis results proved the causality of IBD on diffuse large B-cell lymphoma (DLBCL). The risk of developing DLBCL is increased by 28.6% in patients with IBD [odds ratio (OR)IVW = 1.286, 95% confidence interval (CI) 1.066–1.552, P = 0.009]. The results of the subgroup analysis showed that Crohn’s disease (ORIVW = 1.218, 95% CI 1.030–1.441, P = 0.021) rather than ulcerative colitis (ORIVW = 1.206, 95% CI 0.984–1.478, P = 0.072) had a causal effect on DLBCL. No horizontal and directional pleiotropy was observed in the MR studies.ConclusionsThe above MR study concluded that IBD itself is causally responsible for DLBCL, especially Crohn’s disease. Further investigations are needed to elucidate the mechanism underlying this direct causal link.

Phytoremediation techniques have been widely used in the treatment of heavy metal contaminated soils in recent years, but there is no effective post-treatment method for plant tissues containing heavy metals after remediation. Elsholtzia Harchowensis is a copper hyperaccumulator, commonly distributed in copper mining areas and often used for soil remediation of mine tailings. Moreover, copper-based catalysts are widely used in electrocatalytic reduction of carbon dioxide, which aims to convert carbon dioxide into useful fuels or chemicals. In this study, copper-modified biochar was prepared from Elsholtzia Harchowensis. Its specific surface area can reach as high as 1202.9 m2/g, with a certain porous structure and even distribution of copper on the amorphous carbon. Various products (such as carbon monoxide, methane, ethanol, and formic acid) could be obtained from the electrolytic reduction of carbon dioxide by using the as-prepared catalyst. Instantaneous current density of up to 15.3 mA/cm2 were achieved in 1.0 M KHCO3 solution at a potential of −0.82 V (vs. RHE). Electrolysis at a potential of −0.32 V (vs. RHE) for 8 h resulted in a stable current of about 0.25 mA/cm2, and the Faraday efficiency (FE) of carbon monoxide can reach as high as 74.6%. In addition, electrolysis at a potential of −0.52 V (vs. RHE) for 8 h led to a stable current of about 2.2 mA/cm2 and a FE of 8.7% for the C2 product. The rich variety of elements in plants leads to catalysts with complex structural and elemental characteristics as well, which facilitates the electrolytic reduction of carbon dioxide with a variety of useful products.

For relaxor ferroelectrics, correlating their properties and local structures is challenging. Here, the authors correlate the atomic-scale structure and the large dynamic electromechanical property in Bi0.5Na0.5TiO3-based relaxor ferroelectrics.

Image classification is vital and basic in many data analysis domains. Since real-world images generally contain multiple diverse semantic labels, it amounts to a typical multi-label classification problem. Traditional multi-label image classification relies on a large amount of training data with plenty of labels, which requires a lot of human and financial costs. By contrast, one can easily obtain a correlation matrix of concerned categories in current scene based on the historical image data in other application scenarios. How to perform image classification with only label correlation priors, without specific and costly annotated labels, is an important but rarely studied problem. In this paper, we propose a model to classify images with this kind of weak correlation prior. We use label correlation to recapitulate the sample similarity, employ the prior information to decompose the projection matrix when regressing the label indication matrix, and introduce the ℓ2,1 norm to select features for each image. Finally, experimental results on several image datasets demonstrate that the proposed model has distinct advantages over current state-of-the-art multi-label classification methods.

IntroductionMyxococcus sp. PT13 is a wild strain with multiple predatory properties that prey on multiple model microorganisms preserved in the laboratory. However, the lysis spectrum of PT13 on typical soil bacteria and its driving effect on soil microecosystems are still unclear.MethodsIn this study, the lawn predation method was used to determine the predation diameter of 62 typical soil bacteria by myxobacteria PT13 and analyze their lysis spectra.Results and DiscussionThe results showed that PT13 had a predation diameter greater than 15 mm against typical soil microorganisms such as Aeromonas, Bacillus, Brevibacterium, Fictibacillus, Glutamicibacter, Herbaspirillum, and Leifsonia and had an outstanding lysis effect but a significant preference (p

In the present study, the effects of Humulus scandens extract on growth performance, antioxidant responses and intestinal microflora of Yellow River carp (Cyprinus carpio) were investigated. 240 carps were assigned to four treatments received diets supplemented with 0 (control), 0.5, 1 and 2 g/kg Humulus scandens extract for 8 weeks. At end of the trial, the final body weight, specific growth rate (SGR) and intestinal body index of the 1.0 g/kg and 2.0 g/kg group were significantly higher than those of the control group (P

Objectives The association between remnant lipoprotein cholesterol (RLP-C) levels and the incidence of non-alcoholic fatty liver disease (NAFLD) is unclear, especially in non-obese populations.Setting We used data from a health assessment database. The assessment was conducted at the Wenzhou Medical Center from January 2010 to December 2014. The patients were divided into low, middle and high RLP-C groups according to tertiles of RLP-C, and baseline metabolic parameters were compared among the three groups. Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the relationship between RLP-C and NAFLD incidence. Additionally, sex-specific associations between RLP-C and NAFLD were examined.Participants 16 173 non-obese participants from the longitudinal healthcare database.Outcome measure NAFLD was diagnosed using abdominal ultrasonography and clinical history.Results Participants with higher RLP-C levels tended to have higher blood pressure, liver metabolic index and lipid metabolism index than those with middle or low RLP-C (p

Abstract Background Micronucleus (MN) is an abnormal fragment in a human cell caused by disorders in the mechanism regulating chromosome segregation. It can be used as a biomarker for genotoxicity, tumor risk, and tumor malignancy. The in vitro micronucleus assay is a commonly used method to detect micronucleus. However, it is time-consuming and the visual scoring can be inconsistent. Methods To alleviate this issue, we proposed a computer-aided diagnosis method combining convolutional neural networks and visual attention for micronucleus recognition. The backbone of our model is AlexNet without any dense layers and it is pretrained on the ImageNet dataset. Two attention modules are applied to extract cell image features and generate attention maps highlighting the region of interest to improve the interpretability of the network. Given the problems in the data set, we leverage data augmentation and focal loss to alleviate the impact. Results Experiments show that the proposed network yields better performance with fewer parameters. The AP value, F1 value and AUC value reach 0.932, 0.811 and 0.995, respectively. Conclusion In conclusion, the proposed network can effectively recognize micronucleus, and it can play an auxiliary role in clinical diagnosis by doctors.

Abstract Introduction Anaplastic lymphoma kinase (ALK) gene rearrangements, have been identified in approximately 2-7% of patients with lung adenocarcinoma (LUAD). However, co-occurrence of double ALK fusions in one patient was rare. Herein, we reported two Chinese female LUAD patients with confirmed double ALK fusion variants by next generation sequencing. Case presentation Case 1, a 38-year-old female was diagnosed as peripheral LUAD in left upper lobe with synchronous multiple intrapulmonary metastases (pT2N0M1b, stage IVa). And case 2, a 58-year-old female had left lower lobe primary LUAD and synchronous multiple lung metastases (pT4N2M1b, stage IVa). In both patients, tumor cells displayed strong expression of ALK protein. Genetic profiling by next generation sequencing showed both patients concurrently harbored two types of ALK rearrangements. Case 1 had an unreported ALK-SSH2/EML4-ALK double fusions, and case 2 had an another novel ARID2-ALK/EML4‐ALK double fusions. Both of these patients responded to ALK inhibitor crizotinib. Conclusions Our study reported two novel ALK fusion partners never reported, which expands the knowledge of ALK fusion spectrum and provides insight into therapeutic options for patients with double ALK fusions.

Objective To explore the distribution of immune cell subsets in patients with chronic graft-versus-host disease (cGVHD) and investigate the predictive values of specific cell subsets sorted by surface markers in the development of cGVHD. Methods From October 2020 to July 2021, 58 patients who received hematopoietic stem cell transplantation (HSCT) from the Hematology Medical Center of the Second Affiliated Hospital of the Army Medical University were collected in this study. Flow cytometry was used to detect the ratio of immune cell subpopulations in the cGVHD patients (cGVHD group, n=43) and those without (control group, n=15) who received allogeneic HSCT during the same period. Primary diagnoses of the recruited patients included acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), myelodysplastic syndromes (MDS), severe aplastic anemia (SAA), and β-thalassemia major. The median time to occurrence of cGVHD was 178.5 (47~1 328) d. Peripheral blood (PB) samples were collected for each patient when cGVHD occurred during follow-up or on the day of follow-up during the course of the disease. Results The percentages of PB regulatory T cells (Tregs) and transitional B cells were significantly reduced in the cGVHD group (P < 0.05), and that of CD19+ B lymphocytes was higher than the control group. The percentage of Tregs differed from the cGVHD patients with different severities (P < 0.05). The percentage of Th17-like cells in the patients with moderate cGVHD was significantly higher than patients with mild cGVHD. CD19+ B lymphocytes showed higher percentage in the patients with mild and moderate cGVHD. In the comparison among different targeted organs of cGVHD, only the Tregs percentage was significantly lower in the patients with skin and liver damage than control group, while the percentage of follicular helper T cells in the patients with skin and liver damage was significantly higher than those only having mucous membrane or eye organ involvement. Conclusion Distribution of immune cell subsets after HSCT is an important reference marker for the diagnosis, treatment and prognosis of cGVHD. Treg cells and transitional B cells which are sorted with a special combined strategy of surface markers play specific guiding roles in the pathogenesis, severity and damage of targeted organs of cGVHD.

Objective To compare the efficacy and prognosis of imatinib and sirolimus as second-line treatment for steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Clinical data of 33 patients diagnosed as SR-cGVHD after allo-HSCT in the Medical Center of Hematology of Army Medical University from September 2017 to December 2020 were collected and analyzed retrospectively. Among them, 16 patients were treated with imatinib and 17 with sirolimus. The response rate at the time points of 6 months and 1 year after initiation of second-line treatment, 2-year overall survival (OS), 2-year disease free survival (DFS), 1-year failure free survival and drug-related toxicity were compared between the 2 groups. Results For the imatinib and sirolimus patients, their 6-month overall response rate (ORR) was 62.5% and 41.2% (P=0.303), while 1-year ORR was 73.3% and 43.8% (P=0.149), 6-month complete response (CR) rate was 12.5% and 23.5% (P=0.656), while 1-year CR rate was 20.0% and 31.3% (P=0.685), respectively, and no statistical significance was observed between the 2 groups. The patients with imatinib treatment achieved better outcomes than those treated with sirolimus in terms of 2-year OS and 2-year DFS (P=0.041, P=0.043). There was no significant difference in the occurrence of drug-related toxicity between the 2 groups. Conclusion Imatinib and sirolimus shows similar response rate to SR-cGVHD after allo-HSCT, but the former is superior to the latter in terms of short-term OS and DFS.

Objective To construct a mouse model of skin-dominant chronic graft-versus-host disease (cGVHD). Methods BALB/c mice were irradiated with lethal dose and then received a mixture of bone marrow and spleen cells transplantation from B10.D2 donor mice. Then the clinical manifestations, pathological features of the mice and cell subsets of targeted organs were observed to evaluate the establishment of model. Results The clinical manifestations of the model mice mainly involved skin depilation, sclerosis, dandruff, scab, as well as arched back and joint stiffness due to skin shrinkage and sclerosis. The clinicopathological scores were increased with the progression of cGVHD, while the model mice showed no obvious manifestations of intestinal cGVHD. Moreover, increase of collagen deposition and decrease or even disappearance of hair follicles was observed on the histopathologic sections of skin, while other targeted organs showed no major alterations. T cell subsets analysis indicated that Th1 cells, CD4+IL-13+T cells and Tc1 cells were closely related to the disease progression. Conclusion The skin-dominant cGVHD mouse model is successfully established, with skin damage and fibrosis as main pathological changes.

Abstract Background To reduce disease recurrence after radical surgery for lung squamous cell carcinomas (SQCCs), accurate prediction of recurrent high-risk patients is required for efficient patient selection for adjuvant chemotherapy. Because treatment modalities for recurrent lung SQCCs are scarce compared to lung adenocarcinomas (ADCs), accurately selecting lung SQCC patients for adjuvant chemotherapy after radical surgery is highly important. Predicting lung cancer recurrence with high objectivity is difficult with conventional histopathological prognostic factors; therefore, identification of a novel predictor is expected to be highly beneficial. Lipid metabolism alterations in cancers are known to contribute to cancer progression. Previously, we found that increased sphingomyelin (SM)(d35:1) in lung ADCs is a candidate for an objective recurrence predictor. However, no lipid predictors for lung SQCC recurrence have been identified to date. This study aims to identify candidate lipid predictors for lung SQCC recurrence after radical surgery. Methods Recurrent (n = 5) and non-recurrent (n = 6) cases of lung SQCC patients who underwent radical surgery were assigned to recurrent and non-recurrent groups, respectively. Extracted lipids from frozen tissue samples of primary lung SQCC were analyzed by liquid chromatography-tandem mass spectrometry. Candidate lipid predictors were screened by comparing the relative expression levels between the recurrent and non-recurrent groups. To compare lipidomic characteristics associated with recurrent SQCCs and ADCs, a meta-analysis combining SQCC (n = 11) and ADC (n = 20) cohorts was conducted. Results Among 1745 screened lipid species, five species were decreased (≤ 0.5 fold change; P

Objective To determine the prophylactic effect of human umbilical cord mesenchymal stem cells (HUCMSCs) on murine acute graft-versus-host disease (aGVHD) and preliminarily explore its mechanism. Methods In order to establish a mouse model of aGVHD, the male BALB/c mice were transplanted with bone marrow cells and spleen lymphocytes from male C57BL/6 mice after receiving 7.5 Gy total body irradiation (TBI) on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mice were divided into BM group and aGVHD group, receiving 500 μL cell suspension containing 5×106 bone marrow cells or 5×106 bone marrow cells and 5×106 spleen cells, respectively, by tail vein. Their survival rate, clinical score and loss of body weight were assessed, chimerism was detected by flow cytometry, and pathological changes of target organs (lung, liver, colon, small intestine) were detected by HE staining. The HUCMSCs at passage 4 were collected and transplanted into aGVHD+MSCs group of BALB/c mice. The mice were then divided into aGVHD group (model group), aGVHD+MSCs group (5×106 bone marrow cells and 5×106 spleen cells and 5×105 HUCMSCs). Besides, the serum concentration of IFN-γ and TNF-α were detected by ELISA, and the infiltration and apoptosis of lymphocytes were detected by flow cytometry. Results Compared with the BM group, the aGVHD group showed a decreased survival rate, higher clinical score, and much obvious body weight loss (P < 0.05) and severer pathological injuries (P < 0.05). The mice achieved complete chimerism after transplantation. The aGVHD+MSCs group showed increased survival rate, lower clinical score and slighter pathological injuries (P < 0.05), the serum concentrations of IFN-γ and TNF-α were decreased (P < 0.05), and the apoptosis of CD4+ T cells in target organs was increased while the count was decreased (P < 0.05). Conclusion HUCMSCs infusion effectively prevent the development of murine aGVHD after allo-HSCT through mediating the apoptosis of lymphocytes to decrease their infiltration in target organs and regulating the secretion of inflammatory factors.

PurposeTo search for adaptive response molecules that affect the efficacy of transcatheter arterial chemoembolization (TACE), analyze their clinical correlation with and prognostic value for hepatocellular carcinoma (HCC), and explore their impact on cell biological behavior and their mechanisms of action.MethodsHCC tissue gene sequencing was used to identify differentially expressed genes. The expression of proteoglycan 4 (PRG4) in the serum of 117 patients with HCC who received TACE was detected by enzyme-linked immunosorbent assay. Serum-free medium mimicked TACE-induced nutrient deprivation. Cells with stable knockdown of PRG4 (shPRG4) were constructed to verify the effect and mechanism of PRG4 on the biological behavior of HCC cells in vitro.ResultsThe expression of PRG4 was significantly elevated under TACE-induced starvation conditions. Low PRG4 expression was associated with worse response to TACE treatment, shorter survival time, and stronger HCC migration ability. Furthermore, in vitro experiments showed that knockdown of PRG4 promoted HCC cell migration by enhancing epithelial–mesenchymal transition (EMT) while did not affect proliferation. When PRG4 expression was low, starvation treatment impaired the migratory ability of HCC cells and reduced the chemosensitivity of HCC cells to epirubicin.ConclusionsPRG4 expression predicts survival and TACE treatment response in patients with HCC. Furthermore, knockdown of PRG4 enhanced EMT, leading to HCC cell migration. PRG4 may serve as a biomarker for HCC patients receiving TACE.

Purpose Cognitive impairment (CI) is very common in patients with chronic obstructive pulmonary disease (COPD). Cerebral structural and functional abnormalities have been reported in cognitively impaired patients with COPD, and the neurovascular coupling changes are rarely investigated. To address this issue, arterial spin labeling (ASL) and resting-state blood oxygenation level dependent (BOLD) fMRI techniques were used to determine whether any neurovascular changes in COPD patients. Methods Forty-five stable COPD patients and forty gender- and age-matched healthy controls were recruited. Furthermore, resting-state BOLD fMRI and ASL were acquired to calculate degree centrality (DC) and cerebral blood flow (CBF) respectively. The CBF-DC coupling and CBF/DC ratio were compared between the two groups. Results COPD patients showed abnormal CBF, DC and CBF/DC ratio in several regions. Moreover, lower CBF/DC ratio in the left lingual gyrus negatively correlated with naming scores, lower CBF/DC ratio in medial frontal cortex/temporal gyrus positively correlated with the Montreal Cognitive Assessment (MoCA), visuospatial/executive and delayed recall scores. Conclusion These findings may provide new potential insights into neuropathogenesis of cognition decline in stable COPD patients.