Search

Abstract Background Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. Methods LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. Results The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. Conclusions MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

The biliary epithelial cells release CC chemokine receptor 6 (CCR6) ligand 20 (CCL20), leading to recruitment of CCR6+ T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. Previous genome-wide multi-national meta-analysis, including our Han Chinese cohort, showed significant association of CCR6 and CCL20 single nucleotide polymorphisms (SNP) with PBC. We report here that significantly associated SNPs, identified in the CCR6 locus based on our Han Chinese genome-wide association study, can be separated into “protective” and “risk” groups, but only “risk” SNPs were confirmed using a separate Han Chinese PBC cohort. Only weak association of CCL20 SNPs was observed in Han Chinese PBC cohorts. Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased CCR6 expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort.

Objectives: Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear. Materials and methods: Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296–386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients. Results: In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.β = 0.35, P = 0.003) and gamma-glutamyltransferase (GGT) (st.β = 0.23, P = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease. Conclusions: Our study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.

Abstract Objective To construct a new prediction nomogram to predict the risk of musculoskeletal pain in patients with primary osteoporosis who receive zoledronic acid intravenously for the first time. Method Clinical data of 368 patients with primary osteoporosis who received the first intravenous injection of zoledronic acid in our hospital from December 2019 to December 2022 were studied. Patients were divided into a musculoskeletal pain group (n = 258) and a non-musculoskeletal pain group (n = 110) based on the presence or absence of musculoskeletal pain 3 days after injection. Statistically significant predictors were screened by logistic regression analysis and the minimum absolute contraction and selection operator (LASSO) to construct a nomogram. The nomogram was evaluated by the receiver operating characteristic (ROC) curve, the calibration curve, the C-index, and the decision curve analysis (DCA) and verified in a validation cohort. Results The independent predictors of the nomogram were age, serum 25-hydroxyvitamin D, NSAIDs, prior Vitamin D intake, and BMI. The area under the ROC curve (AUC) was 0.980 (95% CI, 0.915–0.987), showing excellent predictive performance. The nomogram c index was 0.980, and the nomogram c index for internal verification remained high at 0.979. Moreover, calibration curves show that the nomogram has good consistency. Finally, the DCA showed that the net benefit of the nomogram was 0.20–0.49. Conclusion Musculoskeletal pain is a common symptom of APR in OP patients treated with intravenous zoledronic acid. Risk factors for musculoskeletal pain after zoledronic acid injection in OP patients were: non-use of NSAIDs, youth (

The "Internet Plus" era has established a closer connection between sports and individuals. This study used data from the 2018 China Family Panel Studies and focused on the middle- and younger-aged population aged 15 to 59 years. Employing a negative binomial regression model, this study empirically analyzed the impact of Internet use on physical exercise and its internal mechanisms among this population. The findings revealed that (1) Internet use significantly promoted physical exercise in the middle- and younger-aged population, with the frequency of physical exercise increasing to 1.549 times the original value; (2) The positive effects of the internet on physical exercise outweighed the negative effects, with online learning and entertainment enhancing physical exercise and online socialization limiting it. Specifically, online learning and entertainment increased the frequency of physical exercise among the middle- and younger-aged population by 0.063 and 0.018, respectively. Online socialization reduced the frequency by 0.023; and (3) The influence of internet use on physical exercise varies; significantly, it positively affects the exercise frequency among individuals over 35 years old and shows a positive correlation with employment status, including both employed individuals and those out of the labor market. The positive role of Internet use in encouraging physical exercise participation among the middle- and young-aged groups should be valued and enhanced.

IntroductionInfectious diseases are major causes of morbidity and mortality worldwide, necessitating the rapid identification and accurate diagnosis of pathogens. While unbiased metagenomic next-generation sequencing (mNGS) has been extensively utilized in clinical pathogen identification and scientific microbiome detection, there is limited research about the application of nanopore platform-based mNGS in the diagnostic performance of various infectious fluid samples.MethodsIn this study, we collected 297 suspected infectious fluids from 10 clinical centers and detected them with conventional microbiology culture and nanopore platform–based mNGS. The objective was to assess detective and diagnostic performance of nanopore-sequencing technology (NST) in real-world scenarios.ResultsCombined with gold-standard culture and clinical adjudication, nanopore sequencing demonstrated nearly 100% positive predictive agreements in microbial-colonized sites, such as the respiratory and urinary tracts. For samples collected from initially sterile body sites, the detected microorganisms were highly suspected pathogens, and the negative predictive agreements were relatively higher than those in the microbial-colonized sites, particularly with 100% in abscess and 95.7% in cerebrospinal fluid. Furthermore, consistent performance was also observed in the identification of antimicrobial resistance genes and drug susceptibility testing of pathogenic strains of Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii.DiscussionRapid NST is a promising clinical tool to supplement gold-standard culture, and it has the potential improve patient prognosis and facilitate clinical treatment of infectious diseases.

Abstract Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.

Abstract To explore the mechanism of the effect of emotional facial expression on attentional process, time course and topographic map of Electroencephalographic activities affected by emotional stimuli were investigated. Emotional Stroop task was used to collect 64-channel event-related potentials (ERP) in nonclinical participants, and data clustering was applied to find significant effect of sad and happy facial expression on ERP. Several significant ERP clusters were found in the sad and happy conditions respectively. In the sad condition, the decreased N170 in the bilateral parietooccipital areas, the increased P3 in the right centroparietal region and the increased negative deflection between 600 and 650 ms in the prefrontal regions were observed, these alterations reflected inhibited perceptual processing of sad facial expression, and increased activations of the orienting network and the executive control network in attentional system, respectively. In the happy condition, increased negative slow wave was found in the left centroparietal region indicating strengthened awareness and readiness for successive trials. Importantly, nonpathological attentional bias to sad facial expression in nonclinical participants was associated with inhibited perceptual processing and increased activations of the orienting and executive control networks. It provides the basis for better understanding and application of attentional bias in psychiatric clinical utilization.

Abstract Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants. Herein, a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres (KPMs, bilirubin adsorbents) was connected with the principle machine of wearable artificial liver (approximately 9 kg) to treat hyperbilirubinemia beagles for the first time. With the initial normal dose of heparin, the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation. The removal efficiency of the double-deck column for total bilirubin (TBIL) was 31.4%. Interestingly, the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%. The “anticoagulant + column” realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump; however, the proposed principle machine of wearable artificial liver and “anticoagulant + column” cannot completely replace the bio-liver now. The intelligence of the device and the versatility of the adsorbent need to be improved; moreover, advanced experimental techniques need to be developed to validate the survival rates in animals. Overall, this study is a meaningful trial for the development of wearable artificial livers in the future.

Hydrogel treatment as a common cooling method could effectively ease pain and promote wounds healing by reducing thermal injury to the skin. However, the inherent low thermal conductivity of polymers limits the improvement of hydrogels’ cooling performance. The present study reports a simple method by combining thermal conductive fillers 1D hydroxylated multiwall carbon nanotubes (CNT-OH) and 2D hydroxylated hexagonal boron nitride (BN-OH) to construct 3D conductive networks in hydrogels for cooling treatment and burn therapy. It is interesting that the thermal conductive fillers are aligned via varying the mass ratios of CNT-OH to BN-OH. Hence, the utilization efficiency of the thermal conductive fillers is improved; and the thermal conductivity of the hydrogels is enhanced up to 1.31 W*m−1*K−1, which is 226 % to the pristine hydrogel of 0.58 W*m−1*K−1. Consequently, the optimized hydrogel exhibits rapid cooling abilities that the heated porcine skin only takes 168 s to decrease 30 °C with the treatment of the hydrogel. More importantly, the thermal conductivity enhanced hydrogel exhibits the capacities of rapid cooling, reducing heat injury and pain relieving, and promoting wound healing in vivo tests, which prove that the enhanced thermal conductive and moisturizing hydrogel can be a good alternative for burn therapy.

Abstract Barrier membranes incorporated with anti‐adhesion drugs have been widely used for preventing postoperative adhesion. However, the bidirectional release of drugs may interfere with internal tissue healing. Herein, a unidirectional Janus membrane composed of two functional layers is prepared by sequential electrospinning. The outer layer is designed as random polycaprolactone fibers incorporated with tannic acid/Fe3+ particles to prevent tissue adhesion, while the inner layer is designed as oriented gelatin fibers to promote tissue repair. Hydrogen bonding was employed to act as a barrier for preventing the diffusion of the tannic acid to the inner side, and thus the release of tannic acid occurs in a unidirectional manner. As a result, asymmetric biological performances of the Janus membrane are achieved. The outer face can provide anti‐inflammatory capability to the membrane and inhibit the viability of fibroblasts, while the inner face can promote the proliferation and differentiation of tendon stem cells. Tendon injured model confirms the prominent inflammation modulation, adhesion prevention, and repair promotion capabilities of the Janus membrane in vivo. This study provides a new strategy to develop advanced functional barrier membranes for postoperative adhesion prevention and internal tissue repair promotion.

ObjectiveTo examine the clinical efficacy, safety, and resistance of Ceftazidime-Avibactam (CAZ-AVI) in patients with Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections.MethodsWe retrospectively analyzed relevant data of CR-GNB infected patients receiving CAZ-AVI treatment, analyzed relevant factors affecting drug efficacy, and compared the efficacy and safety with patients receiving Polymyxin B treatment.ResultsA total of 139 patients were included. Agranulocytosis, septic shock, SOFA score, and CAZ-AVI treatment course were independent risk factors affecting the prognosis of patients with CR-GNB infection treated with CAZ-AVI while prolonging the treatment course of CAZ-AVI was the only protective factor for bacterial clearance. The fundamental indicators showed no statistically significant differences between CAZ-AVI and Polymyxin B treatment groups. At the same time, the proportion of patients treated with monotherapy was significantly higher in the CAZ-AVI group than in the Polymyxin B group (37.2% vs. 8.9%, p 6, and had a lower incidence of adverse events. We monitored the emergence of CAZ-AVI resistance and should strengthen the monitoring of drug susceptibility in clinical practice and the rational selection of antibiotic regimens to delay the onset of resistance.

Sintering is the process that emits the most pollutants in the iron and steel industry. As people have higher and higher requirements for environmental quality, under the background of strengthening the control of other pollutants in sintering, the issue of CO emissions from sintering of iron ore powder has been widely concerned. CO emission reduction is imperative. The efficient treatment technology for CO emission reduction in sintered flue gas is relatively scarce and cannot meet the CO reduction of sintering machines in the steel industry. This article mainly summarizes the research status and trends of CO emission reduction technology in sintering flue gas at home and abroad, analyzes the mechanism of CO production during sintering process, and discusses CO emission reduction from the three aspects of source, process and end governance.

Abstract Background Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30–40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. Methods IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. Discussion To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, ‘Retrospectively registered’, https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1

ABSTRACT: Paper and plastic bags have been mainly used in fruit bagging of pineapple production. However, they are often discarded as agricultural wastes after harvest of pineapple fruit and threaten environment. In this study, effects of white non-woven fabric bag, expandable polyethylene bag, black plastic bag and kraft paper bag on fruit quality of pineapple cv. ‘MD-2’ were investigated. Results showed that fruits with fruit bagging showed no sunburn. When expandable polyethylene bag was used, fruits of pineapple cv. ‘MD-2’ showed better external qualities, nutrition qualities and texture properties. Expandable polyethylene bag made of degradable and recyclable materials could be recommended as a promising practice to reduce agricultural waste in pineapple production.

Patients with chronic kidney disease are at high risk of hyperkalemia that is associated with various life-threatening complications. Treatments primarily rely on orally administered potassium binding agents, along with low curative effects and various side effects. Herein, direct serum potassium uptake was realized via zeolite–heparin-mimicking-polymer hybrid microbeads. The preparation process involved the synthesis of the heparin-mimicking polymer via the in situ cross-linking polymerization of acrylic acid and N-vinylpyrrolidone in polyethersulfone solution, the fabrication of microbeads via zeolite-mixing, electro-spraying and phase-inversion, and the subsequent aqueous-phase modifications based on ion-exchange and metal-leaching. An ultra-high (about 88%) amount of zeolite could be incorporated and well locked inside the polymer matrix. Potassium uptake capability was verified in water, normal saline and human serum, showing high selectivity and fast adsorption. The microbeads exhibited satisfying blood compatibility, negligible hemolysis ratio, prolonged clotting time, inhibited contact activation, and enhanced antifouling property toward serum proteins and cells. The proposed approach toward zeolite–heparin-mimicking-polymer hybrid microbeads provided a cheap, efficient and safe treatment protocol of hyperkalemia for the high-risk patients.

Endoscopes are used for diagnosis and minimally invasive treatment of the interior regions of the body. The visual fields of endoscopes, especially angioscopes, are often obscured due to the contamination with biological fluids. To avoid the biological fouling, the lubricant liquid infused slippery surfaces with excellent antifouling property have been proposed and fabricated by previous work. Although the slippery surfaces can be transparent, the transmittance is not comparable with bare glass lens, which limits their optical applications. In contrast, nano-structured surfaces, which could eliminate reflection, exhibit excellent transmittance (~98.5%) and antireflection properties for lens applications. However, the nano-structures with large specific surface area increase biofouling, which induces vision loss and hemocompatibility problems in vivo. Herein, we develop an ultra-transparent and antifouling slippery surface on nano-structure glass. It is achieved by infusing lubricant oil on the fluorinated glass surface with semi-hexagonal nanoholes. This semi-hexagonal nanohole structures on the one hand stabilize the lubricant phase by capillary force, on the other hand effectively eliminate reflection. Our ultra-transparent slippery surface exhibits excellent hemocompatibility and antifouling property, as well as the stable transmittance even after being immersed into the whole blood for multiple cycles. This novel functional surface provides new opportunities in design of endoscopes, especially angioscopes, and offers enormous potential for disease diagnosis and treatment.

Aim: Portal vein thrombosis (PVT) is a common complication in cirrhotic patients and will aggravate portal hypertension, thus leading to a series of severe complications. The aim of this study was to develop a nomogram based on a simple and effective model to predict PVT in cirrhotic patients. Methods: Clinical data of 656 cirrhotic patients with or without PVT in the First Affiliated Hospital of Soochow University and The Third Affiliated Hospital of Nantong University from January 2017 to March 2022 were retrospectively collected, and all patients were divided into training, internal and external validation cohorts. SPSS and R software were used to identify the independent risk factors and construct a predictive model. We evaluated the predictive value of the model by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses. The feasibility of the model was further validated in the internal and external cohorts. All enrolled patients were followed up to construct the survival curves and calculate the incidence of complications. Results: The predictors of PVT included serum albumin, D-dimer, portal vein diameter, splenectomy, and esophageal and gastric varices. Based on the clinical and imaging findings, the final model served as a potential tool for predicting PVT in cirrhotic patients, with an AUC of 0.806 (0.766 in the internal validation cohort and 0.845 in the external validation cohort). The decision curve analysis revealed that the model had a high level of concordance between different medical centers. There was a significant difference between the PVT and non-PVT groups in survival analyses, with p values of 0.0477 and 0.0319 in the training and internal validation groups, respectively, along with p value of 0.0002 in the external validation group according to log-rank test; meanwhile, the median survival times of the PVT group were 54, 43, and 40 months, respectively. The incidence of recurrent esophageal and gastric variceal bleeding (EGVB) during the follow-up showed significant differences among the three cohorts (p = 0.009, 0.048, and 0.001 in the training, internal validation, and external validation cohorts, respectively). Conclusion: The nomogram based on our model provides a simple and convenient method for predicting PVT in cirrhotic patients. Cirrhotic patients with PVT had a shorter survival time and were prone to recurrent EGVB compared with those in the non-PVT group.

Background: COVID-19 pandemic is a traumatic event all over the world, and may lead to post-traumatic stress symptom (PTSS) in different population who are under the threat of novel corona virus. Therefore, the aim of our study was to compare the prevalence and risk factors of PTSS between Chinese patients with depression and non-depressed controls during the COVID-19 outbreak.Methods: 437 depressed patients and 2,940 non-depressed controls were enrolled in this cross-sectional study between February 14 and May 9, 2020.The Impact of Events Scale-Revised (IES-R), Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS) and Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the psychological status of all the participants.Results: The prevalence of PTSS (IES-R ≥ 33) in depressed patients (45.08%) was higher than that in non-depressed controls (5.31%). Patients with depression were 16 times more likely to suffer from PTSS than those without depression. Correlation analyses showed that the IES-R total score was positively correlated with SDS, SAS, and PSQI scores in both depressed and non-depressed groups (Bonferroni corrected all p < 0.001). Multiple linear regression analysis showed that SAS score, and PSQI score were independently associated with IES-R total score in both depression and non-depression groups. In depressed patients, education level and duration of media exposure to COVID-19 were positively associated with PTSS, while in the non-depressed group, subjects who were married, in the 31–50 year group or with higher SDS score were more likely to develop PTSS.Conclusions: These results indicate that the prevalence rate of PTSS in patients with depression is very higher than that in subjects without depression. PTSS are associated with a number of socio-demographic and clinical variables.

Background: In microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers, the optimum therapy after the progression of immune checkpoint inhibitors (ICIs) is yet unknown. Here, we compared the efficacy of programmed death 1 (PD1)/programmed death ligand-1 (PD-L1) inhibitors plus other therapy and chemotherapy with or without targeted therapy in MSI/dMMR gastrointestinal cancer patients after progression on anti-PD1/PD-L1 monotherapy. Methods: We retrospectively recruited MSI/dMMR gastrointestinal cancer patients who had progressed on anti-PD1/PD-L1 monotherapy. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and PFS ratio (PFSr) were compared between patients who received anti-PD1/PD-L1 plus other therapy (ICI-plus group) and patients who received chemotherapy with or without targeted therapy (chemo-targeted group). Results: In total, 26 and 25 patients were recruited in the ICI-plus group and chemo-targeted group, respectively. Significantly better DCR (80.8% vs. 44.0%, p = 0.007), PFS (median PFS 6.9 months vs. 3.0 months, p = 0.001), OS (median OS NR vs. 14.1 months, p = 0.043), and PFSr (2.4 vs. 0.9, p = 0.021), along with a numerically higher ORR (23.1% vs. 12.0%, p = 0.503) were observed in the ICI-plus group compared with the chemo-targeted group. Multivariate analyses identified the therapy regimen as an important prognostic factor in gastrointestinal cancers. Conclusions: Compared to conventional chemotherapy with or without targeted therapy, continuing anti-PD1/PD-L1 in combination with other treatments showed better clinical outcomes in MSI/dMMR gastrointestinal cancer patients who progressed on PD1/PD-L1 blockade, which should be validated prospectively in clinical trials.

Sepsis, a life-threatening and intractable disease without any specific treatment, is activated by endotoxin. Some attempts at removing endotoxin to treat sepsis from the blood circulation using different hemoperfusion cartridges have been proposed recently, but they have failed to reduce the mortality of severe septic patients. This review summarizes the latest advances in the development of endotoxin adsorbents. In particular, we highlight two critical parameters for endotoxin adsorbents when they are applied in blood purification: the dissociation constant and the maximum adsorption capacity. We also discuss potential challenges and research directions for the future development of endotoxin adsorbents.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and is associated with high morbidity and mortality. Circulating histones (CHs), a group of damage-associated molecular pattern molecules mainly derived from neutrophil extracellular traps, play a crucial role in sepsis by mediating inflammation response, organ injury and death through Toll-like receptors or inflammasome pathways. Herein, we first elucidate the molecular mechanisms of histone-induced inflammation amplification, endothelium injury and cascade coagulation activation, and discuss the close correlation between elevated level of CHs and disease severity as well as mortality in patients with sepsis. Furthermore, current state-of-the-art on anti-histone therapy with antibodies, histone-binding proteins (namely recombinant thrombomodulin and activated protein C), and heparin is summarized to propose promising approaches for sepsis treatment.

Polyethersulfone (PES) membranes have been widely used as attractive materials especially in the field of blood purification due to their great oxidative, thermal, and chemical stability, as well as outstanding mechanical properties. However, the intrinsic hydrophobic property seriously limits its application because of the relevant side effects, like biofouling, platelet activation, and coagulation. Given the importance of PES membranes for hemodialysis, various modification methods have been developed to address this challenge; and it is necessary to review the research progress in hemocompatibility enhancement of PES membranes, which is also imperative to provide more insights for the development of future PES-based hemodialyzers and perhaps to open the door to extend their applications for the next generation of blood purification instruments, like the wearable artificial kidney. Herein, we review the concept and principles of hemocompatibility for hemodialysis membranes, different strategies developed to improve the hemocompatibility of PES membranes, and the challenges and future perspectives for improvement in hemocompatibility of PES membranes. Most emphasis has been given to the modification strategies including bulk modification, blending modification, and surface modification and their salient features are highlighted.

In order to study the bearing characteristics and failure mechanism of the rigid antislide pile under horizontal load, the stress of rigid antislide pile under transverse axial large displacement load is analyzed by using elastic-plastic theory, finite element analysis, and model test. The theoretical formula of the proximal plastic earth pressure near the pile with the depth of soil under the horizontal force is obtained. The results show that the standard is insensitive to the variation of soil parameters and the influence of soil parameters on allowable soil resistance in front of pile should be considered. With the increase of the horizontal force of the pile top, the soil near the pile is destroyed in this process gradually, which is the decline of the cross section of the maximum soil resistance of the pile. When the horizontal displacement of pile top is 20 mm and 70 mm, the soil resistance value and the ultimate soil resistance value in front of the pile can be selected, respectively. The plastic zone develops to the front and bottom of the pile at the same speed, at an angle of 45° with the direction of gravity. When the displacement reaches 34 mm, the plastic zone develops to the deeper depth obviously. The results can provide a theoretical basis for the design and application of antislide piles during the process of slope protections.

In this paper, an improved obstacle-avoidance-scheme-based kinematic control problem in acceleration level for a redundant robot manipulator is investigated. Specifically, the manipulator and obstacle are abstracted as mathematical geometries, based on the vector relationship between geometric elements, and the Cartesian coordinate of the nearest point to an obstacle on a manipulator can be found. The distance between the manipulator and an obstacle is described as the point-to-point distance, and the collision avoidance strategy is formulated as an inequality. To avoid the joint drift phenomenon of the manipulator, bi-criteria performance indices integrating joint-acceleration-norm minimization and repetitive motion planning is adopted by assigning a weighing factor. From the perspective of optimization, therefore, an acceleration level quadratic programming (QP) problem is eventually formulated. Considering the physical structure of robot manipulators, inherent joint angle, speed, and acceleration limits are also incorporated. To solve the resultant QP minimization problem, a recurrent neural network based neural dynamic solver is proposed. Then, simulation experiments performing on a four-link planar manipulator validate the feasibility and effectiveness of the proposed scheme.

Abstract Our previous studies unexpectedly indicated that the level of serum hepatitis B core antibody (anti-HBc) was positively correlated with the serum alanine aminotransferase (ALT) level. The aim of this study was to determine whether anti-HBc could serve as a potential biomarker for the detection of liver inflammation in chronic hepatitis B (CHB) patients, especially in patients with normal ALT levels. Serum anti-HBc levels were quantified in 655 treatment-naïve CHB patients, including 45 patients who underwent two liver biopsies (baseline phase and the 78th weeks of antiviral-treatment). Serum anti-HBc levels increased significantly along with the increasing histology activity index (HAI) score. After antiviral-treatment, patients with HAI score reduction had significant decline in serum anti-HBc level. Multivariate analysis showed that anti-HBc was independently associated with moderate-to-severe hepatic inflammation in patients with normal ALT level. Furthermore, serum anti-HBc showed a high diagnostic accuracy for predicting moderate-to-severe inflammation in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative CHB patients with normal ALT levels (area under the curve, AUC = 0.87 and 0.75; respectively). Thus, anti-HBc may be a strong indicator for assessing the hepatic inflammatory degree and used for antiviral treatment decisions in CHB patients with normal ALT levels.

Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.

The high overpotentials for oxygen reduction reaction (ORR) create an extremely negative impact on the energy efficiency of the air-based battery systems. To overcome this problem, binuclear ball-type metallophthalocyanines containing methoxy substituents (M2Pc2(EP)4, M = Fe(II), Co(II) and Zn(II)) were wrapped with polystyrene sodium sulfonate (PSS) modified graphene oxide (GO), using a facilely “solvothermal π-π assembly” method to prepare M2Pc2(EP)4/PSS-Gr composites. Compared with the commercial Pt/C catalysts, the M2Pc2(EP)4/PSS-Gr composites enhanced the catalytic activity of oxygen reduction reaction. The π electron conjugated structure of the MN4-type phthalocyanine macrocyclic system strongly influenced the one-step four-electron electrocatalytic process of the M2Pc2(EP)4/PSS-Gr composites. Moreover, the π-π interactions between the M2Pc2(EP)4 and PSS-Gr dramatically enhanced the π electron density in the conjugated structure and oxygen could be reduced more easily. The electrocatalytic activity test was displayed in the order of Fe2Pc2(FP)4/PSS-Gr > Co2Pc2(EP)4/PSS-Gr > Zn2Pc2(EP)4/PSS-Gr. The results indicated that the catalytic performance of M2Pc2Rn could be enhanced by the modification of π electron conjugated structure of M2Pc2(EP)4 and carbon materials.

ABSTRACT The capacity of influenza A viruses (IAVs) to host jump from animal reservoir species to humans presents an ongoing pandemic threat. Birds and swine are considered major reservoirs of viral genetic diversity, whereas equines and canines have historically been restricted to one or two stable IAV lineages with no transmission to humans. Here, by sequencing the complete genomes of 16 IAVs obtained from canines in southern China (Guangxi Zhuang Autonomous Region [Guangxi]) in 2013 to 2015, we demonstrate that the evolution of canine influenza viruses (CIVs) in Asian dogs is increasingly complex, presenting a potential threat to humans. First, two reassortant H1N1 virus genotypes were introduced independently from swine into canines in Guangxi, including one genotype associated with a zoonotic infection. The genomes contain segments from three lineages that circulate in swine in China: North American triple reassortant H3N2, Eurasian avian-like H1N1, and pandemic H1N1. Furthermore, the swine-origin H1N1 viruses have transmitted onward in canines and reassorted with the CIV-H3N2 viruses that circulate endemically in Asian dogs, producing three novel reassortant CIV genotypes (H1N1r, H1N2r, and H3N2r [r stands for reassortant]). CIVs from this study were collected primarily from pet dogs presenting with respiratory symptoms at veterinary clinics, but dogs in Guangxi are also raised for meat, and street dogs roam freely, creating a more complex ecosystem for CIV transmission. Further surveillance is greatly needed to understand the full genetic diversity of CIV in southern China, the nature of viral emergence and persistence in the region’s diverse canine populations, and the zoonotic risk as the viruses continue to evolve. IMPORTANCE Mammals have emerged as critically underrecognized sources of influenza virus diversity, including pigs that were the source of the 2009 pandemic and bats and bovines that harbor highly divergent viral lineages. Here, we identify two reassortant IAVs that recently host switched from swine to canines in southern China, including one virus with known zoonotic potential. Three additional genotypes were generated via reassortment events in canine hosts, demonstrating the capacity of dogs to serve as “mixing vessels.” The continued expansion of IAV diversity in canines with high human contact rates requires enhanced surveillance and ongoing evaluation of emerging pandemic threats.

The urban bus service system is one of the most important components of a public transport system. Thus, exploring the spatial configuration of the urban bus service system promotes an understanding of the quality of bus services. Such an understanding is of great importance to urban transport planning and policy making. In this study, we investigated the spatial characteristics of an urban bus service system by using the complex network approach. First, a three-step workflow was developed to collect a bus operating dataset from a public website. Then, we utilized the P-space method to represent the bus service network by connecting all bus stop pairs along each bus line. With the constructed bus network, a set of network analysis indicators were calculated to quantify the role of nodes in the network. A case study of Shenzhen, China was implemented to understand the statistical properties and spatial characteristics of the urban bus network configuration. The empirical findings can provide insights into the statistical laws and distinct convenient areas in a bus service network, and consequently aid in optimizing the allocation of bus stops and routes.

To provide a new way to increase water storage and retention of dryland wheat, a field study was conducted at Wenxi experimental site of Shanxi Agricultural University. The effect of subsoiling in fallow period on soil water storage, accumulation of proline, and formation of grain protein after anthesis were determined. Our results showed that subsoiling in fallow period could increase water storage in the 0-300 cm soil at pre-sowing stage and at anthesis stage with low or medium N application, especially for the 60-160 cm soil. However, the proline content, glutamine synthetase (GS) activity, glutamate dehydrogenase (GDH) activity in flag leaves and grains were all decreased by subsoiling in fallow period. In addition, the content of albumin, gliadin, and total protein in grains were also decreased while globulin content, Glu/Gli, protein yield, and glutelin content were increased. With N application increasing, water storage of soil layers from 20 to 200 cm was decreased at anthesis stage. High N application resulted in the increment of proline content and GS activity in grains. Besides, correlation analysis showed that soil storage in 40-160 cm soil was negatively correlated with proline content in grains; proline content in grains was positively correlated with GS and GDH activity in flag leaves. Contents of albumin, globulin and total protein in grains were positively correlated with proline content in grains and GDH activity in flag leaves. In conclusion, subsoiling in fallow period, together with N application at 150 kg·hm(-2), was beneficial to increase the protein yield and Glu/Gli in grains which improve the quality of wheat.