Coordination and modularization: the experience of the joint prevention and control mechanism to COVID emergencies in China.

Background: The integration of disparate emergency resources and the improvement of emergency response teamwork are the underlying trends and shared requirements for building resilience in an era of multiple global public health crises. Objective: This study investigated the emergency response with emergency collaboration networks of each functional module and the overall Joint Epidemic Prevention and Control Mechanism (JPCM) network in China's COVID outbreak prevention and control. Methods: The study employed a scholarly framework of "the integration of JPCM coordination and emergency collaborative modularization" to explore the attributes of JPCM using social network analysis. The data were obtained from administrative records from JPCM's official website, spanning January 2020 to December 2022. Results: The study examined the JPCM coordination and found several functional working modules of JPCM, such as Interrupt Spread, Manage Supply, Medical Rescue, Restore Work and Production, and Implement Responsibility modules. The network structure indicators showed that the Manage Supply module had the most extensive network connectivity, the shortest communication distance, and the most consistent collaboration. The E-I index of the overall JPCM network and the Manage Supply network were - 0.192 and - 0.452, respectively (at p < 0.001 and p < 0.05), indicating more internal relationships than external relationships. The E-I index of the Medical Rescue and Implement Responsibility collaboration networks were 0.122 and 0.147, respectively (at p < 0.001 and p < 0.05), indicating more external relationships than internal relationships. The QAP regression analysis showed that the most vital driver on the overall JPCM network was the Interrupt Spread module, followed by the Implement Responsibility and Medical Rescue modules. Discussion: The Interrupt Spread module initiated emergency coordination with most departments and agencies. The Manage Supply module ensured the flow of medical supplies and survival essentials, while the Medical Rescue module addressed the core aspects of the health emergency response. The Restore Work and Production module repaired the halt in production and livelihoods caused by the outbreak, strengthening and developing emergency coordination and roles across emergency organizations. The Implement Responsibility module provided more heterogeneous emergency response resources for the overall JPCM coordination, complementing the COVID cross-organizational emergency response coordination. Conclusion: The study on the JPCM case in China improves public health emergency management and aids informed decision-making.

The Impact of Postures and Moving Directions in Fire Evacuation in a Low-Visibility Environment.

Walking speed is a significant aspect of evacuation efficiency, and this speed varies during fire emergencies due to individual physical abilities. However, in evacuations, it is not always possible to keep an upright posture, hence atypical postures, such as stoop walking or crawling, may be required for survival. In this study, a novel 3D passive vision-aided inertial system (3D PVINS) for indoor positioning was used to track the movement of 20 volunteers during an evacuation in a low visibility environment. Participants' walking speeds using trunk flexion, trunk-knee flexion, and upright postures were measured. The investigations were carried out under emergency and non-emergency scenarios in vertical and horizontal directions, respectively. Results show that different moving directions led to a roughly 43.90% speed reduction, while posture accounted for over 17%. Gender, one of the key categories in evacuation models, accounted for less than 10% of the differences in speed. The speeds of participants under emergency scenarios when compared to non-emergency scenarios was also found to increase by 53.92-60% when moving in the horizontal direction, and by about 48.28-50% when moving in the vertical direction and descending downstairs. Our results also support the social force theory of the warming-up period, as well as the effect of panic on the facilitating occupants' moving speed.

Construction of an infectious clone for enterovirus A89 and mutagenesis analysis of viral infection and cell binding.

Enterovirus A89 (EV-A89) is an unconventional strain belonging to the Enterovirus A species. Limited research has been conducted on EV-A89, leaving its biological and pathogenic properties unclear. Developing reverse genetic tools for EV-A89 would help to unravel its infection mechanisms and aid in the development of vaccines and anti-viral drugs. In this study, an infectious clone for EV-A89 was successfully constructed and recombinant enterovirus A89 (rEV-A89) was generated. The rEV-A89 exhibited similar characteristics such as growth curve, plaque morphology, and dsRNA expression with parental strain. Four amino acid substitutions were identified in the EV-A89 capsid, which were found to enhance viral infection. Mechanistic studies revealed that these substitutions increased the virus's cell-binding ability. Establishing reverse genetic tools for EV-A89 will significantly contribute to understanding viral infection and developing anti-viral strategies.IMPORTANCEEnterovirus A species contain many human pathogens and have been classified into conventional cluster and unconventional cluster. Most of the research focuses on various conventional members, while understanding of the life cycle and infection characteristics of unconventional viruses is still very limited. In our study, we constructed the infectious cDNA clone and single-round infectious particles for the unconventional EV-A89, allowing us to investigate the biological properties of recombinant viruses. Moreover, we identified key amino acids residues that facilitate EV-A89 infection and elucidate their roles in enhancing viral binding to host cells. The establishment of the reverse genetics system will greatly facilitate future study on the life cycle of EV-A89 and contribute to the development of prophylactic vaccines and anti-viral drugs.

Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research.

The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications, enabling the development of effective therapeutic and preventive strategies. In this study, our initial attempts to introduce a NanoLuc luciferase (NLuc) reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies. We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus. Therefore, we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71 (EV-A71), coxsackievirus A10 (CVA10), coxsackievirus A7 (CVA7), coxsackievirus A16 (CVA16), namely EV-A71-HiBiT, CVA16-HiBiT, CVA10-HiBiT, CVA7-HiBiT, and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency. Notably, the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses. A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics. Moreover, these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages. In addition, the HiBiT-tagged viruses were successfully tested in antiviral drug assays, and the sensitivity of the viruses to drugs was not affected by the HiBiT tag. Ultimately, our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal, convenient, and invaluable method for advancing research in the realm of enterovirus virology. Furthermore, HiBiT-tagged enteroviruses exhibit great potential for diverse applications, including the development of antivirals and the elucidation of viral infection mechanisms.

Harnessing the potential of long non-coding RNAs in breast cancer: from etiology to treatment resistance and clinical applications.

Breast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related deaths of females worldwide. It is a complex and molecularly heterogeneous disease, with various subtypes that require different treatment strategies. Despite advances in high-resolution single-cell and multinomial technologies, distant metastasis and therapeutic resistance remain major challenges for BC treatment. Long non-coding RNAs (lncRNAs) are non-coding RNAs with more than 200 nucleotides in length. They act as competing endogenous RNAs (ceRNAs) to regulate post-transcriptional gene stability and modulate protein-protein, protein-DNA, and protein-RNA interactions to regulate various biological processes. Emerging evidence suggests that lncRNAs play essential roles in human cancers, including BC. In this review, we focus on the roles and mechanisms of lncRNAs in BC progression, metastasis, and treatment resistance, and discuss their potential value as therapeutic targets. Specifically, we summarize how lncRNAs are involved in the initiation and progression of BC, as well as their roles in metastasis and the development of therapeutic resistance. We also recapitulate the potential of lncRNAs as diagnostic biomarkers and discuss their potential use in personalized medicine. Finally, we provide lncRNA-based strategies to promote the prognosis of breast cancer patients in clinical settings, including the development of novel lncRNA-targeted therapies.

Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta­analysis of randomized controlled trials.

Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.

Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics.

During the past decade, "membrane lipid therapy", which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of "membrane lipid therapy" for tumors.

An optimized back propagation neural network on small samples spectral data to predict nitrite in water.

Accurate detection of pollutant levels in water bodies using fusion algorithms combined with spectral data has become a critical issue for water conservation. However, the number of samples is too small and the model is unstable, which often leads to poor prediction and fails to achieve the measurement goal well. To address these challenges, this paper proposes a practical and effective method to precisely predict the concentrations of nitrite pollution in aquatic environments. The proposed method consists of three steps. Firstly, the dimension of the spectral data is reduced using Kernel Principal Component Analysis (KPCA), followed by sample augmentation using Generative Adversarial Network (GAN) to reduce calculation cost and increase the diversity and scale of the data. Secondly, several improvement strategies, including multi-cluster competitive and adaptive parameter updating, are introduced to enhance the capability of the Particle Swarm Optimization (PSO) algorithm. The improved PSO algorithm is then applied to optimize the initialization weights and biases of the Back Propagation neural network, thereby improving the model fitting and training performance. Finally, the developed prediction model is employed to predict the test set samples. The result suggests that the R2, RMSE, and MAE values are 0.976290, 0.008626, and 0.006617, which outperform the state-of-the-art and provided a promising model for the prediction of nitrite concentration in water.

Gating of Social Behavior by Inhibitory Inputs from Hippocampal CA1 to Retrosplenial Agranular Cortex.

The retrosplenial cortex has been implicated in processing sensory information and spatial learning, with abnormal neural activity reported in association with psychedelics and in mouse and non-human primate models of autism spectrum disorders (ASDs). The direct role of the retrosplenial cortex in regulating social behaviors remains unclear. In this work, we reveal that neural activity in the retrosplenial agranular cortex (RSA), a subregion of the retrosplenial cortex, is initially activated, then quickly suppressed upon social contact. This up-down phase of RSA neurons is crucial for normal social behaviors. Parvalbumin-positive GABAergic neurons in the hippocampal CA1 region were found to send inhibitory projections to the RSA. Blocking these CA1-RSA inhibitory inputs significantly impaired social behavior. Notably, enhancing the CA1-RSA inhibitory input rescued the social behavior defects in an ASD mouse model. This work suggests a neural mechanism for the salience processing of social behavior and identifies a potential target for ASD intervention using neural modulation approaches.

Research on the Characteristics and Control Technology of Gas Disasters in the Gob of the Nonpillar Working Face Based on the DEM-CFD Coupled Model.

Gob-side entry retained by cutting roof (GERCR) is a novel and widely used nonpillar mining technology, but the gas emissions from gob are large, and the gas migration characteristics change obviously, which easily leads to serious safety accidents such as gas explosions and personnel suffocation. The discrete element method-computational fluid dynamics (DEM-CFD) coupled model was proposed and used to study the gas flow field in gob under this technology. Through the calculation of this coupled model, the gas distribution and emission characteristics of gob under different ventilation modes of GERCR technology were clarified, and the areas where the gas exceeds the limit in the roadway were determined. To prevent and control gas accumulation, three-dimensional gas drainage technology in the GERCR working face was proposed based on the above research conclusions. Through the field application and monitoring, the characteristics of gas emission and the effect of gas drainage in the gob of GERCR technology were verified. The on-site monitoring results show that the DEM-CFD coupled model established above can simulate well the gas emission characteristics of the GERCR gob, and the three-dimensional drainage system can well control the gas accumulation in the roadway. The research results are of great significance to control gas disasters of this novel nonpillar mining technology.

Trends in prescription therapy for adolescents with depression in nine major areas of China during 2017-2021.

Objective: To date, no national-scale drug usage survey for adolescents with depression has been conducted in China, and the purpose of this study was to examine the national trends in prescriptions in Chinese adolescent depression patients from 2017 to 2021. Methods: Prescribing data were extracted from the Hospital Prescription Analysis Cooperative Project. The average number of patients per year, the cost of treatment, and the prescription patterns (monotherapy vs. combination therapy) were analyzed, and subgroup analyses were conducted depending on age, sex, and drug class. Results: The study included 674,099 patients from 136 hospitals located in nine major areas of China. Of all patients, the proportion of adolescents increased from 1.63% in 2017 to 6.75% in 2021. Visits by adolescent depression patients increased from 1,973 in 2017 to 9,751 in 2021, and the corresponding cost increased from 607,598 Chinese Yuan in 2017 to 2,228,884 Chinese Yuan in 2021. The incidence of adolescent depression among female individuals was far beyond that among male individuals. Combination therapy was more frequent than monotherapy, and the most commonly prescribed drugs were antidepressants, antipsychotics, antiepileptics, and antianxietics. Despite the use of sertraline decreasing from 47.90 to 43.39%, it was the most frequently used drug. Conclusion: In summary, the prescriptions and cost of treatment for adolescent depression patients both increased rapidly. The widespread use of those drugs with weak clinical evidence reflects the current state of China, which should arouse our attention. The study can provide references for clinical treatment decisions and a basis for more efficient allocation of healthcare resources by the government.

Efficacy of fecal microbiota transplantation in type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases worldwide, and studies have found significant differences in the composition and ratio of intestinal flora between patients with T2DM and normal glucose tolerance, and fecal microbiota transplantation (FMT) may modulate the composition of the intestinal microbiota thereby alleviating the hyperglycemic state. We conducted a meta-analysis and systematic review of existing randomized controlled trials (RCTs) to assess the efficacy of FMT in T2DM. METHODS: We conducted a computer search of PubMed, Embase, The Cochrane Library, and Web of Science to screen randomized controlled trials studies on FMT treatment for T2DM and extracted data from studies that met inclusion criteria. RevMan 5.4 software and Stata 11 software was used for meta-analysis. The indexes of Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were mainly evaluated after FMT treatment of T2DM patients, and the changes of intestinal flora were evaluated. RESULTS: Four RCTs met the inclusion criteria and were included in the meta-analysis. Results of the meta-analysis showed that compared with the non-FMT group, FMT combined treatment could significantly reduce the PBG level in patients with type 2 diabetes (MD = -0.51, 95% CI: -1.42-0.40, P = 0.27). Compared with single FMT treatment, FMT combined treatment could reduce TG levels in patients with type 2 diabetes (MD = -0.60, 95% CI: -1.12~-0.07, P = 0.03). The levels of TG (MD = -0.26, 95% CI: -0.51~-0.02, P = 0.03), HOMA-IR (MD = -2.73, 95% CI: -4.71~0.75, P = 0.007) and HDL (MD = -0.06,95% CI: -0.10~-0.02, P = 0.003) were significantly decreased after treatment in the single FMT group. The level of TC (MD = -0.65, 95% CI: -1.00~-0.31, P = 0.0002) was significantly decreased after FMT combined treatment. Compared with before treatment, ALT (MD = -2.52, 95% CI: -3.86~-1.17, P = 0.0002) and DBP (MD = -2, 95% CI: -3.32~0.68, P = 0.003) levels decreased after treatment in the single FMT group and the FMT combined group. FPG (MD = -0.94, 95% CI: -1.86~-0.02, P = 0.04), TG (MD = -0.73, 95% CI: -1.42~-0.04, P = 0.04) and TC (MD = -0.94, 95% CI: -1.45~-0.43, P = 0.0003) were significantly decreased after combined drug and diet therapy. Secondly, FMT can promote the colonization and growth of donor-related flora in patients with type 2 diabetes. CONCLUSION: In patients with type 2 diabetes mellitus, FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP, especially in the combined treatment regimen. In addition, FMT can reshape the intestinal flora and establish the balance of dominant flora.

A cysteine protease inhibitor GC376 displays potent antiviral activity against coxsackievirus infection.

Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.

The Evaluation of the Departmental Resources and Positions Within the Inter-Departmental Collaborative Networks: A Case Study on the Joint Prevention and Control Mechanism in China.

Introduction: This study examines the inter-departmental emergency response dynamics within China's Joint Prevention and Control Mechanism (JPCM). Departments' positions in the network are fundamental to understanding the overall structure and operation of the collaborative emergency response. Moreover, understanding the influence of departmental resources on departmental positions promotes efficient inter-departmental collaboration. Methods: The study uses regression analysis to empirically investigate the departmental resources to departments' participation in the JPCM collaboration. The independent variable adopts the departments' positions by statistically presenting the departments' centrality using social network analysis. The dependent variables employ departmental resources, including departmental duties, staffing levels, and approved annual budgets based on data from the government website. Results: The result of social network analysis shows that in JPCM inter-departmental collaboration, the Ministry of Transport, Health Commission, Ministry of Public Security, Ministry of Emergency Management, Ministry of Culture and Tourism, Ministry of Education, and Development and Reform Commission are mainly involved. The regression analysis result indicates that the department's engagement in collaborative actions is determined and influenced by the department's statutory duties. The more statutory duties department has, the more it is in a critical position and role for JPCM. Discussion: The study can assist emergency management practitioners and academic departments in utilizing evidence-based approaches to justify the collaboration and involvement of participating departments. The analysis of the collaborative networks considering JPCM in China by the participation and organization logic is of fundamental significance for arguing for complementing COVID emergency management and inter-departmental emergency collaboration studies.

Carboxylated Poly (p-Phenylene Terephthalamide) Reinforced Polyetherimide for High-Temperature Dielectric Energy Storage.

Dielectric energy storage polymers play a vital role in advanced electronics and electrical systems, due to their high breakdown strength, excellent reliability, and easy fabrication. However, the low dielectric constant and poor thermal resistance of dielectric polymers limit their energy storage density and working temperatures, making them less versatile for broader applications. In this work, a novel carboxylated poly (p-phenylene terephthalamide) (c-PPTA) is synthesized and employed to simultaneously enhance the dielectric constant and thermal resistance of polyetherimide (PEI), leading to a discharged energy density of 6.4 J cm-3 at 150 °C. The introduction of c-PPTA molecules effectively reduces the Πï£¿Π stacking effect and increases the average chain spacing between polymer molecules, which is conducive to improving the dielectric constant. Additionally, c-PPTA molecules with stronger positive charges and high dipole moments can capture electrons, resulting in reduced conduction loss and enhanced breakdown strength at high temperatures. The coiled capacitor fabricated with the PEI/c-PPTA film exhibits superior capacitance performances and higher working temperatures compared to commercial metalized PP capacitors, demonstrating great potential for dielectric polymers in high-temperature electronic and electrical energy storage systems.

Printing Ready Topology Optimization for Material Extrusion Polymer Additive Manufacturing.

Additive manufacturing-oriented topology optimization features in the extreme geometric complexity that magnifies the product functional performance. However, the increased geometric complexity makes postprocessing of the designs technically nontrivial and sometimes inefficient because of too many structural details. To address this issue, this article presents a novel printing-ready topology optimization method whereby the topological designs can be directly exported in the format of a printing-ready G-code, which saves the postprocessing efforts of stereo lithograph (STL) model generation, model slicing, and tool path planning. More importantly, the slicing and tool path information can be tracked all the time during optimization to facilitate the evaluation of the tool path-related material constitutive model, for example, the fiber-reinforced composites, so as to improve the numerical analysis accuracy and the design result optimality. Finally, three case studies are performed to test the postprocessing efficiency of the printing-ready approach and the multi-scale design case, which demonstrates the outstanding high efficiency characteristic of the proposed approach.

Perturbing plasma membrane lipid: a new paradigm for tumor nanotherapeutics.

Cancer is generally considered a result of genetic mutations that cause epigenetic changes, leading to anomalous cellular behavior. Since 1970s, an increasing understanding of the plasma membrane and specifically the lipid alterations in tumor cells have provided novel insights for cancer therapy. Moreover, the advances in nanotechnology offer a potential opportunity to target the tumor plasma membrane while minimizing side effects on normal cells. To further develop membrane lipid perturbing tumor therapy, the first section of this review demonstrates the association between plasma membrane physicochemical properties and tumor signaling, metastasis, and drug resistance. The second section highlights existing nanotherapeutic strategies for membrane disruption, including lipid peroxide accumulation, cholesterol regulation, membrane structure disruption, lipid raft immobilization, and energy-mediated plasma membrane perturbation. Finally, the third section evaluates the prospects and challenges of plasma membrane lipid perturbing therapy as a therapeutic strategy for cancers. The reviewed membrane lipid perturbing tumor therapy strategies are expected to bring about necessary changes in tumor therapy in the coming decades.

Genomic characterisation of de novo EGFR copy number gain and its impact on the efficacy of first-line EGFR-tyrosine kinase inhibitors for EGFR mutated non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation generally respond well to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, genomic characterisation of de novo EGFR copy number gain (CNG) and its impact on the efficacy of first-line EGFR-TKIs remains unclear. METHODS: This multicenter, retrospective and real-world study included two cohorts that enroled EGFR mutant NSCLC patients. EGFR CNG was tested by next-generation sequencing of untreated tissue specimens. Cohort 1 detected the impact of EGFR CNG on first-line EGFR-TKIs treatment, and cohort 2 explored the genomic characterisation. RESULTS: Cohort 1 enroled 355 patients from four cancer centres between January 2013 and March 2022. The patients were divided into three groups, included the EGFR non-CNG, EGFR CNG, and EGFR uncertain-CNG. No significant difference in progression-free survival (PFS) was found between the three groups (10.0 months vs. 10.8 months vs. 9.9 months, respectively, p = 0.384). Furthermore, the overall response rate was not statistically significant in the EGFR CNG group compared to the EGFR non-CNG or uncertain arm (70.3% vs. 63.2% vs. 54.5%, respectively, p = 0.154). Cohort 2 included 7876 NSCLC patients with 16.4% showing EGFR CNG. Gene mutations such as TP53, IKZF1, RAC1, MYC, MET, CDKN2A/B and alterations of the metabolic-related and ERK signalling pathway were significantly associated with patients with EGFR CNG compared to those without. CONCLUSIONS: De novo EGFR CNG had no effect on the efficacy of first-line EGFR-TKI treatment in EGFR mutant NSCLC patients, and tumours with EGFR CNG had more complex genomic profiles than those without.

Understanding the copper-iridium nanocrystals as highly effective bifunctional pH-universal electrocatalysts for water splitting.

It is pivotal to develop an economical, effective, and stable catalyst to promote the oxygen/hydrogen evolution reaction (OER/HER) throughout pH electrolytes, as the demand for hydrogen energy will increase greatly with the future development. Herein, a series of Ir-Cu nanoparticle composite carbon (IrxCuy/C) catalysts are successfully synthesized using ethylene glycol reduction. In addition, the structure, morphology and composition of the electrocatalysts were systematically characterized, and the OER/HER performance of the catalysts was also tested under different pH conditions. According to experimental findings, amorphous Ir3Cu/C has superior competent performance to catalyze oxygen (O2) production in alkaline and acidic environments. The comparatively low overpotentials required are 222 mV and 304 mV, respectively, while generating a current density of 10 mA cm-2. The reduced amount of precious metal and the further improvement in activity and durability make Ir3Cu/C an excellent noble metal-based electrocatalyst. Meanwhile, IrCu/C has significant electrocatalytic performance for the HER in acidic media.

Efficacy and safety of broad spectrum penicillin with or without beta-lactamase inhibitors vs first and second generation cephalosporins as prophylactic antibiotics during cesarean section: a systematic review and meta-analysis.

This study assessed the efficacy and safety between broad spectrum penicillin (P2) with or without beta-lactamase inhibitors (P2+) versus first and second generation cephalosporins (C1&C2) in the prevention of post-cesarean infections. Relevant randomized controlled trials (RCTs) were searched in English and Chinese databases: nine RCTs were involved. Six trials compared P2+ vs C1&C2, no differences were found between interventions for endometritis, wound infection, urinary tract infection, febrile morbidity and maternal rashes. Four trials compared P2 vs C1&C2, no differences were found between interventions for endometritis, febrile morbidity, wound infection and urinary tract infection. Postoperative hospitalization was longer for women in P2 than C1&C2. Based on these results, P2/P2+ and C1&C2 may have similar efficacy on postoperative infections after cesarean section, there is no data on infant outcomes. PROSPERO Registration Number: CRD42022345721.