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Abstract To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), P = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, P

Abstract Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4+ T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4+ T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4+ T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4+ T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development.

Abstract Background As a prevalent and deadly malignant tumor, the treatment outcomes for late-stage patients with cervical squamous cell carcinoma (CSCC) are often suboptimal. Previous studies have shown that tumor progression is closely related with tumor metabolism and microenvironment reshaping, with disruptions in energy metabolism playing a critical role in this process. To delve deeper into the understanding of CSCC development, our research focused on analyzing the tumor microenvironment and metabolic characteristics across different regions of tumor tissue. Methods Utilizing spatial transcriptomics (ST) sequencing technology, we conducted a study on FFPE (formalin-fixed paraffin-embedded) tumor samples from CSCC patients. Coupled with single-cell RNA sequencing (scRNA-seq) data after deconvolution, we described spatial distribution maps of tumor leading edge and core regions in detail. Tumor tissues were classified into hypermetabolic and hypometabolic regions to analyze the metabolism profiles and tumor differentiation degree across different spatial areas. We also employed The Cancer Genome Atlas (TCGA) database to examine the analysis results of ST data. Results Our findings indicated a more complex tumor microenvironment in hypermetabolic regions. Cell-cell communication analysis showed that various cells in tumor microenvironment were influenced by the signalling molecule APP released by cancer cells and higher expression of APP was observed in hypermetabolic regions. Furthermore, our results revealed the correlation between APP and the transcription factor TRPS1. Both APP and TRPS1 demonstrated significant effects on cancer cell proliferation, migration, and invasion, potentially contributing to tumor progression. Conclusions Utilizing ST, scRNA-seq, and TCGA database, we examined the spatial metabolic profiles of CSCC tissues, including metabolism distribution, metabolic variations, and the relationship between metabolism and tumor differentiation degree. Additionally, potential cancer-promoting factors were proposed, offering a valuable foundation for the development of more effective treatment strategies for CSCC.

Abstract Millions of people worldwide die of acute myeloid leukaemia (AML) each year. Although N6-methyladenosine (m6A) modification has been reported to regulate the pathogenicity of AML, the mechanisms by which m6A induces dysfunctional hematopoietic differentiation in elderly AML patients remain elusive. This study elucidates the mechanisms of the m6A landscape and the specific roles of m6A regulators in hematopoietic cells of elderly AML patients. Notably, fat mass and obesity-associated protein (FTO) was found to be upregulated in hematopoietic stem cells (HSCs), myeloid cells, and T-cells, where it inhibits their differentiation via the WNT signaling pathway. Additionally, elevated YT521-B homology domain family proteins 2 (YTHDF2) expression in erythrocytes was observed to negatively regulate differentiation through oxidative phosphorylation, resulting in leukocyte activation. Moreover, IGF2BP2 was significantly upregulated in myeloid cells, contributing to an aberrant chromosomal region and disrupted oxidative phosphorylation. m6A regulators were shown to induce abnormal cell-cell communication within hematopoietic cells, mediating ligand-receptor interactions across various cell types through the HMGB1-mediated pathway, thereby promoting AML progression. External validation was conducted using an independent single-cell RNA sequencing (scRNA-Seq) dataset. The THP-1 and MV411 cell lines were utilized to corroborate the m6A regulator profile; in vitro experiments involving short hairpin RNA (shRNA) targeting FTO demonstrated inhibition of cell proliferation, migration, and oxidative phosphorylation, alongside induction of cell cycle arrest and apoptosis. In summary, these findings suggest that the upregulation of m6A regulators in HSCs, erythrocytes, myeloid cells, and T-cells may contribute to the malignant differentiation observed in AML patients. This research provides novel insights into the pathogenesis of AML in elderly patients and identifies potential therapeutic targets.

Abstract Background Influenza vaccination confers broad benefits in the elderly and certain high-risk populations, but its effectiveness in patients with acute heart failure (HF) is uncertain. Rates of influenza vaccination are low in China due to poor awareness, cultural misunderstandings, and cost. Aims To determine the effectiveness of influenza vaccination in patients with acute HF admitted to hospitals in China. Methods The second Population Assessment of Influenza and Disease Activity (PANDA II) study is a two-arm, parallel-group, county-level hospital-based, cluster randomized controlled trial to determine the benefits and risks of full access to routine free influenza vaccination before hospital discharge, compared to routine limited use of influenza vaccination, on the primary endpoint of death or hospital readmission. Consecutive hospitalized patients at each site are enrolled to a target of 50 participants in each autumn–winter influenza outbreak period (October to March) over 3 consecutive years to reach the required sample size. Patients are centrally followed up at 1, 3, 6, and 12 months after hospital discharge (or death if earlier). Site numbers varied across year according to predicted influenza activity and logistical reasons. Conclusions This study offers a unique chance to clarify uncertainties surrounding the effectiveness of influenza vaccination in patients with HF and to lay the groundwork for future prevention strategies. Trial registration This trial was registered with the acronym PANDA II (Population Assessment of Influenza and Disease Activity) at ChiCTR.org.cn (ChiCTR2100053264). Registered on 17 November 2021.

Abstract Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application in solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T cells. Despite improvements from fourth and next-generation CAR-T cells, new challenges include systemic toxicity from continuously secreted proteins, low productivity, and elevated costs. Recent research targets genetic modifications to boost killing potential, metabolic interventions to hinder tumor progression, and diverse combination strategies to enhance CAR-T cell therapy. Efforts to reduce the duration and cost of CAR-T cell therapy include developing allogenic and in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies and platforms enhance the potential of CAR-T cell therapy to overcome limitations in treating solid tumors. This review explores strategies to optimize CAR-T cell therapies for solid tumors, focusing on enhancing cytotoxicity and overcoming application restrictions. We summarize recent advances in T cell subset selection, CAR-T structural modifications, infiltration enhancement, genetic and metabolic interventions, production optimization, and the integration of novel technologies, presenting therapeutic approaches that could improve CAR-T cell therapy’s efficacy and applicability in solid tumors.

Abstract In recent years, cell therapy research and commercialization have significantly accelerated, especially after the US FDA approved CAR-T therapy. While cell therapy now leads immuno-oncology in clinical trials, challenges such as redundant R&D, target clustering, and unmet clinical need remain. Since 2017, China has established a dual-track regulatory framework, facilitating rapid growth in its cell therapy pipeline, making it the second largest in the world. Despite this progress, China faces similar global challenges. Our study covers 2,794 registered cell therapy clinical trials in China, including 2,045 for immune cell, 683 for stem cell, and 66 for other somatic cell. It compares cell therapy products approved in China, the US, EU, and Japan, analyzes the evolving clinical trials landscape, and highlights the characteristics of investigator-initiated trials (IITs) and industry-sponsored trials (ISTs) in China. Our findings indicate that despite the high disease burden and unmet clinical needs for solid tumors in China, over 38% of trials between 2021 and 2023 focused on hematologic malignancies with established targets like CD19 and BCMA. Over 90% of trials are IITs, which show notable clinical differences from ISTs. We recommend that Chinese regulators establish specific guidelines to promote clinical-value-driven research. Stricter regulatory standards should also be implemented to minimize redundant R&D. Additionally, a value-based reimbursement system for within-class targeted cell therapy products may further reduce duplicated R&D efforts. Given the prevalence of IITs, specifying requirements for IITs could create a new pathway to accelerate product development and better address unmet clinical needs in China.

Abstract Background Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA−I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. Methods The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA−I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA−I interval was analyzed. Results A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6–16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9–40), of whom 18 died during ICU stay. The GA−I levels were negative correlation with CRT (r = 0.369, P

Abstract Background Cystic echinococcosis (CE) is prevalent in livestock farming regions around the world. However, it remains relatively rare compared to other infectious diseases. CE typically affects the liver, lungs, brain, and kidneys. Spinal and pleural wall involvement is exceedingly rare. We report a unique case of intradural and pleural wall CE in a young male, successfully treated with surgery and postoperative medication. Case presentation A 19-year-old Tibetan male from the Qinghai-Tibet Plateau was diagnosed with intradural and pleural wall CE through imaging, serology, and surgical pathology. According to the Dew/Braithwaite & Lees (BL) classification, his condition was an exceptionally rare form of spinal echinococcosis, compounded by an even rarer pleural wall involvement. Prompt surgical intervention and postoperative medication resulted in significant improvement in spinal cord compression symptoms. Conclusions This case highlights the diagnostic and therapeutic challenges of rare CE locations. MRI proved superior to CT in diagnosing bony cystic echinococcosis. Early surgical intervention combined with medication facilitates spinal cord function recovery, providing valuable insights for managing similar cases.

Abstract Background Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. “EMERALD” is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions. Methods The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions. Discussion This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector’s contribution to addressing the growing burden of non-communicable diseases in China. Trial registration The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024).

Abstract In a multicenter case–control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA’s capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Abstract Background Nursing literature suggested that patient mistreatment has significant impacts on nurses’ emotions and job burnout. Yet, further research is needed to understand the underlying mechanism and the spillover effect on nurses’ families. Leveraging the goal progress theory, this study aimed to examine the association between patient mistreatment, nurses’ emotional exhaustion, and work-family conflict, as well as the mediating role of social sharing of negative work events and the moderating role of perceived organizational support. Methods During the COVID-19 pandemic in China, a cross-sectional study was conducted with a sample of 1627 nurses from the Hematology Specialist Alliance of Chongqing from October to November 2022. Questionnaires were administered to measure patient mistreatment, perceived organizational support, social sharing of negative work events, emotional exhaustion, and work-family conflict. Hierarchical linear regression and conditional processes were used for statistical analyses. Results Patient mistreatment was positively associated with emotional exhaustion (β = 0.354, p

The biosorption mechanism of Cr(VI) by live and heat-killed Saccharomyces cerevisiae was investigated in this study. The adsorption behavior of chromium by different active cells was compared based on solution pH, biosorption time, chromium concentration, and cell concentration. The biosorption dynamic process can be categorized into three stages: rapid biosorption stage, stable precipitation stage, and further biomineralization stage. The two kinds of cells have the same ability to remove chromium ions, with the adsorption rate being above 99 % in a certain time (approximately 20 h). When the solution pH value ranged from 1.0 to 5.0, HCrO4- was identified as the main state of chromium species. Rectangular-shaped flakes with dimensions around 100 nanometers were observed on the surface of live cells, while rod precipitate appeared on the heat-killed cells’ surface. These chromium compounds may be mineralized into bentorite Ca6Cr2(SO4)3(OH)12·26 H2O (ICDD-PDF #33–0248) and chromite crystal CrO(OH) (ICDD-PDF #09–0331).

Abstract Optimizing the electronic structure with increasing intrinsic stability is a usual method to enhance the catalysts’ performance. Herein, a series of cerium dioxide (CeO2−δ) based solid solution materials is synthesized via substituting Ce atoms with transition metal (Co, Cu, Ni, etc.), in which Co0.07Ce0.93O2−δ shows optimized band structure because of electron transition in the reaction, namely Co3+ (3d64s0) + Ce3+ (4f15d 06s0) → Co2+ (3d74s0) + Ce4+ (4f05d06s0), with more stable electronic configuration. The in situ Raman spectra show a stable F2g peak at ≈452 cm−1 of Co0.07Ce0.93O2−δ, while the F2g peak in CeO2−δ almost disappeared during HER progress, demonstrating the charge distribution of *H adsorbed on Co0.07Ce0.93O2−δ is more stable than *H adsorbed on CeO2−δ. Density functional theory calculations reveal that Co0.07Ce0.93O2−δ solid solution increases protonation capacity and favors for formation of *H in alkaline media. General guidelines are formulated for optimizing adsorption capacity and the volcano plot demonstrates the excellent catalytic performance of Co0.07Ce0.93O2−δ solid solution. The alkaline anion exchange membrane water electrolysis based on Co0.07Ce0.93O2−δ/NiFe LDH realizes a current density of 1000 mA cm−2 at ≈1.86 V in alkaline seawater at 80 °C and exhibits long‐term stability for 450 h.

BackgroundTo investigate the prognostic factors for stage IIb and IIIa lung adenocarcinoma following radical surgery and to explore the molecular mechanisms underlying these prognostic markers, focusing on the role of PIK3C2G.MethodsA retrospective analysis of patients with stage IIb or IIIa lung adenocarcinoma who underwent radical surgery between January 2017 and June 2023 was conducted. Baseline clinical and pathological data, surgical methods, and postoperative treatments were analyzed to assess overall survival (OS). Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors. Whole-exome sequencing (WES) was performed on a subset of the patients with preserved tumor tissues and no matched targeted therapies to identify high-frequency mutated genes. Functional experiments in A549 lung adenocarcinoma cells were performed to evaluate the role of the significant genes in tumor progression through cell proliferation, migration, invasion, apoptosis, and cell cycle assays.ResultsThe survival analysis of 877 stage IIb and IIIa lung adenocarcinoma cases revealed significant differences in clinical characteristics and outcomes. Stage IIb patients had a median OS of 58 months compared to 37 months for stage IIIa, with 5-year OS rates of 46.9% and 30.5%, respectively. Univariate and multivariate Cox regression identified pathological stage, number of positive lymph nodes, age, and targeted therapy as independent prognostic factors. WES of 184 patients with no matched targeted therapies revealed high-frequency mutations in genes such as TP53 and PIK3C2G, with the latter emerging as the most significant prognostic marker. Functional assays demonstrated that the knockdown of PIK3C2G in A549 cells significantly reduced proliferation, migration and invasion while promoting apoptosis and disrupting cell cycle progression.ConclusionPIK3C2G was identified as a significant prognostic marker in stage IIb and IIIa lung adenocarcinoma, with functional data supporting its therapeutic potential. Taken together, this study integrates clinical and molecular findings, which could be used as a reference to guide personalized treatment strategies.

Parasites in mollusks are often neglected by humans, while some species were reported to be harmful to economic mollusks and caused production decrease. Metazoan parasites of mollusk studies from the China Seas started relatively later than other countries. To promote long-term studies on the distribution and diversity of metazoan parasites of mollusks from the China Seas, a comprehensive review has been carried out based on the available literature. The purpose of this study was to perform a critical review about the metazoan parasites associated with mollusks that are useful for the discovery of new metazoans. This publication summarizes information on metazoan parasites of Chinese mollusks from 1932 to 2024. The information is presented and contains 128 species of parasites, distributed among the higher taxa as follows: Turbellaria (2 species), Trematoda (34 species), Cestoda (1 species), Annelida (38 species), Arthropoda (48 species), Porifera (2 species), Cnidaria (1 species), and Mollusca (2 species). Many records of parasites not identified to the species level are also included. Collectively, this review provides a synopsis of the known metazoan parasites of mollusks from the China Seas, as well as presents the known relationship between metazoan parasites and the mollusks, which will broaden our knowledge on the metazoan parasites of mollusks. It is important as it highlights the lack of metazoan parasite studies done in the China Seas and the need for more parasite biodiversity work.

BackgroundAmmonia (NH3) and hydrogen sulfide (H2S) are produced during digestion in the human gut, yet the impact of these internally generated gases on male reproduction have received limited attention in scientific research.MethodsWe systematically reviewed 935 scientific publications, spanning from 1947 to 2023, focusing on external or internal NH3 and/or H2S, male infertility, and gut microbiota. Meta-analysis was conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies.ResultsOur findings revealed that the internal NH3 and/or H2S were negatively related to the Lactobacillus, which is beneficial to male fertility, whereas NH3 and H2S were positively related to Bacteroides, which showed negative effects on male fertility. The meta-analysis comparing Lactobacillus and Bacteroides levels with NH3 showed statistically significant results (p

BackgroundHypomorphic mutations in the phosphoacetylglucosamine mutase 3 (PGM3) gene cause a glycosylation disorder that leads to immunodeficiency. It is often associated with recurrent infections and atopy. The exact etiology of this condition remains unclear.ObjectiveThis study aimed to characterize the phenotypes and immunological features associated with PGM3 insufficiency and investigate potential disease mechanisms.MethodsA systematic review of 44 published cases of PGM3 variants was performed, followed by T-cell phenotyping of two patients with PGM3 variants. A genotype-phenotypic severity study was conducted by comparing the residual PGM3 expression of the 12 reconstituted variants in human B cells. A PGM3 inhibitor was used to assess its effect on CD4+ T cell proliferation and differentiation.ResultsPatients with PGM3 variants frequently presented with recurrent infections and atopy, accompanied by reduced naïve CD4+ T cell counts. A genotype–phenotype study showed that low levels of residual PGM3 expression are correlated with disease severity. Notably, inhibition of PGM3 activity impaired TCR-mediated CD4+ T cell proliferation and the synthesis of UDP-GlcNAc, complex N-glycans, O-GlcNAc, glycolytic stress, and mitochondrial respiration during proliferation in a dose-dependent manner. Partial loss of PGM3 activity was observed to preferentially enhance Th1 and Th2 differentiation, while attenuating Th17 and Treg differentiation, consistent with clinical observations.ConclusionPGM3 is a critical regulator of CD4+ T-cell proliferation and differentiation. These findings provide new insights into the diverse clinical manifestations and therapeutic development of PGM3 deficiency.

BackgroundAs China is one of the countries with the highest recorded cases of Immune-Mediated Inflammatory Diseases (IMIDs), these diseases have also emerged as a serious public health concern. Biosimilars, potentially lower-cost versions of biologics, may improve access to more affordable yet comparably effective treatments. Encouragingly, China launched its abbreviated biosimilar pathway in 2015, and since then, a large number of biosimilars have been approved. However, systematic studies on the therapeutic efficacy and economic impact of IMIDs biosimilars are lacking in China. This study aims to assess the clinical benefits (including efficacy/effectiveness, safety, and immunogenicity), cost and uptake of adalimumab biosimilars, tocilizumab biosimilars, and infliximab biosimilars compared with their reference biologics in patients with IMIDs in China.MethodsIMIDs biosimilars and their reference drugs approved in China between 2015 and 2024 were identified. Head-to-head randomized clinical trials (RCTs) and real-world cohort studies on adalimumab, tocilizumab and infliximab and their biosimilars for the treatment of IMIDs were assessed. PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and Listed Drug Database of China National Medical Products Administration were searched for clinical trials and cohort studies on biosimilars for IMIDs from their inception to November 1, 2024. We evaluated the monthly treatment costs and quarterly uptakes of these biosimilars and their reference biologics in China. Besides, we simulated the impact of biosimilar substitution in different scenarios. Meta-analyses were performed using a random-effects model to evaluate the efficacy, safety, and immunogenicity of treatments, including pooled risk ratios (RR) for ACR20 for rheumatoid arthritis, ASAS20 for ankylosing spondylitis, and PASI for plaque psoriasis, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), anti-drug antibodies (ADAs), and neutralizing antibodies (Nabs), with 95% credible intervals (CrIs).FindingsA total of 12 RCTs involving 5,717 patients with IMIDs were analyzed, including 12 approved biosimilars of adalimumab, infliximab, and tocilizumab. The primary endpoints of adalimumab (7 RCTs with 3,174 patients; RR, 1.02; 95% CrI, 0.99–1.06, p = 0.33), infliximab (3 RCTs with 1,291 patients; RR, 1.02; 95% CrI, 0.94–1.11, p = 0.98), tocilizumab (2 RCTs with 1,252 patients; RR, 1.01, 95% CrI, 0.94–1.08) met equivalence with reference biologics. Additionally, there was no significant difference between biosimilars and their reference biologics in the secondary endpoints. Overall, biosimilars demonstrated comparable safety (TEAEs: RR, 0.99; 95% CrI, 0.95–1.02, p = 0.44) (SAEs: RR, 0.80; 95% CrI, 0.42–1.54, p = 0.50) and immunogenicity (ADA: RR, 1.00; 95% CrI, 0.95–1.04, p = 0.85) (Nabs: RR, 0.93; 95% CrI, 0.82–1.05, p = 0.25) profiles to reference biologics. These findings were consistent with the cohort studies. In 2024, IMIDs biosimilars are available at 63 to 82% of the price per unit of the reference drugs, with uptake rates of 16.5 to 72.1% in China. Patients with IMIDs using these biosimilars could save between $874 and $2,184 per month in treatment costs, equivalent to 1.8 to 7.0 times the per capita monthly disposable income in China in 2024. Simulation showed that with 100% biosimilar substitution, savings would increase to $22.98 M, $33.83 M, and $3.82 M for adalimumab, infliximab, and tocilizumab, respectively. This would enable treatment for an additional 6,700, 9,863, and 4,373 patients, respectively.InterpretationOur study revealed that IMID biosimilars in China provide clinical benefits comparable to their reference biologics evidenced by high-quality RCTs and cohort studies with offer significant cost savings in China. Encouraging China’s national volume-based procurement and multi-stakeholder collaboration may help accelerate the substitution of IMIDs biosimilars.

Abstract The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the “responders”, n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.

Abstract As one of the most promising electrode materials for capacitive deionization (CDI), the development of carbon materials with controllable pore structure and continuous mass production is essential for their practical application. Herein, a facile ultrasonic spray pyrolysis method was developed to synthesize surface-functionalized wrinkled hierarchical porous carbon spheres (HCS) with unique interconnected multi-cavity structures. The wrinkled and interconnected multi-cavity hierarchical pores of the HCS play a crucial role in providing accessible ion adsorption sites and promoting ion diffusion and storage in the “multi-cavity warehouse”. The carboxyl groups on the surface of HCS generate a negative charge that promotes the adsorption of cations. The optimized HCS possesses outstanding desalination capacity (114.25 mg g− 1), fast adsorption rate (6.57 mg g− 1 min− 1), and superior cycling stability (95%). Meanwhile, the HCS exhibited impressive desalination capacities in brackish water. Furthermore, the density functional theory calculation results confirmed that the synergistic effect of carboxyl groups and defects significantly enhanced the Na+ adsorption capacity and facilitated ion diffusion. This study extends the synthesis method of surface-functionalized hierarchical porous carbon, which is expected to facilitate the development of CDI electrode materials.

Abstract Background Stroke and thromboembolism in nonvalvular atrial fibrillation (NVAF) primarily arise from thrombi or sludge in the left atrial appendage (LAA). Comprehensive insight into the characteristics of these formations is essential for effective risk assessment and management. Methods We conducted a single-center retrospective observational of 176 consecutive NVAF patients with confirmed atrial/appendage thrombus or sludge determined by a pre-ablation transesophageal echocardiogram (TEE) from December 2017 to April 2019. We obtained clinical and echocardiographic characteristics, including left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV). Data analysis focused on identifying the morphology and location of thrombus or sludge. Patients were divided into the solid thrombus and sludge groups, and the correlation between clinical and echocardiographic variables and thrombotic status was analyzed. Results Morphological classification: In total, thrombi were identified in 78 patients, including 71 (40.3%) mass and 7 (4.0%) lamellar, while sludge was noted in 98 (55.7%). Location classification: 92.3% (72/78) of patients had thrombus confined to the LAA; 3.8% (3/78) had both LA and LAA involvement; 2.7% (2/78) had LA, LAA and RAA extended into the RA, the remained 1.2%(1/78) was isolated to RAA. 98.0% (96/98) of patients had sludge confined to the LAA; the remaining 2.0% (2/98) were present in the atrial septal aneurysm, which protrusion of interatrial septum into the RA. The thrombus and sludge groups showed low LAAeV (19.43 ± 9.59 cm/s) or LAAfV (17.40 ± 10.09 cm/s). Only LA dimension ≥ 40 mm was independently associated with the thrombus state in the multivariable model. Conclusion This cohort study identified rare thrombus morphology and systematically summarized the classification of thrombus morphology. The distribution of thrombus and sludge outside limited to LAA was updated, including bilateral atrial and appendage involvement and rare atrial septal aneurysm sludge. LAAeV and LAAfV were of limited value in distinguishing solid thrombus from sludge. Clinical Trial Number ChiCTR-OCH-13,003,729.

ABSTRACT Background Autologous hematopoietic stem cell transplantation (ASCT) has emerged as a cornerstone in multiple myeloma (MM) management, offering the prospect of prolonged disease control. However, the induction chemotherapy drugs required prior to ASCT carry cardiovascular toxicity (CVT), potentially leading to a range of cardiovascular complications. Methods and Results This retrospective observational study, conducted at Guangdong Provincial People's Hospital from January 2020 to December 2023, analyzed 47 of the initial 173 patients who met the criteria. The cohort, comprising 22 males (46.81%) and 25 females (53.19%), had a mean age of 55.68 ± 11.38 years. They underwent various induction chemotherapy regimens, receiving a median of 5 (4–6) cycles of the course over an average duration of 7.10 ± 2.46 months. Before ASCT treatment following induction chemotherapy, echocardiographic findings indicated reductions in left ventricular end‐systolic dimension, right atrial diameter, E‐wave velocity, E/e' ratio, and the E/A ratio. The latter altered from a pretreatment value greater than 1 to posttreatment less than 1, marking diastolic dysfunction emergence or aggravation in 51.06% of patients. The electrocardiographic data indicate a reduced heart rate and prolonged P‐wave duration and P‐R duration, with an increase in arrhythmia incidence to 19.15% following induction chemotherapy. Conclusion Induction chemotherapy, administered prior to ASCT in patients with MM, can lead to the emergence or aggravation of cardiac diastolic dysfunction and increase the incidence of arrhythmic events. Therefore, it is crucial to emphasize the importance of balancing the benefits and risks of induction chemotherapy to maximize its efficacy while minimizing CVT.

IntroductionIntrauterine transfusion of platelet-rich plasma (PRP) has become a new treatment for thin endometrium (TE) in recent years, but its low efficacy due to rapid release of growth factors limits its clinical use. Platelet-rich fibrin (PRF) starts the coagulation cascade reaction immediately after the blood comes into contact with the test tube. The natural coagulation process results in stable platelet activation and the slow release of growth factors.MethodsIn our study, primary human endometrial stromal cells (hESCs) were extracted from endometrial tissue. PRP and PRF were prepared from the patient cubital vein blood. Stromal cells were cultured in conditioned medium supplemented with PRP and PRF. Differences in cell behavior were observed by cell proliferation test and cell migration test. The relative expression levels of apoptotic Bax and antiapoptotic Bcl-2 genes were measured by qRT-PCR. The release of growth factors from PRP and PRF was detected by ELISA.ResultsWe found that both PRP and PRF inhibited apoptosis of hESCs, which favored cell proliferation and migration. In addition, PRF releases growth factors for a longer period of time compared to PRP.DiscussionPRF offer a more sustained therapeutic effect compared to PRP, which provides a new idea for endometrial regeneration and repair.

Abstract Background To investigate factors associated with different reproductive outcomes in patients with Caesarean scar pregnancies (CSPs). Methods Between May 2017 and July 2022, 549 patients underwent ultrasound-guided uterine aspiration and laparoscopic scar repair at the Gynaecology Department of Hubei Maternal and Child Health Hospital. Ultrasound-guided uterine aspiration was performed in patients with type I and II CSPs, and laparoscopic scar repair was performed in patients with type III CSP. The reproductive outcomes of 100 patients with fertility needs were followed up and compared between the groups. Results Of 100 patients, 43% had live births (43/100), 19% had abortions (19/100), 38% had secondary infertility (38/100), 15% had recurrent CSPs (RCSPs) (15/100). The reproductive outcomes of patients with CSPs after surgical treatment were not correlated with age, body mass index, time of gestation, yields, abortions, Caesarean sections, length of hospital stay, weeks of menopause during treatment, maximum diameter of the gestational sac, thickness of the remaining muscle layer of the uterine scar, type of CSP, surgical method, uterine artery embolisation during treatment, major bleeding, or presence of uterine adhesions after surgery. Abortion after treatment was the only risk factor affecting RCSPs (odds ratio 11.25, 95% confidence interval, 3.302–38.325; P

Abstract Cancer stem cells (CSCs) are a sub-population of cells possessing high tumorigenic potential, which contribute to therapeutic resistance, metastasis and recurrence. Eradication of CSCs is widely recognized as a crucial factor in improving patient prognosis, yet the effective targeting of these cells remains a major challenge. Here, we show that the lysosomal cation channel TRPML1 represents a promising target for CSCs. TRPML1 is highly expressed in breast cancer cells and exhibits sensitivity to salinomycin, a drug known to selectively eliminate CSCs. Pharmacological inhibition and genetic depletion of TRPML1 promote ferroptosis in breast CSCs, reduce their stemness, and enhance the sensitivity of breast cancer cells to chemotherapy drug doxorubicin. The inhibition and knockout of TRPML1 also demonstrate significant suppression of tumor formation and growth in the mouse xenograft model. These findings suggest that targeting TRPML1 to eliminate CSCs may be an effective strategy for the treatment of breast cancer.

Abstract Aims Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study. Methods and results We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all‐cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m2), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46–2.32)], all‐cause mortality [HR 1.73 (1.34–2.25)], and HF hospitalization [HR 1.83 (1.40–2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01–1.57), 2.21 (1.45–3.35), and 1.15 (0.81–1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies. Conclusions BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.

Abstract Background As a primary form of work-related violence in the healthcare sector, patient mistreatment negatively impacts nurses’ well-being. To date, there has yet reached a definitive conclusion on the mediating mechanism and boundary conditions behind the influence of patient mistreatment on nurses’ emotional exhaustion. Methods This study employed a convenience sampling method to recruit a sample of 1672 nurses from public hospitals in Western China. The data were collected through anonymous self-report questionnaires and analyzed using hierarchical regression and conditional processes to investigate a theoretical framework encompassing patient mistreatment, emotional exhaustion, social sharing of negative events, organizational support, and trait resilience. Results Patient mistreatment led to emotional exhaustion among nurses (β = 0.625, p

Innate immunity is critical for insects to adjust to complicated environments. Studying the insect immune system can aid in identifying novel insecticide targets and provide insights for developing novel pest control strategies. Insects recognize environmental pathogens through pattern recognition receptors, thus activating the innate immune system to eliminate pathogens. The innate immune system of insects primarily comprises cellular immunity and humoral immunity. Toll, immune deficiency, and Janus kinase/signal transducers and activators of transcription are the main signaling pathways regulating insect humoral immunity. Nevertheless, increasing research has revealed that immune signaling activated by microbes also performs non-immune roles while exerting immune roles, and insulin signaling performs a key role in mediating the connection between the immune system and non-immune physiological activities. Therefore, this paper first briefly reviews the main innate immune signaling and insulin signaling of insects, then summarizes the relationship between immune signaling activated by microbes and insect growth and development, reproduction, pesticide resistance, chemical communication, cell turnover, lifespan, sleep, energy generation pathways and their possible underlying mechanisms. Future research directions and methodologies are also proposed, aiming to provide insights into further study on the physiological mechanism linking microbes and insect hosts.

Observing the intricate microstructure changes in abrasive flow machining with traditional experimental methods is difficult. Molecular dynamics simulations are used to look at the process of abrasive flow processing from a microscopic scale in this work. A molecular dynamics model for micro-cutting a single crystal γ-TiAl alloy with a rough surface in a fluid medium environment is constructed, which is more realistic. The evolution of material removal, cutting force, temperature, energy, and dislocation during micro-cutting are analyzed. The impact of cutting depth, abrasive particle sizes, and abrasive material on the micro-cutting process are analyzed. The analysis shows that the smaller cutting depth and abrasive particle sizes are beneficial to obtain a better machining surface, and the cubic boron nitride (CBN) abrasive is an effective substitute material for diamonds. The purpose of this study is to provide unique insights for improving the material removal rate and subsurface quality by adjusting machining parameters in actual abrasive flow precision machining.

Silkworm (Bombyx mori) is an economically significant insect that produces silk and makes important contributions to the development of silk-producing countries. The genetic diversity and unique adaptive traits of silkworm germplasm resources form the foundation for breeding efforts. In various geographical regions, silkworm have developed distinct traits through long-term adaptive selection. In this study, we focused on identifying and evaluating representative silkworm germplasm resources from both China and Uzbekistan. We discovered notable differences in the morphology and production traits of local silkworm strains, likely influenced by differing geographical environments. It is also possible that China has a long history of silkworm rearing and after a long time of breeding selection, the diversity of silkworm morphology is less than that of Uzbekistan, but the production characteristics are more suitable for silk utilization. Phylogenetic analysis based on genomic comparisons revealed that Uzbekistan’s local silkworm strains are positioned between China’s local and improved strains. This suggests that Uzbekistan silkworms primarily originated from China. The further analysis of genetic diversity and strain differentiation highlights the unique differences of each country’s silkworms, especially in terms of genetic diversity on chromosome 1 (sex chromosome). By identifying and evaluating these germplasm resources and linking them to unique advantageous traits, it provides a scientific basis for improving cocoon silk quality and optimizing sericulture productivity.

2D MoS2 with narrow lateral size and thickness distributions was introduced to promote the anti-friction and anti-wear properties of the bentonite grease (BG) in a state of boundary lubrication. Optical microscopy (OM), and 3D optical profilers (3D OP), Raman spectrometry (Raman), scanning electron microscope, energy dispersion spectrum (SEM-EDS), and X-ray photoelectron spectroscopy (XPS) were applied to characterize the wear surface of the GCr15 bearing steel/GCr15 bearing steel contact. It is found that the average friction coefficient (AFC), wear scar diameter (WSD), surface roughness and average wear scar depth of BG + 1.2 wt.% 2D MoS2 were effectively reduced by approximately 22.15%, 23.14%, 55.15%, and 21.1%, respectilvely, compared with BG under the working condition of 392N, 75 °C, 1 h, and 1200 rpm. Raman, EDS and XPS results jointly demonstrated that a stable adsorbed film and a robust tribochemical film composed of Fe2O3, FeSO4, Fe2(SO4)3, FeSO3, FeS, FeO and MoO3, which further contributes to the enhancement of lubrication performance.

Accurate crop density estimation is critical for effective agricultural resource management, yet existing methods face challenges due to data acquisition difficulties and low model usability caused by inconsistencies between optical and radar imagery. This study presents a novel approach to maize density estimation by integrating optical and radar data, addressing these challenges with a unique mapping strategy. The strategy combines available data selection, key feature extraction, and optimization to improve accuracy across diverse growth stages. By identifying critical features for maize density and incorporating machine learning to explore optimal feature combinations, we developed a multi-temporal model that enhances estimation accuracy, particularly during leaf development, stem elongation, and tasseling stages (R2 = 0.602, RMSE = 0.094). Our approach improves performance over single-temporal models, and successful maize density maps were generated for the three typical demonstration counties. This work represents an advancement in large-scale crop density estimation, with the potential to expand to other regions and support precision agriculture efforts, offering a foundation for future research on optimizing agricultural resource management.

Solar-driven water splitting for photocatalytic hydrogen evolution is considered a highly promising and cost-effective solution to achieve a stable renewable energy supply. However, the sluggish kinetics of electron-hole pairs’ separation poses challenges in attaining satisfactory hydrogen production efficiency. Herein, we synthesized the exceptional performance of highly crystalline C3N5 (HC–C3N5) nanosheet as a photocatalyst, demonstrating a remarkable hydrogen evolution rate of 3.01 ​mmol ​h−1 ​g−1, which surpasses that of bulk C3N5 (B–C3N5) by a factor of 3.27. Experimental and theoretical analyses reveal that HC-C3N5 nanosheets exhibit intriguing macroscopic photoinduced color changes, effectively broadening the absorption spectrum and significantly enhancing the generation of excitons. Besides, the cyano groups in HC-C3N5 efficiently captures and converts photoexcited electrons into bound states, thereby prolonging their lifetimes and effectively separating electrons and holes into catalytically active regions. This research provides valuable insights into the establishment of bound electronic states for developing efficient photocatalysts.

ABSTRACT Antimicrobial resistance has become a growing public health threat in recent years. Klebsiella pneumoniae is one of the priority pathogens listed by the World Health Organization. Antimicrobial peptides are considered promising alternatives to antibiotics due to their broad-spectrum antibacterial activity and low resistance. In this study, we investigated the antibacterial activity of antimicrobial peptide A20L against K. pneumoniae. In vitro antibacterial activity of A20L against K. pneumoniae was demonstrated by broth microdilution method. We confirmed the in vivo efficacy of A20L by Galleria mellonella infection model. In addition, we found that A20L also had certain antibiofilm activity by crystal violet staining. We also evaluated the safety and stability of A20L, and the results revealed that at a concentration of ≤128 µg/mL, A20L exhibited negligible toxicity to RAW264.7 cells and no substantial toxicity to G. mellonella. A20L was stable at different temperatures and with low concentration of serum [5% fetal bovine serum (FBS)]; however, Ca2+, Mg2+, and high serum concentrations reduced the antibacterial activity of A20L. Scanning electron microscope (SEM) and membrane permeability tests revealed that A20L may exhibit antibacterial action by damaging bacterial cell membranes and increasing the permeability of outer membrane. Taken together, our results suggest that A20L has significant development potential as a therapeutic antibiotic alternative, which provides ideas for the treatment of K. pneumoniae infection.IMPORTANCEA20L showed antibacterial and anti-infective efficacy in vitro and in vivo against Klebsiella pneumoniae. It can have an antibacterial effect by disrupting the integrity of cell membranes. A20L displayed anti-biofilm and anti-inflammatory activity against carbapenem-resistant K. pneumoniae and certain application potential in vivo, which provides a new idea for the clinical treatment of biofilm-associated infections.

This study aimed to conduct finite element (FE) analysis matched with an in vitro experiment to analyze traumatic retinal detachments (TrRD) resulting from blunt trauma and provide stress and strain thresholds to predict the occurrence of TrRD. The in vitro experiment was performed on forty-eight porcine eyes using a pendulum device. We examined dynamic mechanical responses at four energy levels. A FE model, based on experimental results and published data, was used to simulate TrRD. Fifty-one additional eyes underwent immediate pathological examination following blunt impact. A dynamic variation of velocities was observed post-impact, displaying an approximate cosine oscillation-attenuation profile. Energy absorption increased as the initial energy and differed significantly at four energy levels (p

BackgroundThe relationship between vitamin D levels, depressive symptoms, and cognitive function has yet to be definitively understood in the elderly, particularly when considering the impact of chronic diseases. This study focuses on how depression mediates the impact of 25-hydroxyvitamin D3 (25(OH)D3) on cognitive performance in older U.S. adults.MethodsWe analyzed data from 2,745 elderly individuals extracted from the NHANES 2011–2014 cycles, applying weighted processing to account for the complex multi-stage sampling design characteristic of NHANES data. Utilizing weighted data for covariate and model selection, we conducted mediation analyses on both the overall population and subgroup data. Significant mediation pathways were validated using a stratified weighted bootstrap approach. For significant subgroup pathways, we explored interactive mechanisms through interactive mediation analysis.ResultsMediation analyses, thoroughly accounting for the impact of chronic conditions, revealed significant pathways in both the weighted overall population and the weighted diabetes subgroup. After 1,000 stratified weighted bootstrap replications, the proportion of mediation effects were 10.6% [0.040, 0.268] and 20.9% [0.075, 0.663], respectively. Interactive mediation analysis for diabetes indicated that the interaction between diabetes and depression was not significant in the direct pathway (estimates = 0.050, p = 0.113) but was significant in the mediation pathway, yielding the largest effect size compared to other covariates (estimates = 0.981, p

Objectives: The purpose of this study was to analyze the effects of lamotrigine on peripheral blood cytokines and depression in patients with epilepsy and to explore the possible mechanism by which lamotrigine regulates depression in patients with epilepsy. Methods: 50 healthy people, 72 patients treated with lamotrigine (LTG group) and 72 patients treated with valproate were enrolled (VPA group). Cytokine levels in the peripheral blood of the subjects were measured and their level of depression was scored according to the self-rating Depression Scale (SDS), Hamilton Depression Scale (HAMD) and Chinese version of Epilepsy Depression Scale (c-NDDI-E). The cytokine levels and depression scale scores were compared between the three groups. The correlation between cytokine levels and depression scale scores was analyzed. Results: The levels of IL-1β, IL-2, IL-6, and TNF-α and the SDS, HAMD, and c-NDDI-E scores in healthy group was lower than that in epileptic group. After 6 months of treatment, the difference valule of IL-1β、IL-6、TNF-α、SDS and HAMD before and after treatment in LTG group significantly higher than that in VPA group. Correlation analysis showed that the SDS scores were correlated with the levels of IL-1β and TNF-α, and the HAMD scores were correlated with the levels of TNF-α. Multiple linear regression analysis showed that the HAMD scores were correlated with the levels of TNF-α. Conclusion: Lamotrigine can inhibit peripheral blood inflammation and improve depression in epileptic patients. Lamotrigine improved depressive mood in epileptic patients, which may be related to reduced TNF-α levels.

This article uses minimum quantity lubrication technology to replace traditional machining. A mixed nanofluid cutting fluid MNFCF was prepared using base oil, LINN4444 ionic liquid, and nanoparticles as raw materials, and its tribological and drilling properties were studied. In the tribological performance test, the friction coefficient of the mixed nanofluid MNFCF is only 0.13. Compared with the control, the wear amount of MNFCF has decreased by about 75%, indicating that MNFCF has good anti friction and wear performance. Similarly, in the drilling performance test, the drilling test temperature of MNFCF cutting fluid decreased by 36.5% compared to the same. After drilling and testing, there was almost no BUE, BUL, or wear on the surface of the tool, with only a small amount of adhesive observed. The results indicate that MNFCF has good potential in drilling Inconel 690 high-temperature alloy.

Vaccines have an essential role in preventing infectious diseases and reducing the burden of disease. The differences in vaccine lists and prices, and the National Immunization Program (NIP) and vaccine development between China and the United States (US) in conjunction with epidemiologic data on infectious diseases were systematically compared. The epidemiologic data of infectious diseases in 2019 were extracted from the China National Health Commission and the US Centers for Disease Control and Prevention (CDC). The vaccine list was identified from the China National Medical Products Administration and US Food and Drug Administration databases. Vaccine prices were obtained via the China government procurement platform and the US CDC. The NIP vaccines for China and the US were obtained from the China and US CDCs. Vaccine candidates investigated in 2015-2022 were identified from the China Clinical Trial Registry Platform and the US clinicaltrials.gov database. Differences in the incidence of infectious diseases between China and the US were detected with both countries facing a lack of available vaccines for prevention of many diseases. The number of listed vaccines and preventable diseases in China was 59 and 36, respectively, which was higher than the US (45 and 31, respectively). The median price of NIP vaccines in China was significantly lower than the price in the US (median: $3.8 vs. $20; P

Currently, the research on virtual power plant (VPP) is mainly divided into internal optimal scheduling and external optimal scheduling, the internal scheduling is mainly carried out from the two sides of the source and load and the application of market mechanism, while the external scheduling is in line with the current diversified power market, and considers the synergistic operation with other VPPs. Therefore, To address the problems faced by VPP in dispatch operation, such as the low economic efficiency of VPPs operating independently and the high impact of grid electricity prices and source-load uncertainty on the safe and stable operation of VPPs, a method for energy sharing operation based on Nash multi-stage robust optimization for multi-VPP is proposed. Firstly, in order to coordinate the economic interests conflict between the operators of the VPP and electric vehicle (EV) users, the Stackelberg game theory is adopted to characterize the interactive behavior between the VPP operator and the EV users. Meanwhile, a multi-stage robust optimization model is used to construct the upper-level entity, taking into account the uncertainty of price-source-load. Unlike traditional models, this paper utilizes a min-maxmin-maxmin construction to describe the internal relationships of the model. Based on this, a multi-VPP energy sharing optimization framework is established using a Nash game. It combines robust optimization with Nash bargaining theory to create a multi-VPP Nash multi-stage robust optimization model. Additionally, nested C&CG algorithms are combined with ADMM algorithms is proposed in order to solve this model effectively. Finally, three multi-energy VPPs were selected for case study analysis in this paper, and the effectiveness of the proposed method was validated through simulation. Finally, through the case study, the results show that the optimization method proposed in this paper is feasible, after the optimization of the Nash three-stage robust model, in the face of the impact of multiple uncertainties, the cooperative operation of each VPP to enhance the revenue of 396.40 yuan, 610.75 yuan, 732.53 yuan, respectively, compared with the independent operation of the operating cost of each VPP have been significantly reduced, and the system load demand of each VPP can be fully satisfied.

Abstract. Background:. Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. Methods:. Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. Results:. A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P 70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Abstract Background For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. Methods In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. Discussion Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. Trial registration chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.

Abstract HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2–76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9–87.5%) and 75.4% (95% CI: 68.9–82.6%)( HR: 0.75, 95% CI 0.47–1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4–84.6%) and 73.0% (95% CI: 66.3–80.3%) (HR: 0.84, 95% CI 0.54–1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

On-board processing has become an inevitable choice for the development of remote-sensing satellites. For the satellites with dual-line array asynchronous push-broom mode, image registration is crucial for pixel localization and alignment between dual-band strip data. However, due to the high computational complexity of feature detection and feature extraction, it is still a challenge to realize real-time registration for on-board edge devices with limited computing power and power consumption. Therefore, this article proposes a hardware-optimized architecture with high-performance and low-energy for on-board registration based on “ARM+FPGA”. On one hand, optimized methods for the image registration algorithm are proposed from both software and hardware perspectives, providing a solution for on-board registration. On the other hand, in the face of the current interface environment of satellites, a design scheme for versatile hardware architecture is proposed. It provides a foundational technical route for hardware deployment of on-board processing. Experimental results show that in this hardware-accelerated architecture, the average acceleration effect of registration algorithm can reach 15 times compared to the unoptimized version. In addition, the average power consumption is reduced by 60%, and the hardware resource utilization is less than 40%. Importantly, the algorithm's accuracy remains unaffected by these optimizations. The on-board intelligent processing payload deployed with this hardware architecture has been successfully launched and validated in February 2022 in the orbit of the MN200Sar-1 satellite from China. It improves the real-time capability for on-board processing, and aims to achieve a new imaging mechanism where target and information transmission replace strip image transmission.