Rapidly-manufactured CD276 CAR-T cells exhibit enhanced persistence and efficacy in pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer. METHODS: In the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T. RESULTS: We found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48-72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal. CONCLUSIONS: In this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.

Dual-Vacancy-Engineered ZnIn2S4 Nanosheets for Harnessing Low-Frequency Vibration Induced Piezoelectric Polarization Coupled with Static Dipole Field to Enhance Photocatalytic H2 Evolution.

This study investigates the impact of In- and S-vacancy concentrations on the photocatalytic activity of non-centrosymmetric zinc indium sulfide (ZIS) nanosheets for the hydrogen evolution reaction (HER). A positive correlation between the concentrations of dual In and S vacancies and the photocatalytic HER rate over ZIS nanosheets is observed. The piezoelectric polarization, stimulated by low-frequency vortex vibration to ensure the well-dispersion of ZIS nanosheets in solution, plays a crucial role in enhancing photocatalytic HER over the dual-vacancy engineered ZIS nanosheets. The piezoelectric characteristic of the defective ZIS nanosheets is confirmed through the piezopotential response measured using piezoelectric force microscopy. Piezophotocatalytic H2 evolution over the ZIS nanosheets is boosted under accelerated vortex vibrations. The research explores how vacancies alter ZIS's dipole moment and piezoelectric properties, thereby increasing electric potential gradient and improving charge-separation efficiency, through multi-scale simulations, including Density Functional Theory and Finite Element Analysis, and a machine-learning interatomic potential for defect identification. Increased In and S vacancies lead to higher electric potential gradients in ZIS along [100] and [010] directions, attributing to dipole moment and the piezoelectric effect. This research provides a comprehensive exploration of vacancy engineering in ZIS nanosheets, leveraging the piezopotential and dipole field to enhance photocatalytic performances.

Mechanism research progress of acupuncture for regulating axon regeneration after stroke. / é’ˆåˆºè°ƒæŽ§è„‘å’ä¸­åŽè½´çªå†ç”Ÿçš„æœºåˆ¶ç ”ç©¶è¿›å±•.

Stroke brings the pathological changes of brain tissues such as hematoma formation or ischemia and hypoxia, which leads to neuronal death and axon degeneration. Axon regeneration after its injury is mainly dependent on the surrounding microenvironment and the related proteins, including glial scar, myelin associated inhibitory factors, axon guidance molecules, and neurotrophic factors. All of them affect axon growth by regulating the morphology and orientation of growth cones, the synaptic stability, and the proliferation and differentiation of neural stem cells. This article summarizes the mechanism of acupuncture in regulating axon regeneration after stroke. Acupuncture inhibits glial scar formation, alleviates the inhibitory effects of its physical and chemical barriers on axon growth, reverses the inhibitory effects of myelin-related inhibitory factors on axon growth, and adjusts the level of axon guidance molecules to promote the proliferation and differentiation of neural stem cells and the regeneration of injured axons, and up-regulates neurotrophic factors. Eventually, post-stroke nerve injury can be ameliorated.

The Potential Role of Non-coding RNAs in Regulating Ferroptosis in Cancer: Mechanisms and Application Prospects.

Cancer is the second leading cause of death globally. Despite some successes, conventional cancer treatments are insufficient to address the growing problem of drug resistance in tumors and to achieve efficient treatment outcomes. Therefore, there is an urgent need to explore new therapeutic options. Ferroptosis, a type of iron- and reactive oxygen species-dependent regulated cell death, has been closely associated with cancer development and progression. Non-coding RNAs (ncRNAs) are a class of RNAs that do not code for proteins, and studies have demonstrated their involvement in the regulation of ferroptosis in cancer. This review aims to explore the molecular regulatory mechanisms of ncRNAs involved in ferroptosis in cancer and to emphasize the feasibility of ferroptosis and ncRNAs as novel therapeutic strategies for cancer. We conducted a systematic and extensive literature review using PubMed, Google Scholar, Web of Science, and various other sources to identify relevant studies on ferroptosis, ncRNAs, and cancer. A deeper understanding of ferroptosis and ncRNAs could facilitate the development of new cancer treatment strategies.

Potential impact of NOTCH1 activation on venetoclax sensitivity in chronic lymphocytic Leukaemia: In vitro insights and clinical implications.

Despite significant progress in treating chronic lymphocytic leukaemia (CLL), resistance to therapy remains challenging. NOTCH1 activation, common in CLL, confers adverse prognosis. This study explores the impact of NOTCH1 signalling on venetoclax sensitivity in vitro. Although NOTCH1 activation minimally impaired the susceptibility of CLL cells to venetoclax, ex vivo cell competition studies reveal that cells with constitutive NOTCH1 activation outgrew their wild-type counterparts in the presence of ongoing venetoclax exposure. Our findings suggest that while NOTCH1 activation is insufficient to confer venetoclax refractoriness, there is enhanced potential for cells with NOTCH1 activation to escape and thus become fully resistant to venetoclax.

Clinical Guidelines on Compression Therapy in Venous Diseases.

BACKGROUND: In recent years, compression therapy has attracted gradually increasing clinical attention in lower extremity venous diseases. However, basic concepts and clear nomenclature, standard treatment methods, and consistent product standards for pressure equipment are lacking. Therefore, developing clinical guidelines for compression therapy is essential to improving the treatment of venous diseases. METHODS: Our panel generated strong (Grade I), moderate (Grade IIa and IIb), and weak (Grade III) recommendations based on high quality (Class A), moderate quality (Class B), and low quality (Class C) evidence, using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach and the European Society of Cardiology (ESC) grading system. RESULTS: The panels made 30 recommendations from current evidence, focusing on seven fields of lower extremity venous disease (venous thromboembolism, post-thrombotic syndrome, chronic venous insufficiency, varicose veins, hemangioma and vascular malformations, lymphedema, and venous ulcers) and 18 topics. CONCLUSIONS: Of the 30 recommendations made across the 18 topics, 7 were strong (Grade I) and 17 were based on high quality (Class A) evidence, highlighting the need for further research of the use of compression therapy for .

Role of combined surgical and radiotherapy treatment in nonmetastatic WHO I nasopharyngeal carcinoma patients.

BACKGROUND: Keratinizing squamous cell carcinoma (KSCC) is recognized as WHO I nasopharyngeal carcinoma (NPC). Current guidelines for treating nasopharyngeal cancer do not delineate specific strategies for individual pathologic subtypes. OBJECTIVES: To explore the optimal treatment for KSCC of the nasopharynx. MATERIAL AND METHODS: Data on patients were extracted from the SEER database. Survival differences between patients treated with radiotherapy alone and combined surgery were assessed using Kaplan-Meier and Cox regression models and compared using propensity score matching (PSM). In addition, we explored the survival differences between the two groups of patients in different risk stratifications. RESULTS: In our study, 165 patients underwent surgical intervention, while 1238 patients did not. In both univariate (CSS: p = .001, HR = 0.612; OS: p < .001, HR = 0.623) and multivariate (CSS: p = .004, HR = 0.655; OS: p < .001, HR = 0.655) analyses, combined surgery was identified as a significant prognostic factor. These findings were consistent after PSM. Using RPA, patients were categorized into two groups. CSS improved in the high-risk group, whereas the difference in low-risk patients was not significant. CONCLUSIONS AND SIGNIFICANCE: For patients diagnosed with WHO I nasopharyngeal carcinoma, the combination of radiotherapy and surgery has significant clinical advantages, especially for patients at high risk.

International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

PURPOSE: Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. While postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. METHODS AND MATERIALS: A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. RESULTS: The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60Gy, and hyperfractionation has shown promise in reducing toxicity. CONCLUSION: These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for the clinical experts involved in the treatment of locally recurrent NPC. SUMMARY: This article provides international recommendations on postoperative management for potentially resectable locally recurrent nasopharyngeal carcinoma (NPC), with a special focus on postoperative re-irradiation (re-RT). The consensus guidelines highlight the importance of achieving clear surgical margins, suggest considering re-RT for patients with positive or close margins, recommend an optimal re-RT dose of around 60Gy, and propose the use of hyperfractionation to reduce toxicity. The aim is to improve patient outcomes in the management of resectable locally recurrent NPC.

Effect of microwaves combined with peracetic acid to improve the dewatering performance of residual sludge.

The activated sludge process plays a crucial role in modern wastewater treatment plants. During the treatment of daily sewage, a large amount of residual sludge is generated, which, if improperly managed, can pose burdens on the environment and human health. Additionally, the highly hydrated colloidal structure of biopolymers limits the rate and degree of dewatering, making mechanical dewatering challenging. This study investigates the impact and mechanism of microwave irradiation (MW) in conjunction with peracetic acid (PAA) on the dewatering efficiency of sludge. Sludge dewatering effectiveness was assessed through capillary suction time (CST) and specific resistance to filtration (SRF). Examination of the impact of MW-PAA treatment on sludge dewatering performance involved assessing the levels of extracellular polymeric substances (EPS), employing three-dimensional excitation-emission matrix (3D-EEM), Fourier transform-infrared spectroscopy (FT-IR), and scanning electron microscopy. Findings reveal that optimal dewatering performance, with respective reductions of 91.22% for SRF and 84.22% for CST, was attained under the following conditions: microwave power of 600 W, reaction time of 120 s, and PAA dosage of 0.25 g/g MLSS. Additionally, alterations in both sludge EPS composition and floc morphology pre- and post-MW-PAA treatment underwent examination. The findings demonstrate that microwaves additionally boost the breakdown of PAA into •OH radicals, suggesting a synergistic effect upon combining MW-PAA treatment. These pertinent research findings offer insights into employing MW-PAA technology for residual sludge treatment.

Learning Virtual View Selection for 3D Scene Semantic Segmentation.

2D-3D joint learning is essential and effective for fundamental 3D vision tasks, such as 3D semantic segmentation, due to the complementary information these two visual modalities contain. Most current 3D scene semantic segmentation methods process 2D images "as they are", i.e., only real captured 2D images are used. However, such captured 2D images may be redundant, with abundant occlusion and/or limited field of view (FoV), leading to poor performance for the current methods involving 2D inputs. In this paper, we propose a general learning framework for joint 2D-3D scene understanding by selecting informative virtual 2D views of the underlying 3D scene. We then feed both the 3D geometry and the generated virtual 2D views into any joint 2D-3D-input or pure 3D-input based deep neural models for improving 3D scene understanding. Specifically, we generate virtual 2D views based on an information score map learned from the current 3D scene semantic segmentation results. To achieve this, we formalize the learning of the information score map as a deep reinforcement learning process, which rewards good predictions using a deep neural network. To obtain a compact set of virtual 2D views that jointly cover informative surfaces of the 3D scene as much as possible, we further propose an efficient greedy virtual view coverage strategy in the normal-sensitive 6D space, including 3-dimensional point coordinates and 3-dimensional normal. We have validated our proposed framework for various joint 2D-3D-input or pure 3D-input based deep neural models on two real-world 3D scene datasets, i.e., ScanNet v2 and S3DIS, and the results demonstrate that our method obtains a consistent gain over baseline models and achieves new top accuracy for joint 2D and 3D scene semantic segmentation. Code is available at https://github.com/smy-THU/VirtualViewSelection.

Single-cell transcriptomics across 2,534 microbial species reveals functional heterogeneity in the rumen microbiome.

Deciphering the activity of individual microbes within complex communities and environments remains a challenge. Here we describe the development of microbiome single-cell transcriptomics using droplet-based single-cell RNA sequencing and pangenome-based computational analysis to characterize the functional heterogeneity of the rumen microbiome. We generated a microbial genome database (the Bovine Gastro Microbial Genome Map) as a functional reference map for the construction of a single-cell transcriptomic atlas of the rumen microbiome. The atlas includes 174,531 microbial cells and 2,534 species, of which 172 are core active species grouped into 12 functional clusters. We detected single-cell-level functional roles, including a key role for Basfia succiniciproducens in the carbohydrate metabolic niche of the rumen microbiome. Furthermore, we explored functional heterogeneity and reveal metabolic niche trajectories driven by biofilm formation pathway genes within B. succiniciproducens. Our results provide a resource for studying the rumen microbiome and illustrate the diverse functions of individual microbial cells that drive their ecological niche stability or adaptation within the ecosystem.

Study of Highly Efficient Au/Pt Nanoparticles for Rapid Screening of Clostridium difficile.

This study synthesized core/shell gold-platinum nanoparticles and characterized their colorimetric properties; ultraviolet-visible spectroscopy revealed that the synthesized nanoparticles exhibited distinct colors from conventional gold nanoparticles. Furthermore, the nanoparticles were subjected to lateral flow assays using Protein A, and the results revealed that they outperformed conventional spherical gold nanoparticles in terms of color development. This improvement can be attributed to the distinct core/shell structures of our nanoparticles. Further evaluation revealed that these nanoparticles could facilitate the detection of Clostridium difficile Toxin B visually at an extremely low concentration (1 ng/mL) without the requirement for advanced instrumentation. This substantial improvement in sensitivity can be attributed to the meticulous design and nanoscale engineering of the structure of the nanoparticles.

Oxygenation heterogeneity facilitates spatiotemporal flow pattern visualization inside human blood vessels using photoacoustic computed tomography.

Hemodynamics can be explored through various biomedical imaging techniques. However, observing transient spatiotemporal variations in the saturation of oxygen (sO2) within human blood vessels proves challenging with conventional methods. In this study, we employed photoacoustic computed tomography (PACT) to reconstruct the evolving spatiotemporal patterns in a human vein. Through analysis of the multi-wavelength photoacoustic (PA) spectrum, we illustrated the dynamic distribution within blood vessels. Additionally, we computationally rendered the dynamic process of venous blood flowing into the major vein and entering a branching vessel. Notably, we successfully recovered, in real time, the parabolic wavefront profile of laminar flow inside a deep vein in vivo-a first-time achievement. While the study is preliminary, the demonstrated capability of dynamic sO2 imaging holds promise for new applications in biology and medicine.

T cell-redirecting antibody for treatment of solid tumors via targeting mesothelin.

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC50: 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential.

Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better.

BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

Perioperative management of sarcopenia in patients undergoing major surgeries in Singapore: a modified delphi consensus.

BACKGROUND: Ageing population is a worldwide phenomenon with correspondingly higher proportion of older patients being treated in the hospital setting. Sarcopenia, which increases with age, has serious negative implications on health, hospitalization and overall postoperative recovery. There is no mutual consensus on perioperative management of sarcopenia in surgical patients in Singapore. The purpose of this study is to create greater clarity pertaining to the recognition of sarcopenia, the application of assessment criteria of sarcopenia and perioperative management of surgical patients in Singapore. METHODS: A modified Delphi consensus consisting of a panel of experts from Singapore forming a multidisciplinary team, including surgeons, geriatricians, anesthesiologists, physiotherapists and dieticians. Eight recommendations were proposed by the steering committee. Literature search from MEDLINE, Embase and Scopus for articles up till June 2023 were performed to support recommendation statements. The expert panel voted on agreement to recommendation statements and graded the level of evidence supporting each statement through surveys to achieve consensus, set at 85% a priori. RESULTS: The panelists underwent two rounds of anonymized, independent voting before reaching consensus for all eight statements. After the first round, seven statements reached consensus, including the corresponding grading for level of evidence. The statement which did not achieve consensus was revised with supporting literature and after the second round of survey, all eight statements and level of evidence reached consensus, completing the Delphi process. These eight statements covered themes to (1) encourage the identification of sarcopenia, (2) guide pre-operative and (3) post-operative management of sarcopenia. CONCLUSION: With the varying approaches in perioperative management, poor understanding of and identification of sarcopenia can result in suboptimal management of sarcopenia in surgical patients. Given the abundance of evidence linking beneficial impact on recovery and post-operative complications with prudent management of sarcopenia, it is imperative and urgent to achieve awareness and consensus.

Study on the Influence of Runner and Overflow Area Design on Flow-Fiber Coupling in a Multi-Cavity System.

Fiber-reinforced composites (FRPs) are characterized by their lightweight nature and superior mechanical characteristics, rendering them extensively utilized across various sectors such as aerospace and automotive industries. Nevertheless, the precise mechanisms governing the interaction between the fibers present in FRPs and the polymer melt during industrial processing, particularly the manipulation of the flow-fiber coupling effect, remain incompletely elucidated. Hence, this study introduces a geometrically symmetrical 1 × 4 multi-cavity mold system, where each cavity conforms to the ASTM D638 Type V standard specimen. The research utilizes theoretical simulation analysis and experimental validation to investigate the influence of runner and overflow design on the flow-fiber coupling effect. The findings indicate that the polymer melt, directed by a geometrically symmetrical runner, results in consistent fiber orientation within each mold cavity. Furthermore, in the context of simulation analysis, the inclusion of the flow-fiber coupling effect within the system results in elevated sprue pressure levels and an expanded core layer region in comparison to systems lacking this coupling effect. This observation aligns well with the existing literature on the subject. Moreover, analysis of fiber orientation in different flow field areas reveals that the addition of an overflow area alters the flow field, leading to a significant delay in the flow-fiber coupling effect. To demonstrate the impact of overflow area design on the flow-fiber effect, the integration of fiber orientation distribution analysis highlights a transformation in fiber arrangement from the flow direction to cross-flow and thickness directions near the end-of-fill region in the injected part. Additionally, examination of the geometric dimensions of the injected part reveals asymmetrical geometric shrinkage between upstream and downstream areas in the end-of-fill region, consistent with microscopic fiber orientation changes influenced by the delayed flow-fiber coupling effect guided by the overflow area. In brief, the introduction of the overflow area extends the duration in which the polymer melt exerts control in the flow direction, consequently prolonging the period in which the fiber orientation governs in the flow direction (A11). This leads to the impact of fiber orientation on the flow of the polymer melt, with the flow reciprocally affecting the fibers. Subsequently, the interaction between these two elements persists until a state of equilibrium is achieved, known as the flow-fiber coupling effect, which is delayed.

Comparing the Prognostic Impacts of Delayed Administration of Appropriate Antimicrobials in Older Patients with Afebrile and Febrile Community-Onset Bacteremia.

Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p < 0.001) was revealed using Cox regression and Kaplan-Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p < 0.001) and 0.2% (AOR, 1.002; p < 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan-Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration > 24 h) had a significant prognostic impact, with AHRs of 1.83 (p < 0.001) and 1.76 (p < 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Impact of remote ischemic postconditioning on acute ischemic stroke in China: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Acute ischemic stroke (AIS) is a significant health burden in China, affecting a sizable portion of the population. Conventional pharmacological treatments frequently fall short of desirable outcomes. Therefore, exploring alternative therapies is crucial. Remote ischemic postconditioning (RIPostC) is a noninvasive and cost-effective adjunctive therapy. This study aimed to investigate the efficacy and safety of RIPostC as an adjunctive therapy for AIS to inform clinical practice. METHODS: A comprehensive search was conducted across the PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, Weipu (VIP), and China Biology Medicine disc (CBM) databases up to October 2023. All included studies underwent bias risk assessment using the Cochrane risk-of-bias assessment tool. The primary outcome measure was the National Institute of Health Stroke Scale (NIHSS), with secondary outcomes including the Barthel index (BI), D-dimer, C-reactive protein (CRP), fibrinogen (FIB), brain-derived neurotrophic factor (BDNF), modified Rankin scale (mRS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. The data were analyzed using fixed-effects and random-effects models in Review Manager, with mean differences (MDs) and 95% confidence intervals (CIs) calculated for each outcome. The grading of recommendations, assessment, development, and evaluations (GRADE) approach was used to evaluate the level of evidence for each outcome measure. RESULTS: This meta-analysis included 38 studies, encompassing 4334 patients. Compared with the control group, the RIPostC group had significantly lower NIHSS scores, serum CRP, D-dimer, IL-6, TNF-α, and FIB levels, and increased BDNF levels. Moreover, it improved the patient's BI and mRS scores. According to the GRADE approach, the quality of evidence for mRS was deemed "moderate," while the NIHSS, BI, and CRP were rated as "low" quality. IL-6, TNF-α, FIB, D-dimer, and BDNF received "very low" quality ratings. CONCLUSION: The findings suggest that RIPostC activates endogenous protective mechanisms, providing benefits to patients with AIS.