Endovascular thrombectomy with or without intravenous alteplase in large-core ischemic stroke: a systematic review and meta-analysis.

The role of bridging intravenous thrombolysis (IVT) with alteplase before endovascular thrombectomy (EVT) in treating large core ischemic stroke remains uncertain. We aimed to compare clinical outcomes and safety of EVT with or without bridging IVT in patients with anterior circulation large vessel occlusion (ACLVO) and baseline Alberta Stroke Program Early CT Score (ASPECTS) ≤ 5. We systematically searched PubMed, Web of Science, Cochrane Library, and Embase from inception until November 2023. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] 0-2). Secondary outcomes included 90-day independent ambulation (mRS 0-3), successful recanalization, any intracranial hemorrhage (ICH), symptomatic ICH (sICH) and 90-day mortality. A random-effects model was used for data pooling. Five high-quality studies, incorporating 2124 patients (41% treated with bridging IVT), were included. Across both unadjusted and adjusted analyses, no significant differences were found between the bridging IVT and EVT-alone groups in terms of functional independence (odds ratios [OR] = 1.36, 95% confidence interval [CI]: 0.90-2.07, P = 0.14; adjusted OR [aOR] = 1.19, 95% CI: 0.68-2.09, P = 0.53) or independent ambulation (OR = 1.14, 95% CI: 0.80-1.62, P = 0.47; aOR = 1.18, 95% CI: 1.00-1.39, P = 0.05) at 90 days. Furthermore, no differences were observed in successful recanalization, any ICH, sICH, and 90-day mortality between the two treatment groups. Bridging IVT exhibits similar functional and safety outcomes compared to EVT alone in ACLVO patients with baseline ASPECTS ≤ 5. Further research is warranted to confirm these findings.

The role of triglyceride-glucose index in the differential diagnosis of atherosclerotic stroke and cardiogenic stroke.

OBJECTIVE: This study aims to investigate the role of the triglyceride glucose (TyG) index in differentiating cardiogenic stroke (CE) from large atherosclerotic stroke (LAA). METHOD: In this retrospective study, patients with acute ischemic stroke were recruited from the First Affiliated Hospital of Soochow University, Lianyungang Second People's Hospital and Lianyungang First People's Hospital. Their general data, medical history and laboratory indicators were collected and TyG index was calculated. Groups were classified by the TyG index quartile to compare the differences between groups. Logistic regression was utilized to assess the relationship between the TyG index and LAA. The receiver operating characteristic curve (ROC) curve was used to evaluate the diagnostic efficiency of the TyG index in differentiating LAA from CE. RESULT: The study recruited 1149 patients. After adjusting for several identified risk factors, groups TyG-Q2, TyG-Q3, and TyG-Q4 had a higher risk of developing LAA compared to group TyG-Q1(odds ratio (OR) = 1.63,95% confidence interval (CI) = 1.11-2.39, OR = 1.72,95%CI = 1.16-2.55, OR = 2.06,95%CI = 1.36-3.09). TyG has certain diagnostic value in distinguishing LAA from CE(AUC = 0.595, 95%CI0.566-0.623;P<0.001). CONCLUSION: Summarily, the TyG index has slight significance in the identification of LAA and CE; it is particularly a marker for their preliminary identification.

PD-1 inhibitor combined with paclitaxel and cisplatin in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma: efficacy and survival outcomes.

Objective: This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC). Methods: Patients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3-4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism. Conclusion: In the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

Two novel variants of the CAPN3 gene in Chinese patients with Limb-Girdle Muscular Dystrophy Recessive 1.

Introduction Recessive mutations in the CAPN3 gene can lead to Limb-girdle muscular dystrophy Recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions. Methods We performed targeted next-generation sequencing of all exons of the CAPN3 gene in four patients with sporadic LGMD and further analyzed the effects of the novel identified variant using various software tools. Results We found 5 variants in CAPN3 gene in four patients, c.82_83insC (insertion mutation) and c.1115+2T>C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation. Discussion Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

CBF Profile in Computed Tomography Perfusion-Based AutoMIStar Software Predicts Futile Recanalization After Basilar Artery Thrombectomy.

Background: Futile recanalization (FR) remains a significant challenge in patients with acute basilar artery occlusion (BAO) following successful endovascular treatment (EVT). This study aimed to investigate the predictive value of computed tomography perfusion (CTP)-based software (AutoMIStar; Apollo) for FR among BAO patients undergoing EVT. Methods: We analyzed a prospectively maintained database to identify consecutive BAO patients who achieved successful recanalization (modified Thrombolysis in Cerebral Infarction grade ≥ 2b) after EVT between January 2020 and September 2022. Clinical characteristics and imaging parameters from non-contrast CT, CT angiography, and CTP-AutoMIStar were collected for analysis. FR was defined as an unfavorable outcome (modified Rankin Scale score > 3) at 90 days despite successful recanalization. Multivariable stepwise logistic regression analysis was performed to identify independent predictors of FR. Results: Of the 54 patients included in this study, 24 (44.4%) experienced FR. In the univariate analysis, admission National Institutes of Health Stroke Scale score, posterior circulation Acute Stroke Prognosis Early CT Score, Basilar Artery on Computed Tomography Angiography (BATMAN) score, hypoperfusion intensity ratio, and perfusion deficit volume in delay time (DT) > 4 s, DT > 6 s, DT > 8 s, and all cerebral blood flow (CBF) thresholds were associated with FR (all P < 0.05). In the multivariate analysis, perfusion deficit volume in CBF < 35% (adjusted odds ratio [aOR] = 1.105, 95% confidence interval [CI]: 1.004-1.215; P = 0.040) and BATMAN score (aOR = 0.662, 95% CI: 0.455-0.964; P = 0.031) remained independent predictors of FR. Conclusion: Perfusion deficit volume in CBF < 35% on CTP-AutoMIStar imaging maps and BATMAN score are independent predictors of FR after EVT in BAO patients. There is a significant positive correlation between perfusion deficit volume in CBF < 35% and the occurrence of FR.

Gas6/AXL Alleviates Hepatic Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via the PI3K/AKT Pathway.

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor tyrosine kinase family (TYRO3, AXL, and MERTK). Our previous study has shown that AXL expression was markedly upregulated in liver transplantation patients. However, the underlying mechanism of AXL in hepatic I/R injury remains unclear. METHODS: A mouse liver warm I/R model and a primary hepatocyte hypoxia/reoxygenation model were established to investigate the role of AXL activation and ferroptosis in hepatic I/R injury by pretreating with recombinant mouse growth arrest-specific protein 6 (AXL activator) or R428 (AXL inhibitor). Moreover, we used LY294002 (phosphatidylinositol 3-kinase [PI3K] inhibitor) to evaluate the relationship between the PI3K/AKT (the Ser and Thr kinase AKT) pathway and ferroptosis in hepatic I/R injury. RESULTS: Hepatic I/R injury decreased phosphorylation AXL expression and enhanced ferroptosis in liver transplantation patients and hepatic I/R-subjected mice. AXL activation attenuated lipid peroxidation and ferroptosis in hepatic I/R injury in vivo and in vitro. Inhibition of AXL activation exacerbated liver pathological damage and liver dysfunction, as well as iron accumulation and lipid peroxidation in hepatic I/R injury. Mechanistically, activated growth arrest-specific protein 6/AXL and its downstream PI3K/AKT signaling pathway inhibited ferroptosis during hepatic I/R injury. CONCLUSIONS: AXL activation protects against hepatic I/R injury by preventing ferroptosis through the PI3K/AKT pathway. This study is the first investigation on the AXL receptor and ferroptosis, and activating AXL to mitigate ferroptosis may be an innovative therapeutic strategy to combat hepatic I/R injury.

Acute ischemic stroke with a diagnosis of Marfan syndrome: A report of 3 cases in multifaceted settings.

RATIONALE: Marfan syndrome (MFS), which is a dominantly inherited connective tissue disease resulting from a mutation in the FBN1 gene, exhibits variable manifestations affecting the cardiovascular, musculoskeletal, ophthalmologic, and pulmonary systems. Notably, neurologic deficiency, which involves ischemic or hemorrhagic stroke, is a rare but severe manifestation. The safety of rt-PA treatment for ischemic stroke caused by MFS is still under discussion. PATIENT CONCERNS: In the current report, we discuss 3 atypical MFS cases presented as acute ischemic stroke, compared to those exhibiting cardiovascular and musculoskeletal abnormalities. DIAGNOSES: Three patients were diagnosed with acute ischemic stroke accompanied by MFS based on clinical manifestations, imaging examinations, and genetic testings. INTERVENTIONS: The first case underwent intravenous thrombolytic therapy with rt-PA, the second case received antiplatelet therapy, and the third case received anticoagulant therapy and perfusion therapy. OUTCOMES: The neurologic deficiency of all three patients showed improvement upon discharge, and there were no symptoms of recurrence observed during the follow-up period. LESSONS SUBSECTIONS: MFS is a rare etiology in young people with embolic stroke of undetermined source. Physicians should take MFS into consideration when they observe the characteristic symptoms during a consultation. The potential pathogenesis of ischemic stroke secondary to MFS may include cardio-embolism, arterial dissection, and hypoperfusion. Although intravenous thrombolysis is a promising therapy to treat acute ischemic stroke, further examinations should be conducted to rule out contraindications in patients with a suspicion of MFS.

Complexity of avian evolution revealed by family-level genomes.

Despite tremendous efforts in the past decades, relationships among main avian lineages remain heavily debated without a clear resolution. Discrepancies have been attributed to diversity of species sampled, phylogenetic method and the choice of genomic regions1-3. Here we address these issues by analysing the genomes of 363 bird species4 (218 taxonomic families, 92% of total). Using intergenic regions and coalescent methods, we present a well-supported tree but also a marked degree of discordance. The tree confirms that Neoaves experienced rapid radiation at or near the Cretaceous-Palaeogene boundary. Sufficient loci rather than extensive taxon sampling were more effective in resolving difficult nodes. Remaining recalcitrant nodes involve species that are a challenge to model due to either extreme DNA composition, variable substitution rates, incomplete lineage sorting or complex evolutionary events such as ancient hybridization. Assessment of the effects of different genomic partitions showed high heterogeneity across the genome. We discovered sharp increases in effective population size, substitution rates and relative brain size following the Cretaceous-Palaeogene extinction event, supporting the hypothesis that emerging ecological opportunities catalysed the diversification of modern birds. The resulting phylogenetic estimate offers fresh insights into the rapid radiation of modern birds and provides a taxon-rich backbone tree for future comparative studies.

Gold Nanoparticle Delivery of Glut1 SiRNA Facilitates Glucose Starvation Therapy in Lung Cancer.

Glucose transporter protein-1 (Glut1), is highly expressed in many cancer types and plays a crucial role in cancer progression through enhanced glucose transport. Its overexpression is associated with aggressive tumor behavior and poor prognosis. Herein, the nucleic acids modified gold nanoparticles (AuNPs) was synthesized to deliver small interfering RNA (siRNA) against Glut1 by microRNA 21 (miR-21) triggers toehold-mediated strand displacement reaction for lung cancer starvation therapy. Overexpression of miR-21 triggers toehold-mediated strand displacement, releasing the siRNA to knockdown of Glut1 in cancer cell instead of normal cell. Furthermore, the glucose oxidase-like activity of the AuNPs accelerates intracellular glucose consumption, promoting cancer cell starvation. The engineered AuNPs@anti-miR-21/siGlut1 complex inhibits cancer cell proliferation, xenograft tumor growth and promotes apoptosis through glucose starvation and ROS cascade signaling, underscoring its potential as an effective therapeutic strategy for lung cancer.

A Principal Component Regression-Based Electrophysiological Study of Patients with Severe Infections.

Objective: Severe infections can lead to neuromyopathy in critically ill patients, resulting in limb weakness and difficulty in weaning from a ventilator. This study aims to assess the electrophysiological test results in patients with severe infection and their correlation with severity scores (APACHE II and SOFA). Methods: Thirty-one patients with severe infection in the EICU were prospectively studied. Factor analysis and principal component regression were applied to develop linear models of electrophysiological diagnostic outcomes with APACHE II and SOFA scores for the entire patient cohort, the younger group (age<55) cohort, and the older group (age>55) cohort of patients with severe infections, respectively. Results: Among patients with a severe infection in the EICU, the proportion of patients without critical neuromyopathy with more than 50% F-wave presence in the median, ulnar, and tibial nerves (64.9%, 56.8%, 48.6%, respectively) was significantly higher than in the group with critical neuromyopathy (52.1%, 35.4%, 29.2%, respectively.), and the proportion of patients with critical neuromyopathy who did not elicit the three types of F wave was significantly higher in the cohort of patients with critical neuromyopathy (40.5%, 32.4%, 35.1%, respectively.) were significantly higher than in the cohort of patients without critical illness (18.8%, 12.5%, 20.8%, respectively). In addition, on average, patients with critical neuromyopathy had a much lower CMAP for the median nerve (wrist, elbow) (2.4, 1.88, respectively) (4.3, 3.9, respectively in undiagnosed cohort), ulnar nerve (wrist, elbow) (2.4, 1.88, respectively) (5.65, 5.4, respectively in undiagnosed cohort), and tibial nerve(ankle, popliteal fossa) (2.7, 1.57, respectively)(6.55, 5.3, respectively in undiagnosed cohort) nerves than patients without critical neuromyopathy, and showed more non-elicitation, which was not seen in the cohort of patients without critical neuromyopathy. The CMAP returned to normal in the cohort of patients without critical neuromyopathy. Therefore, with respect to our selected electrophysiological parameters, the two patient groups showed significant differences in terms of the specific values and statistical analysis (Table 1). Through factor analysis and principal component regression, we found that CMAP and F-wave were highly correlated with APACHE II and SOFA scores, and the correlation between the electrophysiological wave spectrum and the two scores was further quantified by principal component regression. Conclusion: Electrophysiological spectroscopy can serve as an early warning for the development of neuromuscular disease in EICU patients. Abnormal electrophysiological diagnosis prior to actual neuromuscular abnormalities and its subsequent return to normal can help identify high-risk patients and implement early interventions.

A region of suppressed recombination misleads neoavian phylogenomics.

Genomes are typically mosaics of regions with different evolutionary histories. When speciation events are closely spaced in time, recombination makes the regions sharing the same history small, and the evolutionary history changes rapidly as we move along the genome. When examining rapid radiations such as the early diversification of Neoaves 66 Mya, typically no consistent history is observed across segments exceeding kilobases of the genome. Here, we report an exception. We found that a 21-Mb region in avian genomes, mapped to chicken chromosome 4, shows an extremely strong and discordance-free signal for a history different from that of the inferred species tree. Such a strong discordance-free signal, indicative of suppressed recombination across many millions of base pairs, is not observed elsewhere in the genome for any deep avian relationships. Although long regions with suppressed recombination have been documented in recently diverged species, our results pertain to relationships dating circa 65 Mya. We provide evidence that this strong signal may be due to an ancient rearrangement that blocked recombination and remained polymorphic for several million years prior to fixation. We show that the presence of this region has misled previous phylogenomic efforts with lower taxon sampling, showing the interplay between taxon and locus sampling. We predict that similar ancient rearrangements may confound phylogenetic analyses in other clades, pointing to a need for new analytical models that incorporate the possibility of such events.

Trends in Cognitive Function Before and After Diabetes Onset: The China Health and Retirement Longitudinal Study.

BACKGROUND AND OBJECTIVES: Individuals with prevalent diabetes were known to have a higher risk of dementia and lower cognitive function. However, trends of cognitive function before diabetes and in the short term after new-onset diabetes remain unclear. METHODS: This study included participants without baseline diabetes from the China Health and Retirement Longitudinal Study. Cognitive tests were conducted at baseline (wave 1) and at least one time from wave 2 (2013) to wave 4 (2018). Cognitive function was assessed using a global cognition score which was the summary measure of 4 cognitive tests. A linear mixed model was constructed to fit the trends in cognitive function before and after diabetes onset and the trends among nondiabetes. The threshold of statistical significance was p < 0.05. RESULTS: During the 7-year follow-up, 1,207 (9.7% of 12,422, 59.1 ± 8.6 years, 39.9% male participants) participants developed new-onset diabetes. The cognitive function of both the without diabetes group and the diabetes group declined annually during the follow-up. The annual decline rate of the diabetes group before diabetes onset was similar to that of the without diabetes group during the whole follow-up period. After diabetes onset, participants experienced statistically significant faster cognitive declines in global cognition (-0.023 SD/year; 95% CI -0.043 to -0.004; p = 0.019) and visuospatial abilities test (-0.036 SD/year; -0.061 to -0.011; p = 0.004), but not in tests of episodic memory (-0.018 SD/year; -0.041 to 0.004; p = 0.116), attention and calculation (-0.017 SD/year; -0.037 to 0.003; p = 0.090), or orientation (0.001 SD/year; -0.018 to 0.020; p = 0.894), compared with the cognitive slope before diabetes. In subgroup analysis, compared with those who developed diabetes between 45-54 years, those developing diabetes older (55-64 years, p for interaction = 0.701; 65-74 years, p for interaction = 0.996) did not demonstrate different rates of global cognitive decline after diabetes. DISCUSSION: Individuals experienced faster rate of cognitive decline in a few years after diabetes onset, but not during the prediabetes period. Age did not modify the effect of diabetes on postdiabetes cognitive decline. Efforts in eliminating the adverse impacts on cognition should be started on diagnosis of diabetes.

Treatment of multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a relatively uncommon but severe pediatric complication, is associated with coronavirus disease 2019 (COVID-19). A variety of treatment approaches, including intravenous immunoglobulins (IVIGs), glucocorticoids (GCs) and biologic agents, such as anakinra and infliximab, have been described for the management of COVID-19-related MIS-C. Anticoagulant therapy is also important. However, a well-developed treatment system has not been established, and many issues remain controversial. Several recently published articles related to the treatment of MIS-C have been released. Hence, in this review, we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically. DATA SOURCES: We reviewed the literature on the treatment of MIS-C through 20 September 2023. The PubMed/Medline, Web of Science, EMBASE, and Cochrane Library databases were searched with the combination of the terms "multisystem inflammatory syndrome", "MIS-C", "PIMS-TS", "therapy", "treatment", "drug", "IVIG", "GCs", "intravenous immunoglobulin", "corticosteroids", "biological agent", and "aspirin". RESULTS: The severity of MIS-C varies, and different treatment schemes should be used according to the specific condition. Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C. CONCLUSIONS: MIS-C is a disease involving multiple systems and has great heterogeneity. With the accumulation of additional experience, we have garnered fresh insights into its treatment strategies. However, there remains a critical need for greater standardization in treatment protocols, alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols. Supplementary file1 (MP4 208044 kb).

Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: Most previous studies suggested obesity deteriorates the functional outcome after ischemic stroke. But there are researches claiming that obesity is associated with lower mortality, recurrence, and readmission rates, which is known as the obesity paradox. Our current research aimed to investigate the correlation between genetically obesity and the post-stroke outcome with the Mendelian randomization (MR) method. METHODS: The UK Biobank and the GIANT consortium provided instrumental variables for body mass index (BMI, 806,834 individuals) and waist-to-hip ratio (WHR, 697,734 individuals). Data of functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network (6012 individuals). Inverse-variance weighted approach was utilized as the primary analyses. Sensitivity analyses involved the utilization of different MR methods. The heterogeneity among genetic variants was assessed by I2 and Q value statistics. RESULTS: In univariable analysis, there was a significant connection between genetic susceptibility to WHR and worse functional outcome (modified Rankin Scale 3) after ischemic stroke (OR [95%CI] = 1.47 [1.07, 2.02], P = 0.016). Genetic liability to BMI and was not associated with post-stroke functional outcome (all P > 0.05). The overall patterns between genetic liability to WHR and functional outcome post-ischemic outcome no longer existed in the multivariable MR analysis after adjusting for BMI (OR [95%CI] = 1.26[0.76,1.67], P = 0.56). CONCLUSION: The current MR study provided evidence that WHR was correlated to unfavorable outcome post-ischemic stroke. Exploring interventions against obesity may potentially improve recovery after ischemic stroke.

Spaco: A comprehensive tool for coloring spatial data at single-cell resolution.

Understanding tissue architecture and niche-specific microenvironments in spatially resolved transcriptomics (SRT) requires in situ annotation and labeling of cells. Effective spatial visualization of these data demands appropriate colorization of numerous cell types. However, current colorization frameworks often inadequately account for the spatial relationships between cell types. This results in perceptual ambiguity in neighboring cells of biological distinct types, particularly in complex environments such as brain or tumor. To address this, we introduce Spaco, a potent tool for spatially aware colorization. Spaco utilizes the Degree of Interlacement metric to construct a weighted graph that evaluates the spatial relationships among different cell types, refining color assignments. Furthermore, Spaco incorporates an adaptive palette selection approach to amplify chromatic distinctions. When benchmarked on four diverse datasets, Spaco outperforms existing solutions, capturing complex spatial relationships and boosting visual clarity. Spaco ensures broad accessibility by accommodating color vision deficiency and offering open-accessible code in both Python and R.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

A NAD(P)H oxidase mimic for catalytic tumor therapy via a deacetylase SIRT7-mediated AKT/GSK3ß pathway.

Nicotinamide adenine dinucleotide (NADH) and its phosphorylated form, NADPH, are essential cofactors that play critical roles in cell functions, influencing antioxidation, reductive biosynthesis, and cellular pathways involved in tumor cell apoptosis and tumorigenesis. However, the use of nanomaterials to consume NAD(P)H and thus bring an impact on signaling pathways in cancer treatment remains understudied. In this study, we employed a salt template method to synthesize a carbon-coated-cobalt composite (C@Co) nanozyme, which exhibited excellent NAD(P)H oxidase (NOX)-like activity and mimicked the reaction mechanism of natural NOX. The C@Co nanozyme efficiently consumed NAD(P)H within cancer cells, leading to increased production of reactive oxygen species (ROS) and a reduction in mitochondrial membrane potential. Meanwhile, the generation of the biologically active cofactor NAD(P)+ promoted the expression of the deacetylase SIRT7, which in turn inhibited the serine/threonine kinase AKT signaling pathway, ultimately promoting apoptosis. This work sheds light on the influence of nanozymes with NOX-like activity on cellular signaling pathways in tumor therapy and demonstrates their promising antitumor effects in a tumor xenograft mouse model. These findings contribute to a better understanding of NAD(P)H manipulation in cancer treatment and suggest the potential of nanozymes as a therapeutic strategy for cancer therapy.