Enhancing surgical decision-making in NEC with ResNet18: a deep learning approach to predict the need for surgery through x-ray image analysis.

Background: Necrotizing enterocolitis (NEC) is a severe neonatal intestinal disease, often occurring in preterm infants following the administration of hyperosmolar formula. It is one of the leading causes of neonatal mortality in the NICU, and currently, there are no clear standards for surgical intervention, which typically depends on the joint discretion of surgeons and neonatologists. In recent years, deep learning has been extensively applied in areas such as image segmentation, fracture and pneumonia classification, drug development, and pathological diagnosis. Objective: Investigating deep learning applications using bedside x-rays to help optimizing surgical decision-making in neonatal NEC. Methods: Through a retrospective analysis of anteroposterior bedside chest and abdominal x-rays from 263 infants diagnosed with NEC between January 2015 and April 2023, including a surgery group (94 cases) and a non-surgery group (169 cases), the infants were divided into a training set and a validation set in a 7:3 ratio. Models were built based on Resnet18, Densenet121, and SimpleViT to predict whether NEC patients required surgical intervention. Finally, the model's performance was tested using an additional 40 cases, including both surgical and non-surgical NEC cases, as a test group. To enhance the interpretability of the models, the study employed 2D-Grad-CAM technology to describe the models' focus on significant areas within the x-ray images. Results: Resnet18 demonstrated outstanding performance in binary diagnostic capability, achieving an accuracy of 0.919 with its precise lesion imaging and interpretability particularly highlighted. Its precision, specificity, sensitivity, and F1 score were significantly high, proving its advantages in optimizing surgical decision-making for neonatal NEC. Conclusion: The Resnet18 deep learning model, constructed using bedside chest and abdominal imaging, effectively assists clinical physicians in determining whether infants with NEC require surgical intervention.

Evaluating high-flow oxygen therapy after mechanical thrombectomy under general anesthesia in acute ischemic stroke: A retrospective single-center study.

BACKGROUND: The use of mechanical thrombectomy for acute intracranial vascular occlusion under general anesthesia with endotracheal intubation is well-established as a safe and effective method. However, the process of extubation post-surgery presents challenges for certain patients. This retrospective study assesses the safety and efficacy of combining mechanical ventilation with high-flow oxygen inhalation as an interim strategy, while also examining its impact on long-term clinical outcomes. METHODS: This research enrolled 119 patients with acute intracranial large vessel occlusion who underwent mechanical thrombectomy under general anesthesia with tracheal intubation between January 2020 and November 2023. Participants were categorized into two groups: Group 1 (n=55), which received high-flow oxygen (HFO) post-extubation, and Group 2 (n=64), which was treated with routine oxygen supplementation (RO). The study compared reintubation and tracheotomy rates between these groups to determine safety and effectiveness. Additionally, it analyzed long-term clinical outcomes by comparing NIHSS and mRS scores before treatment and at 90-day follow-up. RESULTS: The reintubation rate post-extubation was significantly lower in the HFO group (12.7 %, n=7) compared to the RO group (31.2 %, n=20, p=0.016). The incidence of tracheotomy within 7 days was also reduced in the HFO group compared to the RO group (7.3 %, n=4 vs 20.3 %, n=13, p=0.043). Moreover, a greater proportion of patients in the HFO group achieved mRS scores of 0-2 at 90 days post-stroke than those in the RO group (60 %, n=33 vs 40.6 %, n=26, p=0.035). The median NIHSS score at 90 days was more favorable in the HFO group than in the RO group (6, IQR [1-18] vs 8, IQR [1-20], p=0.005). CONCLUSION: The study suggests that high-flow oxygen therapy after mechanical thrombectomy under general anesthesia with tracheal intubation may lessen the need for reintubation and tracheotomy, potentially leading to improved long-term prognosis.

Surface segregation of rigid polyarylene ether amidoxime on polyurethane nanofiber into hierarchical membranes as substrate of flexible SERS nanosensor for sulfamethoxazole detection.

Electrospun polymeric nanofibrous membranes are emerging as the promising substrates for preparation of flexible SERS nanosensors due to their intrinsic nanoscale surface roughness, easy scalability as well as rich surface reactivity. Although the nanofiber membranes prepared from high performance thermoplastics exhibit good mechanical stability, the SERS nanosensors based on these substrates normally have lower signal-to-noise ratio because of the interference from background Raman signals of aromatic moieties. Herein, we synthesized an optically transparent polyurethane (PU) and rigid polyarylene ether amidoxime (PEA), which were electrospun into core-shell nanofibers membranes with a "beads-on-web" morphology. Furthermore, the PU-PEA membranes were coated with ultra-thin silver layer and thermally annealed to prepare the flexible SERS nanosensor without any background noises. In addition, the Raman enhancement of SERS nanosensor can be readily improved by tuning of PU-PEA composition, silver thickness as well as thermal annealing temperature. Finally, the optimized SERS nanosensor enables label-free detection of sulfamethoxazole as low as 0.1 nM with a good reproducibility and detection performance in real water sample. Meanwhile, the optimized SERS nanosensor shows long term anti-biofouling capacity. Thanks to its facile fabrication, competitive analytical performance and resistance to biofouling, the current work basically open new way for design of flexible SERS nanosensors for biomedical applications.

TET2 Is Downregulated in Early Esophageal Squamous Cell Carcinoma and Promotes Esophageal Squamous Cell Malignant Behaviors.

OBJECTIVE: To explore the expression of the ten eleven translocation (TET) 2 protein in early esophageal squamous cell carcinoma (EESCC), precancerous lesions, and cell lines and to evaluate the effect of TET2 on the functional behavior of EC109 esophageal cancer cells. METHODS: Thirty-one samples of EESCC and precancerous lesions collected via endoscopic submucosal dissection at Taihe Hospital, Shiyan, from February 1, 2017, to February 1, 2019, were analyzed. The study involved evaluating TET2 expression levels in lesion tissue and adjacent normal epithelium, correlating these with clinical pathological features. Techniques including 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide, cell scratch assays, flow cytometry for propidium iodide (PI) staining, Hoechst 333258/PI double staining, and nude mouse tumorigenesis experiments were employed to assess the effect of TET2 on the proliferation, migration, cell cycle, apoptosis, and tumorigenic ability of esophageal cancer cells. RESULTS: TET2 expression was notably reduced in early esophageal cancer tissue and correlated with tumor invasion depth (P < 0.05). Overexpression of TET2 enhanced the proliferation and migration of esophageal cancer cells, increased the cell population in the G0 phase, decreased it in the S phase, and intensified cell necrosis (P < 0.05). There was a partial increase in tumorigenic ability (P = 0.087). CONCLUSION: TET2 downregulation in ESCC potentially influences the necrosis, cell cycle, and tumorigenic ability of esophageal cancer cells, suggesting a role in the onset and progression of esophageal cancer.

Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative.

BACKGROUND: The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and gemtuzumab ozogamicin (GO) treatment on patients with EMI. METHODS: We retrieved the clinical data of 713 pediatric patients with AML from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, and analyzed the clinical and prognostic characteristics of patients with EMI at diagnosis and relapse. RESULTS: A total of 123 patients were identified to have EMI at diagnosis and 64 presented with EMI at relapse. The presence of EMI was associated with age ≤2 years, M5 morphology, abnormal karyotype, and KMT2A rearrangements. Hyperleukocytosis and complex karyotype were more prevalent in patients with EMI at relapse. Additionally, patients with EMI at diagnosis had a reduced incidence of FLT3 ITD-/NPM1+, whereas those with EMI at relapse displayed a lower frequency of FLT3 ITD+. Patients with EMI at diagnosis exhibited a lower complete remission (CR) rate at the end of Induction Course 1 and higher relapse incidence. Importantly, EMI at diagnosis independently predicted both shorter event-free survival (EFS) and overall survival (OS). Regarding relapse patients, the occurrence of EMI at relapse showed no impact on OS. However, relapse patients with myeloid sarcoma (MS)/no central nervous system (CNS) exhibited poorer OS compared to those with CNS/no MS. Furthermore, regarding patients with EMI at diagnosis, SCT failed to improve the survival, whereas GO treatment potentially enhanced OS. CONCLUSION: EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.

Effectiveness of PD1/PD-L1 combined with anti-angiogenic drugs in patients with advanced nonsmall cell lung cancer: A systematic review and meta-analysis.

Background: Protein-1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) therapy have become an important treatment approach for patients with advanced nonsmall cell lung cancer (NSCLC), but primary or secondary resistance remains a challenge for some patients. PD-1/PD-L1 combined with anti-angiogenic drugs (AAs) in NSCLC patients have potential synergistic effects, and the survival benefit may vary based on a treatment order. To investigate the efficacy of PD-1/PD-L1 combined with AAs as the treatment for patients with advanced NSCLC. Materials and Methods: We comprehensively searched EMBASE, PubMed, Web of Science, CNKI, VIP, and Wanfang databases from January 2017 to September 2022. The Cochrane risk bias tool evaluated the quality of included randomized clinical trials. Newcastle-Ottawa-Scale score was used to evaluate the quality of retrospective studies. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Results: Seventeen articles were finally selected, involving 5182 patients. Meta-analysis results showed that PD1/PD-L1 combined with AAs therapy significantly improved progression-free survival (PFS) (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.50-0.75, P < 0.00001), overall survival (OS) (HR = 0.79, 95% CI: 0.71-0.88, P < 0.00001), and objective response rate (ORR) (risk ratio = 0.88, 95% CI: 0.81-0.96, P = 0.004), with the statistically significant difference. The sensitivity analysis demonstrated the robustness of the PFS, ORR, and OS. Conclusion: The combination of PD-1/PD-L1 inhibitors with AAs in treating advanced patients has exhibited notable therapeutic advantages when contrasted with monotherapy. Specifically, the administration of PD-1/PD-L1 inhibitors in conjunction with AAs, or sequential treatment involving PD-1/PD-L1 followed by AAs, has shown enhanced therapeutic efficacy in this patient population.

Functionalized lignin nanoparticles assembled with MXene reinforced polypropylene with favorable UV-aging resistance, electromagnetic shielding effects and superior fire-safety.

Deterioration in mechanical performances and aging resistance due to the introduction of flame retardants is a major obstacle for bio-based fire-safety polypropylene (PP). Herein, we reported a kind of functionalized lignin nanoparticles assembled with MXene (MX@LNP), and applied it to construct the flame-retardant PP composites (PP-MA) with superior fire safety, excellent mechanical performance, electromagnetic shielding effects and aging resistance. Specifically, the PP-MA doped with only 18 wt% flame-retardant additives (PP-MA18) achieved the UL-94 V-0 rating. In comparison to pure PP, PP-MA18 presented a greatly decreased peak of heat release rate (pHRR), total heat rate (THR), and peak smoke production rate (pSPR) by 79.7 %, 69.0 % and 75.8 %, respectively, and satisfactory decrease in total flammable and toxic volatiles evolved. The formed fine solid microstructure of carbon residuals effectively promoted the compactness of char layers. More importantly, the nano-effect and the strong interface interaction between the complexed MX@LNP and PP enhanced the tensile strength (45.78 MPa) and elongation at break (725.95 %) of PP-MA. Additionally, the significant ultraviolet absorption and electromagnetic wave dissipation performance of MXene and lignin enabled excellent aging resistance and electromagnetic shielding effects of PP-MA compared with PP. This achieved MX@LNP afforded a novel approach for developing flame retardant materials with excellent application performance.

Blockage of mechanosensitive Piezo1 channel alleviates the severity of experimental malaria-associated acute lung injury.

BACKGROUND: Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that is partly driven by sequestrations of infected red blood cells (iRBCs) on lung postcapillary induced impaired blood flow. In earlier studies the mechanosensitive Piezo1 channel emerged as a regulator of mechanical stimuli, but the function and underlying mechanism of Piezo1 impacting MA-ALI severity via sensing the impaired pulmonary blood flow are still not fully elucidated. Thus, the present study aimed to explore the role of Piezo1 in the severity of murine MA-ALI. METHODS: Here, we utilized a widely accepted murine model of MA-ALI using C57BL/6 mice with Plasmodium berghei ANKA infection and then added a Piezo1 inhibitor (GsMTx4) to the model. The iRBC-stimulated Raw264.7 macrophages in vitro were also targeted with GsMTx4 to further explore the potential mechanism. RESULTS: Our data showed an elevation in the expression of Piezo1 and number of Piezo1+-CD68+ macrophages in lung tissues of the experimental MA-ALI mice. Compared to the infected control mice, the blockage of Piezo1 with GsMTx4 dramatically improved the survival rate but decreased body weight loss, peripheral blood parasitemia/lung parasite burden, experimental cerebral malaria incidence, total protein concentrations in bronchoalveolar lavage fluid, lung wet/dry weight ratio, vascular leakage, pathological damage, apoptosis and number of CD68+ and CD86+ macrophages in lung tissues. This was accompanied by a dramatic increase in the number of CD206+ macrophages (M2-like subtype), upregulation of anti-inflammatory cytokines (e.g. IL-4 and IL-10) and downregulation of pro-inflammatory cytokines (e.g. TNF-α and IL-1ß). In addition, GsMTx4 treatment remarkably decreased pulmonary intracellular iron accumulation, protein level of 4-HNE (an activator of ferroptosis) and the number of CD68+-Piezo1+ and CD68+-4-HNE+ macrophages but significantly increased protein levels of GPX4 (an inhibitor of ferroptosis) in experimental MA-ALI mice. Similarly, in vitro study showed that the administration of GsMTx4 led to a remarkable elevation in the mRNA levels of CD206, IL-4, IL-10 and GPX-4 but to a substantial decline in CD86, TNF-α, IL-1ß and 4-HNE in the iRBC-stimulated Raw264.7 cells. CONCLUSIONS: Our findings indicated that blockage of Piezo1 with GsMTx4 alleviated the severity of experimental MA-ALI in mice partly by triggering pulmonary macrophage M2 polarization and subsequent anti-inflammatory responses but inhibited apoptosis and ferroptosis in lung tissue. Our data suggested that targeting Piezo1 in macrophages could be a promising therapeutic strategy for treating MA-ALI.

Synthesis and Properties of Semicrystalline Poly(ether nitrile ketone) Copolymers.

As a high-performance engineering plastic, polyarylene ether nitrile (PEN) is widely used in many fields. The presence of cyano groups of PEN ensures its good adhesion to other substrates, but the inherent low crystallinity of PEN limits its application. In this work, the poly(aryl ether ketone) segment was introduced into PEN via copolymerization using both 2,6-Dichlorobenzonitrile and 4,4'-Difluorobenzophenone as the starting reagents to prepare poly (ether nitrile ketone) (BP-PENK). The effect of composition and thermal treatment on the crystallization behavior and properties of poly (ether nitrile ketone) were systematically studied. It was found that when the content of DFBP is 30%, the copolymer BP-PENK30 had the best mechanical properties, with a tensile strength of 109.9 MPa and an elongation at a break value of 45.2%. After thermal treatment at 280 °C for 3 h, BP-PENK30 had the highest crystallinity with a melting point of 306.71 °C, a melting enthalpy of 5.02 J/g, and crystallinity of 11.83%. Moreover, with the increase in crystallinity, the dielectric constant and energy density increased after thermal treatment. Therefore, the introduction of poly(aryl ether ketone) chain segments and thermal treatment can effectively improve the crystallization and the comprehensive properties of PEN.

Difunctional Microelectrode Arrays for Single-Cell Electrical Stimulation and pH Detection.

Due to its direct effect on biomolecules and cells, electrical stimulation (ES) is now widely used to regulate cell proliferation, differentiation, and neurostimulation and is even used in the clinic for pain relief, treatment of nerve damage, and muscle rehabilitation. Conventional ES is mostly studied on cell populations, but the heterogeneity of cancer cells results in the inability to access the response of individual cells to ES. Therefore, detecting the extracellular pH change (ΔpHe) after ES at the single-cell level is important for the application of ES in tumor therapy. In this study, cellular ΔpHe after periodic impulse electrostimulation (IES) was monitored in situ by using a polyaniline (PANI)-modified gold microelectrode array. The PANI sensor had excellent sensitivity (53.68 mV/pH) and linear correlation coefficient (R2 = 0.999) over the pH range of 5.55-7.41. The cells showed different degrees of ΔpHe after the IES with different intervals and stimulation potential. A shorter pulse interval and a higher stimulation potential could effectively enhance stimulation and increase cellular ΔpHe. At 0.5 V potential stimulation, the cellular ΔpHe increased with decreasing pulse interval. However, if the pulse interval was long enough, even at a higher potential of 0.7 V, there was no significant additional ΔpHe due to the insufficient stimulus strength. Based on the above conclusions, the prepared PANI microelectrode arrays (MEAs) were capable of stimulating and detecting single cells, which contributed to the deeper application of ES in tumor therapy.

Genetic evidence suggests a genetic association between major depressive disorder and reduced cortical gray matter volume: A Mendelian randomization study and mediation analysis.

BACKGROUND: Several studies have suggested an association between major depressive disorder (MDD) and abnormal brain structure. However, it is unclear whether MDD affects cortical gray matter volume, a common indicator of cognitive function. We aimed to determine whether MDD was associated with decreased cortical gray matter volume (GMV) through a Mendelian randomization (MR) study. METHODS: We obtained summary genetic data from a study conducted by the Psychiatric Genomics Consortium, which recruited a total of 480,359 participants (135,458 cases and 344,901 controls). Genetic tools-single nucleotide polymorphisms (SNPs)-of MDD were extracted from the study and their effects on gray matter volumes of the cortex and total brain were evaluated in a large cohort from the UK Biobank (n = 8427). The effects of the SNPs were pooled using inverse variance weighted (IVW) analysis and further tested in several sensitivity analyses. We tested whether C-reactive protein (CRP) levels and interleukin-6 signaling were the mediators of the effects using a multivariate MR model. RESULTS: Thirty-three SNPs were identified and adopted as genetic tools for predicting MDD. IVW analysis showed that MDD was associated with lower overall GMV (beta value -0.106, 95%CI -0.188 to -0.023, p = 0.011) in the frontal pole (left frontal pole, -0.152, 95%CI -0.177 to -0.127, p = 0.013; right frontal pole, -0.133, 95%CI -0.253 to -0.013, p = 0.028). Multivariate and mediation analysis showed that interleukin-6 was an important mediator of GMV reduction. Reverse causality analysis found no evidence that total GMV affected the risk of MDD, but showed that increased left precuneus cortex volume and left posterior cingulate cortex volume were associated with increased risk of MDD. LIMITATIONS: Potential pleiotropic effects and overestimation of real-world effects. Key assumptions for MR analysis may not be satisfactorily met. CONCLUSION: MDD was associated with a reduced GMV, and interleukin-6 might be a mediator of GMV reduction.

A blastic plasmacytoid dendritic cell neoplasm-like immunophenotype is negatively associated with CEBPA bZIP mutation and predicts unfavorable prognosis in acute myeloid leukemia.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy which characteristically expresses an atypical phenotype including CD123+, CD56+, and CD4+. We are aimed to investigate the clinical and prognostic characteristics of AML patients exhibiting BPDCN-like immunophenotype and provide additional insights for risk stratification of AML. A total of 241 newly diagnosed AML patients were enrolled in this retrospective study and categorized into BPDCN-like positive (n = 125)/negative (n = 116) groups, determined by the present with CD123+ along with either CD56+ or CD4+, or both. Subsequently, an analysis was conducted to examine the general clinical characteristics, genetic profiles, and prognosis of the two respective groups. Patients with BPDCN-like immunophenotype manifested higher frequencies of acute myelomonocytic leukemia and acute monoblastic leukemia. Surprisingly, the presence of the BPDCN-like immunophenotype exhibited an inverse relationship with CEBPA bZIP mutation. Notably, patients with BPDCN-like phenotype had both worse OS and EFS compared to those without BPDCN-like phenotype. In the CN-AML subgroups, the BPDCN-like phenotype was associated with worse EFS. Similarly, a statistically significant disparity was observed in both OS and EFS within the favorable-risk subgroup, while only OS was significant within the adverse-risk subgrouMoreover, patients possessing favorable-risk genetics without BPDCN-like phenotype had the longest survival, whereas those who had both adverse-risk genetics and BPDCN-like phenotype exhibited the worst survival. Our study indicated that BPDCN-like phenotype negatively associated with CEBPA bZIP mutation and revealed a significantly poor prognosis in AML. Moreover, the 2022 ELN classification, in combination with the BPDCN-like phenotype, may better distinguish between different risk groups.

Immobilization mechanisms of heavy metals by utilizing natural cow bone waste for municipal solid waste incineration fly ash treatment.

Municipal solid waste incinerator (MSWI) fly ash poses intricate compositional challenges and potential environmental hazards. Effective management of such hazardous waste is imperative to mitigate the release of toxic compounds into the environment. Solidification/stabilization (S/S) processes have emerged as a viable strategy to transform MSWI fly ash from incineration waste into a safer and more environmentally benign material. This study aims to comprehensively investigate the potential of utilizing cow bone waste to stabilize heavy metals, focusing on Pb, within municipal solid waste incineration fly ash. Experimental investigations encompassed cow bone-to-fly ash weight ratios ranging from 0.0 (control group) to 7:3, a settling time of 2 h, and a liquid-to-solid (L/S) ratio of 1.0 mL/g. Cow bone waste exhibited pronounced efficacy, particularly within the short settling time, yielding a remarkable Pb removal efficiency of up to 99% at a cow bone waste dose of merely 2% and an L/S ratio of 1.0 mL/g. Concurrently, other heavy metals such as Cd, Cu, and Zn were effectively stabilized with a cow bone waste dose of 1.5% during the same 2-h settling period. The results underscore the pivotal roles of ash/bone ratio and settling time in augmenting Pb stabilization in MSWI fly ash. The application of cow bone waste is anticipated to offer a cost-effective and environmentally sound approach, aligning with sustainable waste management principles.

Correlation between red blood cell distribution width/platelet count and prognosis of newly diagnosed diffuse large B-cell lymphoma.

Background: Red blood cell distribution width/platelet count ratio (RPR) is a reliable prognostic assessment indicator for numerous diseases. However, no studies to date have examined the relationship between RPR and the prognosis of diffuse large B-cell lymphoma (DLBCL). Therefore, this study aimed to investigate the correlation between RPR and the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma. Methods: We retrospectively studied 143 patients with newly diagnosed DLBCL and used the median value as the RPR threshold. We also investigated the correlation of pretreatment RPR level with clinical characteristics and its impact on DLBCL prognosis. Results: Using the median value as the cut-off, patients with DLBCL were divided into a low RPR group (＜0.0549) and a high RPR group (≥0.0549). Patients in the high RPR group were older, had a later Ann Arbor stage, were prone to bone marrow invasion, and had a higher National Comprehensive Cancer Network International Prognostic Index score (P＜0.05). A survival analysis showed that progression-free survival (PFS) (P=0.003) and overall survival (OS) (P＜0.0001) were significantly shorter in the high versus low RPR group. A multifactorial Cox analysis showed that bone marrow invasion and elevated lactate dehydrogenase (LDH) were separate risk factors for PFS (P＜0.05), while an RPR ≥0.0549 and elevated LDH were separate risk factors for OS (P＜0.05). Conclusion: A high RPR (≥0.0549) in patients with newly diagnosed DLBCL is an independent risk factor for a poor prognosis.

Survival benefit of adjuvant chemotherapy in elderly patients with stage I triple-negative breast cancer: a cohort study based on the SEER database.

Background: This study analyzed the trend and prognostic role of postoperative adjuvant chemotherapy (POCT) in patients with stage I triple-negative breast cancer (TNBC) aged more than 65 years. In addition, the relationship between POCT and survival rate was also determined. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was collected to determine 3,307 TNBC elderly women aged ≥65 years between 2010 and 2016, and they were divided into POCT and non-POCT groups. Propensity score matching (PSM) method was used to offset the differences in baseline characteristics between the groups. Kaplan-Meier plots were tested to contrast overall survival (OS) and breast cancer-specific survival (BCSS) between the two groups. The Cox proportional hazard model was constructed to assess the prognostic factors affecting OS and BCSS. Results: Younger age, higher histological grade, married, postoperative radiotherapy, lumpectomy, larger tumor, and closer year of diagnosis were related to an enhanced likelihood of adjuvant chemotherapy. After PSM, POCT was related to increased 5-year OS [hazard ratio (HR): 0.571, 95% confidence interval (CI): 0.432-0.753, respectively], without significant difference in BCSS improvement. Exploratory subgroup analysis demonstrated that POCT contributed to OS improvement in both IA and IB patients, but did not improve BCSS in IA and IB patients. Conclusions: In elderly patients ≥65 years, POCT improved 5-year OS in stage I TNBC patients, while further exploration with larger prospective trials are needed.

Efficacy of metformin adjunctive therapy as the treatment for non-diabetic patients with advanced non-small cell lung cancer: A Systematic review and Meta-analysis.

Background: Currently, the anticancer effects of metformin on different types of lung cancer have been frequently studied. However, the relationship between metformin and prognosis in nondiabetic patients with lung cancer remains controversial. To systematically evaluate the efficacy of metformin adjunctive therapy as the treatment for nondiabetic patients with advanced non-small cell lung cancer (NSCLC) to provide an evidence-based reference for clinical medication. Materials and Methods: The literatures related to Phase II or III randomized controlled trials (RCTs) of metformin adjunctive therapy in nondiabetic patients with advanced NSCLC, including EMBASE, PubMed, the Cochrane Library, and Scopus database, were retrieved by computer, and the search time ranged from January 2017 to August 2022. The risk of bias assessment tool recommended by Cochrane Systematic Evaluator Manual 5.1.0 was used to evaluate the quality of the RCTs included. Rev Man 5.3 software and STATA15.0 were used for meta-analysis. Results: A total of 8 studies were included (925 patients). Meta-analysis results showed that there were no significant differences in progression-free survival (PFS) (hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.66-1.36, P = 0.77), overall survival (OS) (HR = 0.89, 95% CI: 0.61-1.30, P = 0.55, n =7), objective response rate (ORR) (odds ratio [OR] = 1.37, 95% CI: 0.76-2.46, P = 0.30), and 1-year PFS rate (OR = 0.87, 95% CI: 0.39-1.94, P = 0.73, n = 3). Sensitivity analysis showed that PFS and OS indexes were stable. Conclusion: Metformin adjunctive therapy can improve the DCR of nondiabetic patients with advanced NSCLC. In addition, the patients cannot obtain a prolonged PFS, OS, 1-year PFS rate, and higher ORR rate.

Ethanol inhibition of undifferentiated rat neural progenitor cell replication can be prevented by chlorogenic acid via the NFATc4/CSE signaling pathway.

BACKGROUND: Prenatal ethanol exposure hinders oxidative stress-mediated neuroblast/neural progenitor cell proliferation by inhibiting G1-S transition, a process vital to neocortical development. We previously showed that ethanol elicits this redox imbalance by repressing cystathionine γ-lyase (CSE), the rate-limiting enzyme in the transsulfuration pathway in fetal brain and cultured cerebral cortical neurons. However, the mechanism by which ethanol impacts the CSE pathway in proliferating neuroblasts is not known. We conducted experiments to define the effects of ethanol on CSE regulation and the molecular signaling events that control this vital pathway. This enabled us to develop an intervention to prevent the ethanol-associated cytostasis. METHODS: Spontaneously immortalized undifferentiated E18 rat neuroblasts from brain cerebral cortex were exposed to ethanol to mimic an acute consumption pattern in humans. We performed loss- and gain-of-function studies to evaluate whether NFATc4 is a transcriptional regulator of CSE. The neuroprotective effects of chlorogenic acid (CGA) against the effects of ethanol were assessed using ROS and GSH/GSSG assays as measures of oxidative stress, transcriptional activation of NFATc4, and expression of NFATc4 and CSE by qRT-PCR and immunoblotting. RESULTS: Ethanol treatment of E18-neuroblast cells elicited oxidative stress and significantly reduced CSE expression with a concomitant decrease in NFATc4 transcriptional activation and expression. In parallel, inhibition of the calcineurin/NFAT pathway by FK506 exaggerated ethanol-induced CSE loss. In contrast, NFATc4 overexpression prevented loss of ethanol-induced CSE. CGA increased and activated NFATc4, amplified CSE expression, rescued ethanol-induced oxidative stress, and averted the cytostasis of neuroblasts by rescuing cyclin D1 expression. CONCLUSIONS: These findings demonstrate that ethanol can perturb CSE-dependent redox homeostasis by impairing the NFATc4 signaling pathway in neuroblasts. Notably, ethanol-associated impairments were rescued by genetic or pharmacological activation of NFATc4. Furthermore, we found a potential role for CGA in mitigating the ethanol-related neuroblast toxicity with a compelling connection to the NFATc4/CSE pathway.

Sialic acid-targeting multi-functionalized silicon quantum dots for synergistic photodynamic and photothermal cancer therapy.

To explore the potential of silicon quantum dots (SiQDs) in combined photodynamic therapy (PDT) and photothermal therapy (PTT), we engineered the surface of SiQDs with the photosensitizer Ce6 and the tumor-cell-targeting ligand phenylboronic acid (PBA) via polydopamine-mediated chemistry. Upon irradiation with light of specific wavelengths, SiQDs@Ce6/PBA could generate high levels of reactive oxygen species (ROS) and trigger effective photo-to-thermal conversion. PBA-conjugation could not only increase the cellular uptake and transcellular transport capability of nanoparticles, but also enhance their tumor accumulation. In the presence of a 635 nm laser, SiQDs@Ce6/PBA was able to trigger intracellular ROS production, which further altered the mitochondrial membrane potential and promoted apoptosis of tumor cells. Finally, combined PDT/PTT treatments led to synergistically enhanced cancer cell killing and tumor-growth inhibition effects. This study demonstrates the surface engineering of silicon quantum dots for synergistic PDT/PTT cancer therapy.

Scalable fabrication of silver covered polyurethane nanofibers as flexible SERS nanosensors for aflatoxin detection.

Flexible surface enhanced Raman spectroscopy (SERS) nanosensors, constructed by integration of plasmonic nanostructures with polymeric substrates, have received increasing research interests for recent decades. When compared to abundant works on optimization of the plasmonic nanostructures, the research involving the influence of polymeric substrates on analytical performance of resultant flexible SESR nanosensors is unexpectedly limited. Herein, the ultra-thin silver layer has been deposited on the electrospun polyurethane (ePU) nanofibrous membranes via vacuum evaporation to prepare the flexible SRES nanosensors. Interestingly, we find that the molecular weight and polydispersion index of synthesized PU play important roles in regulating the fine morphology of electrospun nanofibers, which in turns determine the Raman enhancement of resultant flexible SERS nanosensors. Specifically, the optimized SERS nanosensor, obtained by evaporating 10 nm silver layer on top of nanofibers derived from electrospinning of PU with a weight-average molecular weight of 140,354 and polydispersion index of 1.26, enables label-free detection of the carcinogen of aflatoxin down to 0.1 nM. Thanks to its scalable fabrication and good sensitivity, the current work opens new way for design of cost-effective flexible SERS nanosensors for environmental monitoring and food security applications.

Sporothrix globosa melanin regulates autophagy via the TLR2 signaling pathway in THP-1 macrophages.

Melanin, an important virulence factor of pathogenic fungi, has been shown to suppress host immune responses in multiple ways. Autophagy is a vital cellular mechanism underlying the host's innate immunity against microbial infections. However, the potential influence of melanin on autophagy has not been explored. We investigated the effect of melanin on autophagy in macrophages, which play a key role in controlling Sporothrix spp. infection, as well as the mechanism of melanin interaction with Toll-like receptor (TLR)-induced pathways. Sporothrix globosa conidia (wild-type and melanin-deficient mutant strains) or yeast cells were co-cultured with THP-1 macrophages to demonstrate that, although S. globosa infection led to the activation of autophagy-related proteins and increased autophagic flux, S. globosa melanin suppressed macrophage autophagy. Incubation with S. globosa conidia also increased the expression levels of reactive oxygen species and multiple proinflammatory cytokines (interleukin-6, tumor necrosis factor-α, interleukin-1ß and interferon-γ) in macrophages. These effects were attenuated as melanin presented. Furthermore, while S. globosa conidia significantly increased the expression of both TLR2 and TLR4 in macrophages, the knockdown of TLR2, but not TLR4, with small interfering RNA suppressed autophagy. Overall, this study revealed the novel immune defense ability of S. globosa melanin to inhibit macrophage functionality by resisting macrophage autophagy through the regulation of TLR2 expression.