The Diagnostic and Prognostic Value of the Combination of Tumor M2-Pyruvate Kinase, Carcinoembryonic Antigen, and Cytokeratin 19 Fragment in Non-Small Cell Lung Cancer.

Objective: Finding biomarkers related to non-small cell lung cancer (NSCLC) is helpful for the diagnosis and precise treatment of lung cancer. The relationship between serum tumor M2-pyruvate kinase (TuM2-PK), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment (CYFRA21-1) and NSCLC was analyzed. Methods: The serum levels of TuM2-PK, CEA, and CYFRA21-1 in 184 patients with the NSCLC group, 60 patients with the benign lung disease (BLD) group, and 90 healthy controls (HC) group were detected. The levels of TuM2-PK were measured by using an enzyme-linked immunosorbent assay. The detection methods of CEA and CYFRA21-1 were electrochemiluminescence. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of TuM2-PK, CEA, and CYFRA21-1 on NSCLC. The Kaplan-Meier survival curve was drawn to evaluate the survival status in NSCLC patients with different serum levels of TuM2-PK, CEA, and CYFRA21-1. Results: Serum levels of TuM2-PK, CEA, and CYFRA21-1 in the NSCLC group were significantly higher than those in the BLD group and the HC group (P < .01). Serum levels of TuM2-PK, CEA, and CYFRA21-1 in NSCLC patients were associated with the tumor lymph node metastasis stage (P < .05), lymph node metastasis (P < .05), and distant metastasis (P < .05). The ROC curve showed that the area under the curve of serum levels of TuM2-PK, CEA, and CYFRA21-1 was 0.814, 0.638, and 0.719, respectively, and that the combination of the above 3 was 0.918. The Kaplan-Meier survival curve showed that the 1-, 3- and 5-year survival rate in NSCLC patients with positive TuM2-PK, CEA, and CYFRA21-1 was significantly lower than that in NSCLC patients with negative TuM2-PK, CEA, and CYFRA21-1, respectively (P < .05). Conclusions: Serum TuM2-PK, CEA, and CYFRA21-1 levels have high clinical values in the diagnosis of NSCLC, and can effectively judge the prognosis of patients.

Trade-off between sulfidated zero-valent iron reactivity and air stability: Regulation of iron sulfides by ammonium dihydrogen phosphate.

The reactivity and stability of zero-valent iron (ZVI) and sulfidated zero-valent iron (S-ZVI) are inherently contradictory. Iron sulfides (FeSX) on the S-ZVI surface play multiple roles, including electrostatic adsorption and catalyzing reduction. We proposed to balance the reactivity and air stability of S-ZVI by regulating FeSX. Benefiting from the superior coordination and accelerate electron transport capabilities of phosphate, herein, eco-friendly ammonium dihydrogen phosphate (ADP) was employed to synthesize N, P, and S-incorporated ZVI (NPS-ZVI) and regulate the FeSX. Raman, FTIR, XPS, and density functional theory (DFT) calculations were combined to reveal that HPO42- acts as the main P species on the Fe surface. The superior reactivity of NPS-ZVI was quantified by kobs, kSA, and kM of Cr(VI), which were 210.77, 27.44, and 211.17-fold than ZVI, respectively. NPS-ZVI demonstrated excellent reusability, with no risk of secondary pollution. Critically, NPS-ZVI could effectively maintain FeSX stability under the combination of diffusion limitation and surface protection mechanisms of ADP. The superior reactivity of NPS-ZVI was attributed to the fact that ADP maintains FeSX stability and accelerates electron transport. This study provides a novel strategy in balancing the reactivity and air stability of S-ZVI and offers theoretical support for material modification.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Single-molecule reconstruction of eukaryotic factor-dependent transcription termination.

Factor-dependent termination uses molecular motors to remodel transcription machineries, but the associated mechanisms, especially in eukaryotes, are poorly understood. Here we use single-molecule fluorescence assays to characterize in real time the composition and the catalytic states of Saccharomyces cerevisiae transcription termination complexes remodeled by Sen1 helicase. We confirm that Sen1 takes the RNA transcript as its substrate and translocates along it by hydrolyzing multiple ATPs to form an intermediate with a stalled RNA polymerase II (Pol II) transcription elongation complex (TEC). We show that this intermediate dissociates upon hydrolysis of a single ATP leading to dissociation of Sen1 and RNA, after which Sen1 remains bound to the RNA. We find that Pol II ends up in a variety of states: dissociating from the DNA substrate, which is facilitated by transcription bubble rewinding, being retained to the DNA substrate, or diffusing along the DNA substrate. Our results provide a complete quantitative framework for understanding the mechanism of Sen1-dependent transcription termination in eukaryotes.

Efficacy and safety of PD-1/PD-L1 inhibitors in elderly patients with advanced non-small cell lung cancer.

OBJECTIVE: This study aimed to investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treatment of elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients with advanced NSCLC ≥70 years old who received PD-1/PD-L1 inhibitors in our hospital were retrospectively analyzed. According to age, the patient were stratified as follows: 70-75 years old, 76-80 years old, and >80 years old. Kaplan-Meier method was used for survival analysis, and univariate and multivariate Cox proportional hazards regression models were used to analyze the correlation between different clinical characteristics and survival. RESULTS: A total of 58 elderly patients with advanced non-small cell cancer were enrolled in this study. Patients aged 70-75, 76-80, and >80 years old were 32, 19, and 7, respectively. For the all, median OS was 17.0 months, and PFS was 7.0 months. PFS and OS did not differ according to age (P = 0.396, 0.054, respectively). Univariate analysis showed that PS of 0-1, stage III, first-line therapy and irAEs were associated with longer PFS, and PS of 0-1, stage III, and first-line therapy were associated with longer OS. Multivariate analysis showed that patients with stage III had longer PFS. PFS and OS of patients with PS ≥ 2 were significantly shorter than those of patients with PS of 0-1. CONCLUSIONS: In the present real-world retrospective cohort, PD-1/PD-L1 inhibitors are effective and well tolerated in elderly patients with advanced NSCLC. Immunotherapy should be actively used as early as possible in older patients advanced NSCLC.

Predictive Value of NLR and PLR in Driver-Gene-Negative Advanced Non-Small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitors: A Single Institutional Cohort Study.

OBJECTIVE: To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for the efficacy and prognosis of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors in driver-gene-negative advanced non-small-cell lung cancer (NSCLC). METHODS: A retrospective analysis of 107 advanced NSCLC patients without gene mutations who received PD-1/PD-L1 inhibitors in our hospital from January 2020 to June 2022 was performed. NLR and PLR were collected before PD-1/PD-L1 inhibitors, the optimal cut-off values of NLR and PLR were determined according to the receiver operating characteristic (ROC) curve, and the effects of NLR and PLR on the efficacy of PD-1/PD-L1 inhibitors in advanced NSCLC patients were analyzed. RESULTS: A total of 107 patients were included in this study. Receiver operating characteristic analysis showed that the optimal cut-off values of NLR and PLR were 3.825, 179, respectively. Kaplan-Meier curve showed that low baseline levels NLR and PLR were associated with an improvement in both progression-free survival (PFS) (P < .001, < .001, respectively) and overall survival (OS) (P = .009, .006, respectively). In first-line treatment and non-first-line treatment, low baseline levels NLR and PLR were associated with an improvement in PFS. In multivariate analysis, low baseline NLR and PLR showed a strong association with both better PFS (P = .011, .027, respectively) and longer OS (P = .042, .039, respectively). CONCLUSION: Low baseline NLR and PLR levels are significantly associated with better response in advanced NSCLC patients treated with PD-1/PD-L1 inhibitors, which may be indicators to predict the efficacy of immunotherapy in advanced NSCLC with driver-gene-negative.

ß-Glucans obtained from fungus for wound healing: A review.

The cell surface of fungus contains a large number of ß-glucans, which exhibit various biological activities such as immunomodulatory, anti-inflammatory, and antioxidation. Fungal ß-glucans with highly branched structure show great potential as wound healing reagents, because they can stimulate the expression of many immune- and inflammatory-related factors beneficial to wound healing. Recently, the wound healing ability of many fungal ß-glucans have been investigated in animals and clinical trials. Studies have proved that fungal ß-glucans can promote fibroblasts proliferation, collagen deposition, angiogenesis, and macrophage infiltration during the wound healing process. However, the development of fungal ß-glucans as wound healing reagents is not systematically reviewed till now. This review discusses the wound healing studies of ß-glucans obtained from different fungal species. The structure characteristics, extraction methods, and biological functions of fungal ß-glucans with wound healing ability are summarized. Researches about fungal ß-glucan-containing biomaterials and structurally modified ß-glucans for wound healing are also involved.

Decoding the divalent cation effect on sulfidation of zero-valent iron: Phase evolution and FeSx assembly.

The decontamination ability of sulfidated zero-valent iron (S-ZVI) can be enhanced by the effective assembly of iron sulfides (FeSx) on neglected heterogeneous surfaces by liquid-phase precipitation. However, S-ZVI preparation with the usual pickling is detrimental to orderly interfacial assembly and leads to an imbalance between electron transfer optimization and electron storage. In this work, S-ZVI was prepared in solutions containing trace divalent cation, and it removed Cr(VI) up to 323.25 times higher than ZVI. This result is achieved by surface sites protonation of divalent cations regulating the phase evolution on the ZVI surface and inducing FeSx chemical assembly. Regulation of divalent cation and S(-II) content further promotes FeSx targeted assembly and reduces electron storage consumption as much as possible. The barrier for FeSx assembly is found to lie at the ZVI interface rather than in the deposition between FeSx. Chemical assembly at heterogeneous interfaces is a prerequisite for the ordered assembly of FeSx. In addition, S-ZVI prepared in simulated groundwater showed extensive preparation pH and universality for remediation scenarios. These findings provide new insights into the development of in-situ sulfidation mechanisms with particular implications for S-ZVI applied to soil and groundwater remediation by the regulation of heterogeneous interfacial assembly.

Docetaxel Plus Nedaplatin or Carboplatin as Second-Line Chemotherapy for Advanced Lung Squamous Cell Carcinoma in Real-World Practice: A Single-Center Experience.

Although single-drug chemotherapy regimens were used as second-line chemotherapy for advanced lung squamous cell carcinoma (LSCC) patients, there are still no standard guidelines for second-line chemotherapy. The purpose of this study was to compare the efficacy and safety of docetaxel combined with nedaplatin or carboplatin in the second-line treatment of advanced LSCC patients. One hundred and ninety-six LSCC patients receiving docetaxel plus nedaplatin (DN, n = 96) or carboplatin (DC, n = 100) were retrospectively collected until disease progression or unacceptable toxicity. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed in the two groups. The ORR was 18.8% versus 16.0%, and the DCR was 39.6% versus 34.0% in DN group and DC group (P > .05 and P > .05), respectively. The PFS was 5.3 versus 3.8 months, and the OS was 8.5 and 6.7 months in DN group and DC group (P = .013 and P = .404), respectively. The rate of digestive reaction and hepatotoxicity was similar in DN and DC groups, whereas more patients in DC group than in DN group suffered from leucopenia (P < .05). Docetaxel combined with nedaplatin is an effective regimen for advanced LSCC patients. Compared with a similar regimen with carboplatin, the response rate was similar; however, nedaplatin regimen shows some superiority as regards survival and some treatment side effect.

Significant association between high neutrophil-lymphocyte ratio and poor prognosis in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

Objective: Whether neutrophil-lymphocyte ratio (NLR) is an applicative predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) remains controversial. In response to the current conflicting data, this meta-analysis was conducted to gain a comprehensive and systematic understanding of prognostic value of NLR in HCC. Methods: Several English databases, including PubMed, EMBASE, and the Cochrane Library, with an update date of February 25, 2023, were systematically searched. We set the inclusion criteria to include randomized controlled trial (RCT) studies that reported the prognostic value of serum NLR levels in patients with HCC receiving treatment. Both the combined ratio (OR) and the diagnosis ratio (DOR) were used to assess the prognostic performance of NLR. Additionally, we completed the risk of bias assessment by Cochrane Risk of Bias Assessment Tool. Results: This meta-analysis ultimately included 16 studies with a total of 4654 patients with HCC. The results showed that high baseline NLR was significantly associated with poor prognosis or recurrence of HCC. The sensitivity of 0.67 (95% confidence interval [CI]. 0.59-0.73); specificity of 0.723 (95% CI: 0.64-0.78) and DOR of 5.0 (95% CI: 4.0-7.0) were pooled estimated from patient-based analyses. Subsequently, the combined positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were calculated with the results of 2.4 (95% CI: 1.9-3.0) and 0.46 (95% CI: 0.39-0.56), respectively. In addition, area under the curve (AUC) of the summary receiver operating characteristic (SROC) reflecting prognostic accuracy was calculated to be 0.75 (95% CI: 0.71-0.78). The results of subgroup analysis suggested that high NLR was an effective predictive factor of poor prognosis in HCC in mainland China as well as in the northern region. Conclusion: Our findings suggest that high baseline NLR is an excellent predictor of poor prognosis or relapse in patients with HCC, especially those from high-incidence East Asian populations. Systematic review registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023440640.

Correlation analysis of hemoglobin, albumin, lymphocyte, platelet score and platelet to albumin ratio and prognosis in patients with lung adenosquamous carcinoma.

Objective: To investigate the effect of hemoglobin, albumin, lymphocytes, platelet (HALP) score and platelet to albumin ratio (PAR) on prognosis of patients with lung adenosquamous carcinoma (ASC) after surgery. Patients and methods: A total of 52 patients diagnosed with ASC after surgical resection were collected from Nanjing Chest Hospital from 2012 to 2021, and their general clinical data, pathological data and laboratory indexes were collected. The changes of Alb and Plt levels before and after surgery, HALP scores (hemoglobin albumin lymphocytes/platelets), and postoperative PAR, PLR, NLR were retrospectively analyzed, and their influence on the prognosis of patients with ASC was investigated. The cut-off value of △Alb, △Plt, postoperative PAR, PLR and NLR were determined by the receiver operating characteristic (ROC) curve, the optimal cut-off value of HALP score before and after surgery was calculated by using X-tile software, and the clinicopathological characteristics were compared between the high PAR and low PAR groups and between high HALP score and low HALP score group to analyze the factors influencing the prognosis of patients with ASC. Univariate and multivariate Cox proportional regression analyses were used to assess independent risk factors affecting overall survival (OS) and disease-free survival (DFS) in patients with ASC. Kaplan-Meier method was used to evaluate the correlation between OS, DFS and PAR and HALP score. Results: A critical value of PAR was 7.40×10^9 and an area under the curve (AUC) of 0.737 (95%CI: 0.597-0.876, P = 0.004). The best cut-off value of the preoperative HALP score was 24.3. Univariate Cox analysis showed that the cut margin (P = 0.013), the degree of differentiation (P = 0.021), N stage (P = 0.049), △Plt (P = 0.010), △Alb (P = 0.016), PAR (P = 0.003), NLR (P = 0.025), PLR (P = 0.029), preoperative HALP score (P = 0.000) and post-operative HALP score (P = 0.010) were all associated with postoperative OS in ASC patients. Cut margin (P = 0.029), the degree of differentiation (P = 0.045), maximum tumor diameter (P = 0.018), N stage (P = 0.035), △Plt (P = 0.007), △Alb (P = 0.007), PAR (P = 0.004), NLR (P = 0.041), PLR (P = 0.030), preoperative HALP score (P = 0.000), and postoperative HALP score (P = 0.011) were related to postoperative DFS in ASC patients. Multivariate analysis revealed that PAR (HR: 6.877, 95%CI: 1.817-26.038, P = 0.005), differentiation degree (HR: 0.059, 95%CI: 0.006-0.591, P = 0.016) and preoperative HALP score (HR: 0.224, 95%CI: 0.068-0.733, P = 0.013) had significant effect on OS. Tumor maximum diameter (HR: 3.442, 95%CI: 1.148-10.318, P = 0.027) and preoperative HALP score (HR: 0.268, 95%CI: 0.085-0.847, P = 0.025) had significant influence on DFS. Conclusion: PAR and preoperative HALP score were potentially useful biomarkers for evaluating the outcome of patients with postoperative ASC. PAR, the degree of differentiation and preoperative HALP score were independent prognostic factors for postoperative OS in ASC patients. Maximum tumor diameter and preoperative HALP score were independent prognostic factors for postoperative DFS in ASC patients.

The prognostic value of pretreatment albumin-to-fibrinogen ratio in small cell lung cancer patients receiving first-line platinum-based chemotherapy.

This study examined the role of pretreatment albumin-to-fibrinogen ratio (AFR) in the prognosis of small-cell lung cancer (SCLC) patients receiving first-line platinum-based chemotherapy. A total of 131 SCLC patients were enrolled. The predictive value of the AFR for progression free survival (PFS) and overall survival (OS) were evaluated by receiver operating characteristic (ROC) curve analysis. The predictive factor of survival was assessed by univariate and multivariate Cox proportional regression analysis. The correlation between OS, PFS and AFR was determined by the log-rank test using the Kaplan-Meier method. AFR was an effective predictor of OS in SCLC patients with a cut-off value of 7.78. AFR was independent risk factors for OS and PFS. Kaplan Meier analysis showed that PFS and OS in patients with high AFR levels were significantly higher than those with low AFR levels. These results suggest that AFR could be an effective predictor of survival in patients with SCLC.

Chemical Bond Bridging across Two Domains: Generation of Fe(II) and In Situ Formation of FeSx on Zerovalent Iron.

Sulfidation of zerovalent iron (SZVI) can strengthen the decontamination ability by promoting the electron transfer from inner Fe0 to external pollutants by iron sulfide (FeSx). Although FeSx forms easily, the mechanism for the FeSx bonding on the ZVI surface through a liquid precipitation method is elusive. In this work, we demonstrate a key pathway for the sulfidation of ZVI, namely, the in situ formation of FeSx on ZVI surface, which leads to chemical bonding across two domains: the pristine ZVI and the newly formed FeSx phase. The two chemically bridged heterophases display superior activity in electron transportation compared to the physically coated SZVI, eventually bringing about the better performance in reducing Cr(VI) species. It is revealed that the formation of chemically bonded FeSx requires balancing the rates for the two processes of Fe(II) release and sulfidation, which can be achieved by tuning the pH and S(-II) concentration. This study elucidates a mechanism for surface generation of FeSx on ZVI, and it provides new perspectives to design high-quality SZVI for environmental applications.

YAP promotes AP-1 expression in tubular epithelial cells in the kidney.

Chronic kidney disease (CKD) is a major health problem. Kidney fibrosis is a hallmark and final common pathway of CKD. The Hippo/yes-associated protein (YAP) pathway regulates organ size, inflammation, and tumorigenesis. Our previous study demonstrated tubular YAP activation by tubule-specific double knockout of mammalian STE20-like protein kinase 1/2 (Mst1/2) induced CKD in mice, but the underlying mechanisms remain to be fully elucidated. Activator protein (AP)-1 activation was found to promote tubular atrophy and tubulointerstitial fibrosis. Therefore, we studied whether YAP regulates AP-1 expression in the kidney. We found that expression of various AP-1 components was induced in kidneys subjected to unilateral ureteric obstruction and in Mst1/2 double knockout kidneys, and these inductions were blocked by deletion of Yap in tubular cells, with Fosl1 being most affected compared with other AP-1 genes. Inhibition of Yap also most highly suppressed Fosl1 expression among AP-1 genes in HK-2 and IMCD3 renal tubular cells. YAP bound to the Fosl1 promoter and promoted Fosl1 promoter-luciferase activity. Our results suggest that YAP controls AP-1 expression and that Fosl1 is the primary target of YAP in renal tubular cells.NEW & NOTEWORTHY Yes-associated protein (YAP) activation leads to tubular injury, renal inflammation, and fibrosis, but the underlying mechanisms are not fully understood. We now provide genetic evidence that YAP promotes activator protein-1 expression and that Fosl1 is the primary target of YAP in renal tubular cells.

The serum IgG antibody level as a biomarker for clinical outcome in patients with cerebral sparganosis after treatment.

Introduction: Cerebral sparganosis is a rare parasitic infection of the brain tissue. The remission of MRI change and clinical symptom has been used to evaluate the therapeutic effect. However, there is no study to correlate the serum IgG antibody level of sparganum to the prognosis of disease after treatment. Methods: 87 patients with cerebral sparganosis were collected from three medical centers. Clinical symptoms and MRI changes were evaluated at 12 months after initial treatment, and serum IgG antibody level of sparganum was evaluated at 2, 6, and 12 months after treatment. The positive cut-off value was based on 2.1 times the optical density (OD) of negative control. The index value was defined as the sample OD divided by the cut-off value. Results: Among the 87 patients after treatment, 71 patients had good clinical outcomes, and 16 had poor clinical outcomes. The area under the curve (AUC) showed that the index value measured at 12 months after treatment had the best prediction effect, with a value of 2.014. In the good-outcome group, the index values were less than 2.014 in all 71 patients, and only 8 patients had mildly enhanced residual lesions on MRI. In the poor-outcome group, the index values were more than 2.014 in all 16 patients, and all patients still showed significantly enhanced lesions on MRI. Compared with poor-outcome patients, only 2 patients with good outcomes had disease recurrence after treatment. Discussion: This study provided evidence that the serum IgG antibody level of sparganum was a promising biomarker to evaluate the prognosis of patients with cerebral sparganosis after treatment.

Evaluating the diagnostic and prognostic value of serum TuM2-PK, NSE, and ProGRP in small cell lung cancer.

BACKGROUND: The aim of this study was to explore the diagnostic and prognostic value of serum tumor M2-pyruvate kinase (TuM2-PK), neuron-specific enolase (NSE), and progastrin-releasing peptide (ProGRP) levels in patients with small cell lung cancer (SCLC). METHODS: The levels of serum TuM2-PK, NSE, and ProGRP in 102 patients with SCLC, 60 patients with benign lung disease (BLD), and 90 healthy controls were detected. RESULTS: The serum TuM2-PK, NSE, and ProGRP levels in the SCLC group were higher than those in BLD group (p < 0.05) and healthy control group (p < 0.05). The sensitivity of TuM2-PK, NSE, and ProGRP detection in SCLC was 82.35%, 60.78%, and 77.45% respectively, and specificity was 91.11%, 81.11%, and 86.67%, respectively. The area under the curve (AUC) of SCLC resulting from TuM2-PK was significantly better than that of NSE and ProGRP. The application of TuM2-PK combined with NSE and ProGRP improved the diagnostic yield of SCLC patients and had better diagnostic value than TuM2-PK alone. Univariate and multivariate analysis indicated that an elevated TuM2-PK level was an independent prognostic factor for shorter survival in SCLC. CONCLUSIONS: These results suggest that TuM2-PK levels in the serum could be an effective biomarker for the diagnosis and prognosis of SCLC.

Extracellular Vesicles Derived from Bone Mesenchymal Stem Cells Carrying circ_0000075 Relieves Cerebral Ischemic Injury by Competitively Inhibiting miR-218-5p and Up-regulating E3 Ubiquitin Ligase SMURF2.

Extracellular vesicle (EV)-encapsulated circRNAs have the potential role in affecting brain disorders. However, the role of circ_0000075 in cerebral ischemic injury remains unclear. Here, we tried to investigate the mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs carrying circ_0000075 in the control of cerebral ischemic injury. Initially, a mouse model with cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO), followed by the determination of circ_0000075 expression. Then, neurons were isolated and subjected to oxygen-glucose deprivation/reperfusion. BMSCs were isolated for extraction of EVs. The correlation among circ_0000075, microRNA (miR)-218-5p, and Smad ubiquitination regulatory factor 2 (SMURF2) was detected with their roles in cerebral ischemic injury analyzed in vivo and in vitro. circ_0000075 was down-regulated in MCAO mice and engineered RVG-EVs were internalized by neurons to up-regulate circ_0000075 expression. Treatment of RVG-circ_0000075-EVs reduced brain tissue damage, increased neuronal count, and significantly curtailed apoptosis rate, suppressing cerebral ischemic injury in vitro and in vivo. miR-218-5p was targeted by circ_0000075 in neurons, which promoted SMURF2 expression. A negative correlation between SMURF2 and transcriptional regulator Yin Yang 1 (YY1) was identified. In vitro experiments further proved that circ_ 00,000 75 could down-regulate the expression of YY1 through SMURF2, and finally relieving cerebral ischemic injury. Collectively, engineered EVs delivered circ_0000075 into brain tissues and increased circ_0000075 expression, which down-regulated miR-218-5p and up-regulated SMURF2, thus alleviating cerebral ischemic injury.

Remediation of Cr(VI)-contaminated soil by sulfidated zero-valent iron: The effect of citric acid as eluant and modifying agent.

Leaching and chemical reduction are two commonly used methods for Cr(VI)-contaminated soil remediation. Leaching focuses more on leaching Cr(VI) out of the soil. Chemical reduction has the disadvantages of poor fluidity of reductant. Combining these two remediation methods, this study investigated the performance of Cr(VI)-contaminated soil when H2O and citric acid were used as eluant separately and sulfidated zero-valent iron (SZVI) as reductant. And based on the properties of Cr(VI) chelated with -COOH to form a complex and the characteristics of -OH anchored to FeSx, citric acid modified SZVI (Cit-SZVI) was prepared. The prepared Cit-SZVI was characterized by SEM-EDS, XPS, XRD to study its surface properties. The transformation of Cr species in soil was explored by BCR sequential extraction. The results indicated Cr(VI) removal by SZVI was significantly promoted when citric acid as eluant compared with H2O. With SZVI dosage of 2.0 wt%, 23.1 mg/L Cr(VI) was basically removed within 60 min when citric acid as eluant, while only 60% Cr(VI) was removed when H2O as eluant even after 3 h. The kobs of Cit-SZVI was 1.4 times that of SZVI when H2O as eluant. The characterization of Cit-SZVI showed that more FeSx was formed on the surface of the Cit-SZVI, and more -OH of citric acid was anchored to FeSx, leaving -COOH available to chelate Cr(VI). Compared with H2O as eluant and SZVI/Cit-SZVI as reducing agent, the removal effect of Cr(VI) was the best when citric acid as eluant and SZVI as reducing agent. BCR sequential extraction showed that Cr(VI) was effectually fixed, weak acid extractable Cr proportion decreased significantly and residual Cr proportion increased in the treated soil. The combination of leaching and chemical reduction proposed in this study can greatly enhance the Cr(VI) removal effect in soil, which is important for the remediation of Cr(VI)-contaminated soil.

A systematic review and meta-analysis of neoadjuvant chemoimmunotherapy in stage III non-small cell lung cancer.

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with different subtypes, multidisciplinary teams-led management, and a poor prognosis. Currently, the clinical benefits of stage III NSCLC in the neoadjuvant setting are still unclear. We performed a meta-analysis of published data on neoadjuvant chemoimmunotherapy in stage III NSCLC to systematically evaluate its efficacy and safety. METHODS: We searched the databases to identify eligible studies of neoadjuvant chemoimmunotherapy for stage III NSCLC. The primary outcomes mainly included pathological and radiological response outcomes, the feasibility of surgery, and the safety of the regimen. The pathological and radiological response included the rate of major pathologic response (MPR), complete pathologic response (pCR), radiological response outcomes, and R0 resection; The feasibility included the rate of surgical resection, conversion to thoracotomy, surgical complications, pathological downstaging of clinical disease stage. The safety included the incidence of treatment-related adverse events (TRAEs) and severe adverse events (SAEs). R 4.1.3 software was conducted for data analysis, and p < 0.05 was considered statistically significant. RESULTS: Nine trials containing a total of 382 populations were eligible for the meta-analysis, with the pooled surgical resection rate of 90%. Owing to the large heterogeneity of the single-rate meta-analysis, the random effect model was adopted. The estimated pooled prevalence of MPR was 56% (95%CI 0.39-0.72) and of pCR was 39% (95%CI 0.28-0.51). The pooled rate of TRAEs was 65% (95%CI 0.17-0.99) and SAEs was 24% (95%CI 0.05-0.49). CONCLUSION: Compared to neoadjuvant chemotherapy or immunotherapy, neoadjuvant chemoimmunotherapy achieved more pathological and radiological relief, and has a high surgical resection rate and low risk of conversion to thoracotomy and surgical complications, with poor tolerance of toxicity but rarely developing life-threatening adverse events. In conclusion, neoadjuvant chemoimmunotherapy is suggested to be beneficial for stage III NSCLC.

Quality of life in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically prolonged survival in non-small cell lung cancer (NSCLC) patients, but little research had focused on its impact on quality of life (QoL). The purpose of our study was to compare the QoL in patients with NSCLC treated with programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors versus chemotherapy. METHODS: We searched for randomized controlled trials utilizing the Quality of Life Questionnaire Core 30 items (QLQ-C30) and the EuroQol Five Dimensions Questionnaire-3L (EQ-5D-3L) to assess the QoL of NSCLC treated with PD-1/PD-L1 inhibitors versus chemotherapy. We collected hazard ratios (HRs) for the time from baseline to the first clinically significant deterioration (TTD) and effect size as the difference in mean change between and within treatment groups in patients' reported outcomes (PROs). (PROSPERO registration number: CRD42022296680). RESULTS: In the five trials reported by QLQ-C30, TTD was longer in PD-1/PD-L1 inhibitors compared with control groups (HR = 0.86; 95% CI = 0.76, 0.97; P = 0.013), with similar results in terms of physical function, role function, and pain. The difference in mean change between the PD-1/PD-L1 inhibitors group and the chemotherapy group in QLQ-C30 and EQ-5D VAS was 3.64 (95% CI = 1.62, 5.66; P = 0.001) and 4.74 (95% CI = 2.65, 6.83; P = 0.001), which supported PD-1/PD-L1 inhibitors. However, for the EQ-5D utility index, there was no statistically significant difference between the two groups, with a mean change difference of 0.03 (95% CI = -0.01, 0.07; P = 0.094). The mean change from baseline to follow-up in PD-1/PD-L1 inhibitors group was 2.57 (95% CI = 0.43, 4.71; P = 0.019), and chemotherapy group was -1.31 (95% CI = -3.71, 1.09; P = 0.284), correspondingly. The subgroup analysis showed that no difference was observed between open-label and double-blind trials in patients treated with chemotherapy or PD-1/PD-L1 inhibitors. CONCLUSION: In conclusion, PD-1/PD-L1 inhibitors could improve the QoL of patients with NSCLC compared to chemotherapy and reduce unfavorable symptoms during treatment.