The secondary visual cortex mediated the enhancement of associative learning on methamphetamine self-administration behaviors.

RATIONALE: Methamphetamine addiction is a persistent and intractable pathological learning and memory, whereas no approved therapeutics is available. However, few attentions have been paid to how associative learning participates in the formation of intractable memory related to drug addiction OBJECTIVES AND METHODS: To investigate the role of associative learning in methamphetamine addiction and the underlying neurobiological mechanism, methamphetamine self-administration, oral sucrose self-administration, chemogenetic neuromanipulation, and fiber photometry in mice were performed in this study. RESULTS: We reported that associative learning increased methamphetamine-induced self-administration, but not oral sucrose self-administration. In addition, the enhancement of methamphetamine-induced self-administration was independent of more methamphetamine consumption, and remained with higher drug-taking and motivation in the absence of visual cues, suggesting the direct effects of the associative learning that enhanced methamphetamine-induced self-administration. Moreover, chemogenetic inactivation of the secondary visual cortex (V2) reduced the enhancement of the drug-taking induced by associative learning but did not alter sucrose-taking. Further fiber photometry of V2 neurons demonstrated that methamphetamine-associative learning elicits V2 neuron excitation, and sucrose-associative learning elicits V2 neuron inhibition. CONCLUSIONS: Therefore, this study reveals the neurobiological mechanism of V2 excitability underlying how associative learning participates in the formation of intractable memory related to drug addiction, and gives evidence to support V2 as a promising target for stimulation therapy for methamphetamine addiction.

YAP1 Regulates the YAP1/AR/PSA Axis through Autophagy in Castration-Resistant Prostate Cancer and Mediates T-Cell Immune and Inflammatory Cytokine Infiltration.

The emergence of castration-resistant prostate cancer (CRPC) following androgen deprivation therapy (ADT) is associated with increased malignancy and limited treatment options. This study aims to investigate potential connections between immune cell infiltration and inflammatory cytokines with the YAP1/AR/PSA axis by exploring their interactions with autophagy. Our research reveals heightened levels of Yes-associated protein 1 (YAP1) expression in CRPC tissues compared with tissues from androgen-dependent prostate cancer (ADPC) and benign prostate hyperplasia (BPH). Additionally, a correlation was observed between YAP1 and PSA expressions in CRPC tissues, suggesting that YAP1 may exert a regulatory influence on PSA expression within CRPC. Enhanced YAP1 expression in C4-2 cells resulted in the upregulation of androgen receptor (AR) nuclear translocation and intracellular prostate-specific antigen (PSA) levels. Conversely, the suppression of YAP1 led to a decrease in PSA expression, suggesting that YAP1 may positively regulate the PSA in castration-resistant prostate cancer (CRPC) by facilitating AR nuclear import. The modulation of the autophagy activity exerts a significant impact on the expression levels of YAP1, the AR, and the PSA. Moreover, recent advancements in immunity and inflammation studies present promising avenues for potential therapies targeting prostate cancer (PC).

The interplay between autophagy and ferroptosis presents a novel conceptual therapeutic framework for neuroendocrine prostate cancer.

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.

Low molecular weight fucoidan LF2 improves the immunosuppressive tumor microenvironment and enhances the anti-pancreatic cancer activity of oxaliplatin.

Chemotherapy remains the cornerstone of pancreatic cancer treatment. However, the dense interstitial and immunosuppressive microenvironment frequently render the ineffective anti-tumor activity of chemotherapeutic agents. Macrophages play a key role in the tumor immunomodulation. In this study, we found that low molecular weight of fucoidan (LF2) directly regulated the differentiation of mononuclear macrophages into the CD86+ M1 phenotype. LF2 significantly upregulated the expressions of M1 macrophage-specific cytokines, including iNOS, IL-6, TNFα and IL-12. LF2 modulated macrophage phenotypic transformation through activation of TLR4-NFκB pathway. Furthermore, we observed that LF2 enhanced the pro-apoptotic activity of oxaliplatin (OXA) in vitro by converting macrophages to a tumoricidal M1 phenotype. Meanwhile, LF2 increased intratumoral M1 macrophage infiltration and ameliorated the immunosuppressed tumor microenvironment, which in turn enhanced the anti-pancreatic ductal adenocarcinoma (PDAC) activity of OXA in vivo. Taken together, our results suggested that LF2 could act as a TLR4 agonist targeting macrophages and has a synergistic effect against PDAC when combined with OXA.

STAT5 is essential for inducing the suppressive subset and attenuate cytotoxicity of Vδ2+ T cells in acute myeloid leukemia.

Under the sustained exposure to tumor microenvironment, effector lymphocytes may transform into the suppressive populations. γδ T cells are recognized as a crucial mediator and effector of immune surveillance and thereby a promising candidate for anti-tumor immunotherapy. Emerging clinical studies implicate that some γδ T subsets play an important role in promoting tumor progression. Our previous study identified an abnormal Vδ2+ T cells subset with regulatory features (Reg-Vδ2) in the patients with newly diagnosed acute myeloid leukemia (AML), and demonstrated that Reg-Vδ2 cells significantly suppressed the anti-AML effects of effector Vδ2 cells (Eff-Vδ2). The molecular mechanism underlying the subset transformation of Vδ2 cells remains unclear. Here, we found that the expression and activity of STAT5 were significantly induced in Reg-Vδ2 cells compared with Eff-Vδ2 cells, which was consistent with the differences found in primary Vδ2 cells between AML patients and healthy donors. In-vitro experiments further indicated that STAT5 was required for the induction of Reg-Vδ2 cells. The combined immunophenotypical and functional assays showed that blockage of STAT5 alleviated the immunosuppressive effect of Reg-Vδ2 cells on Eff-Vδ2 cells and enhanced the anti-AML capacity of Vδ2 cells from health donors and AML patients. Collectively, these results suggest that STAT5 acts as a critical regulator in the transformation of effector Vδ2 cells into a subset with immunosuppressive characteristics, providing a potential target for the improvement the efficacy of γδ T cells-based immunotherapy to treat AML and other hematologic malignancies.

Decoding the transcriptional heterogeneity, differentiation lineage, clinical significance in tissue-resident memory CD8 T cell of the small intestine by single-cell analysis.

Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.

Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study.

BACKGROUND: The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. METHODS: In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two-sided 95% confidence intervals (CIs). Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. RESULTS: At the data cut-off date (August 31, 2022), with a median follow-up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3-53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. CONCLUSION: Ensartinib led to a favorable OS in patients with advanced, crizotinib-resistant, and ALK-positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Targeting Estrogen Receptor Beta Ameliorates Diminished Ovarian Reserve via Suppression of the FOXO3a/Autophagy Pathway.

Diminished ovarian reserve (DOR) refers to a decrease in the number and/or quality of oocytes, leading to infertility, poor ovarian response and adverse pregnancy outcomes. Currently, the pathogenesis of DOR is largely unknown, and the efficacy of existing therapeutic methods is limited. Therefore, in-depth exploration of the mechanism underlying DOR is highly important for identifying molecular therapeutic targets for DOR. Our study showed that estrogen receptor beta (ERß) mRNA and protein expression was upregulated in granulosa cells (GCs) from patients with DOR and in the ovaries of DOR model mice. Mechanistically, elevated ERß promotes forkhead transcription factor family 3a (FOXO3a) expression, which contributes to autophagic activation in GCs. Activation of FOXO3a/autophagy signalling leads to decreased cell proliferation and increased cell apoptosis and ultimately leads to DOR. In a cyclophosphamide (Cy)-induced DOR mouse model, treatment with PHTPP, a selective ERß antagonist, rescued fertility by restoring normal sex hormone secretion, estrus cycle duration, follicle development, oocyte quality and litter size. Taken together, these findings reveal a pathological mechanism of DOR based on ERß overexpression and identify PHTPP as a potential therapeutic agent for DOR.

A convenient and reproducible protocol for acquisition of the hepatocyte phase for liver function-impaired patients in gadoxetic acid disodium-enhanced magnetic resonance imaging.

Background: The hepatocyte phase (HCP) in gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) plays an important role in the detection and characterization of liver lesions, treatment planning, and liver function evaluation. However, the imaging protocol is complicated and time-consuming. This cross-sectional study aimed to develop a convenient and reproducible protocol for the HCP acquisition in Gd-EOB-DTPA-enhanced MRI. Methods: A total of 107 patients were prospectively included and assigned to three groups based on Child-Pugh (CP) classification, with 37, 40, and 30 in the non-cirrhosis, CP A, and CP B groups, respectively. Dynamic HCPs were acquired every 5 min after the Gd-EOB-DTPA administration and ended in 25 min in non-cirrhosis patients and 40 min in cirrhotic patients. The HCP acquired 5 min after the initial visualization of the intrahepatic bile duct (IBD) was selected from the dynamic HCPs as the adequate HCP (HCPproposed) and the corresponding acquisition time was recorded as Timeproposed. In addition, according to the 2016 Expert Consensus (EC) on the definition of the adequate HCP from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the adequate HCPEC and the corresponding TimeEC were also determined from the dynamic HCPs. The hepatic relative enhancement ratio (RER), the contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of hepatic focal lesions in the HCPEC and HCPproposed images, as well as the TimeEC and Timeproposed were compared by the paired t-test for the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed was compared by the χ2 test. Results: The RER, CNR, and SNR showed no significant difference between the HCPEC and HCPproposed in all three groups (all P>0.05). The paired differences between TimeEC and Timeproposed were 1.08±3.56 min (P=0.07), 2.88±4.22 min (P<0.001), and 5.83±5.27 min (P<0.001) in the three groups, respectively. Inter-observer agreement of the determination of the HCPEC and HCPproposed were 0.804 (86/107) and 0.962 (103/107), respectively (χ²=13.09, P=0.001). Conclusions: The adequate HCP could be acquired 5 min after the initial visualization of the IBD, which could serve as a convenient and reproducible protocol for the HCP imaging.

Opportunistic lung cancer screening with low-dose computed tomography in National Cancer Center of China: The first 14 years' experience.

BACKGROUND: In China, over 50% of lung cancer cases occur in nonsmokers. Thus, identifying high-risk individuals for targeted lung cancer screening is crucial. Beyond age and smoking, determining other risk factors for lung cancer in the Asian population has become a focal point of research. Using 30,000 participants in the prospectively enrolled cohort at China's National Cancer Center (NCC) over the past 14 years, we categorized participants by risk, with an emphasis on nonsmoking females. MATERIALS AND METHODS: Between November 2005 and December 2019, 31,431 individuals voluntarily underwent low-dose computed tomography (LDCT) scans for lung cancer screening at the NCC. We recorded details like smoking history, exposure to hazards, and family history of malignant tumors. Using the 2019 NCCN criteria, participants were categorized into high-, moderate-, and low-risk groups. Additionally, we separated non-high-risk groups into female never smokers (aged over 40) exposed to second-hand smoke (SHS) and others. Any positive results from initial scans were monitored per the I-ELCAP protocol (2006), and suspected malignancies were addressed through collaborative decisions between patients and physicians. We analyzed and compared the detection rates of positive results, confirmed lung cancers, and cancer stages across risk, age, and gender groups. RESULTS: Out of 31,431 participants (55.9% male, 44.1% female), 3695 (11.8%) showed positive baseline LDCT scans with 197 (0.6%; 106 females, 91 males) confirmed as lung cancer cases pathologically. Malignancy rate by age was 0.1% among those aged under 40 years, 0.4% among those aged 40-49 years, 0.8% among those aged 50-59 years, and 1.2% among those aged 60 years and older. From the 25,763 participants (56.9% male, 43.1% female) who completed questionnaires, 1877 (7.3%) were categorized as high risk, 6500 (25.2%) as moderate risk, and 17,386 (67.5%) as low risk. Of the 23,886 in the non-high-risk category, 8041 (33.7%) were females over 40 years old exposed to SHS. The high-risk group showed the highest lung cancer detection rate at 1.4%. However, females exposed to SHS had a notably higher detection rate than the rest of the non-high-risk group (1.1% vs. 0.5%; p < 0.0001). In this cohort, 84.8% of the detected lung cancers were at an early stage. CONCLUSIONS: In our study, using LDCT for lung cancer screening proved significant for high-risk individuals. For non-high-risk populations, LDCT screening could be considered for nonsmoking women with exposure to SHS.

Rad51 and Systemic Inflammatory Indicators as Novel Prognostic Markers in Esophageal Squamous Cell Carcinoma.

BACKGROUND: RAD51 is a central protein involved in homologous recombination, which has been linked to cancer development and progression. systemic inflammatory indicator markers such as neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio have also been implicated in cancer. However, the relationship between Rad51 and these inflammatory markers in esophageal cancer patients undergoing esophagectomy is not yet understood. METHODS: We retrospectively observed 320 esophageal cancer patients who underwent esophagectomy. We collected clinical characteristics, postoperative complications, and survival analysis data and analyzed the relationship between Rad51 expression, inflammatory markers, and prognosis. RESULTS: We found significant linear relationships among the inflammatory markers. There were also close relationships between Rad51 expression and neutrophil-to-lymphocyte ratio or C-reactive protein. Patients with low lymphocyte percentage were more likely to have low Rad51 expression (P = .026), high C-reactive protein (P = .007), and high neutrophil-to-lymphocyte ratio (P = .006). Low lymphocyte-to-monocyte ratio was associated with poor overall survival and was an independent prognostic factor (HR = 2.214; 95% confidence interval: 1.044-4.695, P = .038). In patients without lymph node metastases, low albumin (HR= 0.131; 95% confidence interval: 0.025-0.687, P = .016), high neutrophil-to-lymphocyte ratio (HR = 0.002; 95% confidence interval: 0.000-0.221, P = .009), and high Rad51 expression (HR = 14.394; 95% confidence interval: 2.217-97.402, P = .006) were associated with poor overall survival. CONCLUSIONS: Our study found a close correlation between elevated Rad51 expression and inflammatory markers. High Rad51 expression, high neutrophil-to-lymphocyte ratio, and low lymphocyte-to-monocyte ratio are associated with lower survival rates. The combined assessment of Rad51 and inflammatory markers can be useful for preoperative assessment and prognostic evaluation in esophageal squamous cell carcinoma patients.

Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.

Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

The influence of direct anterior approach and postero-lateral approach on wound complications after total hip arthroplasty: A meta-analysis.

To date, we have reviewed the synthesis literature critically through four databases: PubMed, Embase, Cochrane Library and Web of Science. Eight relevant studies were examined after compliance with the criteria for inclusion and exclusion, as well as documentation quality evaluation. This report covered all randomised, controlled studies of total hip arthroplasty (THA) comparing the direct anterior approach (DAA) with the postero-lateral approach (PLA). The main result was surgical site infection rate. The secondary results were duration of the operation, length of the incision and VAS score after surgery. The results of the meta-analyses of wound infections in the present trial did not show any statistically significant difference in DAA versus PLA (between DAA and PLA) (OR = 1.42, 95%CI: 0.5 to 4.04, p = 0.51). Compared with PLA, DAA had shorter surgical incision (WMD = -3.2, 95%CI: -4.00 to -2.41; p < 0.001) and longer operative times(WMD = 14. 67, 95%CI: 9.24 to 20.09; p < 0.001). Postoperative VAS scores were markedly lower in DAA compared with PLA within 6 weeks of surgery (p < 0.05), with low heterogeneities(I2 = 0). We found that DAA did not differ significantly from PLA in terms of the risk of wound infection for THA and that the surgical incisions was shorter and less postoperative pain after surgery, even though DAA surgery takes longer.

Low molecular weight fucoidan restores diabetic endothelial glycocalyx by targeting neuraminidase2: A new therapy target in glycocalyx shedding.

BACKGROUND AND PURPOSE: Diabetic vascular complication is a leading cause of disability and mortality in diabetes patients. Low molecular weight fucoidan (LMWF) is a promising drug candidate for vascular complications. Glycocalyx injury predates the occurrence of diabetes vascular complications. Protecting glycocalyx from degradation relieves diabetic vascular complications. LMWF has the potential to protect the diabetes endothelial glycocalyx from shedding. EXPERIMENTAL APPROACH: The protective effect of LMWF on diabetic glycocalyx damage was investigated in db/db mice and Human Umbilical Vein Endothelial Cells (HUVEC) through transmission electron microscopy and WGA labelling. The effect of LMWF on glycocalyx degrading enzymes expression was investigated. Neuraminidase2 (NEU2) overexpression/knockdown was performed in HUVECs to verify the important role of NEU2 in glycocalyx homeostasis. The interaction between NEU2 and LMWF was detected by ELISA and surface plasmon resonance analysis (SPR). KEY RESULTS: LMWF normalizes blood indexes including insulin, triglyceride, uric acid and reduces diabetes complications adverse events. LMWF alleviates diabetic endothelial glycocalyx damage in db/db mice kidney/aorta and high concentration glucose treated HUVECs. NEU2 is up-regulated in db/db mice and HUVECs with high concentration glucose. Overexpression/knockdown NEU2 results in glycocalyx shedding in HUVEC. Down-regulation and interaction of LMWF with NEU2 is a new therapy target in glycocalyx homeostasis. NEU2 was positively correlated with phosphorylated IR-ß. CONCLUSION AND IMPLICATIONS: NEU2 is an effective target for glycocalyx homeostasis and LMWF is a promising drug to alleviate vascular complications in diabetes by protecting endothelial glycocalyx.

Patterns of major cutaneous surgeries and reconstructions in patients with cutaneous squamous cell carcinoma in the USA.

Aim: Since use of major cutaneous surgeries/reconstructions among patients with cutaneous squamous cell carcinoma (CSCC) is not well described, we sought to quantify major cutaneous surgeries/reconstructions among patients with CSCC who were newly diagnosed and for those treated with systemic therapy, stratified by immune status. Methods: We used the Optum® Clinformatics® Data Mart database (2013-2020) and Kaplan-Meier estimators to assess risk of surgeries/reconstructions. Results: 450,803 patients were identified with an incident CSCC diagnosis, including 4111 patients with CSCC who initiated systemic therapy. The respective 7-year risks of major cutaneous surgeries/reconstructions were 10.9% (95% CI: 10.7-11.0) and 21.8% (95% CI: 17.6-25.8). Overall risk of major cutaneous surgeries/reconstructions was higher in patients who were immunocompromised than those who were immunocompetent. Conclusion: Approximately one in nine patients with CSCC will undergo ≥1 major cutaneous surgeries/reconstructions within 7 years of diagnosis; the risk increases in patients who initiate systemic therapy and among those who are immunocompromised.

Cutaneous squamous cell carcinoma (CSCC) is one of the two most common cancers, and numbers of new cases are increasing each year by 3­7%. A small number of advanced cases require systemic treatments (drugs given by mouth or injection), such as chemotherapy or immunotherapy. Patients with CSCC may require major skin surgeries and reconstructions. Little is known about how these skin procedures are used to treat patients with CSCC, particularly those with a weakened immune system. This analysis used USA insurance data of patients from 2013 to 2020 to assess how they were treated with surgeries, based on patients' immune status and whether they had started systemic treatment for CSCC. Among the 450,803 patients identified with a new CSCC diagnosis, the chances of having a procedure over a 7-year period was 10.9% (around one in nine). For 4111 patients with CSCC who started systemic therapy, this was 21.8% (around one in five). The chances of having a procedure were also significantly higher in patients with a weakened immune system (14.0%, around one in seven), compared with those without. However, this study was potentially limited by the following: the study population might not fully represent the CSCC population, the risk of surgery might be underestimated and information about patients' tumors (e.g., staging) was lacking. These results suggest there is an unmet need for systemic treatments that can reduce the burden of skin surgeries and reconstructions in CSCC.

Preparation of Multifunctional Seaweed Polysaccharides Derivatives Composite Hydrogel to Protect Ultraviolet B-Induced Photoaging In Vitro and In Vivo.

Seaweed polysaccharides can be used for protective skin photoaging which is caused by long-term exposure to ultraviolet B (UVB). In this study, a multifunctional composite hydrogel (FACP5) is prepared using sulfated galactofucan polysaccharides, alginate oligosaccharides as active ingredients, and polyacrylonitrile modified κ-Carrageenan as substrate. The properties of FACP5 show that it has good water retention, spreadability, and adhesion. The antiphotoaging activity is evaluated in vitro and in vivo. In vitro experiments demonstrate that the components of FACP5 exhibit good biocompatibility, antioxidant, and anti-tyrosinase activities, and could reduce the cell death rate induced by UVB. In vivo experiments demonstrate that, compared with the mice skin in model group, the skin water content treated with FACP5 increases by 29.80%; the thicknesses of epidermis and dermis decrease by 53.56% and 43.98%, respectively; the activities of catalase and superoxide dismutase increase by 1.59 and 0.72 times, respectively; the contents of interleukin-6 and tumor necrosis factor-α decrease by 19.21% and 17.85%, respectively; hydroxyproline content increases by 32.42%; the expression level of matrix metalloproteinase-3 downregulates by 42.80%. These results indicate that FACP5 has skin barrier repairing, antioxidant, anti-inflammatory, and inhibiting collagen degradation activies, FACP5 can be used as a skin protection remedy for photoaging.

Predictive value of 18 F-FDG PET/CT and serum tumor markers for tumor mutational burden in patients with non-small cell lung cancer.

PURPOSE: To investigate the correlations between metabolic parameters (MPs) of 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT), serum tumor markers (STMs), and tumor mutational burden (TMB) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this retrospective study, we enrolled 129 patients with NSCLC (males, 78; females, 51) who underwent baseline TMB and STM tests and 18 F-FDG PET/CT scans before treatment between March 2018 and September 2022. Patients were categorized into TMB-high (TMB ≥10 mutations/Mb; n = 27 [20.9%]) and non-TMB-high (TMB <10 mutations/Mb; n = 102 [79.1%]) groups. Binary logistic regression analyses were performed to determine independent predictors of TMB-high. Univariate and multivariate linear regression analyses were performed to determine independent predictors of TMB level on a log scale. Subgroup analyses for adenocarcinoma (ADC), ADC with EGFR+, ADC with EGFR-, and squamous cell carcinoma (SCC) were performed. RESULTS: For ADC, all MPs (SULpeak , SULmax , SULmean , MTV, and TLG) were significantly higher in the TMB-high group than the non-TMB-high group; smoker (odds ratio [OR] = 27.08, p = 0.018), EGFR+ (OR = 0.03, p = 0.033), KRAS+ (OR = 7.98, p = 0.083), high CEA (OR = 33.56, p = 0.029), and high CA125 (OR = 13.68, p = 0.030) were independent predictors of TMB-high; and all MPs showed significant positive linear correlations with TMB on a log scale, with SULpeak as an independent predictor. However, no significant correlation was observed for SCC. CONCLUSION: MPs and STMs can predict the TMB level for patients with ADC, and may serve as potential substitutes for TMB with increased value and easy implementation in guiding immunotherapy through noninvasive methods.

Dose-effect relationship of linear accelerator based stereotactic radiotherapy for brain metastases.

OBJECTIVE: The purpose of this study is to reveal the dose-effect relationship of linear accelerator (LINAC)-based stereotactic radiotherapy (SRT) in patients with brain metastases (BM). MATERIALS AND METHODS: The PubMed, Cochrane, and Web of Science databases were used to identify studies that reported local tumour control after LINAC-based SRT in patients with BMs. Studies of other approaches that could affect local tumour control, such as whole brain radiotherapy, targeted therapy, and immunotherapy, were excluded from the dose-effect relationship analysis. Data extracted included patient and treatment characteristics and tumour local control. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as the statistically significant level. RESULTS: After literature screening, 19 eligible studies involving 1523 patients were included in the probit model regression analysis. There was no significant dose-effect relationship between nominal BED10 and peripheral BED10 versus 12-month local control probability. There were significant dose effect relationships between the centre BED10 and the average BED10 versus the 12-month local control probability, with P values of 0.015 and 0.011, respectively. According to the model, the central BED10 and the average BED10 corresponding to probabilities of 90% 12-month local control were 109.2 GyBED10 (95% confidence interval (CI): 88.7-245.9 GyBED10) and 87.8 GyBED10 (95% CI: 74.3-161.5 GyBED10), respectively. A 12-month local control rate of 86.9% (95% CI: 81.7-89.7%) and 85.5% (95% CI: 81.2-89.2%) can be expected at a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively. CONCLUSION: For patients with BM treated with LINAC-based SRT, more attention should be given to the central and average doses of PTV. A clear definition of the dose prescription should be established to ensure the effectiveness and comparability of treatment.

Cascade signal amplification strategy by coupling chemical redox-cycling and Fenton-like reaction: Toward an ultrasensitive split-type fluorescent immunoassay.

An ultrasensitive split-type fluorescent immunobiosensor has been reported based on a cascade signal amplification strategy by coupling chemical redox-cycling and Fenton-like reaction. In this strategy, Cu2+ could oxidize chemically o-phenylenediamine (OPD) to generate photosensitive 2, 3-diaminophenazine (DAP) and Cu+/Cu0. On one hand, the generated Cu0 in turn catalyzed the oxidation of OPD. On the other hand, the introduced H2O2 reacted with Cu + ion to produce hydroxyl radicals (·OH) and Cu2+ ion through a Cu + -mediated Fenton-like reaction. The produced ·OH and recycled Cu2+ ion could take turns oxidizing OPD to generate more photoactive DAP, which triggering a self-sustaining chemical redox-cycling reaction and leading to a remarkable fluorescent improvement. It was worth mentioning that the cascade reaction did not stop until OPD molecules were completely consumed. Based on the H2O2-triggered cascade signal amplification, the strategy was exploited for the construction of split-type fluorescent immunoassay by taking interleukin-6 (IL-6) as the model target. It was realized for the ultrasensitive determination of IL-6 in a linear ranging from 20 fg/mL to 10 pg/mL with a limit of detection of 5 fg/mL. The study validated the practicability of the cascade signal amplification on the fluorescent bioanalysis and the superior performance in fluorescent immunoassay. It is expected that the strategy would offer new opportunities to develop ultrasensitive fluorescent methods for biosensor and bioanalysis.