An ultrasensitive solid-state electrochemiluminescence sensor based on Ni-MOF@Ru(bpy)32+ and Au NPs@TiO2 for determination of permethrin.

The novel TiO2 and Ni-MOF materials were synthesized and utilized for the detection of permethrin (PET). A highly sensitive solid-state electrochemiluminescence (ECL) sensor was developed based on Ni-MOF@Ru(bpy)32+ and Au NPs@TiO2. In this sensing platform, Ru(bpy)32+-Tripropyl Amine (TPrA) was used as a luminescent signal, Ni-MOF acted as a carrier to carry more luminescent reagents Ru(bpy)32+. Au NPs acted as promoters facilitated electron transport and TiO2 could further enhance the luminescence intensity of the system by synergistical interaction with Au NPs. The possible mechanisms of signal amplification were investigated. The ECL intensity decreased significantly with increasing PET concentration, enabling the determination of PET amount through the observation of the change in ECL signal intensity (ΔI). Under optimal experimental conditions, the linear range of PET concentration from 1.0 × 10-11 mol L-1 to 1.0 × 10-6 mol L-1, with a detection limit of 3.3 × 10-12 mol L-1 (3S/N). This method was successfully applied to determine PET in various vegetable samples.

Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway.

BACKGROUND: Immunosuppressive status is prevalent in cancer patients and increases the complexity of tumor immunotherapy. It has been found that Listeria-vectored tumor vaccines had the potential ability of two-side regulatory effect on the immune response during immunotherapy. RESULTS: The results show that the combined immunotherapy with the LM∆E6E7 and LI∆E6E7, the two cervical cancer vaccine candidate strains constructed by our lab, improves the antitumor immune response and inhibits the suppressive immune response in tumor-bearing mice in vivo, confirming the two-sided regulatory ability of the immune response caused by Listeria-vectored tumor vaccines. The immunotherapy reduces the expression level of myeloid-derived suppressor cells (MDSCs)-inducing factors and then inhibits the phosphorylation level of STAT3 protein, the regulatory factor of MDSCs differentiation, to reduce the MDSCs formation ability. Moreover, vaccines reduce the expression of functional molecules associated with MDSCs may by inhibiting the phosphorylation level of the JAK1-STAT1 and JAK2-STAT3 pathways in tumor tissues to attenuate the immunosuppressive function of MDSCs. CONCLUSIONS: Immunotherapy with Listeria-vectored cervical cancer vaccines significantly reduces the level and function of MDSCs in vivo, which is the key point to the destruction of immunosuppression. The study for the first to elucidate the mechanism of breaking the immunosuppression.

A molecule-imprinted electrochemiluminescence sensor based on CdS@MWCNTs for ultrasensitive detection of fenpropathrin.

A molecularly-imprinted electrochemiluminescence sensor was constructed for the determination of fenpropathrin (FPT) by molecular imprinting technology. In this sensing platform, the introduction of CdS@MWCNTs significantly enhanced the initial ECL signal of the luminol-O2 system. Specifically, MWCNTs was used as a carrier to adsorb more CdS, in which CdS acted as a co-reaction promoter for luminescence. Molecularly imprinted polymer (MIP) containing specific recognition sites of FPT was used as the material for selective recognition. With increasing amount of FPT the ECL signal decreased. Under the optimum conditions, the ECL response was linearly related to the logarithm of FPT concentration. The developed ECL sensor allowed for sensitive determination of FPT and exhibited a wide linear range from 1.0 × 10- 10 mol L- 1 to 1.0 × 10- 6 mol L- 1. The limit of detection was 3.3 × 10- 11 mol L- 1 (S/N = 3). It can be used for the detection of FPT in vegetable samples.

Ultrasensitive solid-state electrochemiluminescence sensor based on lotus root shaped carbon fiber, CdSe QDs and Fe3O4 synergically amplify Ru(bpy)32+ luminophore signal for detection of cyfluthrin.

An efficient and innovative electrochemiluminescence (ECL) sensor was developed for trace detection of cyfluthrin. The sensor utilized materials such as lotus root shaped carbon fiber (Co CNFs), cadmium selenide quantum dots (CdSe QDs), and Fe3O4 to amplify Ru(bpy)32+ signals. Co CNFs, with its large specific surface area and porosity, served the purpose of not only enhancing the stability of the sensor by fixing CdSe QDs and Ru(bpy)32+ on the Co CNFs/GCE, but also facilitating electron transfer. CdSe QDs was involved in the luminescence reaction and collaborated with Ru(bpy)32+ to enhance the sensor's sensitivity, while Fe3O4 promoted electron transfer in the system due to its large surface area. The solid-state ECL sensor achieved satisfactory signal under the synergistic action of these components. The ECL signal of the sensor was quenched by cyfluthrin, and a favorable linear relationship was observed between the sensor and cyfluthrin in the concentration range 1 × 10-12 to 1 × 10-6 M. The detection limit of the sensor was 3.3 × 10-13 M (S/N = 3). The utilization of lotus root shaped carbon fiber, CdSe QDs, and Fe3O4 in the Ru(bpy)32+ system demonstrated a synergistic effect for cyfluthrin detection, presenting a new approach for the rapid determination analysis of pesticide residues in foods.

Streptococcus salivarius K12 Alleviates Oral Mucositis in Patients Undergoing Radiotherapy for Malignant Head and Neck Tumors: A Randomized Controlled Trial.

PURPOSE: Oral mucositis (OM) is a common debilitating toxicity associated with radiotherapy (RT) for malignant head and neck tumors. This prospective, randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy and safety of Streptococcus salivarius K12 (SsK12) in reducing the incidence, duration, and severity of severe OM (SOM). METHODS: A total of 160 patients with malignant head and neck tumors undergoing definitive or postoperative adjuvant RT were randomly assigned (1:1) to receive SsK12 probiotic (n = 80) or placebo (n = 80) at West China Hospital, Sichuan University, Chengdu, China. Patients were instructed to suck SsK12 or placebo lozenges thrice daily from the initiation to the end of RT. OM was evaluated twice a week during RT and once a week thereafter for up to 8 weeks. The primary end point was the incidence of SOM. Adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: Baseline patient characteristics were similar in the SsK12 and placebo groups. The incidence of SOM was significantly lower in the SsK12 group as compared with the placebo group (36.6% v 54.2%; P = .0351). The duration (median, 0.0 days v 7.0 days; mean, 8.9 days v 18.3 days; P = .0084) and time to develop SOM (median, not estimable v 42.0 days; hazard ratio, 0.55 [95% CI, 0.34 to 0.89]; log-rank test: P = .0123) were also improved in the case of the SsK12 group. Adverse events were similar between the groups, and mild or moderate gastrointestinal reactions (flatulence or dyspepsia) associated with the lozenges were observed in two patients in the SsK12 group. High-throughput sequencing results indicated that SsK12 inhibited opportunistic pathogens and enriched oral commensals during RT. CONCLUSION: In this prospective, randomized clinical trial, SsK12 probiotic significantly reduced the incidence, onset, and duration of SOM with a good safety profile.

Association between BMI trajectories in late-middle age and subsequent dementia risk in older age: a 26-year population-based cohort study.

BACKGROUND: The association between body mass index (BMI) and dementia risk differs depending on follow-up time and age at BMI measurement. The relationship between BMI trajectories in late-middle age (50-65 years old) and the risk of dementia in older age (> 65 years old) has not been revealed. METHODS: In the present study, participants from the Health and Retirement Study were included. BMI trajectories were constructed by combining BMI trend and variation information. The association between BMI trajectories at the age of 50-65 years and dementia risk after the age of 65 years was investigated. Participants with European ancestry and information on polygenic scores for cognitive performance were pooled to examine whether genetic predisposition could modify the association. RESULTS: A total of 10,847 participants were included in the main analyses. A declining BMI trend and high variation in late-middle age were associated with the highest subsequent dementia risk in older age compared with an ascending BMI trend and low variation (RR = 1.76, 95% CI = 1.45-2.13). Specifically, in stratified analyses on BMI trajectories and dementia risk based on each individual's mean BMI, the strongest association between a declining BMI trend with high variation and elevated dementia risk was observed in normal BMI group (RR = 2.66, 95% CI = 1.72-4.1). Similar associations were found when participants were stratified by their genetic performance for cognition function without interaction. CONCLUSIONS: A declining BMI trend and high variation in late-middle age were associated with a higher risk of dementia. Early monitoring of these individuals is needed to prevent dementia in older individuals.

The association between aspirin use and immune-related adverse events in specific cancer patients receiving ICIs therapy: analysis of the FAERS database.

Background: The promise of immune checkpoint inhibitors (ICIs) therapy in cancer treatment is tempered by the occurrence of immune-related adverse events (irAEs). Many patients undergoing ICIs also take aspirin, but the association between aspirin and irAEs is not well understood. Methods: This study analyzed adverse reaction data associated with the use of ICIs in the US Food and Drug Administration (FDA) Adverse Event Reporting System FDA Adverse Event Reporting System database, from the approval date of each drug until 1 October 2022. Multivariate logistic regression was employed to assess the association of aspirin use with irAEs in patients receiving ICIs. Results: The results indicated that aspirin use was associated with an increased risk of irAEs in a pan-cancer analysis, with a more pronounced association in specific cancer types such as lung cancer, mesothelioma, and pancreatic cancer. However, in lymphoma, aspirin use was associated with a reduced risk of irAEs. Furthermore, aspirin use was associated with an increased risk of certain irAEs, such as anemia, colitis, myocarditis, myositis, pancreatitis, pericarditis, and pneumonia, while it was associated with a reduced risk of rash, Stevens-Johnson syndrome, and thyroiditis. Conclusion: This study has unveiled an association between aspirin use and irAEs in cancer patients receiving ICIs therapy, emphasizing the need for individualized consideration of patients' medication history when devising cancer treatment plans to enhance efficacy and reduce risks.

Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study.

Background: The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear. Methods: The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane's Q test, MR-Egger, and leave-one-out method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results. Results: In the MR analysis, we found Crohn's disease had a significant causal effect on pancreatic cancer. Specifically, Crohn's disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses. Conclusion: This study indicates that IBD, particularly Crohn's disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients.

Frailty trajectory predicts subsequent cognitive decline: A 26-year population-based longitudinal cohort study.

Frailty refers to a decline in the physiological functioning of one or more organ systems. It remained unclear whether variations in the trajectory of frailty over time were associated with subsequent cognitive change. The aim of the current study was to investigate the association between frailty trajectories and subsequent cognitive decline based on the Health and Retirement Study (HRS). A total of 15,454 participants were included. The frailty trajectory was assessed using the Paulson-Lichtenberg Frailty Index, while the cognitive function was evaluated using the Langa-Weir Classification. Results showed that severe frailty was significantly associated with the subsequent decline in cognitive function (ß [95% CI] = -0.21 [-0.40, -0.03], p = 0.03). In the five identified frailty trajectories, participants with mild frailty (inverted U-shaped, ß [95% CI] = -0.22 [-0.43, -0.02], p = 0.04), mild frailty (U-shaped, ß [95% CI] = -0.22 [-0.39, -0.06], p = 0.01), and frailty (ß [95% CI] = -0.34 [-0.62, -0.07], p = 0.01) were all significantly associated with the subsequent cognition decline in the elderly. The current study suggested that monitoring and addressing frailty trajectories in older adults may be a critical approach in preventing or mitigating cognitive decline, which had significant implications for healthcare.

Assessing the role of lipid-lowering therapy on multi-cancer prevention: A mendelian randomization study.

Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear. Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated. Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVWFE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVWEF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVWFE or multiplicative random-effects IVW (IVWMRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results. Conclusion: The causalities between statin use and cancer risk were only observed in colorectal cancer and bile duct cancer in the European ancestry population. Future works are warranted to provide more robust evidence for supporting statin repurposing for cancer prevention.

BMI trajectories in late middle age, genetic risk, and the incident diabetes in older adults: evidence from a 26-year longitudinal study.

This study investigated the association between BMI trajectories in late middle age and incident diabetes in later years. A total of 11,441 participants aged 50-60 years from the Health and Retirement Study with at least two self-reported BMI records were included. Individual BMI trajectories representing average BMI changes per year were generated using multilevel modeling. Adjusted risk ratios (ARRs) and 95% confidence intervals (95% CIs) were calculated. Associations between BMI trajectories and diabetes risk in participants with different genetic risks were estimated for 5720 participants of European ancestry. BMI trajectories were significantly associated with diabetes risk in older age (slowly increasing vs. stable: ARR 1.31, 95% CI 1.12-1.54; rapidly increasing vs. stable: ARR 1.5, 95% CI 1.25-1.79). This association was strongest for normal-initial-BMI participants (slowly increasing: ARR 1.34, 95% CI 0.96-1.88; rapidly increasing: ARR 2.06, 95% CI 1.37-3.11). Participants with a higher genetic liability to diabetes and a rapidly increasing BMI trajectory had the highest risk for diabetes (ARR 2.15, 95% CI 1.67-2.76). These findings confirmed that BMI is the leading risk factor for diabetes and that although the normal BMI group has the lowest incidence rate for diabetes, people with normal BMI are most sensitive to changes in BMI.

Depression Trajectories, Genetic Risk, and Cognitive Performance in Older Adults: Multilevel Model with a 10-Year Longitudinal Cohort.

INTRODUCTION: Cognitive performance in older ages is strongly affected by individuals' genetic predispositions. We investigated whether depression trajectories were associated with subsequent cognitive performance independent of participants' genetic predispositions. METHODS: Participants from the Health and Retirement Study with European ancestry and aged over 50 were included in the analysis. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale, and the 6-year trajectories were fitted using latent class linear mixed models. Linear multilevel regression was applied to model the associations between depression trajectory and subsequent cognitive performance. Stratified analyses were performed to investigate these associations in participants with different genetic predispositions of cognitive performance and APOE ε4 allelic status. RESULTS: A total of 5,942 eligible participants were included in the study. Four depression trajectories were identified. Compared with the nondepression trajectory, all other depression trajectories were associated with worse cognitive performance (ß [95% CI]: mild-depression trajectory: -0.20 [-0.56, -0.06], p = 0.007; worsening-depression trajectory: -0.29 [-0.47, -0.12], p = 0.001; persistent-depression trajectory: -0.32 [-0.53, -0.13], p = 0.001). Although these associations were independent of participants' inherent genetic risk, the participants with a low polygenetic score for cognitive performance were more likely to have an enhanced association between depression trajectories and cognitive decline. Similar relationships were also found in APOE ε4 noncarriers. CONCLUSION: Among older participants with European ancestry, even a mild-depression trajectory was associated with worse cognitive performance. Early intervention in participants with any degree of depression might benefit regarding preventing cognitive performance decline.

Hepatitis B virus infection: An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk.

The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent findings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, specifically gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine infiltration), epigenetic modification (N6-methyladenosine), molecular signaling pathways (PI3K-Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infection-induced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenesis induction of extrahepatic cancers in chronic HBV conditions.

Survival outcomes following treatment delays among patients with early-stage female cancers: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians. METHODS: We analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients. RESULTS: A total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC (adjustedHazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01-1.23, p = 0.044) and stage I infiltrating breast cancer (adjustedHR = 1.23, 95% CI 1.11-1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC (adjustedHR = 1.04, 95% CI 1.01-1.06, p = 0.010) and in those with stage I breast cancer (adjustedHR = 1.03, 95% CI 1.00-1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I (adjustedHR = 1.31, 95% CI 1.02-1.68, p = 0.032). CONCLUSION: After adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

Hemolysin function of Listeria is related to biofilm formation: transcriptomics analysis.

Listeriolysin O (LLO) is the main virulence protein of Listeria monocytogenes (LM), that helps LM escape lysosomes. We previously found that the cellular immune response elicited by L.ivanovii (LI) is weaker than that elicited by LM. We speculated that this may be related to the function of ivanolysin O (ILO). Here, we constructed hemolysin gene deletion strain, LIΔilo, and a modified strain, LIΔilo::hly, in which ilo was replaced by hly. Prokaryotic transcriptome sequencing was performed on LI, LIΔilo, and LIΔilo::hly. Transcriptome differences between the three strains were compared, and genes and pathways with significant differences between the three strains were analyzed. Prokaryotic transcriptome sequencing results revealed the relationship of ilo to the ribosome, quorum sensing, and phosphotransferase system (PTS) pathways, etc. LIΔilo exhibited attenuated biofilm formation ability compared to LI. Biofilm formation was significantly recovered or even increased after replenishing hly. After knocking out ilo, the relative expression levels of some virulence genes, including sigB, prfA, actA, smcL, and virR, were up-regulated compared to LI. After replenishing hly, these genes were down-regulated compared to LIΔilo. The trend and degree of such variation were not completely consistent when cultured in media containing only monosaccharides or disaccharides. The results confirmed that hemolysin is related to some important biological properties of Listeria, including biofilm formation and virulence gene expression levels. This is the first comprehensive study on ILO function at the transcriptomic level and the first evidence of a relationship between Listeria hemolysin and biofilm formation.

Association between Statin Use and Survival in Cancer Patients with Brain Metastasis: Retrospective Analysis from the Chinese Population.

Brain metastasis predicts a worse clinical outcome in cancer patients. Emerging observational evidence suggests that statin use has a protective role in overall cancer prevention. Whether statin use could also be a supplementary treatment for advanced-stage cancers remains under researched and controversial. Data for cancer patients with brain metastasis were selected from the linked electronic medical care records of the West China Hospital between October 2010 and July 2019. Fisher's exact chi-square test was used to compare the differences between cohorts. Multivariate Cox analysis was conducted to adjust the potential confounders in evaluating the role of statin use in the overall survival (OS) of cancer patients with brain metastasis. There were 4510 brain metastatic patients included in this retrospective study. The overall statin use rate in our patients was 5.28% (219 cases/4510 cases). Compared with the non-statin use cohort, patients who received statin therapy showed a decreased Karnofsky performance score (KPS, p < 0.001) and lower high-density lipoprotein (HDL, p = 0.020) but higher body mass index (BMI, p = 0.002) and triglyceride (TG, p < 0.001) at admission. There was no association between statin use and the OS of the cancer patients with brain metastasis (Hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.73−1.07, p = 0.213) during the univariate analysis. However, after adjusting for baseline patient characteristics, metabolism indicators, and cancer-specific factors, statin use was shown to have a significant protective role, aiding the survival of the cancer patients with brain metastasis (adjustHR = 0.82, 95%CI: 0.69−0.99, p = 0.034). Our results highlight that statin use shows significant survival benefits in cancer patients with brain metastasis. However, future research is needed to validate our findings.

Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis.

PURPOSE: Brain radiotherapy combined with concomitant and six cycles of adjuvant temozolomide (TMZ) is the standard treatment for newly diagnosed high-grade gliomas (HGGs). However, the optimal number of cycles of TMZ is still controversial. We conducted this retrospective cohort study to evaluate whether prolonging adjuvant TMZ beyond six cycles resulted in better survival outcomes. METHODS: Patients with high-grade gliomas treated with standard brain radiotherapy combined with TMZ were retrospectively analysed. The duration of adjuvant TMZ ranged from 6 to 12 cycles. Those with 6 cycles of adjuvant TMZ were defined as the standard STUPP group, and those with 7-12 cycles were called the extended STUPP group. Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazards model was adopted to estimate the Hazard ratio (HR) associated with PFS and OS. RESULTS: From September 2011 to May 2021, 372 patients were eligible (143 in the standard group, 229 in the extended group). Patients who received extended STUPP had better PFS and OS compared with standard STUPP. The median PFS for the standard STUPP group was 12 months and for the extended STUPP group 22 months (log-rank P < 0.001). The median OS for the standard STUPP group and extended STUPP group were 12 months and 36 months, respectively (log-rank P < 0.001). In the subgroup analysis, the two treatments did not differ in IDH-mutated patients, while patients with IDH wild-type had a significantly better response to extended treatment than to standard treatment (PFS: log-rank P = 0.004; OS log-rank P = 0.001). Patients with MGMT promoter methylation treated with extended STUPP obtained longer PFS and OS than those treated with standard STUPP (PFS: log-rank P = 0.015; OS log-rank P = 0.010). Adverse events including leukopenia (P < 0.001), thrombocytopenia (P = 0.090), fatigue (P < 0.001) and nausea/vomiting (P = 0.004) were more frequent in the extended group. CONCLUSION: Extended TMZ treatment was superior to standard 6-cycle TMZ for both PFS and OS. The incidence of toxicities in extended group was higher but tolerable.

Recombinant Listeria ivanovii strain expressing listeriolysin O in place of ivanolysin O might be a potential antigen carrier for vaccine construction.

Listeria monocytogenes (LM) induces efficient and specific T-cell immune responses in the host. Listeriolysin O (LLO) is the main virulence protein of LM. LLO helps LM escape from the lysosome. However, the pronounced pathogenicity of LM limits its practical application as a live bacterial vector. Listeria ivanovii (LI) also displays intracellular parasitic abilities, cell to cell transfer, and other LM properties, with an elevated biosafety relative to LM. We have confirmed that LI can be used as a viable bacterial vaccine vector. However, we have also observed in vivo that LI vector vaccine candidates survive in the immune organ (spleen) for a shorter time compared with the survival time of LM and elicit weaker immune responses compared with LM. Studies have confirmed that hemolysin correlates with some important biological properties of Listeria, including cell invasion, intracellular proliferation, and the ability to induce immune responses. We speculated that the weaker immunogenicity of LI compared to LM may be related to the function of ivanolysin O (ILO). Here, we established a hemolysin gene deletion strain, LIΔilo, and a modified strain, LIΔilo:hly, whose ilo was replaced by hly. The hemolysin-modified strain was attenuated; however, it led to significantly improved invasive and proliferative activities of antigen-presenting cells, including those of RAW 264.7 macrophages, compared with the effects of LI. Mice immunized twice with LIΔilo:hly showed higher cytokine levels and better challenge protection rates than LI-immunized mice. This is the first description in Listeria carrier vaccine research of the modification of LI hemolysin to obtain a better vaccine carrier than LI. The recombinant strain LIΔilo:hly showed good biosafety and immunogenicity, and thus appears to be a good vector strain for vaccine development.

The Development and Validation of a Nomogram Incorporating Clinical, Pathological, and Therapeutic Features to Predict Overall Survival in Patients With Penile Cancer: A SEER-Based Study.

Objective: This study aimed to investigate the prognostic factors of penile cancer and establish a comprehensive predictive model for clinical application. Methods: A total of 581 patients from the Surveillance, Epidemiology, and End Results (SEER) program (2000-2018) were used to develop the prognostic model. The multivariate Cox proportional hazards regression was performed to identify independent prognostic factors to develop the nomogram. The performance of this model was validated internally by a cohort with 143 patients from the SEER database and validated externally by a cohort with 70 patients from the West China Hospital, Sichuan University (2010-2020). Results: Age, marital status, size of the primary lesion, primary tumor (T), regional lymph nodes status, distant metastasis (M), and the surgery of regional lymph node (LND) were the independent prognostic factors for overall survival (OS) and were incorporated in the prognostic model. The prognostic nomogram showed a good risk stratification ability for OS in the development cohort, internal validation cohort, and external validation cohort. Conclusion: This study incorporates the clinical, pathological, and therapeutic features comprehensively to develop a novel and clinically effective prognostic model for patients with penile cancer.

Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study.

STUDY OBJECTIVES: Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. METHODS: Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Odds ratios (ORs) and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. RESULTS: In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR = 1.24, 95% CI = 1.02-1.5; daytime napping [sometimes vs. never]: RR = 1.12, 95% CI = 1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR = 1.04, 95% CI = 1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. CONCLUSIONS: Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.