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Abstract Background Previous research has established connections between gut microbiota, immune modulation, and several virus-related diseases. However, no study has explored the relationships between gut microbiota and herpes zoster and postherpetic neuralgia (PHN). Methods A total of 205 taxa of gut microbiota were regarded as exposures. The occurrences of herpes zoster and PHN were selected as outcomes. The causal effects of gut microbiota on herpes zoster and PHN were estimated with multiple methods for two-sample Mendelian randomization, such as inverse variance weighted (IVW), MR–Egger, and weighted median. All results were subjected to FDR correction to prevent from possibility of multiple comparison. Results Among the significant findings, four taxa and one genus were identified as facilitators of herpes zoster and PHN, respectively. Conversely, six genera and eleven taxa were found to inhibit herpes zoster and PHN, respectively. The causal effect of the Tyzzerella 3 was confirmed through FDR correction, making it a key focus in this study. Specifically, it was found to causally facilitate herpes zoster primarily with IVW (OR 1.420, 95% CI 1.174–1.718, p

Abstract Backgrounds Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride–glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD. Methods Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan–Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices. Results A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05–1.50, P = 0.014; TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07–1.52, P = 0.006; TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25–1.80, P

Abstract 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.

Abstract Cell proliferation and function require nutrients, energy, and biosynthesis activity to duplicate repertoires for each daughter. It is therefore not surprising that tumor microenvironment (TME) metabolic reprogramming primarily orchestrates the interaction between tumor and immune cells. Tumor metabolic reprogramming affords bioenergetic, signaling intermediates, and biosynthesis requirements for both malignant and immune cells. Different immune cell subsets are recruited into the TME, and these manifestations have distinct effects on tumor progression and therapeutic outcomes, especially the mutual contribution of glycolysis and cholesterol metabolism. In particularly, glycolysis-cholesterol metabolic axis interconnection plays a critical role in the TME modulation, and their changes in tumor metabolism appear to be a double-edged sword in regulating various immune cell responses and immunotherapy efficacy. Hence, we discussed the signature manifestation of the glycolysis-cholesterol metabolic axis and its pivotal role in tumor immune regulation. We also highlight how hypothetical combinations of immunotherapy and glycolysis/cholesterol-related metabolic interventions unleash the potential of anti-tumor immunotherapies, as well as developing more effective personalized treatment strategies.

Abstract 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

BackgroundThe 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.MethodsThe 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.ResultsIn 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.ConclusionThis 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.

Abstract 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 (β [95% CI] = −0.21 [−0.40, −0.03], p = 0.03). In the five identified frailty trajectories, participants with mild frailty (inverted U‐shaped, β [95% CI] = −0.22 [−0.43, −0.02], p = 0.04), mild frailty (U‐shaped, β [95% CI] = −0.22 [−0.39, −0.06], p = 0.01), and frailty (β [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.

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.

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.

Abstract Objective To evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT). Methods Based on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff. Results When MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V 5 , V 10 , V 20 of whole lung, D 2% , D 1cc , D 2cc of the rib, V 30 of the rib, D 2% and the maximum dose (D max ) of the skin, and D 2% and D max of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median D max , D 2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R 50% and D 2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V 30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively. Conclusions For peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.

PurposeCurrent deep learning methods for dose prediction require manual delineations of planning target volume (PTV) and organs at risk (OARs) besides the original CT images. Perceiving the time cost of manual contour delineation, we expect to explore the feasibility of accelerating the radiotherapy planning by leveraging only the CT images to produce high-quality dose distribution maps while generating the contour information automatically.Materials and MethodsWe developed a generative adversarial network (GAN) with multi-task learning (MTL) strategy to produce accurate dose distribution maps without manually delineated contours. To balance the relative importance of each task (i.e., the primary dose prediction task and the auxiliary tumor segmentation task), a multi-task loss function was employed. Our model was trained, validated and evaluated on a cohort of 130 rectal cancer patients.ResultsExperimental results manifest the feasibility and improvements of our contour-free method. Compared to other mainstream methods (i.e., U-net, DeepLabV3+, DoseNet, and GAN), the proposed method produces the leading performance with statistically significant improvements by achieving the highest HI of 1.023 (3.27E-5) and the lowest prediction error with ΔD95 of 0.125 (0.035) and ΔDmean of 0.023 (4.19E-4), respectively. The DVH differences between the predicted dose and the ideal dose are subtle and the errors in the difference maps are minimal. In addition, we conducted the ablation study to validate the effectiveness of each module. Furthermore, the results of attention maps also prove that our CT-only prediction model is capable of paying attention to both the target tumor (i.e., high dose distribution area) and the surrounding healthy tissues (i.e., low dose distribution areas).ConclusionThe proposed CT-only dose prediction framework is capable of producing acceptable dose maps and reducing the time and labor for manual delineation, thus having great clinical potential in providing accurate and accelerated radiotherapy. Code is available at https://github.com/joegit-code/DoseWithCT

ObjectiveThis study aimed to investigate the prognostic factors of penile cancer and establish a comprehensive predictive model for clinical application.MethodsA 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).ResultsAge, 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.ConclusionThis study incorporates the clinical, pathological, and therapeutic features comprehensively to develop a novel and clinically effective prognostic model for patients with penile cancer.

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.

The aim of this study is to evaluate the diagnostic accuracy of Raman spectroscopy system in the detection of malignant breast lesions through a systemic review and meta-analysis of published studies.We conducted a comprehensive literature search of PubMed and Embase from 2000 to June 2015. Published studies that evaluated the diagnostic performance of Raman spectroscopy in distinguishing malignant breast lesions from benign lesions and normal tissues were included in our study. The pooled sensitivity, specificity, diagnostic odds ratio, and the area under the curve of summary receiver-operating characteristic curves was derived. A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies guidelines was used to assess the quality of included studies.The initial search produced a total of 157 articles after removing duplicates. Nine studies (8 in vitro and 1 in vivo) were eligible in this meta-analysis. We analyzed the eight in vitro studies with 1756 lesions, the pooled sensitivity and specificity of Raman spectroscopy system for the diagnosis of malignant breast lesions were 0.92 (95% CI 0.86-0.96) and 0.97 (97% CI 0.93-0.98), respectively. Diagnostic odds ratio was 266.70 (95% CI 89.38-795.79), and the area under the curve of summary receiver-operating characteristic curves was 0.98 (95% CI 0.97-0.99). Significant heterogeneity was found between studies. There was no evidence of considerable publication bias.Raman spectroscopy system is an optical diagnostic technology with great value for detecting malignant breast lesions. At the same time, it has advantages of being non-invasive, real-time, and easy to use. Thus it deserves to be further explored for intra-operatory breast tumor margin detection.