The role of toll-like receptors (TLRs) in pan-cancer

BackgroundToll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study''s goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis.MethodsThe expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data.ResultsOur multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research.ConclusionTLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators.

Key Messages

• Toll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.
• In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.
• TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

     

两种给药途径致痫大鼠海马神经元超微结构损伤及caspase-3的表达特征

为了观察两种给药途径致痫大鼠海马神经元超微结构的损伤及caspase-3的表达特征,本研究分别采用海人酸腹膜腔注射(A组)和尾静脉注射(B组)诱发大鼠癫痫持续状态(SE)。分别于SE终止后3、6、24、48和72h取海马,电镜观察神经元超微结构的变化,免疫组化方法检测caspase-3的表达。结果显示:两组大鼠均在SE后3h出现线粒体损伤,细胞核的改变出现于SE后24h。A组致痫的潜伏期为97min±11min,神经元以凋亡为主;B组为48min±13min,神经元以坏死为主。SE后6～24h,两组大鼠海马内caspase-3的表达由胞浆向胞核逐渐移位,且均在SE后6h明显增高,24h达顶峰;A组高表达持续至72h,B组在48h显著降低。上述结果提示,线粒体的损伤出现于SE的早期,且可能是神经元损伤的关键环节;致痫方法不同,神经元的死亡形式也不同;而caspase-3的激活是神经元凋亡和坏死的共同通路。     

Association Between Nap and Reported Cognitive Function and Role of Sleep Debt: A Population-Based Study

Background and PurposeThe relationship between napping and cognition remains controversial. This study aimed to investigate the association between napping and cognition according to sleep debt in the Korean adult population.MethodsA population-based nationwide cross-sectional survey was conducted in 2018. A two-stage stratified random sample of Koreans aged ≥19 years was selected and evaluated using questionnaires by trained interviewers. Cognitive function was assessed using the Mail-In Cognitive Function Screening Instrument (MCFSI). Sleep habits on weekdays and weekends, napping, and subjective sleep requirements were assessed using the questionnaires. Accumulated sleep debt was calculated by subtracting the weekly average sleep duration from subjective sleep requirements. Sleep quality, daytime sleepiness, insomnia, depression, demographics, and comorbidities were assessed. Participants were grouped into those with sleep debt ≤60 min and those with sleep debt >60 min. Multiple linear regression was used to estimate the independent association between the factors and cognition.ResultsIn total, 2,501 participants were included in the analysis. Naps were reported in 726 (29.0%) participants (nappers). The mean MCFSI score was higher in nappers (3.4±3.6) than in non-nappers (2.3±3.0) (p<0.001). Multiple linear regression controlling for age, alcohol, smoking, depression, insomnia, daytime sleepiness, sleep quality, and education revealed that 30 to 60 min of napping was associated with worse cognitive function in participants with sleep debts ≤60 min, while >60 min of napping was associated with better cognitive function in participants with sleep debts >60 min.ConclusionsIn general, naps are associated with worse cognitive function in the Korean adult population. However, for those with sleep debt of >60 min, naps for >60 min were associated with better cognitive function.     

N064A (Alliance): Phase II Study of Panitumumab,Chemotherapy, and External Beam Radiation in Patients with Locally Advanced Pancreatic Adenocarcinoma

BackgroundThis North Central Cancer Treatment Group (NCCTG) N064A (Alliance) phase II trial evaluated upfront chemoradiotherapy incorporating the EGFR inhibitor panitumumab, followed by gemcitabine and panitumumab for unresectable, non-metastatic pancreatic cancer.MethodsThe treatment consisted of fluoropyrimidine and panitumumab given concurrently with radiotherapy followed by gemcitabine and panitumumab for 3 cycles followed by maintenance panitumumab. The primary endpoint was the 12-month overall survival (OS) rate and secondary endpoints included confirmed response rate (RR), OS, progression-free survival (PFS), and adverse events. Enrollment of 50 patients was planned and the study fully accrued.ResultsFifty-two patients were enrolled, but only 51 were treated and included in the analysis. The median age of patients was 65 years and 54.9% were women. Twenty-two patients received at least 1 cycle of systemic therapy following radiotherapy, but 29 patients received chemoradiotherapy only without receiving subsequent chemotherapy after completion of chemoradiotherapy. The overall RR was 5.9% (95% CI: 1.2%-16.2%). The 12-month OS rate was 50% (95% CI: 38%-67%) which fell short of the per-protocol goal for success (51.1%). The median PFS was 7.4 months (95% CI: 4.5-8.6) and the median OS was 12.1 months (95% CI 7.9-15.9). Grade 3 or higher adverse events were reported by 88%.ConclusionThe combination of panitumumab, chemotherapy, and external beam radiation therapy was associated with very high rates of grades 3-4 toxicities and survival results did not meet the trial’s goal for success. This regimen is not recommended for further study (ClinicalTrials.gov Identifier {"type":"clinical-trial","attrs":{"text":"NCT00601627","term_id":"NCT00601627"}}NCT00601627).     

A Case Report of MPO-ANCA-Associated Vasculitis Following Heterologous mRNA1273 COVID-19 Booster Vaccination

Despite that clinical trials have been examining the safety profile of coronavirus disease 2019 (COVID-19) vaccines, there are concerns about long-term side effects as the number of vaccinations increases. Herein, we report a case of new-onset renal-limited anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after booster vaccination with the mRNA 1273 (Moderna) vaccine. A 72-year-old woman with no specific past history, and who had a normal renal function, developed ANCA-associated vasculitis following heterologous booster with mRNA1273 (Moderna) vaccine. After a kidney biopsy, she was diagnosed with ANCA-associated pauci-immune crescentic glomerulonephritis. Her renal function and constitutional symptoms have been improved with treatment with plasmapheresis, intravenous cyclophosphamide and steroid pulse therapy (intravenous 500 mg of methylprednisolone sodium succinate for 3 days) followed by a reduced steroid regimen.     

Comparison of the background echotexture between automated breast ultrasound and handheld breast ultrasound

This study aimed to compare the background echotexture (BE) between automated breast ultrasound (ABUS) and handheld breast ultrasound (HHUS) and evaluate the correlation of BE with mammographic (MG) density and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI). A total of 212 women with newly diagnosed breast cancer who had undergone preoperative ABUS, HHUS, MG, and MRI were included. Two breast radiologists blinded to the menopausal status analyzed the BE of the contralateral breasts of the patients with breast cancer in consensus. The MG density and BPE of breast MRI on the radiologic reports were compared with the BE in the ultrasound. We used the cumulative link mixed model to compare the BE and Spearman rank correlation to evaluate the association between BE with MG density and BPE. BE was more heterogeneous in ABUS than in HHUS (P < .001) and in the premenopausal group than in the postmenopausal group (P < .001). The heterogeneity of BE in the premenopausal group was higher with ABUS than with HHUS (P = .013). BE and MG density showed a moderate correlation in the postmenopausal group, but a weak correlation in the premenopausal group. BE and BPE showed moderate correlations only in the premenopausal group. ABUS showed a more heterogeneous BE, especially in the premenopausal group. Therefore, more attention is required to interpret ABUS screening in premenopausal women.     

Effectiveness and safety of Korean medicine treatment based on the clinical practice guidelines in patients with acute peripheral facial palsy: A protocol for a multicenter,prospective, observational study

Introduction:Peripheral facial palsy (PFP) results in weakness or paralysis of the affected side of the face. In Korea, there is a high demand for Korean medicine treatment for PFP. The clinical practice guidelines (CPGs) of Korean medicine for facial palsy were developed; however, there remains insufficient evidence to support the effectiveness and safety of Korean medicine treatment. Thus, this study aimed to evaluate the effectiveness and safety of Korean medicine treatment based on the CPGs in patients with acute PFP.Methods:This is a multicenter, prospective, observational study. The participants will be recruited from one Korean medicine hospital and eight Korean medicine clinics. The participants will receive Korean medicine treatments based on the CPGs, fill in survey questionnaires, and undergo electrophysiologic testing. The changes in House-Brackmann (H-B) grade, movement of the lip and eye, symptoms related to or accompanied by facial palsy, Facial Disability Index, EuroQol 5-dimension 5-level (EQ-5D-5L), and EuroQol Visual Analogue Scale (EQ-VAS), and the results of electromyography (EMG), electroneurography (ENoG), and Blink Reflex test will be analyzed. For the safety analysis, adverse events will be recorded, and for the feasibility analysis, the results of the Was It Worth It questionnaire will be assessed.Conclusion:We expect to draw real-world clinical data on the effectiveness and safety of Korean medicine treatment based on the CPGs in patients with acute PFP from this study. It would be the basis for complementing and improving the CPGs and provide the basis of clinical and policy decision-making.Trial registration:This study was approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital (2021-06-005-001), and registered with the Korean Clinical Trial Registry (CRIS), Republic of Korea (KCT0006562).     

Prevalence and risk of colorectal polyps among the Korean population under 50 years

Colorectal cancer is a common cancer; generally, adults aged ≥ 50 years are screened using stool occult blood tests and colonoscopy. However, colorectal adenoma and cancer have been found in patients under the aged of 50, and studies on characteristics and risk factors in young patients are lacking. We evaluated the prevalence and risk factors of colorectal adenoma and cancer in young adults aged under 50 years.We retrospectively analyzed 570 individuals aged under 50 years who underwent colonoscopy at the Haeundae Paik Hospital, Korea, from January to June 2018. Logistic regression model was used to identify the risk factors for colorectal adenoma and colorectal cancer.The prevalence of colorectal adenoma in group of 19–29 years was 3.2% (1 of 31), 30–39 years was 13.8% (30 of 217) and in the group of 40–49 years was 21.1% (68 of 322) (P = .009). In multivariable analysis, age over 45 years (adjusted odds ratio [OR], 1.941; 95% confidence interval [CI], 1.187–3.172; P = .008) and male sex (adjusted OR, 1.711; 95% CI, 1.044–2.806; P = .033) were independent risk factors for colorectal neoplasia including cancer.The prevalence of colorectal adenoma increases as the age increased in young adults under 50 years of age, especially after the age of 45 years, the risk of colorectal neoplasia increases; hence, early screening should be considered before the age of 50 years.     

Age-specific influences of refractive error and illuminance on pupil diameter

To assess the most influential factor for pupil diameter changes among age, illuminance, and refractive state and reestablish the optimal procedures for clinical applications based on refractive state and illuminance for different age groups.The study was an observational study (repeated measure study). Participants included 219 Korean adults aged 20 to 69 years. Pupil diameters were measured using a pupilometer under scotopic, mesopic-low, and mesopic-high lighting conditions. Factor interactions among age, illuminance, and refractive state were evaluated using mixed linear model and chi-square automated interaction detection.Illuminance mainly contributed to variations in pupil diameter of participants over 50 years, whereas the refractive state was the dominant controlling factor for the pupil variation in participants below 50 years. For more generalized application, the pupil diameter decreased with older age and brighter illuminance (P < .001, inverse correlation, all comparisons). The mean pupil diameter was significantly higher in myopes and emmetropes than in hyperopes (P < .001). Pupil diameter variation modeled using the mixed model confirmed age, illuminance, and refractive error as significant factors (P < .001).Accounting for the interactions among age, illuminance, and refractive error and establishing their hierarchical dominance can be generalized using the chi-square automated interaction detection method and mixed model. Promoting age-dependent consideration for both illuminance and refractive state is necessary when pupil diameters play significant roles in clinical and manufacturing circumstances.     

The diagnostic efficacy of diffusion tensor imaging generated by gadolinium-based magnetic resonance imaging for patients with chronic kidney disease

Background:Chronic kidney disease (CKD) can lead to systemic inflammatory responses and other cardiovascular disease. Diffusion tensor imaging findings generated by gadolinium-based MRI (DTI-GBMRI) is regarded as a standard method for assessing the pathology of CKD. To evaluate the diagnostic value of DTI-GBMRI for renal histopathology and renal efficiency, renal fibrosis and damage, noninvasive quantification of renal blood flow (RBF) were investigated in patients with CKD.Methods:CKD patients (n = 186) were recruited and underwent diagnosis of renal diffusion tensor imaging findings generated by MRI (DTI-MRI) or DTI-GBMRI to identify the pathological characteristics and depict renal efficiency. The cortical RBFs and estimated glomerular filtration rate were compared in CKD patients undergone DTI-GBMRI (n = 92) or DTI-MRI (n = 94).Results:Gadolinium enhanced the diagnosis generated by DTI-MRI in renal fibrosis, renal damage, and estimated glomerular filtration rate. The superiority in sensitivity and accuracy of the DTI-GBMRI method in assessing renal function and evaluating renal impairment was observed in CKD patients compared with DTI-MRI. Outcomes demonstrated that DTI-GBMRI had higher accuracy, sensitivity, and specificity than DTI-MRI in diagnosing patients with CKD.Conclusion:In conclusion, DTI-GBMRI is a potential noninvasive method for measuring renal function, which can provide valuable information for clinical CKD diagnosis.