Identification of 6-Fluorine-Substituted Coumarin Analogues as POLRMT Inhibitors with High Potency and Safety for Treatment of Pancreatic Cancer.

Increasing evidence has demonstrated that oxidative phosphorylation (OXPHOS) is closely associated with the progression of pancreatic cancer (PC). Given its central role in mitochondrial transcription, the human mitochondrial RNA polymerase (POLRMT) is a promising target for developing PC treatments. Herein, structure-activity relationship exploration led to the identification of compound S7, which was the first reported POLRMT inhibitor possessing single-digit nanomolar potency of inhibiting PC cells proliferation. Mechanistic studies showed that compound S7 exerted antiproliferative effects without affecting the cell cycle, apoptosis, mitochondrial membrane potential (MMP), or intracellular reactive oxygen species (ROS) levels specifically in MIA PaCa-2 cells. Notably, compound S7 inhibited tumor growth in MIA PaCa-2 xenograft tumor model with a tumor growth inhibition (TGI) rate of 64.52% demonstrating significant improvement compared to the positive control (44.80%). In conclusion, this work enriched SARs of POLRMT inhibitors, and compound S7 deserved further investigations of drug-likeness as a candidate for PC treatment.

Risk factors for sternal wound infection after median sternotomy: A nested case-control study and time-to-event analysis.

Although potential risk factors for sternal wound infection (SWI) have been extensively studied, the onset time of SWI and different risk factors for superficial and deep SWI were rarely reported. This nested case-control study aims to compare the onset time and contributors between superficial and deep SWI. Consecutive adult patients who underwent cardiac surgery through median sternotomy in a single center from January 2011 to January 2021 constituted the cohort. The case group was those who developed SWI as defined by CDC and controls were matched 6:1 per case. Kaplan-Meier analysis, LASSO and univariate and multivariate Cox regressions were performed. A simple nomogram was established for clinical prediction of the risk of SWI. The incidence of SWI was 1.1% (61 out of 5471) in our cohort. Totally 366 controls were matched to 61 cases. 26.2% (16 of 61) SWI cases were deep SWI. The median onset time of SWI was 35 days. DSWI had a longer latency than SSWI (median time 46 days vs. 32 days, p = 0.032). Kaplan-Meier analyses showed different time-to-SWI between patients with and without DM (p = 0.0011) or MI (p = 0.0019). Multivariate Cox regression showed that BMI (HR = 1.083, 95% CI: 1.012-1.116, p = 0.022), DM (HR = 2.041, 95% CI: 1.094-3.805, p = 0.025) and MI (HR = 2.332, 95% CI: 1.193-4.557, p = 0.013) were independent risk factors for SWI. Superficial SWI was only associated with BMI (HR = 1.089, 95% CI: 1.01-1.175, p = 0.027), while deep SWI was associated with DM (HR = 3.271, 95% CI: 1.036-10.325, p = 0.043) and surgery time (HR = 1.004, 95% CI: 1.001-1.008, p = 0.027). The nomogram for SWI prediction had an AUC of 0.67, good fitness and clinical effectiveness as shown by the calibration curve and decision curve analyses. BMI, DM and MI were independent risk factors for SWI. DSWI had a longer latency and different risk factors compared to SSWI. The nomogram showed a fair performance and good effectiveness for the clinical prediction of SWI.

Sulforaphane suppresses bladder cancer metastasis via blocking actin nucleation-mediated pseudopodia formation.

Metastasis is the primary stumbling block to the treatment of bladder cancer (BC). In order to spread, tumor cells must acquire increased migratory and invasive capacity, which is tightly linked with pseudopodia formation. Here, we unravel the effects of sulforaphane (SFN), an isothiocyanate in cruciferous vegetables, on the assembly of pseudopodia and BC metastasis, and its molecular mechanism in the process. Our database analysis revealed that in bladder tumor, the pseudopodia-associated genes CTTN, WASL and ACTR2/ARP2 are upregulated. SFN caused lamellipodia to collapse in BC cells by blocking the CTTN-ARP2 axis. SFN inhibited invadopodia formation and cell invasion by reducing WASL in different invasive BC cell lines. The production of ATP, essential for the assembly of pseudopodia, was significantly increased in bladder tumors and strongly inhibited by SFN. Overexpressing AKT1 reversed the downregulation of ATP in SFN-treated bladder cancer cells and restored filopodia and lamellipodia morphology and function. Bioluminescent imaging showed that SFN suppressed BC metastases to the lung of nude mice by downregulating Cttn and Arp2 expression. Our study reveals the mechanism of SFN action in inhibiting pseudopodia formation, and highlights potential targeting options for the therapy of metastatic bladder cancer.

Hsa_circ_0096157 silencing suppresses autophagy and reduces cisplatin resistance in non-small cell lung cancer by weakening the Nrf2/ARE signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide, and new diagnostic markers are urgently needed. We aimed to investigate the mechanism by which hsa_circ_0096157 regulates autophagy and cisplatin (DDP) resistance in NSCLC. METHODS: A549 cells were treated with DDP (0 µg/mL or 3 µg/mL). Then, the autophagy activator rapamycin (200 nm) was applied to the A549/DDP cells. Moreover, hsa_circ_0096157 and Nrf2 were knocked down, and Nrf2 was overexpressed in A549/DDP cells. The expression of Hsa_circ_0096157, the Nrf2/ARE pathway-related factors Nrf2, HO-1, and NQO1, and the autophagy-related factors LC3, Beclin-1, and p62 was evaluated by qRT‒PCR or western blotting. Autophagosomes were detected through TEM. An MTS assay was utilized to measure cell proliferation. The associated miRNA levels were also tested by qRT‒PCR. RESULTS: DDP (3 µg/mL) promoted hsa_circ_0096157, LC3 II/I, and Beclin-1 expression and decreased p62 expression. Knocking down hsa_circ_0096157 resulted in the downregulation of LC3 II/I and Beclin-1 expression, upregulation of p62 expression, and decreased proliferation. Rapamycin reversed the effect of interfering with hsa_circ_0096157. Keap1 expression was lower, and Nrf2, HO-1, and NQO1 expression was greater in the A549/DDP group than in the A549 group. HO-1 expression was repressed after Nrf2 interference. In addition, activation of the Nrf2/ARE pathway promoted autophagy in A549/DDP cells. Moreover, hsa_circ_0096157 activated the Nrf2/ARE pathway. The silencing of hsa_circ_0096157 reduced Nrf2 expression by releasing miR-142-5p or miR-548n. Finally, we found that hsa_circ_0096157 promoted A549/DDP cell autophagy by activating the Nrf2/ARE pathway. CONCLUSION: Knockdown of hsa_circ_0096157 inhibits autophagy and DDP resistance in NSCLC cells by downregulating the Nrf2/ARE signaling pathway.

Dietary isothiocyanates and anticancer agents: exploring synergism for improved cancer management.

Human studies have shown the anticancer effects of dietary isothiocyanates (ITCs), but there are some inconsistencies, and more evidence supports that such anticancer effect is from higher doses of ITCs. The inconsistencies found in epidemiological studies may be due to many factors, including the biphasic dose-response (so called hormetic effect) of ITCs, which was found to be more profound under hypoxia conditions. In this comprehensive review, we aim to shed light on the intriguing synergistic interactions between dietary ITCs, focusing on sulforaphane (SFN) and various anticancer drugs. Our exploration is motivated by the potential of these combinations to enhance cancer management strategies. While the anticancer properties of ITCs have been recognized, our review delves deeper into understanding the mechanisms and emphasizing the significance of the hormetic effect of ITCs, characterized by lower doses stimulating both normal cells and cancer cells, whereas higher doses are toxic to cancer cells and inhibit their growth. We have examined a spectrum of studies unraveling the multifaceted interaction and combinational effects of ITCs with anticancer agents. Our analysis reveals the potential of these synergies to augment therapeutic efficacy, mitigate chemoresistance, and minimize toxic effects, thereby opening avenues for therapeutic innovation. The review will provide insights into the underlying mechanisms of action, for example, by spotlighting the pivotal role of Nrf2 and antioxidant enzymes in prevention. Finally, we glimpse ongoing research endeavors and contemplate future directions in this dynamic field. We believe that our work contributes valuable perspectives on nutrition and cancer and holds promise for developing novel and optimized therapeutic strategies.

Factors influencing length of stay and costs in inpatient cases of human brucellosis as the primary diagnosis over a decade in Beijing, China.

Aims: In the year 2021, human brucellosis ranked fifth in terms of the number of cases among all statutorily notifiable infectious diseases in China, thus remaining a significant concern for public health. This study aims to provide insights into the financial burden of human brucellosis by examining hospital stays and associated costs for affected individuals. Methods: In this retrospective study, we gathered updated data from 467 inpatient cases primarily diagnosed with human brucellosis at eight major tertiary hospitals in Beijing, China, spanning from 2013 to 2023. To comprehensively explore the economic impact on individuals, we not only analyzed the duration of hospital stays and total costs but also examined various charge types, including drug, lab test, medical imaging, medical treatment, surgical procedures, medical supplies and consumables, inpatient bed care, nursing services, and other services costs. Statistical analysis was employed to compare differences among gender, age, ethnicity, type of health insurance, condition at admission, comorbidity index, the performance of surgery, and the site of infection. Results: Both the length of stay and total cost exhibited significant variations among insurance, surgery, and infection site groups. Utilization categories demonstrated significant differences between patients who underwent surgery and those who did not, as well as across different infection sites. Furthermore, multiple linear regression analysis revealed that the condition at admission, Elixhauser comorbidity index, infection site, and surgery influenced both hospital stay and total cost. In addition, age and insurance type were associated with total costs. Conclusion: By delving into various utilization categories, we have addressed a significant gap in the literature. Our findings provide valuable insights for optimizing the allocation and management of health resources based on the influencing factors identified in this study.

RENAL PROTECTIVE EFFECT AND CLINICAL ANALYSIS OF VITAMIN B 6 IN PATIENTS WITH SEPSIS.

ABSTRACT: Objective: To investigate the protective effect and possible mechanisms of vitamin B 6 against renal injury in patients with sepsis. Methods: A total of 128 patients with sepsis who met the entry criteria in multiple centers were randomly divided into experimental (intravenous vitamin B 6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF-α), and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen, serum creatinine, and renal resistance index monitored by ultrasound) were compared between the two groups. Results: After 7 d of treatment, the IL-6, IL-8, TNF-α, and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the blood urea nitrogen, serum creatinine, and renal resistance index values in the experimental group were significantly lower than those in the control group ( P < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality ( P > 0.05). However, the intensive care unit length of stay and the total hospitalization expenses in the experimental group were significantly lower than those in the control group ( P < 0.05). Conclusion: The administration of vitamin B 6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.

Temporal patterns and clinical characteristics of healthcare-associated infections in surgery patients: A retrospective study in a major Chinese tertiary hospital.

Background: Given the preventable nature of most healthcare-associated infections (HAIs), it is crucial to understand their characteristics and temporal patterns to reduce their occurrence. Methods: A retrospective analysis of medical record cover pages from a Chinese hospital information system was conducted for surgery inpatients from 2010 to 2019. Association rules mining (ARM) was employed to explore the association between disease, procedure, and HAIs. Joinpoint models were used to estimate the annual HAI trend. The time series of each type of HAI was decomposed to analyze the temporal patterns of HAIs. Results: The study included data from 623,290 surgery inpatients over 10 years, and a significant decline in the HAI rate was observed. Compared with patients without HAIs, those with HAIs had a longer length of stay (29 days vs. 9 days), higher medical costs (96226.57 CNY vs. 22351.98 CNY), and an increased risk of death (6.42% vs. 0.18%). The most common diseases for each type of HAI differed, although bone marrow and spleen operations were the most frequent procedures for most HAI types. ARM detected that some uncommon diagnoses could strongly associate with HAIs. The time series pattern varied for each type of HAI, with the peak occurring in January for respiratory system infections, and in August and July for surgical site and bloodstream infections, respectively. Conclusions: Our findings demonstrate that HAIs impose a significant burden on surgery patients. The differing time series patterns for each type of HAI highlight the importance of tailored surveillance strategies for specific types of HAI.

Assessing racial, ethnic, and nativity disparities in US cancer mortality using a new integrated platform.

BACKGROUND: Foreign-born populations in the United States have markedly increased, yet cancer trends remain unexplored. Survey-based Population-Adjusted Rate Calculator (SPARC) is a new tool for evaluating nativity differences in cancer mortality. METHODS: Using SPARC, we calculated 3-year (2016-2018) age-adjusted mortality rates and rate ratios for common cancers by sex, age group, race and ethnicity, and nativity. Trends by nativity were examined for the first time for 2006-2018. Traditional cancer statistics draw populations from decennial censuses. However, nativity-stratified populations are from the American Community Surveys, thus involve sampling errors. To rectify this, SPARC employed bias-corrected estimators. Death counts came from the National Vital Statistics System. RESULTS: Age-adjusted mortality rates were higher among US-born populations across nearly all cancer types, with the largest US-born, foreign-born difference observed in lung cancer among Black women (rate ratio = 3.67, 95% confidence interval [CI] = 3.37 to 4.00). The well-documented White-Black differences in breast cancer mortality existed mainly among US-born women. For all cancers combined, descending trends were more accelerated for US-born compared with foreign-born individuals in all race and ethnicity groups with changes ranging from -2.6% per year in US-born Black men to stable (statistically nonsignificant) among foreign-born Black women. Pancreas and liver cancers were exceptions with increasing, stable, or decreasing trends depending on nativity and race and ethnicity. Notably, foreign-born Black men and foreign-born Hispanic men did not show a favorable decline in colorectal cancer mortality. CONCLUSIONS: Although all groups show beneficial cancer mortality trends, those with higher rates in 2006 have experienced sharper declines. Persistent disparities between US-born and foreign-born individuals, especially among Black people, necessitate further investigation.

circNOX4 activates an inflammatory fibroblast niche to promote tumor growth and metastasis in NSCLC via FAP/IL-6 axis.

BACKGROUND: Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain elusive. METHODS: The clinical implications of fibroblast activation protein (FAP)-positive CAFs (FAP+CAFs) were evaluated based on tumor specimens from NSCLC patients and bioinformatic analysis of online databases. CAF-specific circular RNAs (circRNAs) were screened by circRNA microarrays of primary human CAFs and matched normal fibroblasts (NFs). Survival analyses were performed to assess the prognostic value of circNOX4 in NSCLC clinical samples. The biological effects of circNOX4 were investigated by gain- and loss-of-function experiments in vitro and in vivo. Fluorescence in situ hybridization, luciferase reporter assays, RNA immunoprecipitation, and miRNA rescue experiments were conducted to elucidate the underlying mechanisms of fibroblast activation. Cytokine antibody array, transwell coculture system, and enzyme-linked immunosorbent assay (ELISA) were performed to investigate the downstream effectors that promote cancer metastasis. RESULTS: FAP+CAFs were significantly enriched in metastatic cancer samples, and their higher abundance was correlated with the worse overall survival in NSCLC patients. A novel CAF-specific circRNA, circNOX4 (hsa_circ_0023988), evoked the phenotypic transition from NFs into CAFs and promoted the migration and invasion of NSCLC in vitro and in vivo. Clinically, circNOX4 correlated with the poor prognosis of advanced NSCLC patients. Mechanistically, circNOX4 upregulated FAP by sponging miR-329-5p, which led to fibroblast activation. Furthermore, the circNOX4/miR-329-5p/FAP axis activated an inflammatory fibroblast niche by preferentially inducing interleukin-6 (IL-6) and eventually promoting NSCLC progression. Disruption of the intercellular circNOX4/IL-6 axis significantly suppressed tumor growth and metastatic colonization in vivo. CONCLUSIONS: Our study reveals a role of the circRNA-induced fibroblast niche in tumor metastasis and highlights that targeting the circNOX4/FAP/IL-6 axis is a promising strategy for the intervention of NSCLC metastasis.

NEAT1_1 confers gefitinib resistance in lung adenocarcinoma through promoting AKR1C1-mediated ferroptosis defence.

Gefitinib is one of the most extensively utilized epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for treating advanced lung adenocarcinoma (LUAD) patients harboring EGFR mutation. However, the emergence of drug resistance significantly compromised the clinical efficacy of EGFR-TKIs. Gaining further insights into the molecular mechanisms underlying gefitinib resistance holds promise for developing novel strategies to overcome the resistance and improve the prognosis in LUAD patients. Here, we identified that the inhibitory efficacy of gefitinib on EGFR-mutated LUAD cells was partially dependent on the induction of ferroptosis, and ferroptosis protection resulted in gefitinib resistance. Among the ferroptosis suppressors, aldo-keto reductase family 1 member C1 (AKR1C1) exhibited significant upregulation in gefitinib-resistant strains of LUAD cells and predicted poor progression-free survival (PFS) and overall survival (OS) of LUAD patients who received first-generation EGFR-TKI treatment. Knockdown of AKR1C1 partially reversed drug resistance by re-sensitizing the LUAD cells to gefitinib-mediated ferroptosis. The decreased expression of miR-338-3p contributed to the aberrant upregulation of AKR1C1 in gefitinib-resistant LUAD cells. Furthermore, upregulated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) sponged miR-338-3p to neutralize its suppression on AKR1C1. Dual-luciferase reporter assay and miRNA rescue experiment confirmed the NEAT1_1/miR-338-3p/AKR1C1 axis in EGFR-mutated LUAD cells. Gain- and loss-of-function assays demonstrated that the NEAT1_1/miR-338-3p/AKR1C1 axis promoted gefitinib resistance, proliferation, migration, and invasion in LUAD cells. This study reveals the effects of NEAT1_1/miR-338-3p/AKR1C1 axis-mediated ferroptosis defence in gefitinib resistance in LUAD. Thus, targeting NEAT1_1/miR-338-3p/AKR1C1 axis might be a novel strategy for overcoming gefitinib resistance in LUAD harboring EGFR mutation.

Characterization of Thyroid Cancer among Hispanics in California, USA, from 2010 to 2020.

BACKGROUND: Previous studies on Hispanic thyroid cancer cases show sex disparities and an increased prevalence of large tumor sizes and nodal involvement. Here, we characterized Hispanic thyroid cancer cases in California. METHODS: We identified thyroid cancer cases from 2010 to 2020 using the California Cancer Registry by sex, race/ethnicity, histology, TNM stage, tumor size, lymph node involvement, and Charlson comorbidity score. The age-adjusted incidence rate (AAIR) and age-adjusted mortality rate (AAMR) for all causes of death were calculated. A Cox proportional hazards regression analysis was performed to evaluate the mortality risk from all causes of death by race. RESULTS: Overall, 56,838 thyroid cancer cases were identified, including 29.75% in Hispanics. Hispanics had the highest female-to-male incidence rate ratio (IRR 3.54) and the highest prevalence of T3/T4 tumor size (28.71%), the highest N1 nodal status (32.69%), and the highest AAMR (0.79 per 100,000 people). After adjusting for demographic and tumor covariates, compared to non-Hispanic White people, Hispanic ethnicity, with an HR of 1.22 (95% CI 1.18-1.25, p < 0.0001), remained a significant independent contributor to mortality risk. CONCLUSIONS: Hispanics had the greatest female-to-male IRR ratio, a greater prevalence of advanced disease features at diagnosis, along with the highest AAMR and increased mortality risk despite adjustments for demographic and tumor covariates. Further investigation into other risk factors is needed.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

Prognostic Factors in Philadelphia Chromosome-Positive Acute Myeloid Leukemia Using Fluorescence in Situ Hybridization.

BACKGROUND: Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is a rare leukemia subtype first classified by the World Health Organization in 2016. The incidence of Ph+ AML is approximately 0.5 - 3%, and its prognosis is poor. Ph+ AML with additional chromosomal abnormalities in children has rarely been reported, and its treatment and prognosis remain uncertain. METHODS: We retrospectively analyzed 649 patients with AML from 2006 - 2021. Six (0.9%) patients with Ph+ AML were identified and treated with conventional chemotherapy. The clinical features and prognoses were retrospectively analyzed. RESULTS: Six cases of AML with a Ph chromosome were reported. One of the six individuals exhibited a biphenotypic immunophenotype, one exhibited a simple myeloid immunophenotype, and the other four exhibited myeloid and lymphoid expression. Karyotypic analysis (R banding) was performed in six cases, four of which were classical Ph chromosomal abnormalities, two of which had additional abnormalities outside the Ph chromosome. Fluorescence in situ hybridization (FISH) analysis using the BCR/ABL fusion gene distinguished that the BCR major breakpoint break in three cases was type P210 and the BCR minor breakpoint break in three cases was type P190. The complete remission rate of the six patients in this study using conventional chemotherapy was 60%, with a median survival time of 7.5 months. CONCLUSIONS: In summary, Ph+ AML is a heterogeneous disease often associated with additional chromosomal abnormalities. Ph+ AML is seen with a lymphoid immunophenotype and alterations in associated genes such as the IGH gene. Adults were predominantly P210 and two cases in children were both P190. Conventional treatments are less effective, and there are no standard treatment regimens.

Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks.

Current treatment strategies for cancer, especially advanced cancer, are limited and unsatisfactory. One of the most substantial advances in cancer therapy, in the last decades, was the discovery of a new layer of immunotherapy approach, immune checkpoint inhibitors (ICIs), which can specifically activate immune cells by targeting immune checkpoints. Immune checkpoints are a type of immunosuppressive molecules expressed on immune cells, which can regulate the degree of immune activation and avoid autoimmune responses. ICIs, such as anti-PD-1/PD-L1 drugs, has shown inspiring efficacy and broad applicability across various cancers. Unfortunately, not all cancer patients benefit remarkably from ICIs, and the overall response rates to ICIs remain relatively low for most cancer types. Moreover, the primary and acquired resistance to ICIs pose serious challenges to the clinical application of cancer immunotherapy. Thus, a deeper understanding of the molecular biological properties and regulatory mechanisms of immune checkpoints is urgently needed to improve clinical options for current therapies. Recently, circular RNAs (circRNAs) have attracted increasing attention, not only due to their involvement in various aspects of cancer hallmarks, but also for their impact on immune checkpoints in shaping the tumor immune microenvironment. In this review, we systematically summarize the current status of immune checkpoints in cancer and the existing regulatory roles of circRNAs on immune checkpoints. Meanwhile, we also aim to settle the issue in an evidence-oriented manner that circRNAs involved in cancer hallmarks regulate the effects and resistance of ICIs by targeting immune checkpoints.

Multimodal ultrasound evaluation of asymptomatic ulnar nerve dislocation at the cubital tunnel.

Background: Ultrasonography has received broad acceptance as an effective peripheral nervous imaging examination. Shear wave elastography (SWE) can quantitatively assess the stiffness of nerves; however, little research has been conducted on elastography for ulnar nerve dislocation. The purpose of this study was thus to investigate the characteristics of multimodal ultrasound, including high-resolution ultrasonography and SWE, for asymptomatic ulnar nerve dislocation at cubital tunnel. Methods: In this prospective cross-sectional study, 41 participants were recruited in Shandong Provincial Hospital Affiliated to Shandong First Medical University in July 2022. The inclusion criteria for participants were being in good health and being 18-60 years of age. Meanwhile, the exclusion criterion was a history of upper limb pain or fractures, peripheral neuropathy, or systemic or immunological diseases. Finally, 38 participants were enrolled. Two ultrasound doctors measured the maximum diameter, the maximum cross-sectional area (CSA), and the shear modulus of the ulnar nerve at the cubital tunnel independently. Another two ultrasound doctors determined whether dislocation was present during dynamic elbow flexion and extension and divided the elbows into a dislocation group and a control group. The descriptive statistics and independent sample t-test were used for data analysis, and intragroup correlation coefficient (ICC) was used to determine the consistency of evaluation between observers. Results: Ulnar nerve dislocation was observed in 15.8% (12/76) of the ulnar nerves. There was no significant difference in the maximum diameter between the dislocation group (0.194±0.022 cm) and the control group (0.181±0.023 cm) (t=1.888; P=0.063). The CSA and SWE of the ulnar nerve were 0.064±0.009 cm2 and 43.629±6.737 kPa in the dislocation group, respectively, and were 0.050±0.008 cm2 and 31.293±7.858 kPa in the control group, respectively. There were significant differences between the two groups in terms of CSA (P<0.001) and SWE (P<0.001). The ICCs of the maximum diameter, CSA, and SWE values between observers were 0.970, 0.900, and 0.915, respectively. Conclusions: Multimodal ultrasound consisting of high-resolution ultrasonography combined with elastography can comprehensively and quantitatively evaluate the morphological changes and mechanical properties of the dislocated ulnar nerve and monitor disease progress.

Population-based evaluation of disparities in stomach cancer by nativity among Asian and Hispanic populations in California, 2011-2015.

BACKGROUND: Stomach cancer incidence presents significant racial/ethnic disparities among racial/ethnic minority groups in the United States, particularly among Asian and Hispanic immigrant populations. However, population-based evaluation of disparities by nativity has been scarce because of the lack of nativity-specific population denominators, especially for disaggregated Asian subgroups. Population-based stomach cancer incidence and tumor characteristics by detailed race/ethnicity and nativity were examined. METHODS: Annual age-adjusted incidence rates were calculated by race/ethnicity, sex, and nativity and tumor characteristics, such as stage and anatomic subsite, were evaluated using the 2011-2015 California Cancer Registry data. For Hispanic and Asian populations, nativity-specific population counts were estimated using the US Census and the American Community Survey Public Use Microdata Sample data. RESULTS: During 2011-2015 in California, 14,198 patients were diagnosed with stomach cancer. Annual age-adjusted incidence rates were higher among foreign-born individuals than their US-born counterparts. The difference was modest among Hispanics (∼1.3-fold) but larger (∼2- to 3-fold) among Chinese, Japanese, and Korean Americans. The highest incidence was observed for foreign-born Korean and Japanese Americans (33 and 33 per 100,000 for men; 15 and 12 per 100,000 for women, respectively). The proportion of localized stage disease was highest among foreign-born Korean Americans (44%); a similar proportion was observed among US-born Korean Americans, although numbers were limited. For other Asians and Hispanics, the localized stage proportion was generally lower among foreign-born than US-born individuals and lowest among foreign-born Japanese Americans (23%). CONCLUSIONS: Nativity-specific investigation with disaggregated racial/ethnic groups identified substantial stomach cancer disparities among foreign-born immigrant populations.

Disparities among Black and Hispanic colorectal cancer patients: Findings from the California Cancer Registry.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in California and second among Hispanic/Latinx (H/L) males. Data from the California Cancer Registry were utilized to investigate the differential impact on CRC outcomes from demographic and clinical characteristics among non-Hispanic white (NHW), non-Hispanic Black (NHB), U.S. born (USB), and non-U.S. born (NUSB) H/L patients diagnosed during 1995-2020. METHODS: We identified 248,238 NHW, 28,433 NHB, and 62,747 H/L cases (32,402 NUSB and 30,345 USB). Disparities across groups were evaluated through case frequencies, odds ratios (OR) from logistic regression, and hazard ratios (HR) from Cox regression models. All statistical tests were two-sided. RESULTS: NHB patients showed a higher proportion of colon tumors (75.8%) than NHW (71.5%), whereas both NUSB (65.9%) and USB (66.9%) H/L cases had less (p < 0.001). In multivariate models, NUSB H/L cases were 15% more likely than NHW to have rectal cancer. Compared to NHW, NHB cases had the greatest proportion of Stage IV diagnoses (26.0%) and were more likely to die of CRC (multivariate HR = 1.12; 95% CI = 1.10-1.15). Instead, NUSB H/L patients were less likely to die of CRC (multivariate HR = 0.87; 95% CI = 0.85-0.89) whereas USB H/L did not differ from NHW. CONCLUSIONS: NHB and H/L cases have more adverse characteristics at diagnosis compared to NHW cases, with NHB cases being more likely to die from CRC. However, NUSB H/Ls cases showed better survival than NHW and US born H/L patients. These findings highlight the importance of considering nativity among H/L populations to understand cancer disparities.

A FEN 1-driven DNA walker-like reaction coupling with magnetic bead-based separation for specific SNP detection.

Single-nucleotide polymorphism (SNP) plays a key role in the carcinogenesis of the human genome, and understanding the intrinsic relationship between individual genetic variations and carcinogenesis lies heavily in the establishment of a precise and sensitive SNP detection platform. Given this, a powerful and reliable SNP detection platform is proposed by a flap endonuclease 1 (FEN 1)-driven DNA walker-like reaction coupling with a magnetic bead (MB)-based separation. A carboxyfluorescein (FAM)-labeled downstream probe (DP) was decorated on a streptavidin magnetic bead (SMB). The target DNA, as a walker strand, was captured by hybridization with DP and an upstream probe (UP) to form a three-base overlapping structure and execute the walking function on the surface of SMB. FEN 1 was employed to specifically recognize the three-base overlapping structure and cut the 5'flap at the SNP site to report the walking event and signal amplification. Considering the fact that the fluorescence was labeled on the cleavage and uncleavage sequences of DP and the target DNA-triggered walking event was undistinguishable from the mixtures, magnetic separation came in handy for cleavage probe (CP) isolation and discrimination of the amplified signal from the background signal. In comparison with the conventional DNA walker reaction, this strategy was coupling with SMB-based separation, thus promising a powerful and reliable method for SNP detection and signal amplification.