The association between systemic immune-inflammation index and cardiotoxicity related to 5-Fluorouracil in colorectal cancer.

BACKGROUND AND AIMS: The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. METHODS: The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. RESULTS: Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 109/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). CONCLUSION: Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.

Cas9-Based Local Enrichment and Genomics Sequence Revision of Megabase-Sized Shark IgNAR Loci.

The 0.8-Mb Ig new Ag receptor (IgNAR) region of the whitespotted bamboo shark (Chiloscyllium plagiosum) is incompletely assembled in Chr_44 of the reference genome. Here we used Cas9-assisted targeting of chromosome segments (CATCH) to enrich the 2 Mb region of the Chr_44 IgNAR loci and sequenced it by PacBio and next-generation sequencing. A fragment >3.13 Mb was isolated intact from the RBCs of sharks. The target was enriched 245.531-fold, and sequences had up to 94% coverage with a 255× mean depth. Compared with the previously published sequences, 20 holes were filled, with a total length of 3508 bp. In addition, we report five potential germline V alleles of IgNAR1 from six sharks that may belong to two clusters of the IgNAR. Our results provide a new method to research the germline of large Ig gene segments, as well as provide the enhanced bamboo shark IgNAR gene loci with fewer gaps.

Effect of cefuroxime intracameral injection antibiotic prophylactic on postoperative endophthalmitis wound post-cataract: A meta-analysis.

To assess the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract, we conducted a meta-analysis. A thorough review of the literature up to July 2022 revealed that there were 1 167 197 participants with surgery of cataract at the start of the research; 1 004 425 of these subjects received an injection of intracameral of cefuroxime, while 162 772 did not get an antibiotic as a control. Using dichotomous approaches and a random or fixed-effect model, odds ratios (OR) with 95% confidence intervals (CIs) were estimated to evaluate the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract. When comparing no antibiotic in participants who had surgery of cataract, the cefuroxime injection of intracameral significantly reduced the after endophthalmitis operative wound (OR, 0.14; 95% CI, 0.07-0.29, P = 0.001) with high heterogeneity (I2 = 95%). When comparing participants who received no antibiotic after surgery of cataract, the after endophthalmitis operative wound from the cefuroxime injection of intracameral was considerably lower. Although none of the 22 studies encompassed in the meta-analysis had a study with a small sample size, it is nevertheless advisable to proceed with caution when analysing the results.

Everolimus Reverses Palbociclib Resistance in ER+ Human Breast Cancer Cells by Inhibiting Phosphatidylinositol 3-Kinase(PI3K)/Akt/Mammalian Target of Rapamycin (mTOR) Pathway.

BACKGROUND Palbociclib, a specific inhibitor of CDK4/6, has been shown to provide a survival benefit in hormone receptor-positive advanced breast cancer; however, its resistance and related mechanisms are unclear. MATERIAL AND METHODS In this study, we constructed palbociclib-resistant hormone receptor-positive breast cancer cells (MCF-7-P) via culturing with palbociclib for at least 6 months. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of stemness markers in MCF-7-P and MCF-7 cells. Additionally, cell spheroid formation, Transwell migration, ALDH1 activity, and flow cytometry assays were performed to detect stemness and migration ability of MCF-7-P cells, and the effects of everolimus on MCF-7-P cells stemness and migration ability. Growth inhibition assay was used to examine the effect of everolimus on the sensitivity of palbociclib in MCF-7-P and MCF-7 cells. RESULTS MCF-7-P cells had stronger stemness and higher expression of ABCG2 and MDR1. Moreover, PI3K/Akt/mTOR signaling was hyper-activated in MCF-7-P cells. Additionally, everolimus, which is a mTOR inhibitor, attenuated MCF-7-P cells stemness and re-sensitized MCF-7-P cells to palbociclib. Importantly, everolimus enhanced the antitumor effect of palbociclib in palbociclib-sensitive hormone receptor-positive cells (MCF-7 cells). CONCLUSIONS These findings provide a rationale for future clinical trials of palbociclib and everolimus combination-based therapy in hormone receptor-positive breast cancer.

The value of manure - Manure as co-product in life cycle assessment.

Livestock production is important for food security, nutrition, and landscape maintenance, but it is associated with several environmental impacts. To assess the risk and benefits arising from livestock production, transparent and robust indicators are required, such as those offered by life cycle assessment. A central question in such approaches is how environmental burden is allocated to livestock products and to manure that is re-used for agricultural production. To incentivize sustainable use of manure, it should be considered as a co-product as long as it is not disposed of, or wasted, or applied in excess of crop nutrient needs, in which case it should be treated as a waste. This paper proposes a theoretical approach to define nutrient requirements based on nutrient response curves to economic and physical optima and a pragmatic approach based on crop nutrient yield adjusted for nutrient losses to atmosphere and water. Allocation of environmental burden to manure and other livestock products is then based on the nutrient value from manure for crop production using the price of fertilizer nutrients. We illustrate and discuss the proposed method with two case studies.

RNA methylation, homologous recombination repair and therapeutic resistance.

Homologous recombination (HR) repair of DNA double-strand breaks (DSBs) is critical for maintaining genomic integrity and stability. Defects in HR increase the risk of tumorigenesis. However, many human tumors exhibit enhanced HR repair capabilities, consequently endowing tumor cells with resistance to DNA-damaging chemotherapy and radiotherapy. This review summarizes the role of RNA methylation in HR repair and therapeutic resistance in human tumors. We also analyzed the interactions between RNA methylation and other HR-modulating modifications including histone acetylation, histone deacetylation, ubiquitination, deubiquitination, protein arginine methylation, and gene transcription. This review proposes that targeting RNA methylation is a promising approach to overcoming HR-mediated therapeutic resistance.

Risk factors for fluoropyrimidine-induced cardiotoxicity in colorectal cancer: A retrospective cohort study and establishment of a prediction nomogram for 5-FU induced cardiotoxicity.

Background: Fluoropyrimidine is an important component of systemic chemotherapy for colorectal cancer (CRC). Fluoropyrimidine-induced cardiotoxicity (FIC) may result in delay and discontinuation of chemotherapy and, in severe cases, can even be life-threatening. To date, risk factors for FIC have not been well identified. This cohort study aimed to identify the predictors of FIC in CRC patients and develop a risk prediction nomogram model. Methods: Between January 1, 2018 and December 31, 2020, colorectal cancer patients who received 5-fluoropyrimidine(5-Fu)/capecitabine-based chemotherapy in Affiliated Cancer Hospital of Guizhou Medical University were included. FIC was defined as an adverse cardiovascular event related to fluoropyrimidine that occurred during or within four weeks of completing chemotherapy. Risk factors were determined by LASSO algorithm and multivariate logistic regression analysis. Nomogram for predicting 5-Fu-induced cardiotoxicity was established and internally validated. The concordance index (C-index) and calibration curve were used to evaluate the nomogram's discrimination and accuracy. Results: A total of 916 patients were included for analysis, and 200 [21.8%,95% confidence interval (CI):19.12%-24.47%] experienced FIC. LASSO algorithm and multivariate logistic regression analysis determined that chemotherapy ≤3 cycles (OR=4.694, 95%CI=3.184-6.92), age≥ 60 (OR=1.678, 95%CI=1.143-2.464), BMI>22.97 (OR=1.77, 95%CI=1.202-2.606), and simultaneous use of bevacizumab (OR=2.922, 95%CI=1.835-4.653) were significant risk factors, and were included in the prediction model for 5-Fu induced cardiotoxicity. The C-index (95%CI) was 0.751 (0.706-0.795) by internal validation. For patients treated with capecitabine-based regimen, the incidence of FIC increased with the absolute value of neutrophils (OR=5.177, 95%CI=1.684-15.549) and eosinophils (OR=3.377,95% CI=1.237-9.22). Conclusions: Our study identified risk factors for FIC and established a prediction nomogram model based on chemotherapy cycle, age, BMI and use of target therapy for 5-FU induced Cardiotoxicity. The discriminative prediction model can be used for patient counselling and risk-stratification before undergoing chemotherapy in colorectal cancer.

Diversity Analysis of Tick-Borne Viruses from Hedgehogs and Hares in Qingdao, China.

Tick-borne viruses (TBVs) have attracted increasingly global public health attention. In this study, the viral compositions of five tick species, Haemaphysalis flava, Rhipicephalus sanguineus, Dermacentor sinicus, Haemaphysalis longicornis, and Haemaphysalis campanulata, from hedgehogs and hares in Qingdao, China, were profiled via metagenomic sequencing. Thirty-six strains of 10 RNA viruses belonging to 4 viral families, including 3 viruses of Iflaviridae, 4 viruses of Phenuiviridae, 2 viruses of Nairoviridae, and 1 virus of Chuviridae, were identified in five tick species. Three novel viruses of two families, namely, Qingdao tick iflavirus (QDTIFV) of the family of Iflaviridae and Qingdao tick phlebovirus (QDTPV) and Qingdao tick uukuvirus (QDTUV) of the family of Phenuiviridae, were found in this study. This study shows that ticks from hares and hedgehogs in Qingdao harbored diverse viruses, including some that can cause emerging infectious diseases, such as Dabie bandavirus. Phylogenetic analysis revealed that these tick-borne viruses were genetically related to viral strains isolated previously in Japan. These findings shed new light on the cross-sea transmission of tick-borne viruses between China and Japan. IMPORTANCE Thirty-six strains of 10 RNA viruses belonging to 4 viral families, including 3 viruses of Iflaviridae, 4 viruses of Phenuiviridae, 2 viruses of Nairoviridae, and 1 virus of Chuviridae, were identified from five tick species in Qingdao, China. A diversity of tick-borne viruses from hares and hedgehogs in Qingdao was found in this study. Phylogenetic analysis showed that most of these TBVs were genetically related to Japanese strains. These findings indicate the possibility of the cross-sea transmission of TBVs between China and Japan.

Molecular epidemiology and clinical characteristics of respiratory syncytial virus in hospitalized children during winter 2021-2022 in Bengbu, China.

Objective: This study aimed to study the molecular epidemiology and clinical characteristics of respiratory syncytial virus (RSV) infection from hospitalized children with ARTI in Bengbu. Methods: One hundred twenty-four nasopharyngeal swab specimens and clinical data from children with ARTI cases were collected in Bengbu, China, during winter 2021-2022. The samples were detected by qPCR of 13 respiratory viruses. Phylogenetic analysis was constructed using MEGA 7.0. All analyses were performed using SAS software, version 9.4. Results: In winter 2021-2022, URTI, NSCAP, SCAP, and bronchiolitis accounted for 41.03%, 27.35%, 17.09%, and 14.53% of hospitalized children in Bengbu, China. The detection rates of the top three were RSV (41.94%), ADV (5.65%), and FluB (5.65%) in hospitalized children through 13 virus detection. RSV is the main pathogen of hospitalized children under 2 years old. Forty-eight sequences of G protein of RSV were obtained through PCR amplification, including RSV-A 37 strains and RSV-B 11 strains. Phylogenetic analysis showed that all RSV-A and RSV-B were ON1 and BA9 genotypes, respectively. ON1 genotypes were further divided into two clades. The majority of ON1 strains formed a unique genetic clade with T113I, V131D, N178 G, and H258Q mutations. Furthermore, RSV infection was an independent risk factor for ventilator use (OR = 9.55, 95% CI 1.87-48.64). Conclusion: There was a high incidence of RSV among hospitalized children during winter 2021-2022 in Bengbu with ON1 and BA9 being the dominant strains. This study demonstrated the molecular epidemiological characteristics of RSV in children with respiratory infections in Bengbu, China.

Understanding the motivational mechanisms behind the usage frequency of ride-hailing during COVID-19 pandemic.

Introduction: This study aimed to explore the factors influencing people's utilization of ride-hailing services, particularly in the context of the COVID-19 pandemic. Methods: A two-stage survey was conducted among the same group of passengers pre and post COVID-19 pandemic, resulting in a total of 670 valid samples. Exploratory factor analysis (EFA) was applied to the data, followed by the ordered probit and ordered logit models to identify the motivational factors behind passengers' frequency of using ride-hailing. Results: The findings indicated that trust and loyalty were the most influential factors in determining passengers' frequency of using ride-hailing services. However, passengers' perception of the COVID-19 pandemic did not have a significant effect on the frequency of using ride-hailing. Discussion: This research provides empirical evidence and policy implications for understanding people's usage of the ride-hailing services in the context of public-health emergency.

Measuring the effects of mind wandering in people with insomnia: A driving simulator study.

Purpose: Studies have shown that individuals with insomnia experience more frequent and longer episodes of mind wandering (MW) while driving. However, the effect of the interaction between insomnia and MW on driving behavior is not fully understood. This study aimed to gain deeper insights into the relationships among insomnia, MW, and driving behavior. Patients and methods: Forty-two participants (21 diagnosed with insomnia and 21 controls) were recruited, and subjective sleep quality and cognitive function were assessed. A driving simulator experiment with a within-subject design was performed, involving two distraction tasks (no-distraction task versus MW task) and two driving scenarios (lane-keeping versus lane-changing). Results: In the lane-keeping scenario, there was no significant between-group difference (people with insomnia and controls) in longitudinal driving performance for the no-distraction task, although the interaction between MW and insomnia significantly increased drivers' longitudinal control variation. Correlation analysis confirmed that longitudinal driving performance was positively correlated with sleep quality and the cognitive level. Unlike longitudinal driving performance, lateral driving performance was significantly weaker in people with insomnia than in controls under both distraction tasks. In the lane-changing scenario, although there was no between-group difference in driving performance, the MW task led to significant changes in driving performance within each group compared with the no-distraction task, and these findings were associated with cognitive function, but not with sleep quality. Conclusion: These findings show that insomnia and MW combined can lead to reduced driving performance. Further research is needed to elucidate the factors that influence this phenomenon.

Fatigue performance in patients with chronic insomnia.

Insomnia is associated with fatigue and poor driving performance, thus increasing the risk of traffic accidents. This study aimed to evaluate the effect of fatigue on driving in patients with chronic insomnia in a free-flow traffic scenario and car-following scenario, and to investigate the relationships between driving performance, cognitive function, and insomnia. The Trail Making Test (TMT), Stroop Color and Word Test (SCWT), Symbol Digit Modalities Test (SDMT), and Digit Span Test (DST) of 15 participants with mild-to-moderate chronic insomnia and 16 healthy participants were assessed. During the fatigue driving task, drivers completed simulated driving tasks under free-flow traffic and car-following scenarios. The mean speed (MS), mean acceleration (MA), mean lateral position (MLP), and standard deviation of lateral position (SDLP) were measured to assess driving performance. During fatigued tasks, the MA and MLP in the free-driving scenario were higher than those in the car-following scenario (P < 0.01), the SDLP was higher in the insomnia group than in the healthy group (P = 0.02), and the interaction effect was significantly different for MLP between the groups (P = 0.03). MS was negatively correlated with TMT score, SDMT score, and DST score, and positively correlated with time to complete TMT, errors in SCWT, and time to complete SCWT. SDLP was negatively correlated with DST score and positively correlated with time to complete SCWT. Furthermore, the insomnia group had poorer lateral vehicle control ability than the healthy group. The insomnia group had a more impaired driving performance in the free-driving scenario than in the car-following scenario. Drivers with impaired cognitive function exhibited impaired driving performance.

Bamboo Shark as a Small Animal Model for Single Domain Antibody Production.

The development of shark single domain antibodies (sdAbs) is hindered by the high cost and tediousness of large-sized shark farming. Here, we demonstrated white-spotted bamboo sharks (Chiloscyllium plagiosum) being cultivated commercially as a promising small animal model to produce sdAbs. We found that immunoglobulin new antigen receptor (IgNAR) presented in bamboo shark genome, transcriptome, and plasma. Four complete IgNAR clusters including variable domains (vNARs) were discovered in the germline, and the Variable-Joining pair from IgNAR1 cluster was dominant from immune repertoires in blood. Bamboo sharks developed effective immune responses upon green fluorescent protein (GFP), near-infrared fluorescent protein iRFP713, and Freund's adjuvant immunization revealed by elevated lymphocyte counts and antigen specific IgNAR. Before and after immunization, the complementarity determining region 3 (CDR3) of IgNAR were the major determinant of IgNAR diversity revealed by 400-bp deep sequencing. To prove that bamboo sharks could produce high-affinity IgNAR, we isolated anti-GFP and anti-iRFP713 vNARs with up to 0.3 and 3.8 nM affinities, respectively, from immunized sharks. Moreover, we constructed biparatopic vNARs with the highest known affinities (20.7 pM) to GFP and validated the functions of anti-GFP vNARs as intrabodies in mammalian cells. Taken together, our study will accelerate the discovery and development of bamboo shark sdAbs for biomedical industry at low cost and easy operation.

The effectiveness and influencing factors of a penalty point system in China from the perspective of risky driving behaviors.

Many countries have adopted penalty point systems (PPS) to deter drivers from breaking traffic laws. To investigate the effectiveness of PPS on reducing illegal driving behavior, this study analyzed traffic violation data of a Chinese city in 2017. This analysis revealed that 1) risky driving behaviors (RDBs) are among the main causes of traffic violations and 2) almost half of the offenders with multiple violations committed the same traffic rule violations more than once. To further explain these phenomena, a survey in another Chinese city-Tianjin-was conducted. Considering the fact that most types of RDBs will, if detected by the authorities, result in traffic violations, the present study investigated the influence of a PPS, represented by penalty experience (PE), on traffic violation behaviors from the perspective of RDBs. Moreover, the impact of cognitive processes on driving behaviors via self-efficacy was considered. We found that drivers' PE is positively associated with their RDBs and that offenders with more PE are more inclined to commit RDBs; we further observed that self-efficacy partially mediates the relationship between PE and RDBs. However, no gender difference in the effect of PE on RDBs was discovered, thus indicating that PE has the same effect on male and female drivers. Based on these findings, some strategies are suggested (such as the Increasing Block Penalty Points Policy) to improve the effectiveness of the PPS.

Efficacy and Mechanism of Cinnamon Essential Oil on Inhibition of Colletotrichum acutatum Isolated From 'Hongyang' Kiwifruit.

In this study, one of the dominant pathogens, which caused postharvest diseases such as anthracnose, was isolated from decayed 'Hongyang' kiwifruit. It was identified as Colletotrichum acutatum by its morphological characteristics and standard internal transcribed spacer ribosomal DNA sequence. Further, the efficacy and possible mechanism of cinnamon essential oil on inhibition of C. acutatum were investigated. Results showed that C. acutatum was dose-dependently inhibited by cinnamon essential oil. Meanwhile, the mycelial growth and spore germination of C. acutatum were completely inhibited at the concentrations of 0.200 µL/mL and 0.175 µL/mL (v/v), respectively. Indeed, both minimal inhibitory and minimum fungicidal concentrations of cinnamon essential oil were measured as 0.200 µL/mL. Additionally, the possible antifungal mechanism of cinnamon essential oil on C. acutatum was demonstrated. Results showed that the cinnamon essential oil could destroy the cell membrane integrity of C. acutatum, and the structure of cell membrane was changed. Indeed, the cell cytoplasm including soluble protein, sugar, and nucleic acid was released, which significantly changed the extracellular conductivity. Results suggested that the cinnamon essential oil exerted great potential to be used as a natural and efficient preservative for kiwifruit postharvest storage, which were helpful for the better understanding of the efficacy and mechanism of cinnamon essential oil on inhibition of pathogens isolated from decayed 'Hongyang' kiwifruit.

Structural organization of hepatic portal vein in rat with special reference to musculature, intimal folds, and endothelial cell alignment.

Structural organization of hepatic portal vein (HPV) was examined in adult rats by means of light and electron microscopy. Three characteristic features were found in the wall structure of rat HPV. (1) Tunica media consisted of two kinds of smooth muscle. The inner circular smooth muscle (CSM) was composed with one or two layer of smooth muscle cells, and was found in the entire length of the HPV and its tributaries. The outer longitudinal smooth muscle (LSM) was limited to a specific region of HPV; in particular it was well-developed at distal half of HPV. CSM counteracts luminal hydrostatic pressure to prevent circumferential hyperextension of venous wall, whereas LSM is likely to counteract a tractive force produced by gravity and movement of small intestine. (2) Intima of HPV showed a unique feature, intimal folds, which protruded into the lumen and were aligned almost circumferentially. Intimal folds were found only at the same region where the LSM was well-developed. Thus, LSM is presumably involved in the formation of intimal folds. (3) The endothelial cells between intimal folds were circumferentially aligned along the folds, although those in the other regions of HPV were arrayed along the longitudinal axis of HPV or the direction of blood flow as reported in other kinds of blood vessel. This finding implied that the circumferential blood flow locally occurs on the surface of intima between the intimal folds.

[Study on transplantation of marrow stromal stem cells into acellular extra cellular matrix in mice [corrected]].

OBJECTIVE: To study the integration of mice [corrected] marrow stromal stem cells (MSCs) after transplantation into acellular extracellular matrix (AECM). METHODS: We got 16 femurs from 8 Kunming mice [corrected], the femurs were treated by Triton X-100 to get AECM, MSCs were collected from femoral marrow of 20 Kunming rats about a mouth old by PBS 4 ml, centrifuged and primary cultured in bottles, then the mice [corrected] MSCs were transplanted into AECM at a concentration of 5 x 10(6)/ml and cultured for 7 days. The integration of the donor cells was observed using one phase contrast microscope, a light microscope and a scanning electron microscope (SEM). RESULTS: In AECM bone lacunas there were MSCs nuclei stained blue. The nuclei were unevenly distributed in AECM with more in the peripheral AECM than in the central AECM and with more in the layer near culture medium than in the layer far away from culture medium. AECM possessed a good spatial scaffold structure, the marrow stromal stem cells were well integrated into AECM. CONCLUSION: AECM can be used as a good scaffold material for tissue engineered bone construction.