Distribution and typologies of anthropogenic seafloor litter in the Pearl River Estuary and adjacent coastal waters, China.

Marine litter pollution poses a significant threat to offshore ecosystems, eliciting widespread concern. We investigated seafloor litter patterns in the Pearl River Estuary and adjacent coastal waters of China in 2023 via bottom trawl survey. Average number and weight densities were found to be 154.34 ± 30.95 n/km2 and 2384.63 ± 923.98 g/km2, respectively. Plastic was the most abundant material by number density (79.07 %), and rubber the highest by weight density (22.93 %). Overall number density varied from 40.50 ± 22.50 to 221.13 ± 52.44 n/km2, with the highest in Daya Bay and the lowest in Guanghai Bay. Weight density varied from 189.93 ± 71.94 to 5386.70 ± 3050.30 g/km2, with the highest in Qiao Island and the lowest in Honghai Bay. The main source was plastic bags and wrappers. The Pearl River Delta and Daya Bay were identified as seafloor litter distribution hotspots. Controlling plastic waste input is crucial for reducing seafloor litter in the Pearl River Estuary.

Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Cdc42-driven endosomal cholesterol transport promotes collateral resistance in HER2-positive gastric cancer.

Resistance to trastuzumab and the poor efficacy of subsequent chemotherapy have become major challenges for HER2-positive gastric cancer (GC). As resistance evolves, tumor cells may acquire a new drug susceptibility profile, profoundly impacting the subsequent treatment selection and patient survival. However, the interplay between trastuzumab and other types of drugs in HER2-positive GC remains elusive. In our study, we utilized resistant cell lines and tissue specimens to map the drug susceptibility profile of trastuzumab-resistant GC, discovering that resistance to trastuzumab induces collateral resistance to commonly used chemotherapeutic agents. Additionally, patients with collateral resistance distinguished by a 13-gene scoring model in HER2-positive GC cohorts are predicted to have a poor prognosis and may be sensitive to cholesterol-lowering drugs. Mechanistically, endosomal cholesterol transport is further confirmed to enrich cholesterol in the plasma membrane, contributing to collateral resistance through the Hedgehog-ABCB1 axis. As a driver for cholesterol, Cdc42 is activated by the formation of the NPC1-TßRI-Cdc42 complex to facilitate endosomal cholesterol transport. We demonstrated that inhibiting Cdc42 activation with ZCL278 reduces cholesterol levels in the plasma membrane and reverses collateral resistance between trastuzumab and chemotherapy in vitro and in vivo. Collectively, our findings verify the phenomena and mechanism of collateral resistance between trastuzumab and chemotherapy, and propose a potential therapeutic target and strategy in the second-line treatment for trastuzumab-resistant HER2-positive GC.

Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer.

Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single-cell RNA sequencing. The expression of genes of interest was validated by bulk RNA-sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2-like signature and T cells were suppressed and reduced in number. Analysis of cell-cell crosstalk revealed that several signalling pathways involved in neutrophil to T-cell suppression including APP-CD74, MIF-(CD74+CXCR2), and MIF-(CD74+CD44) pathways were increased in HAGC. NETosis-associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.

Induction of filopodia formation by α-Actinin-2 via RelA with a feedforward activation loop promoting overt bone marrow metastasis of gastric cancer.

BACKGROUND: Bone marrow metastasis (BMM) is underestimated in gastric cancer (GC). GC with BMM frequently complicate critical hematological abnormalities like diffused intravascular coagulation and microangiopathic hemolytic anemia, which constitute a highly aggressive GC (HAGC) subtype. HAGC present a very poor prognosis with peculiar clinical and pathological features when compared with not otherwise specified advanced GC (NAGC). But the molecular mechanisms underlying BMM from GC remain rudimentary. METHODS: The transcriptomic difference between HAGC and NAGC were analyzed. Genes that were specifically upregulated in HAGC were identified, and their effect on cell migration and invasion was studied. The function of ACTN2 gene were confirmed by GC cell lines, bone-metastatic animal model and patients' tissues. Furthermore, the molecular mechanism of ACTN2 derived-BMM was explored by multiple immunofluorescence staining, western blot, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: We elucidated the key mechanisms of BMM depending on the transcriptomic difference between HAGC and NAGC. Five genes specifically upregulated in HAGC were assessed their effect on cell migration and invasion. The ACTN2 gene encoding protein α-Actinin-2 was detected enhanced the metastatic capability and induced BMM of GC cells in mouse models. Mechanically, α-Actinin-2 was involved in filopodia formation where it promoted the Actin filament cross-linking by replacing α-Actinin-1 to form α-Actinin-2:α-Actinin-4 complexes in GC cells. Moreover, NF-κB subunit RelA and α-Actinin-2 formed heterotrimers in the nuclei of GC cells. As a direct target of RelA:α-Actinin-2 heterotrimers, the ACTN2 gene was a positive auto-regulatory loop for α-Actinin-2 expression. CONCLUSIONS: We demonstrated a link between filopodia, BMM and ACTN2 activation, where a feedforward activation loop between ACTN2 and RelA is established via actin in response to distant metastasis. Given the novel filopodia formation function and the new mechanism of BMM in GC, we propose ACTN2 as a druggable molecular vulnerability that may provide potential therapeutic benefit against BMM of GC.

Catastrophic health expenditure of households with hypertension: a comparative study in China.

Objectives: The aim of this study was to understand the impact of multimorbidity on catastrophic health expenditures for people with hypertension. Methods: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) in 2018, 8,342 adults were included in our analysis. Propensity score matching method was used to compare the risk of catastrophic health expenditures between the hypertension patients (treatment group) and those without any chronic disease (control group) in middle-aged and older adults. Patients with hypertension were also divided into two groups: only hypertension and multimorbidity. Results: Hypertension increased the likelihood of CHE by 11.3% in older adults. Further analysis showed that hypertension alone does not increase the risk of CHE, and the risk of CHE in hypertension patients with multimorbidity was 12.9% higher than those without chronic disease. Conclusion: Our study highlights the importance of healthy management of patients with only hypertension and preventing them from developing multimorbidity.

Long-term impact of the COVID-19 pandemic on health services utilization in China: A nationwide longitudinal study.

Background: Long-term impact of the COVID-19 pandemic on health services utilization is unknown. We aim to assess the long-term effect of the COVID-19 pandemic on health services utilization in China. Methods: Between Jan 2017 and Dec 2021, we conducted a nationwide longitudinal study using routinely collected data on health services utilization in the National Health Information System of China. We extracted national and provincial data of demographic characteristics, socio-economic characteristics, and health resources. Interrupted time-series segmented negative binominal regression models were used. Results: A total of 34.2 billion health facilities visits and 1.1 billion inpatients discharged were included. The largest negative impact of COVID-19 pandemic on the health services utilization was during containment period, that health facility visits were observed 32% reduction in hospitals (adjusted incidence risk ratios [aRRs] 0.68, 95%CI: 0.50-0.92), 27% reduction in community health centers (aRR 0.73, 95%CI: 0.57-0.93), and 22% reduction township centers (aRR 0.78, 95%CI: 0.67-0.91), respectively. The impact on health facility visits and inpatients discharged were reduced and eliminated over time (all p>0.05). However, the negative impact on utilization rate of beds, average length of stay, average inpatient costs, and average outpatient costs in different level of health facilities still existed two years later (all p<0.05). Conclusions: The impact of the COVID-19 pandemic on health services utilization was largest during containment period and reduced over time, but it still existed two years later. There are disparities in the recovery of health services. Our findings highlighted the importance of maintaining primary healthcare services during the pandemic and strengthen resilient health system on the rapid recovery of medical services.

Whole-exome sequencing analysis identifies distinct mutational profile and novel prognostic biomarkers in primary gastrointestinal diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed. METHODS: We performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. RESULTS: A total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL. CONCLUSIONS: Our study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL.

The relationship between duration of subjective poverty and health among Chinese adults: Evidence from the China Family Panel Study.

Introduction: The disadvantaged socioeconomic status could have accumulated negative effects on individual. In the Chinese context, studying subjective and relative poverty is more important under the implementation of the Targeted Poverty Alleviation campaign. This study aims to provide evidence of the relationship between the duration of subjective poverty and both physical and mental health among Chinese adults, using nationally longitudinal data from 2010 to 2018. Materials and methods: Data were extracted from a nationally representative survey database-the China Family Panel Study (CFPS). The total sample size contains 12,003 adults, with 3,532 in the urban area and 8,471 in the rural area. Self-rated health and depressive symptoms were set as indicators of physical health and mental health, respectively. The duration of subjective poverty was measured by self-rated income level in the local area from 2010 to 2016. A series of ordinary least square regression was adopted to measure the relationship between duration of subjective poverty and health. Results: For the urban residents, the average duration of subjective poverty is 1.99 time points, while 1.98 time points for the rural residents. Net of objective poverty, duration of subjective poverty has a significantly negative association with individual's self-rated health in the rural sample (Coef. = -0.10, p < 0.001). Compared with those who have not experienced subjective poverty, the self-rated health score of people who experienced four time points is likely to decrease by 0.54 in the rural area and 0.30 in the urban area. In terms of mental health, 1 unit increase in the duration of subjective poverty is related to 0.15 unit increase in Center for Epidemiologic Studies Depression Scale-8 (CES-D8) scores in the urban sample and 0.46 in the rural sample. Compared with those who have not experienced subjective poverty, the CES-D8 scores of people who experienced four time points are likely to increase by 1.47 in the rural area and 0.95 in the urban area. Conclusion: A longer duration of subjective poverty has a cumulatively negative effect on Chinese residents' physical and mental health, especially in rural area. Our study advocates researchers and policymakers pay more attention to the cumulative effect of subjective poverty on health.

Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma.

Background: One of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation of NKTCL, we conducted a retrospective study on GI-NKTCL to analyze its clinical features, genomic changes and immune infiltration. Methods: We retrospectively collected patients diagnosed with GI-NKTCL in the Sixth Affiliated Hospital of Sun Yat-sen University from 2010 to 2020. From this cohort we obtained mutation data via whole exome sequencing. Results: Genomic analysis from 15 patients with GI-NKTCL showed that the most common driving mutations were ARID1B(14%, 2/15), ERBB3(14%, 2/15), POT1(14%, 2/15), and TP53(14%, 2/15). In addition, we found the most common gene mutation in patients with GI-NKTCL to be RETSAT(29%, 4/15) and SNRNP70(21%, 3/15), and the most common hallmark pathway mutations to be G2M checkpoint pathway (10/15, 66.7%), E2F targets (8/15, 53.3%), estrogen response late (7/15, 46.7%), estrogen response early (7/15, 46.7%), apoptosis (7/15, 46.7%) and TNFA signaling via NFKB (7/15, 46.7%). In the ICIs-Miao cohort, SNRNP7-wild-type (WT) melanoma patients had significantly prolonged overall survival (OS) time compared with SNRNP7 mutant type (MT) melanoma patients. In the TCGA-UCEC cohort, the patients with RETSAT-MT or SNRNP7-MT had significantly increased expression of immune checkpoint molecules and upregulation of inflammatory immune cells. Conclusions: In this study, we explored GI-NKTCL by means of genomic analysis, and identified the most common mutant genes (RETSAT and SNRNP70), pathway mutations (G2M checkpoint and E2F targets) in GI-NKTCL patients. Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL.

The Effect of Health Check-Ups on Health Among the Elderly in China: Evidence From 2011-2018 Longitudinal Data.

Objectives: To assess the effect of health check-ups on health among the elderly Chinese. Methods: The first dataset was panel data extracted from the 2011, 2014, and 2018 waves of the Chinese Longitudinal Health Longevity Survey (CLHLS). The second dataset was cross-sectional data come from CLHLS 2018 linked with the lagged term of health check-ups in CLHLS 2011. Health check-ups were measured by a binary variable annual health check-up (AHC). Health was assessed by a binary variable self-rated health (SRH). A coarsened exact matching method and individual fixed-effects models, as well as logistic regressions were employed. Results: AHC attendance among the elderly increased from 2011 to 2018, with higher utilization of AHC also detected in the rural group. AHC had positive effects on SRH among rural respondents (short-term effect: OR = 1.567, p < 0.05; long-term effect: OR = 3.385, p < 0.001). Conclusion: This study highlights a higher utilization of AHC in rural area, and the effectiveness of AHC in SRH improvement among rural participants. It indicates enhanced access to public healthcare services in rural area and underlying implications of health check-ups for reducing urban-rural health inequalities.

A Hybrid Imaging Platform(CT/PET/FMI) for Evaluating Tumor Necrosis and Apoptosis in Real-Time.

Multimodality imaging is an advanced imaging tool for monitoring tumor behavior and therapy in vivo. In this study, we have developed a novel hybrid tri-modality system that includes two molecular imaging methods: positron emission computed tomography (PET) and fluorescence molecular imaging (FMI) and the anatomic imaging modality X-ray computed tomography (CT). The following paper describes the system development. Also, its imaging performance was tested in vitro (phantom) and in vivo, in Balb/c nude mice bearing a head and neck tumor xenograft treated with novel gene therapy [a new approach to the delivery of recombinant bacterial gene (IL-24-expressing strain)]. Using the tri-modality imaging system, we simultaneously monitored the therapeutic effect, including the apoptotic and necrotic induction within the tumor in vivo. The apoptotic induction was examined in real-time using an 18F-ML-10 tracer; the cell death was detected using ICG. A CT was used to evaluate the anatomical situation. An increased tumor inhibition (including tumor growth and tumor cell apoptosis) was observed in the treatment group compared to the control groups, which further confirmed the therapeutic effect of a new IL-24-expressing strain gene therapy on the tumor in vivo. By being able to offer concurrent morphological and functional information, our system is able to characterize malignant tissues more accurately. Therefore, this new tri-modality system (PET/CT/FMI) is an effective imaging tool for simultaneously investigating and monitoring tumor progression and therapy outcomes in vivo.

Urban coral communities and water quality parameters along the coasts of Guangdong Province, China.

Coral communities in China's Great Bay Area (GBA) have experienced severe degradation, but only limited information is available about their community structure. We surveyed 20 sites across three regions (Daya Bay, Dapeng Bay, Wanshan Islands) in GBA to provide an updated baseline of these urban coral communities. Live coral cover varied substantially, with the lowest values (<2 %) found inside the highly urbanized Daya Bay, and highest values (40-47 %) from offshore islands that are less affected by human activities. The two sites with the lowest live coral cover had a high percentage of dead coral. Five groups of coral communities could be identified, with most of them characterized by dominance of massive and encrusting coral species. Both coral cover and generic richness were negatively correlated with dissolved inorganic nitrogen in the water column, indicating that nutrient pollution could potentially constrain the development of these urban coral communities.

Does social capital buffer or exacerbate mental health inequality? Evidence from the China Family Panel Study (CFPS).

BACKGROUND: Health inequality, including physical and mental health inequality, is an important issue. What role social capital plays in mental health inequality is still ambiguous, especially in developing countries. The aim of this study is to explore the relationship between social capital and mental health inequality in China. METHOD: Both family-level and community-/village-level social capitals are included in our analysis. Data is mainly extracted from the China Family Panel Studies in 2018, and lagged term of social capital in CFPS 2016 was used to link with other variables in 2018. Depressive symptoms and subjective well-being are set as indicators of mental health. A series of OLS regression models were conducted to estimate the effects of social capital on mental health and mental health inequality. RESULTS: Higher levels of social capital and income are related to a lower level of depressive symptoms and a higher level of subjective well-being. The positive coefficient of interaction term of family-level social capital and income level in the urban area indicates that the inhibiting effect of social capital on depressive symptoms is pro-poor. The negative coefficient of interaction term of village-level social capital and income level in the rural area suggests that the promoting effect of social capital on subjective well-being is pro-poor, too. CONCLUSION: The results show that severe mental health inequality exists in China; family-level social capital can buffer depressive symptom inequality, and village-level social capital can buffer SWB inequality. Although the amount of social capital of the poor is less than the rich, the poor can better use social capital to improve their mental health. Our study advocates enhancing social participation and communication for the poor to reduce mental health inequality.

The pharmacokinetics of tacrolimus in peripheral blood mononuclear cells and limited sampling strategy for estimation of exposure in renal transplant recipients.

PURPOSE: Intracellular exposure of tacrolimus (TAC) may be a better marker of therapeutic effect than whole blood exposure. We aimed to evaluate the influence of genetic polymorphism on the pharmacokinetics of TAC in peripheral blood mononuclear cells (PBMCs) and develop limited sampling strategy (LSS) models to estimate the area under the curve (AUC0-12h) in the PBMC of Chinese renal transplant patients. METHODS: Ten blood samples of each of the 23 renal transplant patients were collected 0-12h after 14 (10-18) days of TAC administration. PBMCs were separated and quantified. The TAC level in PBMCs was determined, and pharmacokinetic parameters were estimated by noncompartmental study. The AUC0-12h of TAC in whole blood was estimated by Bayesian approach based on a population pharmacokinetic model established in 65 renal transplant patients. The influence of CYP3A5 and ABCB1 genotypes on exposure was estimated. By applying multiple stepwise linear regression analysis, LSS equations for TAC AUC0-12h in the PMBC of renal transplant patients were established, and the bias and precision of various equations were identified and compared. RESULTS: We found a modest correlation between TAC exposure in whole blood and PBMC (r2 = 0.5260). Patients with the CYP3A5 6986GG genotype had a higher AUC0-12h in PBMCs than those with the 6986 AA or GA genotype (P = 0.026). Conversely, patients with the ABCB1 3435TT genotype had a higher AUC0-12h in PBMC than those with the 3435 CC and CT genotypes (P = 0.046). LSS models with 1-4 blood time points were established (r2 = 0.570-0.989). The best model for predicting TAC AUC0-12h was C2-C4-C6-C10 (r2 = 0.989). The model with C0.5-C6 (r2 = 0.849) can be used for outpatients who need monitoring to be performed in a short period. CONCLUSIONS: The CYP3A5 and ABCB1 genotypes impact TAC exposure in PBMCs, which may further alter the effects of TAC. The LSS model consisting of 2-4 time points is an effective approach for estimating full TAC AUC0-12h in Chinese renal transplant patients. This approach may provide convenience and the possibility for clinical monitoring of TAC intracellular exposure.

CircKIF4A enhances osteosarcoma proliferation and metastasis by sponging MiR-515-5p and upregulating SLC7A11.

BACKGROUND: Circular RNAs (circRNAs) are forms of non-coding RNAs that have crucial roles in regulation of various biological processes of several malignant tumors. circKIF4A is closely associated with malignant progression of a variety of cancers. However, the molecular mechanisms as well as roles of circKIF4A in osteosarcoma (OS) have not yet been clearly elucidated. METHODS: We evaluated the expression of circKIF4A in OS. Colony-formation, cell counting kit-8 (CCK-8), transwell and mice metastasis model assays were done to explore the roles of circKIF4A in vitro and in vivo. TargetScan database, double luciferase, quantitative reverse transcription polymerase chain reaction analysis (RT-qPCR), and RNA immunoprecipitation (RIP) were done to investigate the associated molecular mechanisms. RESULTS: In both OS cells and tissues, circKIF4A (hsa_circ_0007255) was found to be upregulated. In vitro and in vivo, circKIF4A knockdown markedly suppressed OS proliferation as well as metastasis. circKIF4A enhanced OS growth as well as metastasis by sponging miR-515-5p and by upregulating SLC7A11. CONCLUSIONS: We identified the biological significance of the circKIF4A-miR-515-5p-SLC7A11 axis in OS cell proliferation and metastasis, which is important in OS monitoring and treatment. More studies on circKIF4A will inform on the diagnostic markers for early OS screening.

circ0125803 facilitates tumor progression by sponging miR-197-5p and upregulating E2F1 in neuroblastoma.

BACKGROUND: Circular RNAs (circRNAs) are one type of RNAs with many different functions. circRNAs are very crucial in human malignancy progression. However, few studies have investigated the function and exact mechanism of circRNAs in neuroblastoma. In the current study, we investigated the biological function of circ0125803 in the proliferation and metastasis of neuroblastoma. METHODS: A high-throughput circRNA microarray sequencing was conducted to screen differentially expressed circRNAs and in neuroblastoma. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of circRNA and miRNA. RNA immunoprecipitation and dual luciferase reporter experiments were both conducted to investigate the molecular interaction mechanism of circ0125803 in neuroblastoma. RESULTS: We identified hsa_circ_0125803 (circ0125803) as an extremely upregulated circRNA in neuroblastoma samples. Knockdown of circ0125803 significantly decreased the growth rate and invasion rate in neuroblastoma. Our data demonstrated upregulation of circ0125803 promotes the neuroblastoma progression by blocking miR-197-5p and upregulating E2F1 expression. CONCLUSION: This study uncovered the biological function of the circ0125803-miR-197-5p-E2F1 axis in neuroblastoma metastasis and growth.

Optimization of Data Acquisition Link of University Students' Physical Health Testing System.

University students' physical health test is an important part of university physical education. The data obtained by the physical health test play an extremely important role in the field of students' physical health research. This paper clarifies the current situation of data collection of the physical health test for college students by sorting out the development status and trend of the physical health test system in China. To further ensure the accuracy and validity of the physical health test data, this article puts forward the corresponding optimization measures for the data collection link of the existing physical health testing system given the problems existing in the implementation of university students' physical health tests. Optimization measures are as follows: (1) add a test data collection type for test video collection; (2) optimize the authentication process to increase face recognition; and (3) enhance posttest test data management by stamping time.