A binary pulsar in a 53-minute orbit.

Spider pulsars are neutron stars that have a companion star in a close orbit. The companion star sheds material to the neutron star, spinning it up to millisecond rotation periods, while the orbit shortens to hours. The companion is eventually ablated and destroyed by the pulsar wind and radiation1,2. Spider pulsars are key for studying the evolutionary link between accreting X-ray pulsars and isolated millisecond pulsars, pulsar irradiation effects and the birth of massive neutron stars3-6. Black widow pulsars in extremely compact orbits (as short as 62 minutes7) have companions with masses much smaller than 0.1 M⊙. They may have evolved from redback pulsars with companion masses of about 0.1-0.4 M⊙ and orbital periods of less than 1 day8. If this is true, then there should be a population of millisecond pulsars with moderate-mass companions and very short orbital periods9, but, hitherto, no such system was known. Here we report radio observations of the binary millisecond pulsar PSR J1953+1844 (M71E) that show it to have an orbital period of 53.3 minutes and a companion with a mass of around 0.07 M⊙. It is a faint X-ray source and located 2.5 arcminutes from the centre of the globular cluster M71.

Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma.

BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.

Simple color appearance model (sCAM) based on simple uniform color space (sUCS).

A new color appearance model named sCAM has been developed, including a uniform color space, sUCS. The model has a simple structure but provides comprehensive functions for color related applications. It takes input from either XYZ D65 or signals from an RGB space. Their accuracy has been extensively tested. sUCS performed the best or second-best to the overall 28 datasets for space uniformity and the 6 datasets for hue linearity comparing the state of the art UCSs. sCAM also performed the best to fit all available one- and two-dimensional color appearance datasets. It is recommended to have field tests for all color related applications.

Evidence for Chiral Wobbler in Nuclei.

Three ΔI=1 bands with the πg_{9/2}⊗νg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.

High-throughput combination assay for studying biofilm formation of uropathogenic Escherichia coli.

Uropathogenic Escherichia coli, the most common cause for urinary tract infections, forms biofilm enhancing its antibiotic resistance. To assess the effects of compounds on biofilm formation of uropathogenic Escherichia coli UMN026 strain, a high-throughput combination assay using resazurin followed by crystal violet staining was optimized for 384-well microplate. Optimized assay parameters included, for example, resazurin and crystal violet concentrations, and incubation time for readouts. For the assay validation, quality parameters Z' factor, coefficient of variation, signal-to-noise, and signal-to-background were calculated. Microplate uniformity, signal variability, edge well effects, and fold shift were also assessed. Finally, a screening with known antibacterial compounds was conducted to evaluate the assay performance. The best conditions found were achieved by using 12 µg/mL resazurin for 150 min and 0.023% crystal violet. This assay was able to detect compounds displaying antibiofilm activity against UMN026 strain at sub-inhibitory concentrations, in terms of metabolic activity and/or biomass.

The application of quantitative perfusion analysis of golden-angle radial sparse parallel MRI and R2∗ value for predicting pathological prognostic factors in rectal cancer.

AIM: To investigate the diagnostic value of golden-angle radial sparse parallel magnetic resonance imaging (MRI) (GRASP) and R2∗ in predicting the prognostic factors of resectable rectal cancer. MATERIALS AND METHODS: A total of 108 patients with rectal adenocarcinoma were included in this retrospective study. The volume transfer constant (Ktrans), rate constant (Kep), plasma volume fraction (Ve), and R2∗ were obtained. Univariate and multivariate logistic regression were conducted. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the imaging parameters. RESULTS: The Ktrans was found to be significantly higher in rectal cancers with positive lymph node metastasis (LNM), higher tumour grade, positive lymphovascular invasion (LVI), and higher ki-67 (all p<0.05). The Kep was also significantly higher in the LNM-positive group (p<0.001), while the R2∗ was higher in rectal cancers with LNM-positive, higher tumour grade, LVI-positive, and higher ki-67 (all p<0.05). Combining the Ktrans and R2∗ provided the highest area under the ROC curve (AUC) for LNM-positive and higher ki-67 tumours differentiation (0.790 and 0.823, respectively). DISCUSSION: Combining quantitative parameters of the Ktrans and R2∗ could be used to non-invasively predict pathological prognostic factors preoperatively.

Intravoxel incoherent motion diffusion-weighted imaging of solitary pulmonary lesions: initial study with gradient- and spin-echo sequences.

AIM: To evaluate the feasibility and image quality of intravoxel incoherent motion diffusion-weighted imaging (IVIM) using gradient- and spin-echo (GRASE) in solitary pulmonary lesions (SPLs) compared to echo planar imaging (EPI) and turbo spin-echo (TSE) at 3 T. MATERIALS AND METHODS: Forty-two patients with SPLs underwent lung magnetic resonance imaging (MRI) using TSE-IVIM, GRASE-IVIM, and EPI-IVIM at 3 T. Signal ratio (SR), contrast ratio (CR), and image distortion ratio (DR) of three sequences were compared. The reproducibility and repeatability of the apparent diffusion coefficient (ADC) and IVIM-derived parameters were assessed using the interclass correlation coefficient (ICC) and coefficient of variation (CV). The repeatability of the ADC and IVIM-derived parameters between all sequences was evaluated using the Bland-Altman method. RESULTS: EPI-IVIM had a higher SR, lower CR, and higher DR (p<0.05); however, there was no significant difference between TSE-IVIM and GRASE-IVIM (p>0.05). Compared to the D and f values of TSE-IVIM (ICC lower limit >0.90), GRASE-IVIM and EPI-IVIM showed poor reproducibility (ICC lower limit<0.90). The repeatability of the ADC and D values obtained by TSE-IVIM (CV, 1.93-2.96% and 2.44-3.18%, respectively) and GRASE-IVIM (CV, 2.56-3.12% and 3.21-3.51%, respectively) were superior to those of EPI-IVIM (CV, 10.03-10.2% and 11.30-11.57%). The repeatability of D∗ and f values for all sequences was poor. Bland-Altman analysis showed wide limits of agreement between the ADC and IVIM-derived parameters for all sequences. CONCLUSION: GRASE-IVIM reduced the DR, improved the stability of the ADC and D values on repeated scans, and had the shortest scanning time.

Convolutional neural network for identifying common bile duct stones based on magnetic resonance cholangiopancreatography.

AIMS: To develop an auto-categorization system based on machine learning for three-dimensional magnetic resonance cholangiopancreatography (3D MRCP) to detect choledocholithiasis from healthy and symptomatic individuals. MATERIALS AND METHODS: 3D MRCP sequences from 254 cases with common bile duct (CBD) stones and 251 cases with normal CBD were enrolled to train the 3D Convolutional Neural Network (3D-CNN) model. Then 184 patients from three different hospitals (91 with positive CBD stone and 93 with normal CBD) were prospectively included to test the performance of 3D-CNN. RESULTS: With a cutoff value of 0.2754, 3D-CNN achieved the sensitivity, specificity, and accuracy of 94.51%, 92.47%, and 93.48%, respectively. In the receiver operating characteristic curve analysis, the area under the curve (AUC) for the presence or absence of CBD stones was 0.974 (95% CI, 0.940-0.992). There was no significant difference in sensitivity, specificity, and accuracy between 3D-CNN and radiologists. In addition, the performance of 3D-CNN was also evaluated in the internal test set and the external test set, respectively. The internal test set yielded an accuracy of 94.74% and AUC of 0.974 (95% CI, 0.919-0.996), and the external test set yielded an accuracy of 92.13% and AUC of 0.970 (95% CI, 0.911-0.995). CONCLUSIONS: An artificial intelligence-assisted diagnostic system for CBD stones was constructed using 3D-CNN model for 3D MRCP images. The performance of 3D-CNN model was comparable to that of radiologists in diagnosing CBD stones. 3D-CNN model maintained high performance when applied to data from other hospitals.

Distinguishment between high-grade gliomas and solitary brain metastases in peritumoural oedema: quantitative analysis using synthetic MRI at 3 T.

AIM: To investigate the efficacy of synthetic magnetic resonance imaging (MRI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs) in peritumoural oedema. MATERIALS AND METHODS: Thirty-five patients with HGGs and 25 patients with SBMs were recruited and scanned using synthetic MRI using a 3 T scanner. Two radiologists measured synthetic MRI-derived relaxation values independently (T1, T2, proton density [PD]) in the peritumoural oedema, which was used to generate quantitative metrics before (T1native, T2native, and PDnative) and after (T1post, T2post, and PDpost) contrast agent injection. Student's t-test or the Mann-Whitney U-test was performed to detect statistically significant differences in the aforementioned metrics in peritumoural oedema between HGGs and SBMs. The receiver operating characteristic (ROC) curves were plotted to evaluate the efficacy of each metric in distinguishing the two groups, and the areas under the curves (AUCs) were compared pairwise by performing the Delong test. RESULTS: The mean T1native, T2native, and T1post values in the peritumoural oedema of HGGs were significantly lower compared with SBMs (all p<0.05). The T1post value had a higher AUC (0.843) in differentiating HGGs and SBMs than all other individual metrics (all p<0.05). The combined T1native, T2native, and T1post model had the best distinguishing performance with an AUC, sensitivity, and specificity of 0.987, 94.3%, and 100%, respectively. CONCLUSIONS: Synthetic MRI may be a potential supplement to the preoperative diagnosis of HGGs and SBMs in clinical practice, as the synthetic MRI-derived tri-parametric model in the peritumoural oedema showed significantly improved diagnostic performance in distinguishing HGGs from SBMs.

Genotype-phenotype relationship and comparison between eastern and western patients with osteogenesis imperfecta.

PURPOSE: To evaluate the genotypic and phenotypic relationship in a large cohort of OI patients and to compare the differences between eastern and western OI cohorts. METHODS: A total of 671 OI patients were included. Pathogenic mutations were identified, phenotypic information was collected, and relationships between genotypes and phenotypes were analyzed. Literature about western OI cohorts was searched, and differences were compared between eastern and western OI cohorts. RESULTS: A total of 560 OI patients were identified as carrying OI pathogenic mutations, and the positive detection rate of disease-causing gene mutations was 83.5%. Mutations in 15 OI candidate genes were identified, with COL1A1 (n = 308, 55%) and COL1A2 (n = 164, 29%) being the most common mutations, and SERPINF1 and WNT1 being the most common biallelic variants. Of the 414 probands, 48.8, 16.9, 29.2 and 5.1% had OI types I, III, IV and V, respectively. Peripheral fracture was the most common phenotype (96.6%), and femurs (34.7%) were most commonly affected. Vertebral compression fracture was observed in 43.5% of OI patients. Biallelic or COL1A2 mutation led to more bone deformities and poorer mobility than COL1A1 mutation (all P < 0.05). Glycine substitution of COL1A1 or COL1A2 or biallelic variants led to more severe phenotypes than haploinsufficiency of collagen type I α chains, which induced the mildest phenotypes. Although the gene mutation spectrum varied among countries, the fracture incidence was similar between eastern and western OI cohorts. CONCLUSION: The findings are valuable for accurate diagnosis and treatment of OI, mechanism exploration and prognosis judgment. Genetic profiles of OI may vary among races, but the mechanism needs to be explored.

Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma.

PURPOSE: Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL). METHODS: A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and ß-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. RESULTS: PPGL patients had a higher level of ß-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent. CONCLUSIONS: PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.

Correlation of lipocalin 2 and glycolipid metabolism and body composition in a large cohort of children with osteogenesis imperfecta.

PURPOSE: Lipocalin 2 (LCN2) is a newly recognized bone-derived factor that is important in regulation of energy metabolism. We investigated the correlation of serum LCN2 levels and glycolipid metabolism, and body composition in a large cohort of patients with osteogenesis imperfecta (OI). METHODS: A total of 204 children with OI and 66 age- and gender-matched healthy children were included. Circulating levels of LCN2 and osteocalcin were measured by enzyme-linked immunosorbent assay. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated chemical analyzers. The body composition was measured by dual-energy X-ray absorptiometry. Grip strength and timed-up-and-go (TUG) were tested to evaluate the muscle function. RESULTS: Serum LCN2 levels were 37.65 ± 23.48 ng/ml in OI children, which was significantly lower than those in healthy control (69.18 ± 35.43 ng/ml, P < 0.001). Body mass index (BMI) and serum FBG level were significantly higher and HDL-C levels were lower in OI children than healthy control (all P < 0.01). Grip strength was significantly lower (P < 0.05), and the TUG was significantly longer in OI patients than healthy control (P < 0.05). Serum LCN2 level was negatively correlated to BMI, FBG, HOMA-IR, HOMA-ß, total body, and trunk fat mass percentage, and positively correlated to total body and appendicular lean mass percentage (all P < 0.05). CONCLUSIONS: Insulin resistance, hyperglycemia, obesity, and muscle dysfunction are common in OI patients. As a novel osteogenic cytokine, LCN2 deficiency may be relevant to disorders of glucose and lipid metabolism, and dysfunction of muscle in OI patients.

Correlation of serum DKK1 level with skeletal phenotype in children with osteogenesis imperfecta.

PURPOSE: We aim to detect serum DKK1 level of pediatric patients with OI and to analyze its relationship with the genotype and phenotype of OI patients. METHODS: A cohort of pediatric OI patients and age-matched healthy children were enrolled. Serum levels of DKK1 and bone turnover biomarkers were measured by enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by Dual-energy X-ray absorptiometry. Pathogenic mutations of OI were detected by next-generation sequencing and confirmed by Sanger sequencing. RESULTS: A total of 62 OI children with mean age of 9.50 (4.86, 12.00) years and 29 healthy children were included in this study. The serum DKK1 concentration in OI children was significantly higher than that in healthy children [5.20 (4.54, 6.32) and 4.08 (3.59, 4.92) ng/mL, P < 0.001]. The serum DKK1 concentration in OI children was negatively correlated with height (r = - 0.282), height Z score (r = - 0.292), ALP concentration (r = - 0.304), lumbar BMD (r = - 0.276), BMD Z score of the lumbar spine and femoral neck (r = - 0.32; r = - 0.27) (all P < 0.05). No significant difference in serum DKK1 concentration was found between OI patients with and without vertebral compression fractures. In patients with spinal deformity (22/62), serum DKK1 concentration was positively correlated with SDI (r = 0.480, P < 0.05). No significant correlation was observed between serum DKK1 concentration and the annual incidence of peripheral fractures, genotype and types of collagen changes in OI children. CONCLUSION: The serum DKK1 level was not only significantly elevated in OI children, but also closely correlated to their skeletal phenotype, suggesting that DKK1 may become a new biomarker and a potential therapeutic target of OI.

Changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in lactating dairy cows with subacute rumen acidosis following rumen content transplantation.

Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery of its function and metabolism. However, the regulatory mechanisms governing the remodeling of rumen epithelial morphology and function, rumen metabolism, and host metabolism in cows of SARA remain poorly understood. Here, we explored the changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in SARA cows following rumen content transplantation (RCT). The entire experiment consisted of 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were randomly allocated into 2 groups, fed either a conventional diet (CON; n = 4; 40% concentrate, DM basis) or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). Following the SARA induction period, the RCT period started. The HG cows were randomly assigned to 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group. Rumen contents were entirely removed from both groups before RCT. For the DR group, cows were administered 70% rumen content from the CON cows, paired based on comparable BW; for the SR group, each cow received 70% self-derived rumen content. The results revealed no significant differences in the thicknesses of the stratum corneum, granulosum, and spinosum or basale layers, as well as the total depth of the epithelium between the SR and DR groups. All these measurements exhibited a decreasing trend and fluctuations over time after the transfer. Notably, these fluctuations tended to stabilize at 13 or 16 d after RCT in the SR group, whereas they tended to stabilize after 8 or 13 d of transfer for the DR group. Transcriptome sequencing revealed that a total of 277 differentially expressed genes (DEG) were identified between the 2 groups. Enrichment analysis showed that the DEG were significantly enriched in 11 Gene Ontology biological processes and 14 Kyoto Encyclopedia of Genes and Genomes pathways. The DEG corresponding to almost any of these 11 biological process terms and 14 pathways showed mixed up- or downregulation following RCT. Metabolomics analysis indicated that a total of 33 differential metabolites were detected between the SR and DR groups, mainly enriched in 5 key metabolic pathways, including plant polysaccharides and starch degradation, lipid metabolism, amino-sugar and nucleotide-sugar metabolism, purine metabolism, and Krebs cycle. Among them, the levels of differential metabolites associated with the degradation of plant polysaccharides and starches, metabolism of amino sugars and nucleotides, and purine metabolism pathways were significantly elevated in the DR cows. The results of blood biochemical parameters showed that the triglyceride concentration of the DR cows was increased than that of the SR cows, comparable to the level observed in the CON cows during the SARA induction period. Generally, our findings indicated that RCT facilitated the recovery of rumen epithelial morphological structure but did not promote its function recovery. Moreover, RCT enhanced rumen plant polysaccharide and starch degradation, amino-sugar and nucleotide-sugar metabolism, as well as purine metabolism. Additionally, it further promoted the recovery of plasma metabolites related to lipid metabolism.

Clinical and socioeconomic factors predicting return-to-work times after cholecystectomy.

BACKGROUND: Cholecystectomy, a type of surgery commonly performed globally, has possible mutual effects on the socioeconomic conditions of different countries due to various postoperative recovery times. AIMS: This study evaluated the medical and socioeconomic factors affecting delayed return-to-work (RTW) time after elective cholecystectomy. METHODS: This retrospective study analysed patients who underwent elective cholecystectomy for benign gallbladder diseases from January 2022 to April 2023. The patients' medical and socioeconomic data were collected to investigate the clinical and socioeconomic factors correlated with RTW time of >30 days after surgery. RESULTS: This study included 180 consecutive patients. Significant correlations were found between delayed RTW time (>30 days) and age (odds ratio [OR]: 1.059, 95% confidence interval [CI] 1.008-1.113, P = 0.024), lack of medical insurance (OR: 2.935, 95% CI 1.189-7.249, P = 0.02) and high-intensity labour jobs (OR: 3.649, 95% CI 1.495-8.909, P = 0.004). Patients without medical insurance (26.6 versus 18.9 days) and those with high-intensity labour jobs (23.9 versus 18.8 days) had a higher mean RTW time than those with insurance and a less-intense labour job (P < 0.001). CONCLUSIONS: After cholecystectomy, older age, lack of medical insurance and high-intensity labour job were correlated with a delayed RTW time. Informing patients about their expected RTW time after surgery can help reduce costs.

Burden of gastrointestinal cancers among people younger than 50 years in China, 1990 to 2019.

OBJECTIVES: This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. STUDY DESIGN: A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. RESULTS: In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75-4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020-2030. CONCLUSIONS: The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge.

Integrating genomics and transcriptomics to identify candidate genes for high-altitude adaptation and egg production in Nixi chicken.

1. This study combined genome-wide selection signal analysis with RNA-sequencing to identify candidate genes associated with high altitude adaptation and egg production performance in Nixi chickens (NXC).2. Based on the whole-genome data from 20 NXC (♂:10; ♀:10), the population selection signal was analysed by sliding window analysis. The selected genes were screened by combination with the population differentiation statistic (FST). The sequence diversity statistic (θπ). RNA-seq was performed on the ovarian tissues of NXC (n = 6) and Lohmann laying hens (n = 6) to analyse the differentially expressed genes (DEGs) between the two groups. The functional enrichment analysis of the selected genes and differentially expressed genes was performed.3. There were 742 genes under strong positive selection and 509 differentially expressed genes screened in NXC. Integrated analysis of the genome and transcriptome revealing 26 overlapping genes. The candidate genes for adaptation to a high-altitude environment, as well as for egg production, disease resistance, vision and pigmentation in NXC were preliminarily screened.4. The results provided theoretical guidance for further research on the genetic resource protection and utilisation of NXC.

Disturbance of mitochondrial dynamics in myocardium of broilers with pulmonary hypertension syndrome.

1. The following study investigated the relationship between pulmonary hypertension syndrome (PHS) and mitochondrial dynamics in broiler cardiomyocytes.2. An animal model for PHS was established by injecting broiler chickens with CM-32 cellulose particles. Broiler myocardial cells were cultured under hypoxic conditions to establish an in vitro model. The ascites heart index, histomorphology, mitochondrial ultrastructure, and mitochondrial dynamic-related gene and protein expression were evaluated.3. The myocardial fibres from PHS broilers had wider spaces and were wavy and twisted and the number of mitochondria increased. Compared with the control group, the gene and protein expression levels were decreased for Opa1, Mfn1, and Mfn2 in the myocardium of PHS broilers. The gene and protein expression was significantly increased for Drp1 and Mff.4. This study showed that PHS in broilers may cause myocardial mitochondrial dysfunction, specifically by diminishing mitochondrial fusion and enhancing fission, causing disturbances in the mitochondrial dynamics of the heart.

[Gene mutation characteristics of clinical stage â A lung adenocarcinoma and their relations with patients' long-term prognosis].

Objective: To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage ⅠA lung adenocarcinoma patients. Methods: A retrospective analysis was conducted on 63 clinical stage ⅠA lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis. Results: After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations (HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations (HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations (HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations (HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations (HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage ⅠA lung adenocarcinoma patients. Conclusions: PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage ⅠA lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.

[Circ_0000263 improves radiosensitivity of Hela cells by inhibiting the activity of telomerase protein through miR-338-3p/TERT].

Objective: To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity. Methods: The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity. Results: Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation (P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells (P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group (P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group (P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group (P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group (P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group (P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group (P＜0.05). Conclusion: Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.