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Abstract. Background:. Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented. Methods:. In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs). Results:. In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years. Conclusion:. These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Background: A milestone goal of the Healthy China Program (2019–2030) is to achieve 5-year cancer survival at 43.3% for all cancers combined by 2022. To assess the progress towards this target, we analyzed the updated survival for all cancers combined and 25 specific cancer types in China from 2019 to 2021. Methods: We conducted standardized data collection and quality control for cancer registries across 32 provincial-level regions in China, and included 6,410,940 newly diagnosed cancer patients from 281 cancer registries during 2008–2019, with follow-up data on vital status available until December 2021. We estimated the age-standardized 5-year relative survival overall and by site, age group, and period of diagnosis using the International Cancer Survival Standard Weights, and quantified the survival changes to assess the progress in cancer control. Results: In 2019–2021, the age-standardized 5-year relative survival for all cancers combined was 43.7% (95% confidence interval [CI], 43.6–43.7). The 5-year relative survival varied by cancer type, ranging from 8.5% (95% CI, 8.2–8.7) for pancreatic cancer to 92.9% (95% CI, 92.4–93.3) for thyroid cancer. Eight cancers had 5-year survival of over 60%, including cancers of the thyroid, breast, testis, bladder, prostate, kidney, uterus, and cervix. The 5-year relative survival was generally lower in males than in females. From 2008 to 2021, we observed significant survival improvements for cancers of the lung, prostate, bone, uterus, breast, cervix, nasopharynx, larynx, and bladder. The most significant improvement was in lung cancer. Conclusions: Progress in cancer control was evident in China. This highlights the importance of a comprehensive approach to control and prevent cancer.

ABSTRACT Objective This study explored the distributions of gastric mucosal status and their links to gastric cancer within urban high‐risk individuals in China. Methods From 2014 to 2015, a questionnaire survey was administered among individuals aged 40 to 69 years, residing for over 3 years in seven selected cities across China. Utilizing the questionnaire data, high‐risk individuals for gastric cancer were screened. These identified high‐risk individuals were invited to undergo endoscopy, followed by pathological examinations conducted for those with suspicious lesions. Prior cancer patients and those newly diagnosed with gastric cancer were excluded, and the remaining endoscopic participants were prospectively followed up until December 2021. Results The prospective study followed 8911 individuals at high risk of gastric cancer for a median duration of 6.77 years. The incidence density of gastric cancer was 58.55 per 100,000 person‐years. At baseline, the distributions of subjects across normal gastric mucosa, gastritis/ulcer/polyp, atrophic gastritis/intestinal metaplasia, and intraepithelial neoplasia groups were 47.09%, 36.27%, 9.57%, and 7.07%, respectively. Compared with normal gastric mucosa, the hazard ratios (HRs) for gastric cancer in the other groups were 0.89 [95% confidence interval (95%CI): 0.38–2.08], 1.52 (95%CI: 0.50–4.66), and 4.63 (95%CI: 1.98–10.82). When using the 40–54 age group as the reference, the HR for 55–69 age group was 3.49 (95%CI: 1.52–7.98). Conclusion Among high‐risk individuals with gastric cancer, the proportions of individuals exhibiting different gastric mucosal status inversely correlated with the severity of mucosal lesions, whereas the risk of gastric cancer progressively escalated with the increasing severity of mucosal lesions and advancing age.

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

Abstract The reconstruction of a stable, nipple-shaped cartilage graft that precisely matches the natural nipple in shape and size on the contralateral side is a clinical challenge. While 3D printing technology can efficiently and accurately manufacture customized complex structures, it faces limitations due to inadequate blood supply, which hampers the stability of nipple-shaped cartilage grafts produced using this technology. To address this issue, we employed a biodegradable biomaterial, Poly(lactic-co-glycolic acid) (PLGA), loaded with Cell-Free Fat Extract (Ceffe). Ceffe has demonstrated the ability to promote angiogenesis and cell proliferation, making it an ideal bio-ink for bioprinting precise nipple-shaped cartilage grafts. We utilized the Ceffe/PLGA scaffold to create a porous structure with a precise nipple shape. This scaffold exhibited favorable porosity and pore size, ensuring stable shape maintenance and satisfactory biomechanical properties. Importantly, it could release Ceffe in a sustained manner. Our in vitro results confirmed the scaffold’s good biocompatibility and its ability to promote angiogenesis, as evidenced by supporting chondrocyte proliferation and endothelial cell migration and tube formation. Furthermore, after 8 weeks of in vivo culture, the Ceffe/PLGA scaffold seeded with chondrocytes regenerated into a cartilage support structure with a precise nipple shape. Compared to the pure PLGA group, the Ceffe/PLGA scaffold showed remarkable vascular formation, highlighting the beneficial effects of Ceffe. These findings suggest that our designed Ceffe/PLGA scaffold with a nipple shape represents a promising strategy for precise nipple-shaped cartilage regeneration, laying a foundation for subsequent nipple reconstruction.

Abstract To validate the feasibility of a fiber-optic pressure sensor-based pressure measurement device for monitoring intrarenal pressure and to analyze the effects of ureteral acess sheath (UAS) type, surgical location, perfusion flow rate, and measurement location on intrarenal pressure (IRP). The measurement deviations and response times to transient pressure changes were compared between a fiber-optic pressure sensing device and a urodynamic device IRP in an in vitro porcine kidney and in a water tank. Finally, pressure measurements were performed in anesthetized female pigs using fiber-optic pressure sensing device with different UAS, different perfusion flow rates, and different surgical positions at different renal calyces and ureteropelvic junctions (UPJ). According to our operation, the result is fiber optic pressure sensing devices are highly accurate and sensitive. Under the same conditions, IRP varied among different renal calyces and UPJ (P

Background: The National Cancer Center (NCC) of China regularly reports the nationwide statistics on cancer incidence and mortality in China. The International Agency for Research on Cancer (IARC) calculates and publishes the cancer burden of countries around the world every two years. To ensure consistency between the actual surveillance data in China and the data published by IARC, NCC has received approval from the National Health Commission and IARC to simultaneously release the cancer burden data for China in GLOBOCAN 2022. Methods: There were a total of 700 registries reporting high-quality data on cancer incidence and mortality across China in 2018, of which 106 registries with continuous monitoring from 2010 to 2018 were used to establish an age-period-cohort model to simulate the trend of cancer incidence and mortality and to estimate the incidence and mortality in China in 2022. In addition, we analyzed the temporal trends of age-standardized cancer incidence and mortality from 2000 to 2018 using data from 22 continuous cancer registries. Results: It was estimated about 4,824,700 new cancer cases and 2,574,200 new cancer deaths occurred in China in 2022. Cancers of the lung, colon-rectum, thyroid, liver and stomach were the top five cancer types, accounting for 57.42% of new cancer cases. Cancers of the lung, liver, stomach, colon-rectum and esophagus were the five leading causes of cancer deaths, accounting for 67.50% of total cancer deaths. The crude rate and age-standardized incidence rate (ASIR) were 341.75 per 100,000 and 201.61 per 100,000, respectively. The crude mortality rate was 182.34 per 100,000 and the age-standardized mortality rate (ASMR) was 96.47 per 100,000. The ASIR of all cancers combined increased by approximately 1.4% per year during 2000–2018, while the ASMR decreased by approximately 1.3% per year. We observed decreasing trends in ASIR and ASMR for cancers of the esophagus, stomach, and liver, whereas the ASIR increased significantly for cancers of the thyroid, prostate, and cervix. Conclusions: Cancer remains a major public health concern in China, with a cancer profile that reflects the coexistence of developed and developing regions. Sustained implementation of prevention and control measures has resulted in significant reductions in the incidence and mortality rates of certain historically high incidence cancers, such as esophageal, stomach and liver cancers. Adherence to the guidelines of the Healthy China Action Plan and the Cancer Prevention and Control Action Plan, along with continued efforts in comprehensive risk factor control, cancer screening, early diagnosis and treatment, and standardization of diagnostic and therapeutic protocols, are key strategies to effectively mitigate the increasing cancer burden by 2030.

Abstract Autophagy modulates the degradation and recycling of intracellular materials and contributes to male gametophyte development and male fertility in plants. However, whether autophagy participates in seed development remains largely unknown. Here, we demonstrate that autophagy is crucial for timely programmed cell death (PCD) in the integumentary tapetum, the counterpart of anther tapetum, influencing embryo pattern formation and seed viability. Inhibition of autophagy resulted in delayed PCD of the integumentary tapetum and defects in embryo patterning. Cell-type-specific restoration of autophagic activities revealed that the integumentary tapetum plays a non-autonomous role in embryo patterning. Furthermore, high-throughput, comprehensive lipidomic analyzes uncovered an unexpected seed-developmental-stage-dependent role of autophagy in seed lipid metabolism: it contributes to triacylglycerol degradation before fertilization and to triacylglycerol biosynthesis after fertilization. This study highlights the critical role of autophagy in regulating timely integumentary tapetum PCD and reveals its significance in seed lipid metabolism and viability.

Abstract Background Major depressive disorder (MDD) is a common but severe psychiatric illness characterized by depressive mood and diminished interest. Both nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 1 (NLRP1) inflammasome and autophagy have been reported to implicate in the pathological processes of depression. However, the mechanistic interplay between NLRP1 inflammasome, autophagy, and depression is still poorly known. Methods Animal model of depression was established by chronic social defeat stress (CSDS). Depressive-like behaviors were determined by social interaction test (SIT), sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail-suspension test (TST). The protein expression levels of NLRP1 inflammasome complexes, pro-inflammatory cytokines, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K)/PI3K, phosphorylated-AKT (p-AKT)/AKT, phosphorylated-mechanistic target of rapamycin (p-mTOR)/mTOR, brain-derived neurotrophic factor (BDNF), phosphorylated-tyrosine kinase receptor B (p-TrkB)/TrkB, Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl2) and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) were examined by western blotting. The mRNA expression levels of pro-inflammatory cytokines were tested by quantitative real-time PCR. The interaction between proteins was detected by immunofluorescence and coimmunoprecipitation. Neuronal injury was assessed by Nissl staining. The autophagosomes were visualized by transmission electron microscopy. Nlrp1a knockdown was performed using an adeno-associated virus (AAV) vector containing Nlrp1a–shRNA–eGFP infusion. Results CSDS exposure caused a bidirectional change in hippocampal autophagy function, which was activated in the initial period but impaired at the later stage. In addition, CSDS exposure increased the expression levels of hippocampal NLRP1 inflammasome complexes, pro-inflammatory cytokines, p-PI3K, p-AKT and p-mTOR in a time-dependent manner. Interestingly, NLRP1 is immunoprecipitated with mTOR but not PI3K/AKT and CSDS exposure facilitated the immunoprecipitation between them. Hippocampal Nlrp1a knockdown inhibited the activity of PI3K/AKT/mTOR signaling, rescued the impaired autophagy and ameliorated depressive-like behavior induced by CSDS. In addition, rapamycin, an autophagy inducer, abolished NLRP1 inflammasome-driven inflammatory reactions, alleviated depressive-like behavior and exerted a neuroprotective effect. Conclusions Autophagy dysfunction contributes to NLRP1 inflammasome-linked depressive-like behavior in mice and the regulation of autophagy could be a valuable therapeutic strategy for the management of depression.

Wide field of view (WFV) push-broom optical satellites can acquire ground images over hundreds to thousands of kilometers in a single pass, thanks to their large field of view (FOV) cameras consisting of tens or even hundreds of thousands of detectors, which also makes their relative radiometric correction (RRC) difficult. Existing side-slither-based RRC approaches overlook the distinct structural design of WFV push-broom optical satellite cameras, thus failing to rectify nonlinear distortions in side-slither images stemming from the nonflat arrangement of camera detectors. Furthermore, these methods necessitate the corresponding pixels (pixels of the same ground object) covering the entire FOV in side-slither images. However, the brief duration of side-slither imaging makes it unfeasible to cover the entire FOV with calibration data. To address these issues, we propose a novel RRC approach for WFV push-broom optical satellites, achieved based on a thorough analysis of the unique structural traits of WFV push-broom optical cameras, enabling precise standardization of the nonlinear distortions in side-slither data. Additionally, a local-to-global side-slither calibration strategy is proposed to obviate the requirement for corresponding pixels to cover the entire FOV in calibration data. Experiments using the Haiyang-1D Coastal Zone Imager satellite indicate that our method effectively rectified nonlinear distortions in side-slither data, and evident RRC accuracy improvement with that of the existing methods can be obtained.

Abstract Background Overload and anxiety were common phenomena among frontline nurses during the pandemic. Understanding the potential pathway for fostering engagement in high-stress working conditions can provide evidence of targeted intervention to facilitate nurses’ well-being and safety practices. This study aims to investigate the level of nurses’ work engagement during nucleic acid collection tasks in the COVID-19 pandemic and identify its potential antecedents. Methods A cross-sectional design was adopted. A sample of 824 nurses who engaged in nucleic acid collection tasks completed an online self-report questionnaire between 1 March and 31 May 2022. Descriptive and path analyses were utilized to analyse the interrelationships among anxiety, perceived workload, affective commitment, perceived organizational support and work engagement. This study was conducted and reported under the guidelines for Strengthening the Reporting of Observational Studies in Epidemiology. Results The results showed that frontline nurses engaged in such tasks reported high levels of anxiety and task load and low levels of work engagement. Path analysis identified anxiety symptoms, perceived workload, perceived organizational support, and affective commitment as associated with work engagement, and among these factors, perceived organizational support and affective commitment played key roles in mediating the relationship of anxiety, workload and work engagement in high-stress working conditions. Conclusions Affective commitment and perceived organizational support were associated with frontline nurses’ level of work engagement during the COVID-19 pandemic; these two variables might explain how engagement is generated in high-anxiety and high-workload situations. When healthcare organizations give more attention to frontline nurses’ physical and psychological conditions and are able to innovatively motivate affective commitment and facilitate organizational support, nurses’ work engagement in high-level tasks may increase, thus enhancing work safety and personal well-being.

Improving apple peel color has been an important objective in apple production. To better understand the effect and mechanism of the combined application of urea and FA (fulvic acid) regulation of anthocyanin biosynthesis, a field experiment was performed in 2022 and 2023, respectively, under five treatments of urea + FA (CK, urea only; FA50, urea + 50 kg ha−1 FA; FA100, urea + 100 kg ha−1 FA; FA150, urea + 150 kg ha−1 FA; FA200, urea + 200 kg ha−1 FA), using isotope (13C and 15N) marking to analyze the changes in carbon (C) and nitrogen (N) nutrient distribution as well as anthocyanin biosynthesis in fruits. We observed that, under FA application conditions, anthocyanin content in the peel was elevated in both years, with increases of 15.98~52.88% in 2022 and 15.93~52.94% in 2023. The best promotion effects were observed under FA150 treatment. Apart from the expression levels of anthocyanin biosynthesis-related genes and transcription factors in the apple peel, this positive effect on anthocyanin content induced by FA addition was also found to be associated with the optimization of C and N distribution in leaves and fruits. On the one hand, the application of FA not only enhanced leaf photosynthetic-related indexes (such as Pn, Gs, and Rubisco activity) and influenced (increased) S6PDH, SPS, and SS activities in leaves, but also elevated fruit sugar metabolism-related enzyme (SDH, SS-c, AI, and NI) activity and upregulated fruit stalk sugar transporter (MdSOT1, MdSOT3, MdSUT1 and MdSUT4) gene expression, which ultimately promoted the synthesis and the leaf to fruit transport of photosynthates, thus promoting 13C-photosynthate accumulation in fruits. On the other hand, FA application elevated leaves’ N metabolism-related enzyme (GS and GOGAT) activity and optimized 15N distribution in leaves and fruits. Moreover, we also observed that FA application altered the fate of N fertilizer in apple orchards, showed an elevation in apple tree 15NUE and soil 15N residuals and showed a decrease in soil 15N loss. In summary, the appropriate application of FA150 (urea + 150 kg ha−1) synergistically optimized C and N nutrient distribution, and promoted anthocyanin biosynthesis in apple trees.

Summary: Background: The incidence of gastric cancer (GC) decreased in past decades, which was thought largely attributable to risk factors control, yet China still accounts for 44% of global GC burdens. We aimed to estimate changing trajectories of proportions of GC burdens attributable to modifiable risk factors from 2000 to 2050 in China, to inform future targeted preventive strategies. Methods: The incidence and new cases of GC were predicted to 2050 using Bayesian age-period-cohort model based on incidence data by anatomical subsites drawn from 682 cancer registries from National Central Cancer Registry. Population attributable fractions (PAFs) were calculated based on prevalence of risk factors and relative risks with GC. Temporal trends of PAFs were described by sex and categories of risk factors using joinpoint analysis. Findings: We observed declining trends of PAFs of Helicobacter pylori (H. pylori) infection, smoking, pickled vegetable and alcohol consumption, but increasing trends of PAFs of unhealthy body mass index and diabetes for GC in China. The combined PAFs of these risk factors were estimated to decrease by 10.57% from 2000 to 2050 for GC. We estimated there will be 279,707 GC (122,796 cardia gastric cancer [CGC] and 156,911 non-cardia gastric cancer [NCGC]) cases in 2050. Out of these cases, 70.18% of GC cases could be attributable to modifiable risk factors, while H. pylori infection was predicted to be responsible for 40.7% of CGC and 62.1% of NCGC cases in 2050. Interpretation: More than half of GC remained attributable to modifiable risk factors in China. Continued effective strategies on risk factors control are needed to reduce the burden of this highly life-threatening cancer in future. Funding: Beijing Nova Program (No. Z201100006820069), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-023), CAMS Innovation Fund for Medical Sciences (CIFMS, grant No. 2021-I2M-1-010), Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star).

Abstract Background RNASET2 has been identified as an oncogene with anti-angiogenic and immunomodulatory effects in a variety of cancers, but its function in clear cell renal cell carcinoma (ccRCC) is still not well understood. Methods The RNASET2 expression matrix was extracted from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and analyzed for diagnostic and prognostic value. RNASET2 mRNA expression was detected by quantitative polymerase chain reaction (qPCR) in ccRCC patients and renal cancer cell lines. Wound healing assay, transwell assay, western blotting, and tube formation assays were used to evaluate the function of RNASET2 in renal cancer in vitro. In addition, transcriptome sequencing was performed on knockdown RNASET2 kidney cancer cells to analyze their potential signaling pathways. Moreover, the immune microenvironment and mutational status were evaluated to predict the potential mechanisms of RNASET2 involvement in renal cancer progression. Sensitivity to common chemotherapeutic and targeted agents was assessed according to the Genomics of Drug Sensitivity in Cancer (GDSC) database. Results RNASET2 expression was significantly upregulated in ccRCC tissues and renal cancer cell lines, predicting poor prognosis for patients. In vitro experiments showed that silencing RNASET2 inhibited the migration and pro-angiogenic ability of renal cancer cells. Transcriptome sequencing suggested its possible involvement in the remodeling of the immune microenvironment in renal cell carcinoma. Furthermore, bioinformatics analysis and immunohistochemical staining showed that RNASET2 was positively correlated with the infiltration abundance of regulatory T cells. Finally, we mapped the mutational landscape of RNASET2 in ccRCC and found its predictive value for drug sensitivity. Conclusions Our results suggest that RNASET2 is a promising biomarker and therapeutic target in ccRCC.

Abstract Objective This study aimed to investigate the safety of coronavirus disease 2019 (COVID‐19) vaccination in patients with epilepsy (PWE) and their willingness to undergo vaccination. Methods This study was a survey the survey questionnaire, which included general, epilepsy‐specific, and COVID‐specific questions, was completed by patients of the outpatient clinic and hospital ward at The Third Xiangya Hospital in 2021. Results A total of 120 valid questionnaires were returned. Eighty‐nine of 120 responders (74.2%) were not vaccinated, and 31 (25.8%) were vaccinated against COVID‐19. Of the 31 vaccinated PWE, one (3.2%) had worsening of seizures and four (12.9%) had adverse reactions that were characteristic of the COVID‐19 vaccine. The other 26 patients (83.9%) reported no adverse reactions, Moreover, there was no significant difference between the 18 PWE with well‐controlled seizures and the 13 PWE with poorly‐controlled seizures. Of the 89 unvaccinated PWE, 69.7% (62/89) were willing to receive the COVID‐19 vaccine, 28.1% (25/89) were unsure, and 2.2% (2/89) declined to be vaccinated. Significance Among PWE, few adverse reactions occurred following the COVID‐19 vaccination. Most PWE were willing to receive the COVID‐19 vaccine. COVID‐19 vaccination is safe for PWE.

The Southern Ocean is characterized by high levels of eddy activity, which are crucial for the vertical exchange or transfer of matter, energy, and momentum. Previous studies have shown that the variability of eddy kinetic energy (EKE) in the Southern Ocean is primarily intrinsic. However, the factors that modulate the forced and intrinsic variability of the EKE remain unclear. In this study, we conduct a series of idealized simulations and apply ensemble analysis to investigate the impact of topography and wind-stress perturbations on the forced and intrinsic variability of the EKE and their relative contributions. The results show that while the large wind-stress perturbation obviously increases the forced variability of EKE by enhancing the Ekman response, the topography not only amplifies the forced variability by sharpening isopycnals and energizing the mean flow but also intensifies the intrinsic variability of EKE. However, EKE variabilities in both complex-topographic and flat-bottom cases are dominated by their intrinsic components, even when driven by escalated wind-stress perturbations. These findings deepen our understanding of the eddy field, its ongoing variability in the Southern Ocean, and its potential impact on the balance of heat, carbon, and freshwater.

Numerous studies have been conducted on the US Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database to assess post-marketing reporting rates for drug safety review and risk assessment. However, the drug names in the adverse event (AE) reports from FAERS were heterogeneous due to a lack of uniformity of information submitted mandatorily by pharmaceutical companies and voluntarily by patients, healthcare professionals, and the public. Studies using FAERS and other spontaneous reporting AEs database without drug name normalization may encounter incomplete collection of AE reports from non-standard drug names and the accuracies of the results might be impacted. In this study, we demonstrated applicability of RxNorm, developed by the National Library of Medicine, for drug name normalization in FAERS. Using prescription opioids as a case study, we used RxNorm application program interface (API) to map all FDA-approved prescription opioids described in FAERS AE reports to their equivalent RxNorm Concept Unique Identifiers (RxCUIs) and RxNorm names. The different names of the opioids were then extracted, and their usage frequencies were calculated in collection of more than 14.9 million AE reports for 13 FDA-approved prescription opioid classes, reported over 17 years. The results showed that a significant number of different names were consistently used for opioids in FAERS reports, with 2,086 different names (out of 7,892) used at least three times and 842 different names used at least ten times for each of the 92 RxNorm names of FDA-approved opioids. Our method of using RxNorm API mapping was confirmed to be efficient and accurate and capable of reducing the heterogeneity of prescription opioid names significantly in the AE reports in FAERS; meanwhile, it is expected to have a broad application to different sets of drug names from any database where drug names are diverse and unnormalized. It is expected to be able to automatically standardize and link different representations of the same drugs to build an intact and high-quality database for diverse research, particularly postmarketing data analysis in pharmacovigilance initiatives.

The prevalence rate of allergic rhinitis (AR) is high worldwide. The inhalation of allergens induces AR, which is an immunoglobulin E-mediated and type 2 inflammation-driven disease. Recently, the role of neuroimmune communication in AR pathogenesis has piqued the interest of the scientific community. Various neuropeptides, such as substance P (SP), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), and neuromedin U (NMU), released via “axon reflexes” or “central sensitization” exert regulatory effects on immune cells to elicit “neurogenic inflammation,” which contributes to nasal hyperresponsiveness (NHR) in AR. Additionally, neuropeptides can be produced in immune cells. The frequent colocalization of immune and neuronal cells at certain anatomical regions promotes the establishment of neuroimmune cell units, such as nerve-mast cells, nerve-type 2 innate lymphoid cells (ILC2s), nerve-eosinophils and nerve-basophils units. Receptors expressed both on immune cells and neurons, such as TRPV1, TRPA1, and Mas-related G protein-coupled receptor X2 (MRGPRX2) mediate AR pathogenesis. This review focused on elucidating the mechanisms underlying neuroimmune communication in AR.

Abstract. Background:. Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period. Methods:. Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States. Results:. The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas. Conclusions:. The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.

Abstract Background Although endoscopic screening for esophageal cancer has been performed in high‐risk areas in China for decades, there is limited and inconsistent evidence regarding the starting age for individuals participating in screening. The aim of this study is to investigate the optimal starting age of esophageal cancer screening. Methods This study is based on a multicenter prospective cohort consisting 338,017 permanent residents aged 40–69 years in six high‐risk areas of esophageal cancer in China. The participation rate, detection rate, hazard ratios (HRs), cumulative incidence and mortality and number needed to screen (NNS) were calculated in each age group. Screening burden, benefit and risk were compared among screening strategies with different initiation ages to explore the optimal starting age for population‐based screening in high‐risk areas. Results Individuals aged 50–69 had a higher participation rate, a higher detection rate and improved screening effectiveness than those aged 40–49. The endoscopic screening had no significant effect on reducing the incidence of esophageal cancer in individuals under 55 and mortality in individuals under 45. Increasing the starting age to 50 years reduced the screening demand and NNS by 40% and 55%, and resulted in 12% of detectable positive cases, 16% of preventable incident cases, and 14% of preventable deaths being missed. Conclusions Postponing the starting age of endoscopic screening to 50 years might yield a more‐favorable balance between screening benefit and burden in high‐ risk areas with limited resources.

Abstract Background Adults aged 65 years and above account for over half of all cancer diagnoses in the United States, but little is known about trend of elderly cancer survival in the United States. We aimed to assess the survival trend for elderly cancer in the United States from 1995 to 2014. Methods We used data from Surveillance, Epidemiology, and End Results 12 registries and included 1,112,441 eligible patients aged 65 years or older who were diagnosed between 1995 and 2014 with cancer and followed up until December 2019. Overall and stage‐specific 5‐year relative survival, ratio of observed survival to expected survival, with 95% confidence intervals (CIs) of elderly cancer patients stratified by age were estimated during four periods (1995–1999, 2000–2004, 2005–2009, and 2010–2014). Cox proportional hazards models were used to estimate hazard ratios for cancer‐specific death among patients diagnosed during 2000–2004, 2005–2009, 2010–2014, compared diagnoses in 1995–1999. We also calculated stage distribution and treatment rate during four periods. Results In the United States, 5‐year relative survival for elderly cancer patients improved from 57.3% (95% CIs 57.0–57.5) in 1995–1999 to 60.7% (60.5–60.9) in 2010–2014. After controlling for sociodemographic and tumor characteristics, about a 19% reduction in cancer‐specific deaths among diagnoses in 2010–2014 compared with 1995–1999. Cancer survival improved for elderly patients in all age groups, with exception of stable survival for patients aged 85 and above. Comparing 1995–1999 with 2010–2014, relative survival improved from 84.7% (84.3–85.1) to 86.7% (86.3–87.0) for localized stage and from 12.4% (12.1–12.7) to 18.7% (18.4–19.0) for distant stage for all cancers combined. The trends in stage distribution and treatment rate for all cancers combined were relatively stable. Conclusions In the United States, survival for elderly cancer patients has improved slightly from 1995 to 2014, possibly mainly due to advances in treatment. Further studies are warranted to explore interventions to improve elderly cancer survival.

Abstract Background Current evidence on the psychological impact of screening and diagnosis of esophageal cancer (EC) is limited and unclear. Methods This multicenter, population‐based, prospective study was conducted in five high‐incidence regions in China from 2017 to 2020. The screened participants were diagnosed as healthy, esophagitis, low‐grade intraepithelial neoplasia (LGIN), high‐grade intraepithelial neoplasia (HGIN), or EC based on pathological biopsy. The psychological impact of the screening was assessed by comparing anxiety and depression symptoms at baseline and follow‐up. Results A total of 1973 individuals were ultimately included, with an average follow‐up of 22.2 months. The prevalence of anxiety and depression symptoms in screened population at baseline was 14.3% and 18.4%. The prevalence of anxiety and depression symptoms of screeners at follow‐up declined (all p

Background: The stage at diagnosis is a major factor in making treatment strategies and cancer control policies. However, the stage distribution for liver cancer in China was not well studied. In this multi-center hospital-based study, we aimed to identify the distribution and factors associated with stage at diagnosis for liver cancer in China. Methods: We included patients diagnosed with primary liver cancer in 13 hospitals of 10 provinces covering various geographic and socioeconomic populations during 2016–2017 in China. The stage distribution overall, and by sex and age at diagnosis were analyzed. We used logistic regression to identify the factors associated with stage III-IV disease. We further compared these estimates with data from the USA. Results: We included 2,991 patients with known stage at diagnosis in China. The proportion of patients diagnosed with stage I, II, III, and IV was 17.5%, 25.6%, 29.3%, and 27.6%, respectively. The proportion of stage III-IV cases was higher in women [65.1% vs 54.9%, adjusted odds ratio (OR) = 1.5, 95% CI: 1.2, 1.8] and those ≥ 60 years (61.6% vs 52.8%, OR = 1.4, 95% CI: 1.2, 1.6). We found an increased risk of stage III-IV among drinkers and those without a family history of cancer. Compared to the USA, our study population had a substantially higher proportion of stage III-IV cases (56.9% vs 45.6%). Conclusion: The disparities in liver cancer stage at diagnosis among different populations within China, and between China and the USA, imply the necessity for improving cancer awareness and early detection for liver cancer in China.

Background: Esophageal cancer poses a significant global burden, while its patterns and trends remain to be clarified. The aim of this study is to provide an update on the incidence and mortality rates of esophageal cancer and their trends in China based on data from the National Cancer Registry. Methods: We extracted data from the National Central Cancer Registry (NCCR) of China from 2000 to 2016 and performed comprehensive quality control. We calculated age-standardized rates of China (ASR China) and world (ASR world) using the Chinese population in 2000 and the Segi's world standard population, and performed a joinpoint regression analysis to examine the trend in incidence and mortality of esophageal cancer. The annual percent change (APC) and weighted average APC (AAPC) over the entire study period were estimated to measure the changing trend. Subgroup analyses were conducted by sex, region and pathological type. Results: A total of 487 eligible cancer registries were included in the data analysis and 22 registries with uninterrupted registration data were used for trend analysis. In 2016, there were an estimated of 184,500 incident cases of esophageal cancer and 142,300 deaths in China. The crude incidence, ASR China and ASR world were 25.25/100,000, 11.00/100,000 and 11.13/100,000, respectively. And the crude mortality, ASR China and ASR world were 19.38/100,000, 8.25/100,000 and 8.28/100,000, respectively. Esophageal squamous cell carcinoma (ESCC) was the most common histological type, accounting for 85.79% of all cases, followed by esophageal adenocarcinoma (EAC) (11.00%) and others (3.21%). There was a decreasing trend of ASR world in incidence and mortality during 2000–2016 with the AAPC of -4.6% (95% CI: -5.7%, -3.4%) and -4.6% (95% CI: -5.2%, -3.9%). The pattern and trend of esophageal cancer differ in sex, region and pathological type. Conclusions: The burden of esophageal cancer in China remains high with sex, regional and subtype differences. The incidence and mortality of esophageal cancer have continued to decline over the past decade, which was due in part to the reductions in risk factor exposure and the implementation of screening.

ObjectiveTo identify risk factors of secondary pelvic malignant neoplasms (SPMNs) among prostate cancer (PCa) patients treated with radiotherapy. Simultaneously, population-based data were used to validate the high risk of SPMNs in PCa patients with radiotherapy.Materials and methodsWe identified male patients diagnosed with PCa (localized and regional) as the first primary cancer and pelvic malignant neoplasm (including bladder and rectal cancer) as secondary cancer from Surveillance, Epidemiology, and End Results database (1975-2020). An external validation cohort was obtained from the First Affiliated Hospital of Nanchang University. The Fine-Gray competing risk regression and Poisson regression were utilized to evaluate the risk of SPMNs development. Poisson regression was also performed to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to assess the overall survival (OS) of patients with SPMNs.Results89397 PCa patients treated with radiotherapy were enrolled. We identified associated factors of SPMNs, including age at diagnosis, race, year of diagnosis, marital status, radiation strategy and latency. In the multivariable competing risk regression model and Poisson regression model, a significantly higher risk of SPMNs development was observed in patients over 50 years(P

Abstract Background Early diagnosis and treatment of esophageal squamous cell dysplasia (ESCdys) and esophageal squamous cell carcinoma (ESCC) could significantly reduce the incidence and mortality of ESCC. This pilot study aimed to investigate whether P16/CDKN2A methylation could serve as a cytologic biomarker for early detection of ESCdys and ESCC. Methods Paired esophageal biopsy and cytology specimens (exfoliated cells) were obtained from subjects at different stages of ESCC development. The methylation status of P16 gene in these two specimen types was determined using a 115‐bp MethyLight assay. Categorical data were compared by the Chi‐square test. Logistic regression was performed to assess adjusted odds ratios of P16 methylation associated with ESCC and ESCdys. Prediction models for identifying individuals at risk of ESCC and high‐grade ESCdys (high‐grade intraepithelial neoplasia, HGIN) were developed by multivariable logistic regression. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Internal validation of the prediction models was performed using the 1000‐bootstrap resample. Results A total of 105 subjects with diagnoses ranging from normal mucosa through ESCC were included in this study. An increase in P16 methylation frequency was observed with increasing severity of esophageal lesions (p for trend

Abstract The frequent and massive use of pesticides has led to pesticide residues in apricot, threatening food safety and human health. A reliable and simple modified QuEChERS method with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of 11 pesticides in apricot. Method validation indicated that satisfied linearity (R2 ≥ 0.9959), accuracy (recoveries of 72–119%), sensitivity (limits of detection, 0.03–0.30 μg/kg; limits of quantification, 0.13–1.00 μg/kg), and precision (relative standard deviations ≤ 11.9%), and matrix effects were 0.89–1.13. Apricot samples from different ecological regions in China were collected and tested using the proposed methods. Monitoring results were used to assess the dietary intake risk of Chinese populations of different ages and genders. Dietary risk assessment revealed that the risk quotients were 0.003–1.184% for different gender and age groups in China, indicating none unacceptable public health risk for general population. This work was thus significant in developing a simpler, more efficient and economical analysis method and food safety risks of the 11 pesticides on apricot and facilitated the establishment of maximum residue limits.

Objectives: The aim of this study was to investigate the dose-response relationship of admission fasting glucose (FBG) with corona virus disease 2019 (COVID-19) mortality and to further evaluate potential interactions of hyperglycemia with inflammation and hypercoagulation on COVID-19 outcomes. Methods: This retrospective study included 2555 consecutively hospitalized patients with COVID-19, until death or discharge, in Wuhan Union hospital between January 1 and April 9, 2020. The poor early outcomes included admission to intensive care unit, intubation, and deaths occurring within 28 days. We used splines nested in Cox regression to visualize dose-response associations and generalized additive models to fit three-dimensional (3D) trend plots for joint effects of FBG with markers of inflammation and coagulation. Results: J-shaped associations existed between hospitalized mortality or poor early outcomes and FBG with a nadir at 5 mmol/L, which were more evident in women. 3D plots demonstrated significant joint effect trends, and patients with hyperglycemia and high neutrophil-lymphocyte ratio, C-reactive protein, lactate dehydrogenase, procalcitonin, d-dimer, and interleukin-6 had 7.4-25.3-fold risks; the proportions of joint associations attributed to additive interactions reached 30% to 54%. Conclusions: FBG was associated with hospitalized mortality and poor early outcomes in a J-shaped manner, and a combination of hyperglycemia, inflammation, hypercoagulation, and cytokines conferred a dramatically higher risk.

Background: Updated systematic statistics on lung cancer are the underpinning cornerstones for formulating prevention and control strategies for the disease. The incidence and mortality data of lung cancer in China in 2016 were estimated, and also used to analyze the temporal trends of lung cancer from 2000 up to 2016 in this study. Methods: The burden of lung cancer in China in 2016 was estimated using data from 487 cancer registries, which were abstracted from the database of the National Cancer Center of China (NCC). The temporal trends were estimated with the data of 2000 to 2016 from 22 cancer registries. Results: About 828,100 new lung cancer cases and 657,000 lung cancer deaths were estimated in China in 2016. The crude incidence and mortality rates in the eastern region were the highest nationwide. The incidence and mortality of lung cancer increased with age, and most of the new cases occurred in the age group of over 60 years. The age-standardized incidence increased by about 0.8% per year during 2000 to 2016, especially in woman, whose annual increase rate reached 2.1%. The age-standardized mortality rate decreased by about 0.6% per year, with a decrease of 1.3% per year in urban areas and an increase of 2.3% per year in rural areas. The numbers of new cases and deaths increased by 162.6% and 123.6%, respectively, during 2000 to 2016, which can be explained mainly by the change of the age structure. Conclusions: The burden of lung cancer is serious in China, and increased especially rapidly for women in rural areas. The disease is expected to threaten the lives of more people in the future due to factors such as aging and population growth. Lung cancer prevention and control strategies and resources should be leveraged toward women and rural areas in the future.

Mixing induced by oceanic mesoscale eddies can affect tracer distributions in the ocean and thus modulate the evolution of the physical and biochemical marine system. In the context of global warming, regionally different trends in eddy mixing could exist. Motivated by this hypothesis, we quantified the trend in surface eddy diffusivity, a metric widely used to quantify the eddy mixing rate, in the global ocean using satellite altimetry data. The global average of the particle-based eddy diffusivity increases by 284.1 m2s−1 per decade during the period of 1994-2017, or 3.7% per decade relative to its climatological mean value. In 54% of the global ocean, eddy diffusivity shows an increasing trend. The diffusivity trend can be decomposed into two components: one related to changes in eddy mixing length and the other related to eddy velocity magnitude. In 73% of the global ocean, changes in eddy mixing length account for more than 50% of the diffusivity trend. The suppressed mixing length theory (SMLT) is employed to interpret the trend in eddy mixing length. SMLT well captures the sign of the trend in two of the representative regions. Among all the parameters (e.g., eddy size, phase speed) inherent in SMLT, the eddy velocity magnitude plays a dominant role in determining the trend in the SMLT-based eddy mixing length. Diagnosing the geostrophic eddy kinetic energy budget reveals that the dominant mechanism for the trend in eddy velocity magnitude is the pressure work induced by ageostrophic flows. Our results suggest that a time-dependent eddy parameterization scheme should be employed in non-eddy-resolving models to account for the trend in eddy mixing.

Marigold can protect crops against soil-borne diseases. However, the effects of intercropping with marigold on apple rhizosphere soils are not known. In this study, we investigated the metabolite profiles and bacterial community structures in rhizosphere soils of the apple-marigold intercropping system by high-throughput sequencing and soil metabolomics. The results show that intercropping marigold could significantly enhance soil moisture, nitrogen, and enzyme activities compared with clean tillage. The soil metabolite profiles and the soil bacterial community structures in the rhizosphere soils were different between the inter-and mono-cropping systems. Among nine metabolites, carbohydrates were more increased in the intercropping system than in the monocropping system. Pathway enrichment analysis revealed that the greatest differential, in terms of metabolic pathway, was starch and sucrose metabolism. Moreover, intercropping marigold significantly increased the relative abundance of plant growth promoting bacteria in rhizosphere soils, such as Rhizobiales, Pseudomonadales, and Bacillales. These results indicate that marigold intercropping positively affected the apple orchard’s soil quality and may provide a new intercropping technique to improve soil fertility in orchards and promote plant growth.

Although eddy parameterization schemes are often based on the local assumption, previous studies indicate that the nonlocality of total eddy mixing is prevalent at the Kuroshio Extension (KE). For eddy-permitting climate models, only mixing induced by eddies smaller than the resolvable scale of climate models (L*) needs to be parameterized. Therefore, here we aim to estimate and predict the nonlocality of scale-dependent eddy mixing at the KE region. We consider the separation scale L* ranging from 0.2∘ to 2.5∘, which is comparable to the typical resolution of the ocean component of climate models. Using a submesoscale-permitting model solution (MITgcm llc4320) and Lagrangian particles, we estimate the scale-dependent mixing (SDM) nonlocality ellipses and then diagnose the square root of the ellipse area (Ln,particle). Ln,particle is a metric to quantify the degree of SDM nonlocality. We found that, for all the available L* values we consider, the SDM nonlocality is prevalent in the KE region, and mostly elevated values of Ln,particle occur within the KE jet. As L* decreases from 2.5∘ to 0.2∘, the ratio Ln,particle/L* increases from 0.8 to 8.9. This result indicates that the SDM nonlocality is more non-negligible for smaller L*, which corresponds to climate models with relatively high resolution. As to the SDM nonlocality prediction, we found that compared to the conventional scaling and the curve-fitting methods, the random forest approach can better represent Ln,particle, especially in the coastal regions and within the intense KE jet. The area of the Eulerian momentum ellipses well capture the spatial pattern, but not the magnitude, of Ln,particle. Our efforts suggest that eddy parameterization schemes for eddy-permitting models may be improved by taking into account mixing nonlocality.

PurposeMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier for patients in the prostate-specific antigen gray zone are to be developed and compared, identifying valuable predictors. Predictive models are to be integrated into actual clinical decisions.MethodsPatient information was collected from December 01, 2014 to December 01, 2022 from the Department of Urology, The First Affiliated Hospital of Nanchang University. Patients with a pathological diagnosis of prostate hyperplasia or prostate cancer (any PCa) and having a prostate-specific antigen (PSA) level of 4–10 ng/mL before prostate puncture were included in the initial information collection. Eventually, 756 patients were selected. Age, total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), fPSA/tPSA, prostate volume (PV), prostate-specific antigen density (PSAD), (fPSA/tPSA)/PSAD, and the prostate MRI results of these patients were recorded. After univariate and multivariate logistic analyses, statistically significant predictors were screened to build and compare machine learning models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier to determine more valuable predictors.ResultsMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier exhibit higher predictive power than individual metrics. The area under the curve (AUC) (95% CI), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score of the LogisticRegression machine learning prediction model were 0.932 (0.881–0.983), 0.792, 0.824, 0.919, 0.652, 0.920, and 0.728, respectively; of the XGBoost machine learning prediction model were 0.813 (0.723–0.904), 0.771, 0.800, 0.768, 0.737, 0.793 and 0.767, respectively; of the GaussianNB machine learning prediction model were 0.902 (0.843–0.962), 0.813, 0.875, 0.819, 0.600, 0.909, and 0.712, respectively; and of the LGBMClassifier machine learning prediction model were 0.886 (0.809–0.963), 0.833, 0.882, 0.806, 0.725, 0.911, and 0.796, respectively. The LogisticRegression machine learning prediction model has the highest AUC among all prediction models, and the difference between the AUC of the LogisticRegression prediction model and those of XGBoost, GaussianNB, and LGBMClassifier is statistically significant (p < 0.001).ConclusionMachine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier algorithms exhibit superior predictability for patients in the PSA gray area, with the LogisticRegression model yielding the best prediction. The aforementioned predictive models can be used for actual clinical decision-making.​

The deep learning teaching model is a student-centred teaching method that emphasizes guiding students to deep understanding and internalization of knowledge. Compared with traditional shallow learning, it focuses on the cultivation of students' critical thinking, innovation ability and cooperation spirit. And under today's trend of deep integration of information technology and teaching, how to utilize information technology to promote deep learning of college students has become a hot topic in educational research. In this paper, we design a teaching strategy aimed at promoting educational change and innovation through modernized information technology, and take the course "Programming Fundamentals" as an example, and carry out research from the aspects of design principles, learning activities, teaching mode construction, and effect evaluation, aiming to improve the teaching effect of the course and cultivate talents with independent learning ability, teamwork ability and innovation ability.

A sulfated polysaccharide (AG) was extracted and isolated from the sea cucumber H. fuscopunctata, consisting of GlcNAc, GalNAc, Gal, Fuc and lacking any uronic acid residues. Importantly, several chemical depolymerization methods were used to elucidate the structure of the AG through a bottom-up strategy. A highly sulfated galactose (oAG-1) and two disaccharides labeled with 2,5-anhydro-D-mannose (oAG-2, oAG-3) were obtained from the deaminative depolymerized product along with the structures of the disaccharide derivatives (oAG-4~oAG-6) identified from the free radical depolymerized product, suggesting that the repeating building blocks in a natural AG should comprise the disaccharide β-D-GalS-1,4-D-GlcNAc6S. The possible disaccharide side chains (bAG-1) were obtained with mild acid hydrolysis. Thus, a natural AG may consist of a keratan sulfate-like (KS-like) glycosaminoglycan with diverse modifications, including the sulfation types of the Gal residue and the possible disaccharide branches α-D-GalNAc4S6S-1,2-α/β-L-Fuc3S linked to the KS-like chain. Additionally, the anticoagulant activities of the AG and its depolymerized products (dAG1-9) were evaluated in vitro using normal human plasma. The AG could prolong activated partial thromboplastin time (APTT) in a dose-dependent manner, and the activity potency was positively related to the chain length. The AG and dAG1-dAG3 could prolong thrombin time (TT), while they had little effect on prothrombin time (PT). The results indicate that the AG could inhibit the intrinsic and common coagulation pathways.

Objective: To estimate the incidence and mortality of cervical cancer in China based on the cancer registration data in 2015, collected by the National Central Cancer Registry (NCCR). Methods: There were 501 cancer registries that submitted data to the NCCR, whose data were the basis for estimating the incidence and mortality of cervical cancer in China in 2015. After evaluating the data quality, 368 registries’ data were accepted for the analysis and stratified by area (urban/rural) and age group. Combined with data on the national population in 2015, the nationwide incidence and mortality of cervical cancer were estimated. Cervical Cancer cases of 22 cancer registries were applied for temporal trends from 2000 to 2015. The Chinese population census in 2000 and Segi's population were used to calculate age-standardized incidence and mortality rates. Results: An estimated 111,000 new cases were attributed to cervical cancer in China in 2015, accounting for 6.24% of all female new cancer cases in that year in China. The crude rate (CR) of incidence and age-standardized incidence rates by the China standard population (ASIRC) and by Segi's world standard population (ASIRW) of cervical cancer were 16.56/100,000, 11.78/100,000, and 10.86/100,000, respectively. The cumulative incidence rate from birth to 74 years old was 1.15%, whereas the calculation of incidence rates over the truncated age range of 35-64 years by Segi's world standard population (T-ASIRW) was 27.66/100,000. The estimates of cervical cancer deaths were about 33,800 and 3.94% of all female cancer-related deaths in China in 2015, with a crude mortality rate of 5.04/100,000. The age-standardized mortality rates adjusted by the Chinese standard population (ASMRC) and by world Segi's population (ASMRW) were 3.29/100,000 and 3.15/100,000, respectively, with a cumulative mortality rate (0-74 years old) of 0.35%. Both the incidence and mortality were higher in rural than in urban areas. The age-specific cervical cancer incidence significantly increased with age, particularly after age 25 years, and peaked at 50–54 years old, whereas age-specific mortality increased rapidly after 35 years old, peaking at 80–84 years old. The age-standardized incidence rates increased by about 8.6 (95% CI: 6.9, 10.3) per year during the period of 2000−2015. The age at diagnosis of patients with cervical cancer tended to be younger. In rural areas, the mean age at diagnosis decreased about 3.22 years from 2000 to 2015 (β = –0.33, P < 0.001). Conclusions: China has a high burden of cervical cancer and important disparities among different regions. Especially in the middle and western areas and rural areas, cervical cancer is a serious issue in women's health, and prevention strategies need to be enhanced. Prevention and control strategies need to be enhanced and implemented with reference to local status, such as human papillomavirus (HPV) vaccination and screening programs.

Background Previous studies have confirmed the higher risk of bladder cancer (BC) and rectal cancer (RC) development among prostate cancer (PCa) patients receiving radiotherapy. In this study, we intend to explore the long-term trend in second BC and RC incidence among PCa patients undergoing radiotherapy. Method We identified first primary PCa patients diagnosed between 1975 and 2014 from the Surveillance, Epidemiology, and End Results (SEER)-9 cancer registries. Standardized incidence ratios (SIRs) were calculated by calendar year of diagnosis among PCa patients receiving radiotherapy and not. P trends were evaluated using Poisson regression. 10-year cumulative incidence of BC and RC was calculated utilizing competing risk regression model. Result Of PCa patients treated with radiotherapy, SIRs of BC increased from .82 (95% CI: .35- 1.61) in 1980–1984 to 1.58 (95% CI: 1.48–1.68) in 2010-2014 ( Ptrend =.003). SIRs of RC increased from 1.01 (95% CI: .27-2.58) in 1980–1984 to 1.54 (95% CI: 1.31–1.81) in 2010-2014 ( Ptrend =.025). No statistically significant change in both BC and RC incidence was observed. The 10-year cumulative incidence of BC increased from 1975–1984 (.04%) to 2005–2014 (.15%) among PCa treated with radiotherapy. Simultaneously, the 10-year cumulative incidence of RC was demonstrated to range from 1975–1984 (.02%) to 2005–2014 (.11%). Conclusion we have observed an increasing trend in second BC and RC incidence in PCa patients receiving radiotherapy. There was no significant change in the incidence of second BC and RC in PCa without radiotherapy. These results reflect the increasing clinical burden of second malignant tumors in PCa patients undergoing radiotherapy.

EIF4A3 (Eukaryotic translation initiation factor 4A3 (EIF4A3) was recently recognized as an oncogene; however, its role in BLCA (bladder cancer) remains unclear. We explored EIF4A3 expression and its prognostic value in BLCA in public datasets, including the TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). Thereafter, the association between EIF4A3 expression and the infiltration of immune cells and immune-checkpoint expression was determined using TIMER2 (Tumor Immune Estimation Resource 2) tool. Additionally, the impact of EIF4A3 on cellular proliferation and apoptosis events in BLCA cell lines was determined by siRNA technology. In this study, EIF4A3 was found to be significantly upregulated in BLCA, upregulated expression of EIF4A3 was related to poor prognosis, advanced histologic grade, subtype, pathological stage, white race, and poor primary therapy outcome. The immune infiltration analysis revealed that EIF4A3 expression was negatively associated with CD8+ and CD4+ T cells and positively with myeloid-derived suppressor cells, macrophage M2, cancer-associated fibroblasts, and Treg cells. Moreover, EIF4A3 was coexpressed with PD-L1 (programmed cell death 1-ligand 1) and its expression was higher in patients responding to anti-PD-L1 therapy. EIF4A3 knockdown significantly inhibited proliferation and promoted apoptosis in 5,637 and T24 cells. In summary, BLCA patients with elevated EIF4A3 expression had an unfavorable prognosis and immunosuppressive microenvironment, and EIF4A3 may facilitate BLCA progression by promoting cell proliferation and inhibiting apoptosis. Furthermore, our study suggests that EIF4A3 is a potential biomarker and therapeutic target for BLCA.

Abstract Background Screening for upper gastrointestinal cancer (UGC) effectively reduces morbidity and mortality in gastric and esophageal cancers. It is considered one of the effective measures for cancer control in China, but studies on its functional quality are lacking. Our study assessed the quality of screening service funded by Upper Gastrointestinal Cancer Early diagnosis and treatment (UGCEDAT) and its correlation in Yangzhong People’s hospital, China. Methods A cross-sectional study was conducted among 516 screening users at a screening centre in Yanghzong People’s hospital from April to July 2021. The service quality questionnaire (SERVQUAL) based on the service quality gap (SQG) model was adopted. We calculated the mean scores of perceptions and expectations and their gap. To determine the association between overall SQG and related features of participants, we used a multivariate logistic regression. Results The average scores of screening service users’ perceptions and expectations were 4.05 and 4.55, respectively. The SQG of five dimensions (tangibles, reliability, responsiveness, assurance and empathy) were negative, and the overall SQG was -0.51. The responsiveness dimension had the largest gap, and tangibles had the smallest gap. Occupation status (AOR: 0.57; CI: 0.37–0.89), health self-assessment (AOR: 4.97; CI: 1.35–18.23), endoscopy experience (AOR: 0.55; CI: 0.38–0.81), distance from screening hospital (AOR: 1.85; CI: 1.25–2.73) and frequency of visit (AOR: 1.65; CI: 1.10–2.46) were associated with the overall SQG. Conclusions We observed a negative gap between perceptions and expectations of the function quality of screening service, implying a high dissatisfaction across different dimensions. Service providers should take adequate measures to bridge the dimension with the largest quality gap. Meanwhile, attention should be paid to identifying the influencing factors of the overall SQG and the characteristics of dimensional expectations and perceptions to improve the effectiveness of the screening program.

Abstract Background Chloroplast and endoplasmic reticulum (ER)-localized fatty acid (FA) transporters have been reported to play important roles in oil (mainly triacylglycerols, TAG) biosynthesis. However, whether these FA transporters synergistically contribute to lipid accumulation, and their effect on lipid metabolism in microalgae are unknown. Results Here, we co-overexpressed two chloroplast-localized FA exporters (FAX1 and FAX2) and one ER-localized FA transporter (ABCA2) in Chlamydomonas. Under standard growth conditions, FAX1/FAX2/ABCA2 over-expression lines (OE) accumulated up to twofold more TAG than the parental strain UVM4, and the total amounts of major polyunsaturated FAs (PUFA) in TAG increased by 4.7-fold. In parallel, the total FA contents and major membrane lipids in FAX1/FAX2/ABCA2-OE also significantly increased compared with those in the control lines. Additionally, the total accumulation contribution ratio of PUFA, to total FA and TAG synthesis in FAX1/FAX2/ABCA2-OE, was 54% and 40% higher than that in UVM4, respectively. Consistently, the expression levels of genes directly involved in TAG synthesis, such as type-II diacylglycerol acyltransferases (DGTT1, DGTT3 and DGTT5), and phospholipid:diacylglycerol acyltransferase 1 (PDAT1), significantly increased, and the expression of PGD1 (MGDG-specific lipase) was upregulated in FAX1/FAX2/ABCA2-OE compared to UVM4. Conclusion These results indicate that the increased expression of FAX1/FAX2/ABCA2 has an additive effect on enhancing TAG, total FA and membrane lipid accumulation and accelerates the PUFA remobilization from membrane lipids to TAG by fine-tuning the key genes involved in lipid metabolism under standard growth conditions. Overall, FAX1/FAX2/ABCA2-OE shows better traits for lipid accumulation than the parental line and previously reported individual FA transporter-OE. Our study provides a potential useful strategy to increase the production of FA-derived energy-rich and value-added compounds in microalgae.

Abstract Background Gastric and esophageal cancer (GEC) have made a great contribution to the cancer burden in China. This study aims to report GEC incidence and mortality trends in 2000–2015 and their predictions to 2030. Methods We collected GEC data from 22 cancer registries for Joinpoint temporal trend analysis between 2000 and 2015 and average annual percent change was calculated. Based on the historical changes, combined with the 2015 GEC national incidence and mortality rate, the rate from 2016 to 2030 was predicted grouped by sex and age. The crude rate, standardized rate, and cumulative rate were calculated. The number of cases were obtained by multiplying the United Nations' World Population Prospects and the predicted rate of corresponding years. Attribution changes between 2015 and 2030 were apportioned into demographics and risk factors. Results There were decreasing trends of age‐standardized incidence rate world (ASIRW) and age‐standardized mortality rate world (ASMRW) during 2000–2015 in China (p

Abstract. Background:. Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. Methods:. This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. Results:. Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36–1.62), 1.52-fold (95% CI: 1.38–1.67), or 1.66-fold (95% CI: 1.50–1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47–1.84) or 1.93-fold (95% CI: 1.46–2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30–12.65), 2.11-fold (95% CI: 1.37–3.25), and 1.91-fold (95% CI: 1.44–2.54) higher risks of ECPL, respectively. Conclusions:. Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. Trial registration:. ChiCTR-EOC-17010553.

Background: National Cancer Center (NCC) of China annually reports the nationwide statistics for cancer incidence and mortality using population-based cancer registry data from all available cancer registries in China. Methods: There were a total of 487 registries which reported high quality data of cancer incidence and mortality across China in 2016. The nationwide numbers of new cancer cases and deaths were estimated using the pooled cancer registry data, which were stratified by area (urban/rural), sex, age group (0, 1-4, 5-9, 10-14…85+) and cancer site for incidence and mortality, and then multiplied by corresponding national population. The world Segi's population was applied for the calculation of age-standardized rates. Results: About 4,064,000 new cancer cases and 2,413,500 new cancer deaths occurred in China in 2016. Cancers of the lung, colon-rectum, stomach, liver and female breast were the top five common cancers, accounting for 57.4% of total cancer new cases. Cancers of the lung, liver, stomach, colon-rectum and esophagus were the five leading causes of cancer deaths, accounting for 69.3% of total cancer deaths. The crude and age-standardized incidence rates (ASIR) were 293.91 and 186.46 per 100,000 population, respectively. The crude mortality rate was 174.55/100,000 and the age-standardized mortality rate (ASMR) was 105.19/100,000. The ASIR was higher but the ASMR was lower in urban areas than that in rural areas. In past decades, the ASIR was relatively stable in males, but significantly increased by about 2.3% per year in females for overall cancers combined. In contrast, the ASMR significantly decreased by about 1.2% per year for both sexes during 2000-2016. Notably, the cancer-specific ASIR and ASMR of esophageal, stomach, and liver cancers decreased significantly, whereas both rates for cancers of the colon-rectum, prostate, female breast, cervix, and thyroid increased significantly. Conclusions: Cancer remains a major public health problem in China, which demands long-term collaborative efforts of a broad community. With the national guideline on cancer prevention and control, tailored cancer prevention and control programs are needed in different regions to help reduce the burden of these highly fatal diseases in China.

Background: Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. The tumor microenvironment plays a significant role in CRC development, progression and metastasis. Oxidative stress in the colon is a major etiological factor impacting tumor progression. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial member of the heat shock protein 90 (HSP90) family that is involved in modulating apoptosis in colon cancer cells under oxidative stress. We undertook this study to provide mechanistic insight into the role of TRAP1 under oxidative stress in colon cells. Methods: We first assessed the The Cancer Genome Atlas (TCGA) CRC gene expression dataset to evaluate the expression of TRAP1 and its association with oxidative stress and disease progression. We then treated colon HCT116 cells with hydrogen peroxide to induce oxidative stress and with the TRAP1 inhibitor gamitrinib-triphenylphosphonium (GTPP) to inhibit TRAP1. We examined the cellular proteomic landscape using liquid chromatography tandem mass spectrometry (LC-MS/MS) in this context compared to controls. We further examined the impact of treatment on DNA damage and cell survival. Results: TRAP1 expression under oxidative stress is associated with the disease outcomes of colorectal cancer. TRAP1 inhibition under oxidative stress induced metabolic reprogramming and heat shock factor 1 (HSF1)-dependent transactivation. In addition, we also observed enhanced induction of DNA damage and cell death in the cells under oxidative stress and TRAP1 inhibition in comparison to single treatments and the nontreatment control. Conclusions: These findings provide new insights into TRAP1-driven metabolic reprogramming in response to oxidative stress.

The experiment was conducted at the Taidong Base of Shandong Institute of Pomology, Tai’an City, Shandong Province, China, from May to October 2022. Using Fuji Apple Tianhong.2/SH/Malus robusta (M. robusta) as experimental materials, the differences and mechanisms of the effects of non-bagging and bagging cultivation on the growth and changes in some substance content of Fuji apple fruits were studied. The results showed that compared with bagging, non-bagging cultivation increased single fruit weight and decreased fruit shape index, increased fruit sugar content, reduced acid content, and increased taste. It increased the content of vitamin C (VC) and protein in the fruit, increased the types and content of aromatic components in the fruit, significantly increased the activity of sugar- and acid-related enzymes, and improved the antioxidant capacity of the fruit. Compared to bagging cultivation, non-bagging cultivation improved the weight, taste (sugar acid ratio), and aroma of Fuji fruit, which is related to increasing the content of auxin (IAA), cytokinin (ZR), and salicylic acid (SA) and reducing the content of abscisic acid (ABA) in the fruit, as well as increasing the content of medium and trace elements calcium (Ca), iron (Fe), manganese (Mg), and boron (B). One of the mechanisms involved is the significant increase in gene expression related to phenylpropanoid biosynthesis, pentose and glucuronate interconversion, starch and sucrose metabolism, zeatin biosynthesis, microtubules, motor proteins microtubule movement, xyloglucan metabolic process, cell division, and peroxidase activity. In short, non-bagging cultivation is more conducive to improving the intrinsic quality and flavor development of Fuji apples, and one of the mechanisms is that non-bagging cultivation is beneficial for increasing the expression of related genes.

BackgroundChemotherapy has been proven to bring survival benefit in patients with resected muscle-invasive bladder cancer (MIBC), which is increasingly recommended. Our objective was to establish an effective model for estimating the overall survival (OS) and cancer-specific survival (CSS) in these patients.Methods2,030 patients diagnosed with resected MIBC receiving chemotherapy were acquired from the Surveillance, Epidemiology, and End Result (SEER) database, which were randomized 7:3 into a primary set (1,421 patients) and an internal validation set (609 patients). Significant predictors for OS and CSS were identified by Cox regression models, which were then utilized to develop prognostic nomogram. The performance of the model was assessed by utilizing calibration, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA).ResultsSix independent prognostic factors, including age, race, histology, T stage, N stage and regional nodes examined, made up the nomogram. The AUCs of the primary cohort was 0.751 and 0.753 for 3- and 5- year OS and 0.751 and 0.754 for 3-and 5- year CSS, respectively. The calibration plots proved the nomograms' satisfactory discrimination. The results of DCA manifested that our models had an excellent clinical applicability. In addition, a risk stratification system was established according to the nomogram' risk score. Obvious difference was found in different groups (P

Internal tides have a great impact on the meridional overturning circulation and climate variability through contributing to diapycnal mixing. The Luzon Strait (LS) is one of the most important sites of internal tide generation in the global ocean. In this study, we evaluate the effect of the Kuroshio on the M2 and K1 internal tides in both summer and winter seasons in the South China Sea (SCS), particularly within the LS. High-resolution ocean numerical simulations with the Kuroshio Current were compared with those without. We found that the Kuroshio has negligible impact on the generation site of internal tides. Compared to seasonal variability in the total barotropic to baroclinic conversion rate over the LS, the Kuroshio has relatively little influence. However, the Kuroshio flow strongly guides the propagating direction of the internal tides from the LS into the SCS. The Kuroshio also substantially decreases the southward energy fluxes going out of the LS. For both M2 and K1 tides, turning off the Kuroshio leads to a weaker energy exchange between the background shear and internal tides. Turning off the Kuroshio also weakens the divergence of internal tide energy due to the advection of background flow. Thus, our results reveal a non-negligible effect of the Kuroshio on the internal tides in the LS. If one aims to realistically simulate, or better understand, internal tides, these results indicate that one should include realistic oceanic circulation fields.

Abstract Background Esophageal cancer (EC) is one of the leading contributors to the global burden of cancer, and the underlying mechanism is still unknown. Recently, there has been a growing interest in understanding modifiable psychosocial risk factors, particularly depression, to prevent EC and reduce morbidity and mortality. However, related research is sparse and has been ignored. The study was designed to assess the association between depression and EC in China. Methods From 2017 to 2019, a population-based multicenter study was conducted in high-risk regions of EC. Participants underwent a free endoscopy screening. If the endoscopic results were suspicious, a pathological biopsy was applied to confirm. Depression was measured with Patient Health Questionnaire-9 (PHQ-9). In addition, information on demographic characteristics and risk factors was collected from participants by trained interviewers using uniform questionnaires. Results After Endoscopy and pathologic diagnosis, 15,936 participants in high-risk regions of EC (ECHRRs) were enrolled, 10,907 (68.44%) of which were diagnosed health, 4048 (25.40%) with esophagitis, 769 (4.83%) with low-grade intraepithelial neoplasia (LGIN), 157 (0.99%) with high-grade intraepithelial neoplasia (HGIN), and 55 (0.35%) with EC, respectively. The overall prevalence of depression symptoms of participants was 4.16% (health: 4.63%, esophagitis: 2.99%, LGIN: 2.99%, HGIN: 5.73%, and EC: 9.09%). Multiple logistic regression analyses revealed that the unadjusted OR (95% CI) between depression and each esophageal pathology grades were esophagitis 0.93 (0.92-0.95), LGIN 0.97 (0.94-0.99), HGIN 1.05 (1.00-1.10), and EC 1.04 (0.97-1.14), respectively. However, after adjustment for potential confounders (age, gender, region, alcohol consumption, BMI), no statistically significant associations between depression and EC (adjusted OR = 1.10, 0.99-1.21) and esophageal lesions (esophagitis: adjusted OR = 1.02, 0.99-1.04; LGIN: adjusted OR = 0.98, 0.95-1.01; HGIN: adjusted OR = 1.04, 0.98-1.11) were observed in this study. Conclusions No significant association was observed between depression and EC in the study. Future prospective cohort studies are needed to verify this preliminary finding.

Abstract Background Breast cancer is the most commonly diagnosed cancer and leading cause of cancer death among women worldwide but has patterns and trends which vary in different countries. This study aimed to evaluate the global patterns of breast cancer incidence and mortality and analyze its temporal trends for breast cancer prevention and control. Methods Breast cancer incidence and mortality data in 2020 were obtained from the GLOBOCAN online database. Continued data from the Cancer Incidence in Five Continents Time Trends, the International Agency for Research on cancer mortality and China National Central Cancer Registry were used to analyze the time trends from 2000 to 2015 through Joinpoint regression, and annual average percent changes of breast cancer incidence and mortality were calculated. Association between Human Development Index and breast cancer incidence and mortality were estimated by linear regression. Results There were approximately 2.3 million new breast cancer cases and 685,000 breast cancer deaths worldwide in 2020. Its incidence and mortality varied among countries, with the age‐standardized incidence ranging from the highest of 112.3 per 100,000 population in Belgium to the lowest of 35.8 per 100,000 population in Iran, and the age‐standardized mortality from the highest of 41.0 per 100,000 population in Fiji to the lowest of 6.4 per 100,000 population in South Korea. The peak age of breast cancer in some Asian and African countries were over 10 years earlier than in European or American countries. As for the trends of breast cancer, the age‐standardized incidence rates significantly increased in China and South Korea but decreased in the United States of America (USA) during 2000‐2012. Meanwhile, the age‐standardized mortality rates significantly increased in China and South Korea but decreased in the United Kingdom, the USA, and Australia during 2000 and 2015. Conclusions The global burden of breast cancer is rising fast and varies greatly among countries. The incidence and mortality rates of breast cancer increased rapidly in China and South Korea but decreased in the USA. Increased health awareness, effective prevention strategies, and improved access to medical treatment are extremely important to curb the snowballing breast cancer burden, especially in the most affected countries.