Personalized starting age of gastric cancer screening based on individuals' risk profiles: a population-based prospective study.

BACKGROUND: The current recommended starting age for gastric cancer (GC) lacks unified guideline and individualized criteria. We aimed to determine risk-stratified starting age for GC screening in China based on individuals' risk profiles, and develop an online calculator for clinical application. METHODS: In this multi-center population-based prospective study, we divided participants enrolled during 2015-2017 (n = 59,771, aged 40-69) into screened and unscreened groups and observed them for primary endpoints-GC occurrence, all-cause and GC-specific deaths. The median follow-up was 6.07 years. To determine the reference starting age, the effectiveness of GC screening was assessed by age-groups after propensity-score-matching. Further, we categorized the calculated individual risk scores (using well-established risk factors) by quantiles. Subsequently, we used age-specific 10-year cumulative risk curves to estimate the risk-stratified starting age-when the individual's risk level matches reference starting age risk threshold. RESULTS: During follow-up, 475 GC cases, 182 GC deaths and 1,860 all-cause deaths occurred. All-cause and GC-specific mortality decreased among screened individuals aged ≥45 and 50-59 years, respectively. Thus, the average population (reference) starting age was set as 50 years. The 10-year cumulative risk of GC in average population aged 50 was 1.147%. We stratified the starting age using eight risk factors, and categorized participants as low-, medium-, and high-risk individuals, whose risk-stratified starting age was 58, 50, and 46, respectively. CONCLUSION: While high-risk individuals warrant 3-5 years earlier GC screening than average population (age 50), low-risk individuals can tolerate delayed screening. Our online, personalized starting-age calculator will help risk-adapted GC screening (https://web.consultech.com.cn/gastric/#/).

Attributable liver cancer deaths and disability-adjusted life years in China and worldwide: profiles and changing trends.

OBJECTIVE: Liver cancer is a major health concern globally and in China. This analysis investigated deaths and disability-adjusted life years (DALYs) with respect to etiologies and risk factors for liver cancer in China and worldwide. METHODS: Global and China-specific data were collected on liver cancer deaths, DALYs, and age-standardized rates (ASRs) from the Global Burden of Disease Study 2019 database. Liver cancer etiologies were classified into five groups and risk factors were categorized into three levels. Each proportion of liver cancer burden was calculated in different geographic regions. The joinpoint regression model were used to assess the trends from 1990-2019. RESULTS: Liver cancer accounted for 484,577 deaths worldwide in 2019 with an ASR of 5.9 per 100,000 population. China had an elevated liver cancer death ASR in 2019 and males had an ASR 1.7 times the global rate. The global ASR for DALYs peaked at 75-79 years of age but peaked earlier in China. Hepatitis B virus was the prominent etiology globally (39.5%) and in China (62.5%), followed by hepatitis C virus and alcohol consumption. In high sociodemographic index countries, non-alcoholic steatohepatitis has gained an increasing contribution as an etiologic factor. The liver cancer burden due to various etiologies has decreased globally in both genders. However, metabolic risk factors, particularly obesity, have had a growing contribution to the liver cancer burden, especially among males. CONCLUSIONS: Despite an overall decreasing trend in the liver cancer burden in China and worldwide, there has been a rising contribution from metabolic risk factors, highlighting the importance of implementing targeted prevention and control strategies that address regional and gender disparities.

Esophageal cancer global burden profiles, trends, and contributors.

OBJECTIVE: This study aimed to provide a comprehensive overview of the global burden of esophageal cancer (EC) and determine the temporal trends and factors influencing changes in the global burden. METHODS: The latest incidence and mortality data for EC worldwide were obtained from GLOBALCAN 2022. The mortality and disability-adjusted life years (DALYs) rates for EC from 1990-2019 were sourced from the 2019 Global Burden of Diseases. Trends in EC mortality and DALYs attributable to 11 risk factors or clusters of risk were analyzed using the joinpoint regression model. The trends in age-related EC burden were assessed using a decomposition approach. RESULTS: An estimated 511,054 new cases of EC were diagnosed in 2022 with 445,391 deaths worldwide. Approximately 75% of cases and deaths occurred in Asia. Nearly 50% of global EC deaths and DALYs were attributed to tobacco use in men in 2019, while 20% were attributed to high body mass index (BMI) in women. From 1990-2019, EC deaths and DALYs attributable to almost all risk factors had declining trends, while EC deaths and DALYs attributed to high BMI in men had upward trends. The age-related EC burden exhibited an upward trend driven by population growth and aging, which contributed to 307.4 thousand deaths and 7.2 million DALYs due to EC. CONCLUSIONS: The EC burden remains substantial worldwide. Effective tobacco and obesity control measures are critical for addressing the risk-attributable burden of EC. Population growth and aging pose challenges for EC prevention and control efforts.

Capsular Repair Versus No Repair After Hip Arthroscopy in Patients Without Dysplasia or Generalized Ligamentous Laxity: A Systematic Review and Meta-analysis.

Background: Many recent studies have shown that patients who undergo capsular repair after hip arthroscopy achieve superior clinical outcomes compared with those who do not. However, patients with dysplasia or generalized ligamentous laxity (GLL) were not excluded from most of these studies, which may have affected the outcomes. Purpose: To determine whether capsular repair influences the outcomes of hip arthroscopy for patients without dysplasia or GLL. Study Design: Systematic review; Level of evidence, 1. Methods: Under the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, randomized controlled trials comparing the outcomes of capsulotomy with versus without repair were included, but studies that included patients with dysplasia or GLL were excluded. The study outcomes were patient-reported outcome measures (PROMs) at 6 months and 2 years postoperatively-including the modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sport-Specific Subscale (HOS-SSS)- and were compared between the repair and no-repair groups. A narrative analysis and meta-analysis were performed to integrate and compare the results of the 2 groups. In the meta-analysis of the outcome measures, studies with significant differences in the preoperative scores between the repair and no-repair groups were excluded because previous studies have shown that these can affect the outcomes. Results: A total of 761 studies were initially identified, of which 3 were included. Of the 322 included patients, 136 underwent capsular repair, and 186 underwent capsulotomy with no repair. The meta-analysis showed that capsular repair was associated with significantly higher postoperative PROMs: the mHHS at 2 years (P = .03), the HOS-ADL at 6 months (P = .02) and 2 years (P < .0001), and the HOS-SSS at 6 months (P = .02) and 2 years (P = .001). Conclusion: Capsular repair after hip arthroscopy was associated with superior clinical outcomes when compared with no capsular repair in patients without dysplasia or GLL.

The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Survey of hepatitis B virus infection for liver cancer screening in China: A population-based, cross-sectional study.

BACKGROUND: Hepatitis B virus (HBV) infection is the primary cause of hepatocellular carcinoma (HCC) in China. The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen (HBsAg). However, current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking. We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China. METHODS: Questionnaires including information of sex, age, ethnicity, marital status, educational level, source of drinking water, as well as smoking and alcohol consumption history and serum samples were collected from females aged 45-64 years and males aged 35-64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023. Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg. RESULTS: A total of 603,082 individuals were enrolled, and serum samples were collected for analysis from January 1, 2015 to December 31, 2023. The prevalence of HBsAg positive in the study population was 5.23% (31,528/603,082). The prevalence of HBsAg positive was greater in males than in females (5.60% [17,660/315,183] vs . 4.82% [13,868/287,899], χ 2  = 187.52, P  <0.0001). The elderly participants exhibited a greater prevalence of HBV infection than younger participants (χ 2  = 41.73, P  <0.0001). Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and females. Individuals born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born earlier. CONCLUSIONS: The current prevalence of HBV infection remains above 5% in populations eligible for HCC screening in China. Further efforts should be made to increase the accessibility of HCC screening among individuals with HBV infection.

Metabolic Regulation-Mediated Reversion of the Tumor Immunosuppressive Microenvironment for Potentiating Cooperative Metabolic Therapy and Immunotherapy.

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

Enhancing prime editor flexibility with coiled-coil heterodimers.

BACKGROUND: Prime editing enables precise base substitutions, insertions, and deletions at targeted sites without the involvement of double-strand DNA breaks or exogenous donor DNA templates. However, the large size of prime editors (PEs) hampers their delivery in vivo via adeno-associated virus (AAV) due to the viral packaging limit. Previously reported split PE versions provide a size reduction, but they require intricate engineering and potentially compromise editing efficiency. RESULTS: Herein, we present a simplified split PE named as CC-PE, created through non-covalent recruitment of reverse transcriptase to the Cas9 nickase via coiled-coil heterodimers, which are widely used in protein design due to their modularity and well-understood sequence-structure relationship. We demonstrate that the CC-PE maintains or even surpasses the efficiency of unsplit PE in installing intended edits, with no increase in the levels of undesired byproducts within tested loci amongst a variety of cell types (HEK293T, A549, HCT116, and U2OS). Furthermore, coiled-coil heterodimers are used to engineer SpCas9-NG-PE and SpRY-PE, two Cas9 variants with more flexible editing scope. Similarly, the resulting NG-CC-PE and SpRY-CC-PE also achieve equivalent or enhanced efficiency of precise editing compared to the intact PE. When the dual AAV vectors carrying CC-PE are delivered into mice to target the Pcsk9 gene in the liver, CC-PE enables highly efficient precise editing, resulting in a significant reduction of plasma low-density lipoprotein cholesterol and total cholesterol. CONCLUSIONS: Our innovative, modular system enhances flexibility, thus potentially facilitating the in vivo applicability of prime editing.

Widespread stable noncanonical peptides identified by integrated analyses of ribosome profiling and ORF features.

Studies have revealed dozens of functional peptides in putative 'noncoding' regions and raised the question of how many proteins are encoded by noncanonical open reading frames (ORFs). Here, we comprehensively annotate genome-wide translated ORFs across five eukaryotes (human, mouse, zebrafish, worm, and yeast) by analyzing ribosome profiling data. We develop a logistic regression model named PepScore based on ORF features (expected length, encoded domain, and conservation) to calculate the probability that the encoded peptide is stable in humans. Systematic ectopic expression validates PepScore and shows that stable complex-associating microproteins can be encoded in 5'/3' untranslated regions and overlapping coding regions of mRNAs besides annotated noncoding RNAs. Stable noncanonical proteins follow conventional rules and localize to different subcellular compartments. Inhibition of proteasomal/lysosomal degradation pathways can stabilize some peptides especially those with moderate PepScores, but cannot rescue the expression of short ones with low PepScores suggesting they are directly degraded by cellular proteases. The majority of human noncanonical peptides with high PepScores show longer lengths but low conservation across species/mammals, and hundreds contain trait-associated genetic variants. Our study presents a statistical framework to identify stable noncanonical peptides in the genome and provides a valuable resource for functional characterization of noncanonical translation during development and disease.

Differential mRNA profiles reveal the potential roles of genes involved in lactate stimulation in mouse macrophages.

Lactate is a glycolysis end product, and its levels are markedly associated with disease severity, morbidity, and mortality in sepsis. It modulates key functions of immune cells, including macrophages. In this investigation, transcriptomic analysis was performed using lactic acid, sodium lactate, and hydrochloric acid-stimulated mouse bone marrow-derived macrophages (iBMDM), respectively, to identify lactate-associated signaling pathways. After 24 h of stimulation, 896 differentially expressed genes (DEG) indicated were up-regulation, whereas 792 were down-regulated in the lactic acid group, in the sodium lactate group, 128 DEG were up-regulated, and 41 were down-regulated, and in the hydrochloric acid group, 499 DEG were up-regulated, and 285 were down-regulated. Subsequently, clinical samples were used to further verify the eight genes with significant differences, among which Tssk6, Ypel4, Elovl3, Trp53inp1, and Cfp were differentially expressed in patients with high lactic acid, indicating their possible involvement in lactic acid-induced inflammation and various physiological diseases caused by sepsis. However, elongation of very long chain fatty acids protein 3 (Elovl3) was negatively correlated with lactic acid content in patients. The results of this study provide a necessary reference for better understanding the transcriptomic changes caused by lactic acid and explain the potential role of high lactic acid in the regulation of macrophages in sepsis.

Evaluation of Open Versus Arthroscopic Anterior Talofibular Ligament Reconstruction for Chronic Lateral Ankle Instability With Talar and Subtalar Cartilage MRI T2 Mapping: A 3-Year Prospective Study.

BACKGROUND: Previous studies have examined patients with chronic lateral ankle instability (CLAI) undergoing open and arthroscopic anterior talofibular ligament (ATFL) reconstruction, reporting equivalent clinical results between the 2 procedures. However, data on the magnetic resonance imaging (MRI) outcomes on cartilage health after the 2 procedures are limited. PURPOSE: To compare the cartilage MRI T2 values of the talar and subtalar joints between patients with CLAI undergoing open and arthroscopic ATFL reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A prospective study was conducted on patients who underwent open or arthroscopic ATFL reconstruction between January 2018 and December 2019, with a mean follow-up duration of 3 years. MRI scans and American Orthopaedic Foot & Ankle Society (AOFAS) and Tegner score estimations were completed by patients ≤1 week before surgery, as a baseline measurement, and at a 3-year follow-up. A total of 21 healthy volunteers were included who underwent MRI at baseline. Cartilage health was evaluated using MRI T2 mapping. The talar and subtalar cartilage regions were segmented into 14 subregions. RESULTS: At baseline, patients with CLAI had substantially higher T2 values in the medial anterior, medial center, medial posterior, and lateral center regions on the talus compared with the healthy controls (P = .009, .003, .001, and .025, respectively). Remarkable increases in T2 values in the lateral posterior region on the talus were observed from baseline to follow-up in the open group (P = .007). Furthermore, T2 values were considerably higher in the medial center, medial posterior, lateral posterior, and lateral posterior calcaneal facets of the posterior subtalar joint at follow-up in the arthroscopic group compared with the baseline values (P = .025, .002, .006, and .044, respectively). No obvious differences in ΔT2 values were noted between the 2 groups at follow-up. The AOFAS and Tegner scores remarkably improved from baseline to follow-up for the 2 groups (open: 3.25 ± 0.58 vs 5.13 ± 0.81, P < .001; arthroscopic: 3.11 ± 0.90 vs 5.11 ± 1.08, P < .001), with no considerable difference between them. CONCLUSION: The elevated T2 values of cartilage could not be fully recovered after open or arthroscopic ATFL reconstruction. Both arthroscopic and open ATFL reconstruction displayed similar effects on cartilage health concerning ΔT2, but the arthroscopic group demonstrated more degenerative cartilage subregions than the open group.

Bioorthogonal "Click and Release" Reaction-Triggered Aggregation of Gold Nanoparticles Combined with Released Lonidamine for Enhanced Cancer Photothermal Therapy.

Cancer has been the most deadly disease, and 13 million cancer casualties are estimated to occur each year by 2030. Gold nanoparticles (AuNPs)-based photothermal therapy (PTT) has attracted great interest due to its high spatiotemporal controllability and noninvasiveness. Due to the trade-off between particle size and photothermal efficiency of AuNPs, rational design is needed to realize aggregation of AuNPs into larger particles with desirable NIR adsorption in tumor site. Exploiting the bioorthogonal "Click and Release" (BCR) reaction between iminosydnone and cycloalkyne, aggregation of AuNPs can be achieved and attractively accompanied by the release of chemotherapeutic drug purposed to photothermal synergizing. We synthesize iminosydnone-lonidamine (ImLND) as a prodrug and choose dibenzocyclooctyne (DBCO) as the trigger of BCR reaction. A PEGylated AuNPs-based two-component nanoplatform consisting of prodrug-loaded AuNPs-ImLND and tumor-targeting peptide RGD-conjugated AuNPs-DBCO-RGD is designed. In the therapeutic regimen, AuNPs-DBCO-RGD are intravenously injected first for tumor-specific enrichment and retention. Once the arrival of AuNPs-ImLND injected later at tumor site, highly photothermally active nanoaggregates of AuNPs are formed via the BCR reaction between ImLND and DBCO. The simultaneous release of lonidamine further enhanced the therapeutic performance by sensitizing cancer cells to PTT.

[Production of adeno-associated virus in insect cells using multiple gene deleted baculovirus].

Adeno-associated virus (AAV) is one of the most frequently used viral vectors in the field of gene therapy. However, the industrial production of AAV is facing key bottlenecks such as low yield and high-cost. The aim of this study was to establish a technology system for production of AAV in the double virus infected insects by using multiple-gene deleted baculovirus. First, a multiple gene deleted baculovirus for AAV production was constructed, and the baculovirus titer and its effect on infected cells was examined. Subsequently, the insect cells were co-infected with the double baculovirus and the infection conditions were optimized. At the final stage, we performed AAV production based on optimized conditions, and evaluated relevant parameters including production titer and quality. The results showed that the titer of AAV produced in the multiple gene deleted baculovirus was not different from that of the wild type, but the rate of cell death was significantly slower upon infection. Using the double virus route for optimized production of AAV, the genome titers were 1.63×1011 VG/mL for Bac4.0-1 and 1.02×1011 VG/mL for Bac5.0-2, which were elevated 240% and 110%, respectively, compared with that of the wild-type. Electron microscopy observations revealed that all three groups exhibited normal AAV viral morphology and they showed similar transduction activity. Taken together, we developed an AAV production system based on the infection of insect cells using multiple-gene deleted baculovirus, which significantly improved the virus yield and showed application potential.

Lnc-PSMA8-1 activated by GEFT promotes rhabdomyosarcoma progression via upregulation of mTOR expression by sponging miR-144-3p.

BACKGROUND: GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS. METHODS: GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT-PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT-PCR analysis, Western blot analysis, and cell functional experiments. RESULTS: The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA-miRNA-mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression. CONCLUSION: Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.

Prevalence and Injury Patterns of CFL Injury in Chronic Lateral Ankle Instability: An Observational Cross-Sectional Study Using Ultrasound.

The purpose of this paper is to assess the prevalence and injury patterns of the calcaneofibular ligament (CFL) in chronic lateral ankle instability (CAI) patients using ultrasound imaging. This retrospective study included 938 ankle ultrasound images from January 2016 to May 2018. The patients' demographic data and the injury pattern classified by the injury location and the remnant quality were recorded and correlated using t tests, Fisher's exact tests, and post hoc tests accordingly. Of the 938 CAI patients, CFL injury was found in 408/938 (44%). Among the 408 anterior talofibular ligament (ATFL) and CFL complex injury patients, 71/408 (17%) presented with a completely absorbed ATFL, whereas 13/71 (18%) presented with an absorbed CFL. The total CFL absorption proportion in all patients was relatively low (30/938 = 3%). Post hoc tests indicated a negative association between thickened ATFLs and complex injuries. In addition, a positive association existed between absorbed ATFLs and complex injuries as well as absorbed ATFLs and absorbed CFLs. Thus, the results indicated that total tearing and absorption injury patterns of the CFL in CAI are not common. Even when the ATFL is absorbed, only approximately one-fifth (13/71 = 18%) of CFLs require reconstruction, suggesting that it is unnecessary to routinely repair or reconstruct CFLs in all lateral ligament surgeries.

Cancer profiles in China and comparisons with the USA: a comprehensive analysis in the incidence, mortality, survival, staging, and attribution to risk factors.

China faces a disproportionate cancer burden to the population size and is undergoing a transition in the cancer spectrum. We extracted data in five aspects of cancer incidence, mortality, survival, staging distributions, and attribution to risk factors in China, the USA and worldwide from open-source databases. We conducted a comprehensive secondary analysis of cancer profiles in China in the above aspects, and compared cancer statistics between China and the USA. A total of 4,546,400 new cancer cases and 2,992,600 deaths occurred in China in 2020, accounting for 25.1% and 30.2% of global cases, respectively. Lifestyle-related cancers including lung cancer, colorectal cancer, and breast cancer showed an upward trend and have been the leading cancer types in China. 41.6% of new cancer cases and 49.3% of cancer deaths occurred in digestive-system cancers in China, and the cancers of esophagus, nasopharynx, liver, and stomach in China accounted for over 40% of global cases. Infection-related cancers showed the highest population-attributable fractions among Chinese adults, and most cancers could be attributed to behavioral and metabolic factors. The proportions of stage I for most cancer types were much higher in the USA than in China, except for esophageal cancer (78.2% vs. 41.1%). The 5-year relative survival rates in China have improved substantially during 2000-2014, whereas survival for most cancer types in the USA was significantly higher than in China, except for upper gastrointestinal cancers. Our findings suggest that although substantial progress has been made in cancer control, especially in digestive system cancers in China, there was still a considerable disparity in cancer burden between China and the USA. More robust policies on risk factors and standardized screening practices are urgently warranted to curb the cancer growth and improve the prognosis for cancer patients.

Cancer statistics for young adults aged 20 to 49 years in China from 2000 to 2017: a population-based registry study.

An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple countries. We aimed to report cancer profiles and trends among young adults in China. Data from the China Cancer Registry Annual Report were used to estimate incidence and mortality among young adults (ages 20-49 years) in China in 2017, and an age-period-cohort model was employed to estimate the average annual percent change (AAPC) in incidence and mortality from 2000 to 2017. All 25 cancer types were grouped into obesity- or overweight-associated cancers (12 cancer types) and additional cancers (13 cancer types). In 2017, there were 681,178 new cases and 214,591 cancer deaths among young adults in China. Among young adults, the most common cancers were thyroid, breast, cervical, liver, lung, and colorectal cancer, and the leading causes of cancer deaths were liver, lung, cervical, stomach, breast, and colorectal cancer. From 2000 to 2017, the cancer incidence increased for all cancers combined among young adults, with the highest AAPC (1.46%) for adults aged 20-24 years, while cancer mortality decreased, with the highest AAPC (-1.63%) for those aged 35-39 years. In conclusion, the cancer incidence in China has increased among young adults, while cancer mortality has decreased for nearly all ages. Cancer control measures, such as obesity control and appropriate screening, may contribute to reducing the increasing cancer burden among young adults.

A spatially-controlled DNA triangular prism nanomachine for AND-gated intracellular imaging of ATP in acidic microenvironment.

A DNA triangular prism nanomachine (TPN)-based logic device for intracellular AND-gated imaging of adenosine triphosphate (ATP) has been constructed. By using i-motif sequences and ATP-binding aptamers as logic control units, the TPN logic device is qualified to respond to the acidic environment and ATP in cancer cell lysosomes. Once internalized into the lysosome, the specific acidic microenvironment in lysosome causes the i-motif sequence to fold into a tetramer, resulting in compression of DNA tri-prism. Subsequently, the split ATP aptamer located at the tip of the collapsed triangular prism binds stably to ATP, which results in the fluorescent dyes (Cy3 and Cy5) modified at the ends of the split aptamer being in close proximity to each other, allowing Förster Resonance Energy Transfer (FRET) to occur. The FRET signals are excited at a wavelength of 543 nm and can be collected within the emission range of 646-730 nm. This enables the precise imaging of ATP within a cell. We also dynamically operate AND logic gates in living cells by modulating intracellular pH and ATP levels with the help of external drugs. Owing to the AND logic unit on TPN it can simultaneously recognize two targets and give corresponding intelligent logic judgment via imaging signal output. The accuracy of molecular diagnosis of cancer can be improved thus eliminating the false positive signal of single target-based detection. Hence, this space-controlled TPN-based logical sensing platform greatly avoids sensitivity to extracellular targets during the cell entry process, providing a useful tool for high-precision imaging of the cancer cell's endogenous target ATP.

Long-term esophageal cancer risk and distinct surveillance intervals after a single endoscopy screening: a multicentre population-based cohort study.

Background: Endoscopy surveillance is recommended for mild-moderate dysplasia and negative endoscopy findings every 3 years and 5 years, respectively, but evidence is limited. This study aimed to assess long-term esophageal cancer (EC) incidence and mortality after a single endoscopy screening. Methods: We included individuals at high risk of EC aged 40-69 years who underwent endoscopy screening in 2007-2012 at six centres in rural China and had a baseline diagnosis of negative endoscopy findings, mild dysplasia, or moderate dysplasia. Participants were followed up for EC incidence and mortality. Cumulative incidence and mortality rates of EC were estimated by Kaplan-Meier analyses. Cox regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between baseline endoscopy diagnosis and the risk of EC incidence and mortality. EC incidence and mortality after a single endoscopy screening were compared with those of the population in rural China by the standardized incidence ratio (SIR) and standardized mortality ratio (SMR). Findings: A total of 42,827 participants (40,977 with negative endoscopy findings, 1562 with mild dysplasia, and 288 with moderate dysplasia) were included; 268 EC cases and 128 EC deaths were identified during a median follow-up of 10.62 years. The cumulative EC incidence at 10 years was 0.45% (0.38-0.52) in the group with negative endoscopy findings, 2.39% (1.62-3.16) in the mild dysplasia group, and 8.90% (5.57-12.24) in the moderate dysplasia group, and the cumulative EC mortality at 10 years was 0.23% (0.18-0.27), 0.96% (0.46-1.46), and 2.50% (0.67-4.33), respectively. Compared with individuals with negative endoscopy findings, the HRs for EC incidence and mortality in the mild dysplasia group were 3.52 (2.49-4.97) and 2.43 (1.41-4.19), and those in the moderate dysplasia group were 13.18 (8.78-19.76) and 6.46 (3.13-13.29), respectively. The SIR was 0.53 (0.40-0.70) for the group with negative endoscopy findings, 1.95 (1.69-2.24) for the mild dysplasia group, and 6.75 (6.25-7.28) for the moderate dysplasia group, with the SMRs of 0.43 (0.31-0.58), 1.07 (0.88-1.29) and 2.67 (2.36-3.01), respectively. Interpretation: Individuals with negative endoscopy findings after a single endoscopy screening had a lower EC risk than the general population for up to 10.62 years, while those with mild-moderate dysplasia had an elevated risk. Our results support endoscopy surveillance for mild-moderate dysplasia every 3 years and suggest extending the interval to 10 years after a negative endoscopy finding. Funding: National Key R&D Programme of China, Special Project of Beijing-Tianjin-Hebei Basic Research Cooperation, and Sanming Project of Medicine in Shenzhen.

Besides TLR2 and TLR4, NLRP3 is also involved in regulating Escherichia coli infection-induced inflammatory responses in mice.

The host Toll-like Receptor-2 (TLR2) and Toll-like Receptor-4 (TLR4) play critical roles in defense against Escherichia coli (E. coli) infection is well-known. The NLR pyrin domain-containing 3 (NLRP3) inflammasome is also an important candidate during the host-recognized pathogen, while the roles of NLRP3 in the host inflammatory response to E. coli infection remains unclear. This study aimed to explore the roles of NLRP3 in regulating the inflammatory response in E. coli infection-induced mice. Our result indicated that compared to wild-type mice, the TLR2-deficient (TLR2-/-), TLR4-deficient (TLR4-/-), and NLRP3-deficient (NLRP3-/-) mice had significant decrease in liver damage after stimulation with Lipopolysaccharide (LPS, 1 µg/mL), Braun lipoprotein (BLP, 1 µg/mL), or infected by WT E. coli (1 × 107 CFU, MOI 5:1). Meanwhile, compared with wild-type mice, the TNF-α and IL-1ß production in serum decreased in TLR2-/-, TLR4-/-, and NLRP3-/- mice after LPS, BLP treatment, or WT E. coli infection. In macrophages from NLRP3-/- mice showed significantly reduced secretion of TNF-α and IL-1ß in response to stimulation with LPS, BLP, or WT E. coli infection compared with macrophages from wild-type mice. These results indicate that besides TLR2 and TLR4, NLRP3 also plays a critical role in host inflammatory responses to defense against E. coli infection, and might provide a therapeutic target in combating disease with bacterium infection.