Objectives: Retinal ischemia-reperfusion (RIR) injury results in irreversible visual impairments. The disruption of the outer blood-retinal barrier (OBRB) is a major ocular pathogenic process that RIR injury affects. Current clinical strategies are limited. This study aimed to elucidate how electroacupuncture (EA) protects the OBRB against RIR injury. Methods: Male Wistar rats (7 weeks old, 250 g to 280 g) were used in this study. Three independent experiments were conducted. First, Opioid peptide levels were quantified using enzyme-linked immunosorbent assay (ELISA). 42 rats were randomly divided into 7 groups ( n = 6/group): Control: No treatment; high intraocular pressure(HIOP): Acute intraocular pressure elevation-induced RIR injury; HIOP + SHAM EA: RIR injury + sham EA at Xinming (Extra acupoint) and Jingming (BL1) for 30 min (shallow needle insertion but without electric stimulation); HIOP + 2 Hz EA: RIR injury + 2 Hz EA at Xinming and BL1 for 30 min; HIOP + 100 Hz: RIR injury + 100 Hz EA at Xinming and BL1 for 30 min; HIOP + 2/100 Hz EA: RIR injury + 2/100 Hz EA at Xinming and BL1 for 30 min; HIOP + 4/20 Hz EA: RIR injury + 4/20 Hz EA at Xinming and BL1 for 30 min. Second, retinal morphology was assessed by hematoxylin and eosin (HE) staining. 20 rats were randomly allocated into 4 groups ( n = 5/group): Control: No treatment; HIOP: Acute intraocular pressure elevation-induced RIR injury; HIOP + SHAM EA: RIR injury + sham EA at Xinming and BL1 for 30 min (shallow needle insertion but without electric stimulation); HIOP + 2 Hz EA: RIR injury + 2 Hz EA at Xinming and BL1 for 30 min. Third, the permeability of OBRB was evaluated using the fluorescein isothiocyanate(FITC)-dextran leakage assay. 15 rats were randomly divided into 5 groups ( n = 3/group): Control: No treatment; HIOP: Acute intraocular pressure elevation-induced RIR injury; HIOP + SHAM EA: RIR injury + sham EA at Xinming and BL1 for 30 min (shallow needle insertion but without electric stimulation); HIOP + 2 Hz EA: RIR injury + 2 Hz EA at Xinming and BL1 for 30 min; Nal + HIOP + 2 Hz EA: Intravitreal injection of delta-opioid receptor antagonist Naltridole (10 mu l, 100 nM) 30 min before RIR injury induction, followed by 2 Hz EA treatment at Xinming and BL1 for 30 min. In vitro studies examined enkephalins' effects on oxygen-glucose deprivation /reperfusion (OGD/R) induced injury in ARPE-19 cells. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay, and morphological changes were recorded by Molecular Devices. Apoptosis was detected by Annexin V-FITC flow cytometry. Delta opioid receptor (DOR) expression in total protein and membrane protein were analyzed by western blotting (WB). Immunofluorescence (IF) staining and WB assessed ZO-1 and Claudin-19. For cell-based assays, n indicates the number of biologically independent replicates. Results: It was found that 2 Hz EA treatment increased enkephalins (methionine-enkephalin and leucineenkephalin) levels ( P < 0.01), restoring the increased retinal thickness ( P < 0.05) and mitigating RGCs loss ( P < 0.05) post-RIR injury. FITC-dextran leakage in the outer retina was ameliorated by 2 Hz EA ( P < 0.05), reversibly countered by Naltrindole(P < 0.05), a DOR antagonist. Treatment with 30 mu M enkephalins enhanced ARPE-19 cell viability ( P < 0.001, P < 0.0001) and inhibited apoptosis ( P < 0.0001). Enkephalins elevated DOR levels in total protein ( P < 0.05) and membrane protein fractions ( P < 0.001, P < 0.0 0 01), as well as elevated ZO-1 ( P < 0.001, P < 0.01) and Claudin-19 ( P < 0.0 0 01, P < 0. 0 01) levels following OGD/R, counteracted by Naltrindole. Conclusion: It was found that 2 Hz EA inhibits the breakdown of OBRB via enkephalins activate DOR in RIR injury. (c) 2025 World Journal of Acupuncture-Moxibustion House. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

OBJECTIVE:To analyze the DTA (DNMT3A, TET2, ASXL1) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism. METHODS:Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed. RESULTS:75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were TET2 (38.7%, 24/62), DNMT3A (9.7%, 6/62) and ASXL1 (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old (P =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) (P =0.002). The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) (P =0.00). CONCLUSION:Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with TET2 mutation should be vigilant for thromboembolic events.

Endogenous opioid peptides (EOP) are the neurochemical basis of the anesthetic and analgesic effects of acupuncture, and the quantity of acupuncture stimulus can be controlled accurately by using electroacupuncture (EA). The present study explores the dose-effect relationship between EA with different parameters and the regulation of EOP system. In this paper, the intervention effects of EA on EOP system were specially discussed in terms of the single factor and the different combinations of the frequency, waveform and current intensity. This study shows that EOP system presents a frequency-response specificity. The low frequency of EA promotes the release of enkephalin, β-endorphin and endomorphin, the high one activates the dynorphin system selectively, and the intermediate frequency works on promoting the release of enkephalin and β-endorphin, as well as dynorphin. Sparse-dense wave of EA may induce the release of enkephalin, β-endorphin, endomorphin and dynorphin, presenting a synergistic effect. However, the waveform of EA should be selected flexibly in clinical practice. Sometimes the better therapeutic effect can also be obtained with the continuous wave of EA. EOP system is involved in mediating appropriate intensity of EA, while the acupuncture effect generated by an extra strong EA stimulation refers to a kind of stress response of non-opioid mechanism. The different combinations of EA parameters result in various effects. The combination of EA parameters should be optimized in accordance with different diseases, which is valuable for guiding clinical practice and the development of EA therapy.

Endogenous opioid peptides (EOP) are the neurochemical basis of the anesthetic and analgesic effects of acupuncture, and the quantity of acupuncture stimulus can be controlled accurately by using electroacupuncture (EA). The present study explores the dose-effect relationship between EA with different parameters and the regulation of EOP system. In this paper, the intervention effects of EA on EOP system were specially discussed in terms of the single factor and the different combinations of the frequency, waveform and current intensity. This study shows that EOP system presents a frequency-response specificity. The low frequency of EA promotes the release of enkephalin, β-endorphin and endomorphin, the high one activates the dynorphin system selectively, and the intermediate frequency works on promoting the release of enkephalin and β-endorphin, as well as dynorphin. Sparse-dense wave of EA may induce the release of enkephalin, β-endorphin, endomorphin and dynorphin, presenting a synergistic effect. However, the waveform of EA should be selected flexibly in clinical practice. Sometimes the better therapeutic effect can also be obtained with the continuous wave of EA. EOP system is involved in mediating appropriate intensity of EA, while the acupuncture effect generated by an extra strong EA stimulation refers to a kind of stress response of non-opioid mechanism. The different combinations of EA parameters result in various effects. The combination of EA parameters should be optimized in accordance with different diseases, which is valuable for guiding clinical practice and the development of EA therapy.

Objectives: Retinal ischemia-reperfusion injury (RIRI) is the common pathological basis of many ophthalmic diseases in the later stages, and inflammation is the primary damage mechanism of RIRI. Our study aimed to assess whether electroacupuncture (EA) has a protective effect against RIRI and to elucidate its related mechanisms. Methods: A high-intraocular pressure (HIOP) model was used to simulate RIRI in Wistar rats. EA was applied to the EA1 group [Jingming (BL1) + Shuigou (GV26)] and the EA2 group [Jingming (BL1) + Hegu (LI4)] respectively for 30 min starting immediately after the onset of reperfusion and repeated (30 min/time) at 12 h and then every 24 h until days 7 after reperfusion. The pathological changes in the retina were observed by H and E staining after HIOP. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was utilized to observe retinal cell apoptosis. The mRNA expression of IL1-β, TNF-α, IL-4, IL-10, δ-opioid receptor (DOR), brain-derived neurotrophic factor (BDNF), and tropomyosin-related kinase B (TrkB) in the retina was measured by quantitative real-time PCR. Results: HIOP caused structural disorders of the retina, decreased RGCs, and increased retinal cell apoptosis. At 1 and 3 days of RIRI, retinal apoptotic cells in the EA group were significantly reduced, while there was no distinct difference in the EA group compared with the HIOP group at 7 days of RIRI. Compared with that in the HIOP group, the expression of anti-inflammatory factors, DOR and TrkB was increased, and the expression of pro-inflammatory factors was decreased in the EA group. In contrast, HIOP had no appreciable effect on BDNF expression. Conclusion: EA at Jingming (BL1) and Shuigou (GV26) or at Jingming (BL1) and Hegu (LI4) may inhibit RIRI induced inflammation through activating the DOR-BDNF/TrkB pathway to protect the retina, especially the pair of Jingming (BL1) and Shuigou (GV26) has better inhibitory effects on inflammation.

Diabetic kidney disease (DKD), a common cause of end-stage renal disease, is a serious complication that develops with the progression of chronic diabetes. Its main clinical manifestations are persistent proteinuria and/or a progressive decline in the estimated glomerular filtration rate. Podocytes, terminally differentiated glomerular visceral epithelial cells, constitute the glomerular filtration barrier together with the basement membrane and endothelial cells, and the structural and functional barrier integrity is closely related to proteinuria. In recent years, an increasing number of studies have confirmed that podocyte injury is the central target of the occurrence and development of DKD, and research on exosomes in podocyte injury associated with DKD has also made great progress. The aim of this review is to comprehensively describe the potential diagnostic value of exosomes in podocyte injury associated with DKD, analyze the mechanism by which exosomes realize the communication between podocytes and other types of cells and discuss the possibility of exosomes as targeted therapy drug carriers to provide new targets for and insights into delaying the progression of and treating DKD.

IDDF2018-ABS-0134 Table 1 Participant characteristics and colonoscopy findings (n=2,813) Total Percentage (%) Gender (male) 1463 52.0 Ever smoking 931 33.1 Alcohol drinking 823 29.3 Family history in FDR 390 13.9 Hypertension 1004 35.7 Diabetes 293 10.4 Heart disease 156 5.5 COPD 19 0.7 Stroke 18 0.6 Cirrhosis 5 0.2 Fatty Liver 135 4.8 Personal cancer history (rather than CRC) 64 2.3

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes and is a chronic progressive condition. It is also a common cause of end-stage renal disease (ESRD), which is characterized by proteinuria or a progressive decline in the glomerular filtration rate. Due to their dependence on high-energy and aerobic metabolism, renal tubules are more susceptible to the metabolic disturbances associated with DKD, leading to inflammation and fibrosis. Consequently, tubular injury has become a recent research focus, and significant advancements have been made in studying the role of extracellular vesicles in DKD-associated tubular injury. This review aimed to elucidate the mechanisms and potential applications of different types of extracellular vesicles in tubular injury in DKD to provide new insights for the prevention and treatment of DKD.

Purpose. Retinal ischemia–reperfusion injury (RIRI) is the basis of the pathology that leads to many retinal diseases and induces necroptosis and apoptosis. Tumor necrosis factor-α (TNF-α) is critically involved in necroptosis and apoptosis. Delta-opioid receptor (DOR) activation inhibits TNF-α release in our previous studies, it might prevent necroptosis and apoptosis by inhibiting the release of TNF-α. However, the role of TNF-α and DOR in necroptosis and apoptosis of retinal pigment epithelial (RPE) cells remains largely unknown. Here, we explored the mechanisms of TNF-α and DOR in necroptosis and apoptosis using an oxygen-glucose deprivation/reoxygenation (OGD/R) model of adult retinal pigment epithelial cell line-19 (ARPE19) cells. Materials and Methods. ARPE19 cells were exposed to OGD/R conditions to mimic RIRI in vitro. Cell viability was quantified using the Cell Counting Kit-8 (CCK-8) assay. Morphological changes were observed by inverted microscopy. TNF-α protein levels in cell lysates were measured by enzyme-linked immunosorbent assay (ELISA). The DOR agonist TAN-67 and antagonist naltrindole (NTI) were used to pretreat cells for 1 or 2 hours before OGD24/R36 administration. Calcein acetoxymethylester/propidium iodide (Calcein-AM/PI) and Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to detect necroptotic and apoptotic ARPE19 cells, respectively. The protein expression of DOR, p-RIP1 (RIP1), p-RIP3 (RIP3), p-MLKL (MLKL), and cleaved Caspase3 (Caspase3) was measured by western blotting. Results. OGD severely damaged ARPE19 cells. Prolonged reoxygenation significantly increased TNF-α level and decreased DOR expression in ARPE19 cells. Pretreatment with the DOR agonist TAN-67 (10 µM) significantly improved ARPE19 cell viability after OGD24/R36 by reducing the number of necroptotic and apoptotic cells. Furthermore, DOR activation significantly inhibited TNF-α release and suppressed the expression of proteins related to necroptosis and apoptosis, including p-RIP1, p-RIP3, p-MLKL, and cleaved Caspase3, after OGD24/R36. This effect was reversed by the DOR antagonist NTI. Conclusion. These results strongly suggest that DOR activation inhibits necroptosis and apoptosis by decreasing TNF-α release, leading to the prevention of OGD/R-induced injury in ARPE19 cells. This study provides an innovative idea for clinical treatment strategies for retinal damage and vision loss due to RIRI.

3591 Background: Raltitrexed-based chemotherapy regimen is one of the common regimens for the treatment of metastatic colorectal cancer (mCRC). This prospective observational real-world study aimed to evaluate the safety and effectiveness of raltitrexed administered to Chinese patients with mCRC in real life setting. Methods: This is a prospective, multicenter, real-world study. Prospectively registered Patients received second-line treatment of raltitrexed plus irinotecan combined with or without target therapy until progression disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality of life (QOL) and safety. Totally,1000 patients were required for primary point testing. Results: Between May 2018 and December 2021,a total of 1039 patients from 57 centers were screened for enrollment,among which 271 patients were treated with raltitrexed plus irinotecan, 753 patients accepted target therapy (bevacizumab or cetuximab) additionally, and 15 patients combined with other drugs. Overall mPFS was 6.8 months (95%CI: 6.5-7.1),ORR was 20.2%, and DCR was 85.7%; The ORR of combined with or without target therapy were 21.6% and 16.2% ( p = 0.038),respectively, the DCR were 88.2% and 79.0% ( p < 0.001). The mPFS of combined without or with target therapy were 5.2 months (95% CI: 4.7 to 5.7) and 7.3 months respectively (95% CI: 7.0-7.7) [HR = 0.67, 95% CI 0.56̃0.80, p < 0.001], The mPFS of combined with bevacizumab or cetuximab were 7.4 months (95% CI: 7.0 -7.8) and 6.8 months (95% CI: 5.9-7.7) [HR = 1.15, 95% CI 0.88̃1.51, p = 0.3]. mOS has not yet reached. Majority of treatment-related adverse events (TEAEs) were grade I or II. The most common grade III or IV TRAEs reported by 116 patients (11.2%) were aspartate aminotransferase increased (4.0%), alanine aminotransferase increased (3.7%), neutrocytopenia (2.7%), glutamyltransferase increased (2.5%), leukocytopenia (1.1%). Conclusions: The real-world study confirmd that raltitrexed was an effective and safe regimen for the second-line treatment in Chinese patients with mCRC, especially combined with target therapy additionally, which was aligned with previous trials. Clinical trial information: ChiCTR1800016185.

Several vaccines have been developed for COVID-19 since the pandemic began. This study aimed to evaluate the factors associated with COVID-19 vaccination intention. A global survey was conducted across 26 countries from October, 2020 to December, 2021 using an online self-administered questionnaire. Demographic information, socio-economic status, and clinical information were collected. A logistic regression examined the associations between vaccine intention and factors such as perceptions and the presence of chronic physical and mental conditions. The sample included 2459 participants, with 384 participants (15.7%) expressing lower COVID-19 vaccination intent. Individuals who identified as female; belonged to an older age group; had a higher level of education; were students; had full health insurance coverage; or had a previous history of influenza vaccination were more willing to receive vaccination. Conversely, those who were working part-time, were self-employed, or were receiving social welfare were less likely to report an intention to get vaccinated. Participants with mental or physical health conditions were more unwilling to receive vaccination, especially those with sickle cell disease, cancer history within the past five years, or mental illness. Stronger vaccination intent was associated with recommendations from the government or family doctors. The presence of chronic conditions was associated with lower vaccine intention. Individuals with health conditions are especially vulnerable to health complications and may experience an increased severity of COVID-19 symptoms. Future research should evaluate the effectiveness of interventions targeting the vaccine perceptions and behaviours of at-risk groups. As such, public awareness campaigns conducted by the government and proactive endorsement from health physicians may help improve COVID-19 vaccination intention.

Background: This study aimed to evaluate the updated disease burden, risk factors, and temporal trends of liver cancer based on age, sex, and country. Methods: We estimated the incidence of liver cancer and its attribution to hepatitis B virus (HBV) and hepatitis C virus (HCV) in 2018 based on the Global Cancer Observatory and World Health Organization (WHO) Cancer Causes database. We extracted the prevalence of risk factors from the WHO Global Health Observatory to examine the associations by weighted linear regression. The trend analysis used data from the Cancer Incidence in Five Continents and the WHO mortality database from 48 countries. Temporal patterns of incidence and mortality were calculated using average annual percent change (AAPC) by joinpoint regression analysis. Results: The global incidence of liver cancer was (age-standardized rate [ASR]) 9.3 per 100,000 population in 2018, and there was an evident disparity in the incidence related to HBV (ASR 0.2–41.2) and HCV (ASR 0.4–43.5). A higher HCV/HBV-related incidence ratio was associated with a higher level of alcohol consumption (β 0.49), overweight (β 0.51), obesity (β 0.64), elevated cholesterol (β 0.70), gross domestic product (β 0.20), and Human Development Index (HDI; β 0.45). An increasing trend in incidence was identified in many countries, especially for male individuals, population aged ≥50 years, and countries with a higher HCV/HBV-related liver cancer incidence ratio. Countries with the most drastic increase in male incidence were reported in India (AAPC 7.70), Ireland (AAPC 5.60), Sweden (AAPC 5.72), the UK (AAPC 5.59), and Norway (AAPC 4.87). Conclusion: We observed an overall increasing trend of liver cancer, especially among male subjects, older individuals, and countries with a higher prevalence of HCV-related liver cancer. More efforts are needed in enhancing lifestyle modifications and accessibility of antiviral treatment for these populations. Future studies should investigate the reasons behind these epidemiological changes.

This study aimed to examine the global burden, risk factors, and trends of esophageal cancer based on age, sex, and histological subtype. The data were retrieved from cancer registries database from 48 countries in the period 1980–2017. Temporal patterns of incidence and mortality were evaluated by average annual percent change (AAPC) using joinpoint regression. Associations with risk factors were examined by linear regression. The highest incidence of esophageal cancer was observed in Eastern Asia. The highest incidence of adenocarcinoma (AC) was found in the Netherlands, the United Kingdom, and Ireland. A higher AC/squamous cell carcinoma (SCC) incidence ratio was associated with a higher prevalence of obesity and elevated cholesterol. We observed an incidence increase (including AC and SCC) in some countries, with the Czech Republic (female: AAPC 4.66), Spain (female: 3.41), Norway (male: 3.10), Japan (female: 2.18), Thailand (male: 2.17), the Netherlands (male: 2.11; female: 1.88), and Canada (male: 1.51) showing the most significant increase. Countries with increasing mortality included Thailand (male: 5.24), Austria (female: 3.67), Latvia (male: 2.33), and Portugal (male: 1.12). Although the incidence of esophageal cancer showed an overall decreasing trend, an increasing trend was observed in some countries with high AC/SCC incidence ratios. More preventive measures are needed for these countries.

Background This study aimed to evaluate the global incidence, mortality of gallbladder cancer, and their associations with human development index (HDI), gross domestic products (GDP), smoking, alcohol drinking, and overweight for 180 countries. Methods The regional and national incidence and mortality figures for gallbladder cancer in 2018 were retrieved from the GLOBALCAN database. Age-standardized rates (ASRs) were evaluated by the Segi–Doll world standard population. HDI and GDP per capita in 2018 for each country were collected from the United Nation and World Bank. Prevalence of smoking, alcohol drinking, and overweight in 2010 was retrieved from the Global Health Observatory. The association between the incidence/mortality and these factors was examined by Pearson’s correlation coefficient (r). Results The global ASR of the incidence of gallbladder cancer was 2.3 per 100,000 persons in 2018. The highest rates were reported in Eastern Asia (ASR=3.0), whilst the lowest rates were found in Middle Africa (0.35). The incidence was the highest in countries with very high HDI (2.5) as compared to those with high (2.4), medium (2.0), and low HDI (0.55). Countries with higher incidence were correlated with higher HDI (r=0.31, p<0.001) and a higher prevalence of smoking (0.26, 0.005) and overweight (0.20, 0.011, figure 1). The global ASR of mortality was 1.7. The highest rates were reported in Eastern Asia (ASR=2.4), whilst the lowest rates were found in Middle Africa (0.29). The mortality was the highest in countries with high HDI (1.9) as compared to those with very high (1.5), medium (1.5), and low HDI (0.45). Countries with higher mortality were correlated with higher HDI (r=0.22, p=0.005) and a higher prevalence of smoking (0.27, 0.003). No correlations with GDP or alcohol drinking were found (p>0.05). Conclusions Higher incidence and mortality of gallbladder cancer were found in regions with higher HDI, higher prevalence of smoking and overweight. With population aging and growth, we might expect a further substantial increase in its disease burden, especially for countries with high socioeconomic development. Preventive interventions on reducing the prevalence of risk factors for gallbladder cancer are warranted.

BACKGROUND:IgA nephropathy (IgAN) is achronic immuno-inflammatory progressive disease. Several systemic inflammatory indicators, mainly the neutrophil-to-lymphocyte ratio (NLR), are regarded as valuable markers for many diseases, such as IgA vasculitis and chronic kidney disease. Here, we investigated multiple peripheral blood indicators in a large IgAN registry with regular follow-up to evaluate their effects on IgAN phenotypes and progression.METHODS:Totally, 1151 IgAN patients with regular follow-up, and 251 healthy volunteers were enrolled. Complete blood count test results, including counts of white blood cells (WBC), neutrophils (NE), lymphocyte (LY), and platelets (PLT), were collected from medical records. Then, NLR and PLR were calculated.RESULTS:IgAN patients presented with increased WBC, NE, NLR and PLR levels and decreased LY levels compared with controls. In univariate survival analysis, WBC, NE and NLR showed significant associations with IgAN progression, and NLR had a higher area under the ROC curves than NE and WBC. When adjusted for well-known risk factors, NLR remained an independent risk factor for poor renal outcome in IgAN patients and performed better than NE. By using NLR 2.40 as cutoff point, IgAN patients were divided into two groups. IgAN patients in the high NLR group presented with lower eGFR, higher proteinuria, higher incidence of hypertension, and more severe pathological lesions, as well as lower event-free renal survival rate.CONCLUSIONS:We found patients with IgAN had elevated NLR levels than healthy controls, and the easily available NLR in clinical practice could serve as an independent risk factor for IgAN progression.

Background Worldwide, oesophageal cancer is one of the most common cancers and a leading cause of cancer mortality. Owing to its aggressive disease nature and poor survival rate, it contributes to a substantial burden to global health and clinical practice. This study aimed to estimate the worldwide incidence and risk factors of oesophageal cancer by histological subtypes using data from 178 countries. Methods The data on the incidence of oesophageal cancer by histological types in 2018 were estimated from GLOBALCAN and Cancer Incidence in Five Continents (CI5). Age-standardized rates (ASRs) for oesophageal cancer incidence by histological subtypes were evaluated by Segi–Doll population. The prevalence of tobacco use, alcohol drinking, physical inactivity, obesity, diabetes, and lipid disorders for each country were retrieved from the Global Health Observatory. The association between the ratio of histological subtypes and risk factors was examined by multivariable linear regression. Results We estimated a total of 63,470 (12.6%) and 502,669 new cases of oesophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) in 2018, respectively. The incidence among males was 3.6-fold and 2.2-fold of that among females for AC and SCC, respectively. The highest AC:SCC ratio was found in the UK (ratio 2.880, ASR 7.5), New Zealand (2.667, 4.2), the Netherlands (2.536, 7.7), Bahrain (2.143, 0.9), and Canada (2.000, 3.7) among males (figure 1). As for females, the highest AC:SCC ratio was observed in Moldova (1.000, 0.2), the Netherlands (0.800, 1.2), Iceland (0.750; 0.5), the UK (0.700; 1.4), and Cyprus (0.667; 0.3). A higher AC:SCC ratio was associated with a higher prevalence of obesity (male: β 0.039, 95% CI 0.023 to 0.055; female: 0.009, 0.004 to 0.146) and high cholesterol (male: 0.028, 0.010 to 0.047; female: 0.011, 0.004 to 0.019); but a lower prevalence of tobacco use (male: -0.007, -0.014 to -0.001) and diabetes (male: 0.009, 0.004 to 0.146; female: -0.021, -0.038 to -0.003). Conclusions While SCC is the predominant subtype of oesophageal cancer, the incidence of AC has surpassed SCC in a substantial proportion of countries, probably due to the increasing prevalence of obesity and metabolic disorders. Future research should investigate the reasons behind these epidemiological changes.

*Corresponding author: Yunlin Wu, Department of Gastroenterology, Shanghai Jiaotong University Medical School, Ruijin North Hospital, Shanghai, China, E-mail: 15026691592@139.com Introduction Colorectal Cancer (CRC) is a common malignancy associated with mutations in multiple genes. It may take 10 years to progress from a benign tumor to CRC in 80% of the affected people. Therefore, CRC screening is critical for early detection and treatment of this disease. The Fecal Occult Blood Test (FOBT) and colonoscopy are the mainstay of CRC screening. However, the FOBT has a low diagnostic performance especially for colorectal adenoma [1-3]. Colonoscopy is the gold standard for diagnosing CRC with good sensitivity and specificity but is associated with a high risk of complications and low compliance [3]. Cancer cells from early-stage CRC are continuously shed into the colonic lumen and mixed into stool. Tests for genetic and Abstract

Colonoscopy is effective in the prevention and screening of colorectal cancer. Whether terminal ileal (TI) intubation is required during conventional colonoscopy and whether it offers clinical benefits with respect to polyp detection rate (PDR) remain unclear. This retrospective study included patients who underwent colonoscopy at our hospital between July 1, 2018 and April 20, 2019. The positive findings and time for TI intubation were recorded. Univariate and multivariate analyses were performed to identify factors associated with PDR. There were 1675 patients with cecal intubation colonoscopy, including 994 (59 %) with TI intubation and 8 (1 %) with intestinal disease. The mean time for TI intubation was 40 seconds (3-338), and the mean time from cecal intubation to arrival at the deep part of TI mucosa was 24 seconds (2-118). The overall PDR was 27 %. On multivariable analysis, age > 50 years [95 % confidence interval (CI) 2.837-4.590], male sex (95 % CI, 0.406-0.649), presence of symptoms (abdominal symptoms vs. asymptomatic, 95 % CI, 1.146-2.468; stool changes vs. asymptomatic, 95 % CI, 1.070-1.834), and non-TI intubation (95 % CI, 1.040-1.648) were independent predictors of higher PDR. Trend analysis indicated decreasing trend of PDR among non-TI intubation group, 0-5cm TI intubation group, and > 5cm TI intubation group (30 % vs. 27 % vs. 24 %, respectively; p < 0.05). TI intubation is necessary to identify small bowel disease among a designated population, but it was not suggested to be routinely performed as part of colonoscopy, owing to limited positive intestinal findings, extra time requirement, and possible PDR worsening.

Non‑alcoholic fatty liver disease (NAFLD) and colorectal polyps have been shown to have similar pathogenic factors. The understanding of the association between these two pathologies may contribute to the early diagnosis and treatment of colorectal tumors. The present study compared the biological characteristics of colorectal polyps between patients with and without NAFLD. For this purpose, 1,538 patients with colorectal polyps treated from July, 2013 and June, 2020 were included and divided into the NAFLD and control group (non‑NAFLD group). The location, number, morphology, size and pathology of the polyps were compared between the 2 groups. For the analysis of the biological characteristics of the polyps, the multiple of number (74.5%), percentages of polyps >1.0 cm in diameter (62%) and polyps with advanced adenomas. For the analysis of the biological characteristics of the polyps, the multiple of number (74.5%), percentages of polyps in diameter of 1.0 to <2.0 cm + ≥2.0 cm (48.4 and 13.6%, respectively) and polyps with advanced adenomas (62.9%) in the NAFLD group exhibited significant differences compared with the control group (69.5, 39.2, 6.3 and 55.3%, respectively; all P<0.05); however, no significant differences were observed in the location and morphology of the colorectal polyps between the patients with NAFLD and the controls (P>0.05). When the patients were stratified by sex, age and body mass index, it was found that the patients in the NAFLD group with a polyp size <1.0 cm and those with advanced adenomas exhibited significant differences compared with the control group (P<0.05, respectively). Further analysis revealed that the classification percentage of advanced adenomas in the NAFLD group only exhibited a statistically significant difference compared with the control group in patients with a lower weight (P<0.05). On the whole, the present study demonstrates that NAFLD is significantly associated with the presence of colorectal polyps, particularly in patients with multiple polyps, those with a large size and with villous features (advanced adenomas). Patients with NAFLD may thus be considered a target group for screening colonoscopy.