Prevalence and risk factors of colorectal neoplasia in individuals aged 40-49 years: Findings from screening program in China.

BACKGROUND AND AIM: The incidence of colorectal cancer (CRC) in individuals under 50 is increasing worldwide. We conducted an analysis of colonoscopy findings in high-risk individuals under 50 in the CRC screening program in Tianjin, China, to determine the detection rate and risk factors of advanced adenomas (AA), advanced colorectal neoplasia (ACN), colorectal neoplasia (CN). METHODS: Our study investigated individuals aged 40-49 who underwent CRC screening and completed colonoscopy, 2012-2020, while the 50-54 age group served as a control. We compared the detection rates of AA, ACN, and CN among three age groups using univariate and multivariable logistic regression analyses, and investigated the risk factors associated with AA, ACN, and CN among individuals aged 40-49. RESULTS: We found a gradual increase in the detection rate of AA, ACN, and CN among individuals aged 40-54. The detection rates for AA (OR 0.58; 95% CI 0.41-0.81), ACN (OR 0.58; 95% CI 0.43-0.77), and CN (OR 0.64; 95% CI 0.56-0.74) were lower in individuals aged 40-44 compared to 45-49. The detection rates of AA (OR 1.08; 95% CI 0.87-1.34) and ACN (OR 1.12; 95% CI 0.93-1.35) in individuals aged 45-49 were comparable with 50-54. Besides, lifestyle factors, BMI, and FIT are not associated with the detection rates of AA, ACN, and CN among individuals aged 40-49. CONCLUSIONS: Our study reveals screening data in individuals under 50, indicating comparable detection rates of AA and ACN in individuals aged 45-49 and 50-54. These findings provide valuable data support for optimizing the optimal age to initiate screening.

Screening of host gut-derived probiotics and effects of feeding probiotics on growth, immunity, and antioxidant enzyme activity of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂).

In recent years, the widespread use of antibiotics in intensive grouper mariculture has resulted in the ineffectiveness of antibiotic treatment, leading to an increasing incidence of diseases caused by bacteria, viruses, and parasites, causing serious economic losses. Hence, it is crucial to develop alternative strategies to antibiotics for healthy and sustainable development of the mariculture industry. Here, we aimed to screen host gut-derived probiotics and evaluate its effects on growth and immunity of grouper. In this study, 43 bacterial strains were isolated from the intestine of the hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂), and a potential probiotic strain G1-26, which can efficiently secrete amylase, protease, and lipase, was obtained using different screening mediums. Based on 16S rDNA sequencing, the potential probiotic strain G1-26 was identified as Vibrio fluvialis. The results of a biological characteristic evaluation showed that V. fluvialis G1-26 could grow at 25-45 °C, pH 5.5-7.5, salinity 10-40, and bile salt concentration 0-0.030%, and produce amylase, lipase, and protease under different culture conditions. Additionally, V. fluvialis G1-26 is sensitive to many antibiotics and does not exhibit aquatic biotoxicity. Subsequently, hybrid groupers were fed diets containing V. fluvialis G1-26 at different concentrations (0, 106, 108, and 1010 CFU/g) for 60 d. The results showed that V. fluvialis G1-26 at 108 CFU/g did not significantly affect the growth performance of the hybrid grouper (P > 0.05). V. fluvialis G1-26 supplementation at 108 and 1010 CFU/g significantly promoted the relative expression of immune-related genes in hybrid groupers (TLR3, TLR5, IL-1ß, IL-8, IL-10, CTL, LysC, TNF-2, and MHC-2) and improved the activities of alkaline phosphatase, acid phosphatase, total superoxide dismutase, and total protein in the liver. In conclusion, V. fluvialis G1-26, a potential probiotic strain isolated from the intestine of the hybrid grouper, can be used as an effective immunopotentiator at an optimal dose of 108 CFU/g diet. Our results provide a scientific basis for the development and utilization of probiotics in the grouper mariculture industry.

Per- and polyfluoroalkyl substances in Chinese surface waters: A review.

The contamination of surface waters in China with Per- and polyfluoroalkyl (PFASs) has been extensively studied in recent decades, however, almost all studies have been conducted in small areas and/or limited samples, which are not representative of the nationwide contamination of surface water environments with PFASs. In this study, attempt was made to provide a comprehensive report about PFASs pollution in Chinese surface water based on the PRISMA. By analyzing 111 papers published between 2006 and 2022, we provide a systematic review of the pollution of PFASs in surface water environments in China. The results show that 26 PFASs contaminants were detected at least once in China's surface water environment and were mainly concentrated in the eastern part of China. Most surface water environments in China had mean PFASs concentrations below 100 ng/L. The most polluted place was the Xiaoqing River, where sampling results in 2020 showed PFASs concentrations as high as 25,429 ng/L, followed by the Tangxun Lake, the Xi River, the Daling River, the Majia River, the Baiyangdian Lake, the Liuxi River, the Jiaolai River, the Tuo River and the Zhimai River. The Xiaoqing River also has the highest concentration of the novel pollutant, with concentrations of HFPO-TA and HFPO-DA as high as 1039 ng/L and 164 ng/L. Based on the source analysis, fluoropolymer manufacturing plants are the main source of PFASs pollutants in surface water. The results of the base risk analysis using risk quotients value (RQ) method show that the RQ values of the Xiaoqing River, the surface water near Bohai Bay, the Majia River and the Tuo River PFOA are 36.9, 7.7, 3.6 and 2.1 respectively, which are high risk areas and require enhanced control. This study provides information on surface waters contaminated by PFASs nationwide, and the results can be used as a reference for the development of pollution control and management strategies for PFASs in surface waters in China.

The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma.

The identification of the prognostic markers and therapeutic targets might benefit the diagnosis and treatment of pancreatic adenocarcinoma (PAAD), one of the most aggressive malignancies. Vacuolar protein sorting associated protein 26 A (VPS26A) is a candidate prognosis gene for hepatocellular carcinoma, but its expression and function in PAAD remain unknown. The mRNA and protein expression of VPS26A in PAAD was explored and validated by bioinformatics and immunohistochemical analysis. The correlation between VPS26A expression and various clinical parameters, genetic status, diagnostic and prognostic value, survival and immune infiltration were evaluated, and the co-expressed gene-set enrichment analysis for VPS26A was performed. Cytologic and molecular experiments were further carried out to investigate the role and potential mechanism of VPS26A in PAAD. The mRNA and protein levels of VPS26A were elevated in PAAD tissues. High VPS26A expression was associated with the advanced histological type, tumor stage simplified, smoking status and tumor mutational burden score, and the poor prognosis of PAAD patients. VPS26A expression was significantly correlated with immune infiltration and immunotherapy response. VPS26A-co-expressed genes were mainly enriched in the regulation of cell adhesion and actin cytoskeleton and the immune-response-regulating signaling pathway. Our experiments further demonstrated that VPS26A promoted the proliferation, migration and invasion potentials of PAAD cell lines through activating the EGFR/ERK signaling. Our study suggested that VPS26A could be a potential biomarker and a therapeutic target for PAAD through comprehensive regulation of its growth, migration and immune microenvironment.

A Novel Vermiculite/TiO2 Composite: Synergistic Mechanism of Enhanced Photocatalysis towards Organic Pollutant Removal.

There has been increasing concern over water pollution, which poses a threat to human life and health. Absorption by low-cost absorbents is considered to be a cost-effective and efficient route. However, the non-reusability of absorbents greatly limits their applications. In this study, a novel vermiculite/TiO2 composite combining the inexpensive absorbent with the commonly used photocatalyst was firstly synthesized via the sol-gel method. On the one hand, the organic pollutants are absorbed by vermiculite and then decomposed through the photocatalysis process, enabling the next round of absorption and creating an absorption-decomposition reusable cycle. On the other hand, the modulation effect of optical and electronic structure on the prepared TiO2 photocatalyst by the vermiculite incorporation could significantly improve the photocatalytic activity and eventually enhance the aforementioned cyclic degradation capacity. The layer-structured vermiculite (Vt) supports a uniform coverage of TiO2 at an optimized ratio, providing an optimal adsorption environment and contact area between the photocatalyst and methylene blue (MB) molecules. Vt/TiO2 heterojunction is formed with Si-O-Ti bonding, at which electrons transfer from Vt to TiO2, enriching electron density in TiO2 and favoring its photocatalytic activity. Furthermore, the incorporation of Vt increases the light absorption of TiO2 in the visible range by narrowing the optical band gap to 1.98 eV, which could promote the generation of photo-excited carriers. In addition, PL measurements revealed that the carrier recombination is substantially suppressed, and the charge separation and migration are greatly enhanced by a factor of 3. As a result, the decomposition rate of MB is substantially increased 5.3-fold, which is ascribed to the synergistic effects of the elevated photocatalysis and the large absorption capacity governed by the chemisorption mechanism of the intra-particle diffusion. These results pave the way for composite design towards efficient, economical, and pragmatic water pollution treatment.

Nonradiation-to-endoscopist ERCP is non-inferior to standard ERCP.

BACKGROUND: Radiation exposure is inherently involved in endoscopic retrograde cholangiopancreatography (ERCP), which could cause radiation-induced injury to endoscopists with long-term exposure. Nonradiation ERCP has been applied to pregnant patients. Conceivably, the same techniques could be used to benefit endoscopists. This study was designed to evaluate the effectiveness and safety of nonradiation-to-endoscopist (NRE) ERCP, compared with standard ERCP. METHODS: A retrospective, single-center study was conducted from August 2010 to December 2015. Patients aged 18-90 years and with choledocholithiasis (< 15 mm) or distal biliary stricture were eligible. Pre-ERCP evaluation with magnetic resonance cholangiopancreatography was mandatory. To overcome selection bias, we performed 1:2 match using propensity score matching (PSM) between NRE and standard groups. The primary endpoint was overall ERCP success rate. Secondary endpoints were cannulation success rate, stone clearance rate, complication rate, and duration of hospitalization. RESULTS: A total of 329 patients met inclusion criteria. After PSM, 73 patients were included in the NRE group and 146 in the standard group. The ERCP overall success rate for NRE and standard groups was equivalent (94.5% vs. 93.2%, P = 0.70). There was no difference in cannulation success rates between the two groups (95.6% vs. 97.8%, P = 0.39). A total of 88.3% of patients in the NRE group and 93.9% of patients in the standard group had stones cleared at initial ERCP (P = 0.57). No difference in overall stone clearance rate between the two groups (95.0% vs. 93.9%, P = 0.77) was found after second ERCP. The complication rate (1.4% vs. 1.4%, P = 1.00) and hospital duration (8.3 ± 5.1 vs. 10.2 ± 8.8 days, P = 0.07) were not different between the two groups. CONCLUSION: Although technically demanding, NRE-ERCP is both safe and feasible in selected patients compared with standard ERCP.

[Expression of glucocorticoid receptor in prostate cancer and its clinical significance].

OBJECTIVE: To investigate the expression of glucocorticoid receptor (GR) in the PCa tissue and its correlation with the clinicopathological characteristics and prognosis of PCa. METHODS: Using immunohistochemical staining, we determined the expression of GR in the PCa tissue and analyzed its correlation with the clininicopathological features and prognosis of the malignancy. RESULTS: The positive expression of GR in the PCa tissue was 64%, of which the strongly positive rate was 34.7%. The GR expression was positively correlated with preoperative androgen-deprivation therapy (ADT) (χ2 = 22.307, P < 0.01), Gleason grades (χ2 = 16.534, P = 0.002) and clinical stages of the tumor (χ2 = 9.969, P = 0.041). Kaplan-Meier analysis showed that the GR expression was correlated not with the overall survival (P = 0.156), but with the PSA progression-free survival rate of the PCa patients (P = 0.042), with a shorter PSA progression-free survival time in those with a higher GR expression. Multivariate COX regression analysis revealed that the expression of GR was not an independent prognostic factor for PSA progression-free survival of the PCa patients. CONCLUSION: The expression of GR is related with preoperative ADT, and closely with the biological behavior of the malignancy and treatment resistance of the patients. GR is expected to be a new effective therapeutic target and a prognostic biomarker for PCa.

Premedication with reformulated simethicone and sodium bicarbonate improves mucosal visibility during upper gastrointestinal endoscopy: a double-blind, multicenter, randomized controlled trial.

BACKGROUND: The reformulated simethicone emulsion from Berlin Chemical AG might develop white flocculate precipitate covering the gastric mucosa when used before esophagogastroduodenoscopy (EGD). We aim to investigate whether combining the reformulated simethicone emulsion with 5% sodium bicarbonate solution could prevent the development of white precipitate and improve visibility during EGD. METHODS: Our clinical study involved 523 patients. They were randomly assigned to two groups. In Group A, patients received a warm solution containing 30 ml 5% sodium bicarbonate solution and 15 ml reformulated simethicone emulsion. In Group B, patients received 45 ml 40 °C lukewarm water. Visibility scores were recorded and analyzed. Flushes, volume of flush water, overall time taken for EGD and complications during or after the procedure were also recorded. RESULTS: We found that no white precipitate was observed during EGD in Group A. Moreover, visibility scores in Group A were significantly lower (P < 0.01). Patients in Group A had fewer flushes (P < 0.01) and smaller volume of flush water (P < 0.01). In addition, the overall time taken for the EGD procedure was significantly shorter in Group A (P < 0.01). The percentage of patients who had no adverse response was significantly higher in Group A than in Group B (P < 0.01). CONCLUSIONS: Premedication with a mixed solution of 15 ml reformulated simethicone emulsion and 30 ml 5% sodium bicarbonate solution can prevent the development of white precipitate, substantially enhancing mucosal visibility safely. TRIAL REGISTRATION: The registered name of the trial is "Efficacy of using premedication with reformulated simethicone emulsion during upper gastrointestinal endoscopy examination". Its Current Controlled Trials number is ChiCTR1900021689. Its date of registration is 11 September 2019. Retrospectively registered, http://www.medresman.org.cn/uc/sindex.aspx .

Application of ultrasound-guided intranodal lymphangiography and embolisation in cancer patients with postoperative lymphatic leakage.

BACKGROUND: Traumatic lymphatic leakage is a rare but potentially life-threatening complication. The purpose of this study was to introduce ultrasound-guided intranodal lymphangiography and embolisation techniques for postoperative lymphatic leakage in patients with cancer. METHODS: From January 2018 through June 2020, seven cancer patients (three males, four females, aged 59-75 years [mean 67.57 ± 6.11 years]) developed lymphatic leakage after abdominal or pelvic surgery, with drainage volumes ranging from 550 to 1200 mL per day. The procedure and follow-up of ultrasound-guided intranodal lymphangiography and embolisation were recorded. This study retrospectively analysed the technical success rate, operative time, length of hospital stay, clinical efficacy, and complications. RESULTS: The operation was technically successful in all patients. Angiography revealed leakage, and embolisation was performed in all seven patients (7/7, 100%). The operative time of angiography and embolisation was 41 to 68 min, with an average time of 53.29 ± 10.27 min. The mean length of stay was 3.51 ± 1.13 days. Lymph node embolisation was clinically successful in five patients (5/7, 71.43%), who had a significant reduction in or disappearance of chylous ascites. The other two patients received surgical treatment 2 weeks later due to poor results after embolisation. All patients were followed for 2 weeks. No serious complications or only minor complications were found in all the patients. CONCLUSIONS: Ultrasound-guided intranodal lymphangiography and embolisation were well tolerated by the patients, who experienced a low incidence of complications. Early intervention is recommended for cancer patients with postoperative lymphatic leakage.

Long Non-Coding RNA SOX2 Overlapping Transcript Aggravates H9c2 Cell Injury via the miR-215-5p/ZEB2 Axis and Promotes Ischemic Heart Failure in a Rat Model.

Heart failure is a common cardiovascular disease, which has been regarded as one of the highest health care costs with high morbidity and mortality in the western countries. Long noncoding RNAs have been widely reported to regulate the initiation or progression of cardiovascular diseases. However, the specific role of SOX2 overlapping transcript (SOX2-OT) in ischemic heart failure remains uncharacterized. The present study aimed to explore the function and mechanism of SOX2-OT in ischemic heart failure. The starBase website was used to predict potential miRNAs or target mRNAs. Western blot assay was implemented to test collagen protein levels. Functional assays were conducted to evaluate the effects of SOX2-OT on H9c2 cell viability and apoptosis. RNA pull down and luciferase reporter assays were used to confirm the combination between miR-215-5p and SOX2-OT. We found out that SOX2-OT level was increased by oxygen glucose deprivation/reoxygenation treatment in H9c2 cells. Silencing of SOX2-OT ameliorated cell injury by promoting cell viability, inhibiting cell apoptosis and reducing productions of collagens. Mechanistically, miR-215-5p was confirmed to bind with SOX2-OT after prediction and screening. In addition, we discovered that miR-215-5p negatively regulated zinc finger E-box binding homeobox 2 (ZEB2) protein level by directly binding with ZEB2 3' untranslated region. Finally, we verified that SOX2-OT aggravated cell injury by targeting ZEB2 in H9c2 cells. In conclusion, SOX2-OT aggravated heart failure in vivo and promoted H9c2 cell injury via the miR-215-5p/ZEB2 axis in vitro, implying a novel insight into heart failure treatment.

Preparation of Ag3PO4/TiO2(B) Heterojunction Nanobelt with Extended Light Response and Enhanced Photocatalytic Performance.

Photocatalytic degradation, as an emerging method to control environmental pollution, is considered one of the most promising environmental purification technologies. As Tibet is a region with some of the strongest solar radiation in China and even in the world, it is extremely rich in solar energy resources, which is ideal for applying photocatalytic technology to its ecological environment protection and governance. In this study, Na2Ti3O7 nanobelts were prepared via a hydrothermal method and converted to TiO2∙xH2O ion exchange, which was followed by high-temperature calcination to prepare TiO2(B) nanobelts ("B" in TiO2(B) means "Bronze phase"). A simple in situ method was used to generate Ag3PO4 particles on the surface of the TiO2 nanobelts to construct a Ag3PO4/TiO2(B) heterojunction composite photocatalyst. By generating Ag3PO4 nanoparticles on the surface of the TiO2(B) nanobelts to construct heterojunctions, the light absorption range of the photocatalyst was successfully extended from UV (ultraviolet) to the visible region. Furthermore, the recombination of photogenerated electron-hole pairs in the catalyst was inhibited by the construction of the heterojunctions, thus greatly enhancing its light quantum efficiency. Therefore, the prepared Ag3PO4/TiO2(B) heterojunction composite photocatalyst greatly outperformed the TiO2(B) nanobelt in terms of photocatalytic degradation.

Molecular cloning and functional characterization of growth hormone-releasing hormone in Mastacembelus armatus.

Growth hormone-releasing hormone (GHRH) is a neuropeptide that controls growth hormone (GH) synthesis and release. In this study, the full-length cDNA of Mastacembelus armatus ghrh was obtained by rapid amplification of cDNA ends method. Sequence analysis showed that the cloned sequence is 1090 bp in length, containing an open reading frame (ORF) of 429 bp that encodes a precursor protein of 142 amino acids. Sequence alignment revealed that the 27-amino acid mature peptide of Ghrh in M. armatus is conserved. Real-time PCR showed that ghrh is highly expressed in the brain, with very low or no expression in other tissues. During embryonic and larval development, ghrh expression was low in embryos but increased gradually in the stages of larval development. The biological function of Ghrh peptide was further investigated in vivo. Ghrh injection could significantly upregulate the mRNA expression of growth hormone (gh) and insulin-like growth factor-1/2 (igf-1/2) in M. armatus. Our data indicate that Ghrh is able to activate the GH-IGFs axis in M. armatus.

The role of mSEPT9 in screening, diagnosis, and recurrence monitoring of colorectal cancer.

BACKGROUND: The application of circulating, cell-free, methylated Septin9 (mSEPT9) DNA in screening and recurrence monitoring is highly promising. CpG island methylator phenotype (CIMP) is associated with microsatellite instability (MSI). The present study was performed to determine the diagnostic accuracy of mSEPT9 for colorectal cancer (CRC) and to evaluate its utility in CRC screening and recurrence monitoring. METHODS: For screening and diagnosis of CRC, peripheral mSEPT9 detection and fecal occult blood test (FOBT) were performed in 650 subjects, then the level of CEA, CA19-9 and CA724 was quantified in 173 subjects. Clinicopathological parameters and mismatch repair protein were detected among subjects with CRC. For recurrence monitoring of CRC, the sensitivity of mSEPT9 of 70 subjects was compared with tumor markers and contrast enhanced computed tomography (CECT). RESULTS: Seventy-three percent of CRC patients were mSEPT9-positive at 94.5% specificity, and 17.1% of patients with intestinal polyps and adenoma were mSEPT9-positive at 94.5% specificity, which were higher than FOBT for the screening of CRC. The sensitivity and specificity of mSEPT9 for diagnosis and recurrence monitoring were higher than that of CEA, CA19-9 and CA724. The combined detection of mSEPT9 and CECT enhanced the sensitivity for recurrence monitoring. Pre-therapeutic levels of mSEPT9 were strongly associated with TNM stage, Dukes stages and mismatch repair deficiency (dMMR). CONCLUSIONS: mSEPT9 analysis might be popularized as a routine biomarker for CRC screening. The combined detection of mSEPT9 and CECT can play an important role for recurrence monitoring. CIMP was highly associated with the pathological stage of CRC and dMMR.

Construction of an miRNA-mRNA regulatory network in colorectal cancer with bioinformatics methods.

Colorectal cancer (CRC) is the third most common cancer worldwide. This study aimed to explore the regulatory mechanisms of miRNAs in CRC. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in CRC tissue samples compared with control samples in mRNA and miRNA datasets were screened. Functional and pathway enrichment analysis of the DEGs was carried out. Targets of the DEMs were identified. Overlaps between the DEGs and targets of DEMs were selected. The miRNA-mRNA regulatory network of these overlaps was constructed and visualized. The candidate genes selected were validated by quantitative real-time PCR. DEGs were identified and considered DEGs-1 and DEGs-2. A total of 584 genes in DEGs-1 and 527 genes in DEGs-2 were obtained, including 465 overlaps, and 44 DEMs were identified. The overlaps were enriched in 46 Gene Ontology terms and 19 Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, 137 overlapped genes between targets of the DEMs and the 465 overlaps were obtained. The miRNA-mRNA regulating network of the 137 overlapped genes was constructed. Extracellular matrix-related proteins and pathways might play critical roles in the development of CRC. The quantitative real-time PCR results of the candidates were in agreement with the bioinformatics analysis. miR-128, miR-182, and miR-143 might be key miRNAs regulating cell proliferation and metastasis of CRC.

Isobaric tags for relative and absolute quantification-based proteomic analysis that reveals the roles of progesterone receptor, inflammation, and fibrosis for slow-transit constipation.

BACKGROUND AND AIM: Progesterone receptor, inflammation, neurotransmitter expression, and fibrosis are involved in slow-transit constipation. The aim of the present study was to examine whether patients with slow-transit constipation have an overexpression of progesterone receptor and serotonin, which may impair the fibrosis of muscularis propria in colorectal wall. METHODS: High-resolution colon manometry was used to record the colorectal peristaltic contractions of the proximal ascending and sigmoid colon in patients. Protein samples prepared from frozen sigmoid colon tissue and the proximal margin of the ascending colon of four female patients were compared using isobaric tags for relative and absolute quantification labeling technique coupled to 2D liquid chromatography-tandem mass spectrometry analysis. Immunohistochemical staining of progesterone receptor, serotonin, and fibronectin was performed in paraffin-embedded sigmoid colon tissues and the proximal margin of the ascending colon or ileum from 43 patients with slow-transit constipation. RESULTS: Among these differentially regulated proteins based on isobaric tags for relative and absolute quantification and liquid chromatography-tandem mass spectrometry analysis, 56 proteins involved in the response to progesterone, inflammation, matrix remodeling, fibrosis, and muscle metabolism. Immunohistochemical staining confirmed that there was significantly higher expression of progesterone receptor (t = 19.19, P = 0.000) and serotonin (t = 13.52, P = 0.004) in sigmoid colon than in the proximal margin of the ascending colon and ileum. Progesterone receptor and fibronectin expression in the outer layer of muscularis propria were higher than in the middle layer. CONCLUSIONS: These results demonstrate that progesterone receptor, along with inflammation and fibrosis, may take part in slow-transit constipation development.

Extreme phenophase delays and their relationship with natural forcings in Beijing over the past 260 years.

By merging reconstructed phenological series from published articles and observations of China Phenology Observation Network (CPON), the first blooming date of Amygdalus davidiana (FBA) in Beijing between 1741 and 2000 is reconstructed. The Butterworth method is used to remove the multi-year variations for generating the phenological series of annual variations in the first blooming date of A. davidiana. The extreme delay years in the phenological series are identified using the percentage threshold method. The characteristics of the extreme delays and the correspondence of these events with natural forcings are analysed. The main results are as follows. In annual phenological series, the extreme delays appeared in single year as main feature, only A.D.1800-1801, 1816-1817 and 1983-1984 were the events of two consecutively extreme years. Approximately 85% of the extreme delays occurred during 1-2 years after the large volcanic eruptions (VEI ≥ 4) in the eastern rim or the western rim of the Pacific Ocean, as the same proportion of the extreme delays followed El Niño events. About 73% years of the extreme delays fall in the valleys of sunspot cycles or the Dalton minimum period in the year or the previous year. According to the certainty factor (CF), the large eruptions have the greatest influence to the extreme delays; sunspot activity is the second, and ENSO is the last one. The extreme phenological delayed year is most likely to occur after a large eruption, which particularly occurs during El Niño year and its previous several years were in the descending portion or valley of sunspot phase.