BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

BACKGROUND:Obesity is not only related to metabolic diseases such as diabetes and cardiovascular disease,but also closely related to the increased risk of cognitive decline,dementia and other neurodegenerative diseases.Studies have found that aerobic exercise and resistance exercise can help improve obesity-related cognitive impairment,but their therapeutic effects and related mechanisms of action are still unclear.OBJECTIVE:To explore the protective effects of aerobic and resistance exercises on the nervous center of obesity-related cognitive impairment mice.METHODS:Forty-eight 8-week-old C57BL/6J wild-type male mice were randomly divided into four groups:a control group was fed normally for 20 weeks;a high fat group was fed with high fat diet(60％fat energy)for 20 weeks;an aerobic exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of aerobic exercise;and a resistance exercise group was fed with 12 weeks of high-fat diet followed by 8 weeks of resistance exercise.After the exercise intervention,body mass was weighed,insulin tolerance and glucose tolerance were tested to evaluate insulin resistance,and cognitive function of mice in each group was detected by new object recognition experiment and Y-maze experiment.The morphology of hippocampal and cortical tissue cells was observed by hematoxylin-eosin staining.The mRNA relative expression levels of tumor necrosis factor-α and interleukin-6 were detected by real-time fluorescence quantitative PCR,and the protein expressions of Bax,Bcl-2,nuclear factor-κB,Cleaved Caspase-1,Caspase-3,synapsin 1 and brain-derived neurotrophic factor were detected by western blot.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of mice increased in the high-fat group(P＜0.05),accompanied by insulin resistance and cognitive dysfunction,the expression levels of nuclear factor-κB,Bax,Caspase-3,Cleaved Caspase-1 in the hippocampus were significantly increased(P＜0.05),the expression levels of brain-derived neurotrophic factor,synapsin 1and Bcl-2 proteins were significantly decreased(P＜0.05),Bcl-2/Bax ratio was significantly decreased(P＜0.05),and the mRNA levels of inflammatory cytokines,tumor necrosis factor-α and interleukin-6,were significantly up-regulated(P＜0.05).(2)Compared with the high-fat group,the above indexes were significantly improved in the aerobic exercise group(P＜0.05),while in the resistance exercise group,the body mass of mice was significantly decreased,the levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 mRNA were significantly decreased(P＜0.05),the protein expression of Caspase-3 was significantly decreased(P＜0.05),and the protein expression of brain-derived neurotrophic factor was significantly up-regulated(P＜0.05),but no significant changes were observed in the other indexes(P＞0.05).In conclusion,long-term exercise can reduce insulin resistance,down-regulate the expression of nuclear factor-κB pathway,weaken inflammatory response,inhibit neuronal apoptosis and improve synaptic plasticity,resulting in neuroprotective effects,and effectively alleviate obesity-related cognitive dysfunction in obese mice.The therapeutic effect of aerobic exercise is superior to that of resistance exercise.

BACKGROUND:Exercise interventions,recognized for their economic and non-pharmaceutical efficacy,have demonstrated the potential to upregulate brain-derived neurotrophic factor levels,thereby offering a therapeutic approach to the prevention and management of Parkinson's disease.However,the specific mechanisms by which exercise targeting brain-derived neurotrophic factor expression to delay Parkinson's disease onset and progression are not clear.OBJECTIVE:To explore the interplay between brain-derived neurotrophic factor and Parkinson's disease,to analyze the specific regulatory effect and mechanism of exercise on the expression of brain-derived neurotrophic factor in the pathological state of Parkinson's disease,to review the improvement effect of different exercise methods mediated by brain-derived neurotrophic factor on Parkinson's disease,to clarify the potential mechanism of exercise therapy targeting brain-derived neurotrophic factor in the prevention and treatment of Parkinson's disease,in order to provide a new theoretical basis for exercise prevention and treatment of Parkinson's disease.METHODS:A systematic literature review was conducted using"Parkinson's disease,brain-derived neurotrophic factor,neuroprotection,dopamine,neuronal apoptosis,neuroinflammation,and synaptic plasticity"as Chinese keywords,and"Parkinson's disease,BDNF,neuroprotection,neuroinflammation,and synaptic plasticity"as English keywords.Databases including CNKI,WanFang Data,PubMed,and Web of Science were searched for relevant articles published up to February 2024.Totally 98 core articles were selected based on inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Within the pathophysiological framework of Parkinson's disease,exercise has been shown to stimulate the release of the myokine Irisin and to specifically enhance brain-derived neurotrophic factor expression,counteracting kynurenine pathway metabolic dysregulation.(2)Aerobic activities,notably specialized forms such as Running on a Wheel with Electrical Stimulation(rotarod walking exercise)in animals and Nordic Walking in humans,along with multimodal exercise regimens,have been demonstrated to significantly enhance brain-derived neurotrophic factor expression.This upregulation is instrumental in ameliorating the motor symptoms associated with Parkinson's disease.Furthermore,brain-derived neurotrophic factor is implicated in the beneficial modulation of non-motor symptoms,including cognitive and sleep disturbances,through the practice of mind-body interventions like Tai Chi.(3)Exercise-induced high expression of brain-derived neurotrophic factor exerts a neuroprotective effect through several mechanisms:By upregulating the expression of anti-inflammatory cytokines such as interleukin-10,nerve growth factor-beta,and transforming growth factor-beta,and concurrently downregulating the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta,thereby suppressing the activation of microglia via the inhibition of the nuclear factor-kappa B signaling pathway,leading to a reduction in neuroinflammatory responses;by augmenting the activity of tyrosine hydroxylase,which facilitates the synthesis and release of dopamine.This is complemented by the inhibition of matrix metalloproteinase-3 and glycogen synthase kinase-3 beta,preventing the hyperphosphorylation of alpha-synuclein at serine 129,thus counteracting abnormal neuronal apoptosis.By inducing long-term potentiation and promoting the robust expression of post-synaptic density protein 95 and synaptophysin,thereby enhancing synaptic plasticity and exerting a neuroprotective influence that may delay the onset and progression of Parkinson's disease.(4)Considering the pivotal role of brain-derived neurotrophic factor in Parkinson's disease progression and treatment,targeted exercise therapies could advance"Exercise+Medicine"precision medicine for Parkinson's disease.However,current research is limited by a narrow focus on motor symptoms and a lack of diverse exercise protocols.There is a need for more comprehensive,longitudinal studies using varied exercise modalities to better understand and address non-motor symptoms in Parkinson's disease patients to improve the lack of research in the field of Parkinson's disease exercise prevention and treatment.

Nonalcoholic fatty liver disease(NAFLD)is characterized by the pathological accumulation of lipid droplets(LDs)in the liver and is recognized as a chronic metabolic disorder linked to lifestyle-induced dyslipidemia.Li-pophagy,a specialized form of selective autophagy,targets intracellular LDs for degradation through the autophagy-lyso-some pathway,serving as a critical regulatory mechanism for maintaining hepatic lipid homeostasis.In the context of NAFLD,lipophagy is often impaired,which can affect disease progression.Exercise-regulated lipophagy pathways and factors play a crucial role in alleviating the phenotypes associated with NAFLD,indicating that enhancing lipophagy may be a key target for exercise interventions aimed at improving this condition.This article examines the process of liver-relat-ed lipophagy,focusing on its role in the development of NAFLD.It further elucidates the regulatory effects and mecha-nisms by which exercise influences lipophagy within the pathological context of NAFLD,thereby providing a novel theoreti-cal framework and perspective for clinical intervention and exercise rehabilitation strategies in NAFLD management.The review highlights that the role of lipophagy varies across different stages of NAFLD,with both acute and chronic exercise impacting lipophagy through several mechanisms:modulation of the expression of factors related to LD metabolism,en-hancement of lysosomal function during lipophagy,induction of muscle factor FGF21 secretion to activate lipophagy-relat-ed signaling pathways,and regulation of autophagy-associated epigenetic modifications.

BACKGROUND:Exercise interventions,recognized for their economic and non-pharmaceutical efficacy,have demonstrated the potential to upregulate brain-derived neurotrophic factor levels,thereby offering a therapeutic approach to the prevention and management of Parkinson's disease.However,the specific mechanisms by which exercise targeting brain-derived neurotrophic factor expression to delay Parkinson's disease onset and progression are not clear.OBJECTIVE:To explore the interplay between brain-derived neurotrophic factor and Parkinson's disease,to analyze the specific regulatory effect and mechanism of exercise on the expression of brain-derived neurotrophic factor in the pathological state of Parkinson's disease,to review the improvement effect of different exercise methods mediated by brain-derived neurotrophic factor on Parkinson's disease,to clarify the potential mechanism of exercise therapy targeting brain-derived neurotrophic factor in the prevention and treatment of Parkinson's disease,in order to provide a new theoretical basis for exercise prevention and treatment of Parkinson's disease.METHODS:A systematic literature review was conducted using"Parkinson's disease,brain-derived neurotrophic factor,neuroprotection,dopamine,neuronal apoptosis,neuroinflammation,and synaptic plasticity"as Chinese keywords,and"Parkinson's disease,BDNF,neuroprotection,neuroinflammation,and synaptic plasticity"as English keywords.Databases including CNKI,WanFang Data,PubMed,and Web of Science were searched for relevant articles published up to February 2024.Totally 98 core articles were selected based on inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Within the pathophysiological framework of Parkinson's disease,exercise has been shown to stimulate the release of the myokine Irisin and to specifically enhance brain-derived neurotrophic factor expression,counteracting kynurenine pathway metabolic dysregulation.(2)Aerobic activities,notably specialized forms such as Running on a Wheel with Electrical Stimulation(rotarod walking exercise)in animals and Nordic Walking in humans,along with multimodal exercise regimens,have been demonstrated to significantly enhance brain-derived neurotrophic factor expression.This upregulation is instrumental in ameliorating the motor symptoms associated with Parkinson's disease.Furthermore,brain-derived neurotrophic factor is implicated in the beneficial modulation of non-motor symptoms,including cognitive and sleep disturbances,through the practice of mind-body interventions like Tai Chi.(3)Exercise-induced high expression of brain-derived neurotrophic factor exerts a neuroprotective effect through several mechanisms:By upregulating the expression of anti-inflammatory cytokines such as interleukin-10,nerve growth factor-beta,and transforming growth factor-beta,and concurrently downregulating the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta,thereby suppressing the activation of microglia via the inhibition of the nuclear factor-kappa B signaling pathway,leading to a reduction in neuroinflammatory responses;by augmenting the activity of tyrosine hydroxylase,which facilitates the synthesis and release of dopamine.This is complemented by the inhibition of matrix metalloproteinase-3 and glycogen synthase kinase-3 beta,preventing the hyperphosphorylation of alpha-synuclein at serine 129,thus counteracting abnormal neuronal apoptosis.By inducing long-term potentiation and promoting the robust expression of post-synaptic density protein 95 and synaptophysin,thereby enhancing synaptic plasticity and exerting a neuroprotective influence that may delay the onset and progression of Parkinson's disease.(4)Considering the pivotal role of brain-derived neurotrophic factor in Parkinson's disease progression and treatment,targeted exercise therapies could advance"Exercise+Medicine"precision medicine for Parkinson's disease.However,current research is limited by a narrow focus on motor symptoms and a lack of diverse exercise protocols.There is a need for more comprehensive,longitudinal studies using varied exercise modalities to better understand and address non-motor symptoms in Parkinson's disease patients to improve the lack of research in the field of Parkinson's disease exercise prevention and treatment.

Nonalcoholic fatty liver disease(NAFLD)is characterized by the pathological accumulation of lipid droplets(LDs)in the liver and is recognized as a chronic metabolic disorder linked to lifestyle-induced dyslipidemia.Li-pophagy,a specialized form of selective autophagy,targets intracellular LDs for degradation through the autophagy-lyso-some pathway,serving as a critical regulatory mechanism for maintaining hepatic lipid homeostasis.In the context of NAFLD,lipophagy is often impaired,which can affect disease progression.Exercise-regulated lipophagy pathways and factors play a crucial role in alleviating the phenotypes associated with NAFLD,indicating that enhancing lipophagy may be a key target for exercise interventions aimed at improving this condition.This article examines the process of liver-relat-ed lipophagy,focusing on its role in the development of NAFLD.It further elucidates the regulatory effects and mecha-nisms by which exercise influences lipophagy within the pathological context of NAFLD,thereby providing a novel theoreti-cal framework and perspective for clinical intervention and exercise rehabilitation strategies in NAFLD management.The review highlights that the role of lipophagy varies across different stages of NAFLD,with both acute and chronic exercise impacting lipophagy through several mechanisms:modulation of the expression of factors related to LD metabolism,en-hancement of lysosomal function during lipophagy,induction of muscle factor FGF21 secretion to activate lipophagy-relat-ed signaling pathways,and regulation of autophagy-associated epigenetic modifications.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Objective:To evaluate the influence of different detector widths and signal acquisition positions of wide-detector CT in different scanning modes on CT number and noise, and to provide a basis for reasonable selection of scanning modes and related parameters in clinical practice.Methods:The body dose phantom was scanned by GE Revolution CT. The scan was performed with detector widths of 40, 80 and 160 mm in sequential scanning mode and with detector width/pitch combinations of 40 mm/0.516, 40 mm/0.984, 80 mm/0.508 and 80 mm/0.992 in spiral scanning mode. The phantom was placed at the central and peripheral of the selected detector widths, and the adjacent positions between two axial scans. The images of the phantom were evaluated subjectively and the CT numbers and SDs were measured. The differences between the measured values at different imaging parameters were compared. The multi-group Friedman test was used to compare CT numbers and SD under different scanning parameters in sequential scanning mode, and the Wilcoxon test was used to compare CT numbers and SD in spiral scanning mode.Results:There was no statistically significant difference in the geometric shapes of the phantom images obtained at any combination of parameters. In sequential scanning mode, the differences at different detector widths were statistically significant (χ 2=14.00, P=0.001) with CT numbers at 40 mm and 160 mm greater than CT numbers at 80 mm ( P<0.05). The differences at different signal acquisition positions were statistically significant (χ 2=12.04, P=0.002) with CT numbers at peripheral and adjacent greater than CT numbers at central ( P<0.05). In spiral scanning mode CT numbers at detector width at 80 mm were greater than CT numbers at 40 mm ( Z=-2.10, P=0.036). For SD, the differences at different detector widths were statistically significant in sequential scanning modes (χ 2=8.17, P=0.017) with SD at 160 mm greater than SD at 80 mm ( P<0.05). The differences at different signal acquisition positions were statistically significant (χ 2=13.50, P=0.001) with SD at peripheral greater than SD at central ( P<0.05). In spiral scanning mode SDs at pitches 0.984 and 0.992 were greater than SDs at 0.516 and 0.508 ( Z=-2.66, P=0.008). There were no significant differences among other groups. Conclusion:The selection of scanning mode, detector width and signal acquisition position of wide-detector CT will affect the image CT numbers and SDs.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.