The transformation from inflammation to cancer is a complex pathological process, in which the inflammatory state progresses to the formation of malignant tumors. Chronic pancreatitis (CP) is a progressively inflammatory and fibrosing disease, predominantly featuring acinar cell atrophy owing to the cellular damage and fibrosis of the pancreatic parenchyma. This review centers on elucidating how prolonged exposure to a chronic inflammatory environment prompts adaptive changes in acinar cells, which may ultimately lead to their conversion into cancerous cells. By delving into the pivotal role of acinar-to-ductal metaplasia, this article investigates the multi-stage pathway of CP progression into pancreatic cancer, as well as the underlying molecular regulatory networks. We aim to light on the profound mechanisms of CP's inflammation-driven carcinogenic transformation, and thus provide a scientific foundation for devising innovative preventive strategies and therapeutic interventions targeted at mitigating or halting this lethal conversion process.

Dyspepsia is a common group of clinical symptoms and can be classified into organic and functional dyspepsia. Patients with chronic pancreatitis （CP） often have the symptoms of dyspepsia such as fatty diarrhea， abdominal distention， and abdominal pain， and most patients have pancreatic exocrine insufficiency （PEI）， which belongs to organic dyspepsia. In clinical practice， the diagnosis of PEI and dyspepsia requires a comprehensive assessment of clinical manifestations， nutritional status， and pancreatic exocrine function， and an individualized treatment regimen should be developed based on such factors. However， some patients with normal exocrine function may have the symptoms of dyspepsia， and the diagnosis and treatment of such patients are still difficulties in clinical practice. This article reviews the advances in the diagnosis and treatment of dyspepsia in CP patients.

With the increase in global life expectancy, the incidence of neurodegenerative diseases is increasing year by year. Studies have confirmed that patients with different types of neurodegenerative diseases have circadian rhythm disorder and gut microbiota dysregulation. The occurrence of neurodegenerative diseases and circadian rhythm disorder are mutually causal, and in this causal relationship, gut microbiota may play an important role. Gut microbiota affects the communication between gut and brain through "microbiota ⁃ gut ⁃ brain axis", and can affect neural development. Gut microbiota dysregulation can increase the risk of neurodegenerative diseases. At the same time, the diurnal fluctuation of gut microbiota themselves is also regulated by the host biological clock. This article reviewed the progress of research on relationship of circadian rhythm disorder and gut microbiota involved in neurodegenerative diseases.

Objective:To identify the risk factors and develop nomogram for idiopathic chronic pancreatitis (ICP) patients with common bile duct stricture (CBDS).Methods:The clinical data of 1 633 ICP patients admitted to the Department of Gastroenterology of First Affiliated Hospital of Naval Medical University from January 2000 to December 2013 were collected retrospectively and prospectively. The patients were classified into CBDS group ( n=259) and non-CBDS group ( n=1 374) according to whether CBDS occurred. The cumulative incidence of CBDS after the onset and diagnosis of ICP were calculated by Kaplan-Meier method. After excluding patients who had developed CBDS before/or at the diagnosis of ICP, the remaining patients were randomly divided into the training set and the validation set. The univariate and multivariate Cox proportional hazards regression analysis were used to establish a risk predicting nomogram for CBDS after ICP onset. Its clinical application value was evaluated through the consistency index (C index). Results:15.9%(259/1 633) of patients developed CBDS after the onset of ICP. The cumulative incidence of CBDS at 3, 5, and 10 years after the onset of ICP was 9.6% (95% CI 0.082-0.111), 11.2% (95% CI 0.097-0.129) and 16.2% (95% CI 0.142-0.184), respectively. 9.4%(143/1 517) of patients developed CBDS after the diagnosis of ICP. The cumulative incidence of CBDS at 3, 5, and 10 years after the diagnosis of ICP was 8.3% (95% CI 0.069-0.099), 8.9% (95% CI 0.074-0.105) and 13.3% (95% CI 0.110-0.162), respectively. Univariate analysis found that factors including gender, age at onset of ICP, age at diagnosis of ICP, being adolescents at onset of ICP, smoking history, alcohol intake, initial manifestations, pancreatic duct stones, fatty steatorrhea, main pancreatic duct (MPD) morphology and pain type were significantly different between CBDS group and non-CBDS group. Multivariate analysis showed that male ( HR 2.134, 95% CI 1.336-3.408), age at diagnosis of ICP ( HR 1.038, 95% CI 1.024-1.052), first manifestation (pancreatic abdominal pain) and main duct morphology (complex lesion) were identified as independent risk factors for CBDS in ICP patients. A nomogram for predicting CBDS after ICP diagnosis was established based on the above four variables. The nomogram had a C-index of 0.740 (95% CI 0.700-0.790) for internal validation in the training set and 0.650 (95% CI 0.570-0.730) for external validation in the validation set. Conclusions:The nomogram established in this study can evaluate the risk of developing CBDS in ICP patients, benefit the early diagnosis and timely intervention of CBDS in clinical practice, and prevent potential related complications.

Benign distal biliary strictures (BDBS) are fibrous tissue proliferation and biliary stricture caused by long-term stimulation of the affected bile ducts due to non-neoplastic factors such as iatrogenic injury, chronic inflammation, and bile duct stones, which further leads to recurrent cholangitis, obstructive jaundice, and liver impairment. Relieving distal biliary obstruction and maintaining bile duct patency for a long time are the core of the treatment of BDBS. With the continuous innovation of endoscopic retrograde cholangiopancreatography techniques, new techniques such as endoscopic stenosis dilatation, stent implantation, and magnetic compression anastomosis are gradually becoming effective treatment methods for BDBS. This article elaborates on the advances in endoscopic therapy for BDBS, so as to provide a reference for clinical research.

Objective:To study the effects of naringenin on pancreatic fibrosis in the mouse model of chronic pancreatitis (CP) and its effects on the activation, proliferation and apoptosis of pancreatic stellate cells (PSCs).Methods:Eighteen C57BL/6 mice were randomly divided into control group, CP group and naringenin group, with 6 mice in each group. The CP mouse model was established by intraperitoneal injections of caerulein. Naringenin group was given naringenin (200 mg/kg/day) by gavage once a day from the first day of the fourth week of modeling process to the day before the killing; the control group and CP group were treated by gavage with an equivalent amount of drug solvent containing 0.5% sodium carboxymethyl cellulose (CMC-Na). Mice were killed 5 days after the last caerulein injection, and their pancreatic tissues were collected for hematoxylin-eosin staining and Sirius Red staining, pathological scoring and collagen sedimentation detection. Naringenin with different concentrations (0, 5, 10, 20, 50, 100, 150, 200 μmol/L) were used to intervene HPSC for 24 hours, and CCK-8 method was used to detect the cell activity. TGF-β1 recombinant protein (2 ng/ml) was used to induce PSCs for 1 hour (TGF-β1 stimulation group), and naringenin with low (50 μmol/L), middle (100 μmol/L) and high (150 μmol/L) concentration was used to intervene for 36 hours after TGF-β1 stimulation, respectively. Western Blotting was used to detect the expression of PSC activation related proteins FN and COL1A1, cell proliferation marker p21, anti-apoptotic protein Bcl-xL, pro-apoptotic protein Bax and Bid.Results:The pathological scores of pancreatic tissue [(7.33±1.15), (4.67±1.15)] and the percentage of collagen positive areas [(46±4), (28±2)%] in CP group and naringenin group were higher than those in the control group [0, (4±2)%]. However, these indexes in the naringenin group were lower than those in CP group, and the differences were all statistically significant (all P value <0.05). The relative expression of FN in control group, TGF-β1 stimulation group and low, medium and high naringenin group was 0.02, 0.76, 0.67, 0.34 and 0.07, respectively; the expression of COL1A1 in these groups was 0.51, 1.71, 1.34, 0.84 and 0.11. The expression of FN and COL1A1 in TGF-β1 stimulation group was significantly higher than that in control group, and the expression of FN and COL1A1 in low, medium and high naringenin group was significantly lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). The expression of p21 in the above five groups was 0.87, 1.18, 1.27, 1.22 and 1.00. The expression of p21 in TGF-β1 stimulation group was higher than that in control group, and the expression of p21 in high naringenin group was obviously lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). In addition, the expression of Bcl-xL in these groups was 2.09, 2.21, 2.38, 2.50 and 2.12; the expression of Bax was 0.98, 0.88, 0.98, 1.00 and 0.88; the expression of Bid was 1.15, 1.09, 1.14, 1.18 and 1.18. There was no statistically significant difference among these groups (all P value >0.05). Conclusions:Naringenin could significantly alleviate the inflammation, atrophy and fibrosis in the CP mouse model, and inhibit the activation and proliferation of PSCs. However, naringenin had no significant effect on the apoptosis of PSCs, indicating that naringenin may be potentially used to treat pancreatic fibrosis in CP.

Objective:To summarize the experience of treatment for chronic pancreatitis by analyzing the clinical information of 10 533 patients with chronic pancreatitis admitted to First Affiliated Hospital of Naval Medical University (Changhai Hospital) in the past 28 years.Methods:Clinical data including the age, sex, place of birth, admission time, admission age, admission department, discharge time, hospitalization times and treatment methods of chronic pancreatitis patients admitted to Changhai Hospital from January 1995 to February 2022 were analyzed retrospectively. The changes of chronic pancreatitis patients′ admission, demographic characteristics and treatment mode were summarized.Results:A total of 10 533 patients were analyzed, including 7 443 males (70.66%) and 3 090 females (29.34%), and male to female ratio was 2.41∶1. The average age of admission was (45.7±15.0) years. In terms of geographical distribution, East China was the largest, followed by North China and Northwest China. 10 533 patients were admitted for 19 920 times, and there were 18 156 times (91.14%) in gastroenterology department and 1 452 times (7.29%) in general surgery department. Patients in gastroenterology department were admitted for (1.88±1.45) times and the average length of hospitalization was (10.33±5.63) days. A total of 14 134 endoscopic retrograde cholangiopancreatography [(1.45±1.41) times per patient] were performed among 8 022 patients, and 13 882 pancreatic extracorporeal shock wave lithotripsy [(2.22±0.36) times per patient] were performed among 6 629 patients. In general surgery department, patients were admitted for (1.03±0.16) times and the average length of hospitalization was (14.90±9.00) days. 1 242 patients underwent surgical treatment. The ratio of endoscopic therapy to surgery increased from 0.12∶1 in 1995 to 15.72∶1 in 2021.Conclusions:The study shows that chronic pancreatitis was more common in middle-aged males in China, and the treatment modes of chronic pancreatitis in Changhai Hospital had changed from surgery to endoscopic therapy.

Objective:To explore the safety and efficacy of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating painful chronic pancreatitis patients with pancreatic stones.Methods:The painful chronic pancreatitis patients receiving P-ESWL alone or P-ESWL combined with ERCP at Shanghai Pudong New Area Gongli Hospital from August 2019 to December 2021 were retrospectively analyzed. The success rate of stone fragmentation following P-ESWL, occurrence of postoperative complications, stone clearance rate of the main pancreatic duct and degree of pain relief in the follow-up were evaluated.Results:Among 113 patients, 7 patients were treated with P-ESWL alone and 106 patients were treated by P-ESWL combined with ERCP. The success rate of stone fragmentation was 98.2%. The occurrence of P-ESWL complications was 6.2%. Complete clearance of the main pancreatic duct stones was achieved in 75.2% of patients. With the mean follow-up of 17.5(3-31) months, complete pain relief was achieved in 84.1% of patients. The pain frequency and VAS score of patients treated with P-ESWL alone and P-ESWL combined with ERCP were obviously lower than those before treatment, and the body weight and body mass index were significantly higher than those before treatment, all with statistically significant differences (all P value <0.01). Conclusions:P-ESWL is safe and effective for the management of painful chronic pancreatitis patients with main pancreatic duct stones.

Chronic pancreatitis (CP) during pregnancy is rare but complicated in clinic, and its pathophysiology, clinical manifestations, diagnosis and treatment are special, which may seriously harm the health of mother and fetus if not properly treated. During pregnancy, physiological changes such as insulin resistance, mechanical pressure caused by the enlarged uterus and increased secretion of estrogen and progesterone will affect patients with CP. CP may increase the risk of pregnancy⁃related complications and adverse perinatal outcomes. The management of pregnant patients with CP mainly includes the improvement of lifestyle, symptomatic treatment and obstetric management. This article mainly reviewed the pancreatic physiology, clinical manifestations and management of pregnant patients with CP.

Chronic pancreatitis is a disease of progressive fibrosis in pancreatic tissue, with the characteristic pathological changes of pancreatic duct stones and main pancreatic duct stenosis, some patients may frequently experience pancreatic abdominal pain or acute pancreatitis or develop the complications such as pancreatic pseudocyst and biliary stricture. Endoscopic therapy is the first-line treatment of chronic pancreatitis and has a good clinical effect in the treatment of pancreatic duct stones, main pancreatic duct stenosis, abdominal pain, and complications. With the development of technology, the complications of endoscopic therapy will be further reduced, and patients’ treatment outcome will be further improved. Endoscopic therapy may bring more benefits to patients with chronic pancreatitis.