Diabetes of the exocrine pancreas(DEP)used to be called pancreatic diabetes,pancreatogenic diabetes or type 3c diabetes mellitus.Currently,the incidence of DEP is higher than that of type 1 diabetes mellitus.The pathogenesis and clinical manifestations of DEP are related to primary pancreatic diseases.In terms of management,we need to consider both pancreatic endocrine and exocrine functions,and comprehensively treat diabetes mellitus and primary pancreatic diseases.By now,there has been no guideline related to DEP;its diagnostic criteria,differentiation with type 2 diabetes mellitus,and selection of hypoglycemic programs are challenges in clinical practice.This article reviews the clinical studies related to DEP,and summarizes the evolution of its terminology,pathogenesis,clinical manifestations,complications,diagnosis,treatment and management.

Fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix due to the imbalance between injury and repair.It can affect multiple organs,including the heart,lungs,liver,kidneys,and pancreas.The progression of fibrosis is usually slow and difficult to reverse,and it can severely impair organ functions.In industrialized countries,deaths caused by fibrosis account for up to 45％,resulting in a tremendous disease burden.Thus,there is an urgent need for drugs that can reverse or delay the progression of fibrosis.In recent years,remarkable progress has been made in the research on the pathogenesis of fibrosis in different organs,and relevant drugs targeting fibrosis are also under active development.This article briefly summarizes the drugs currently marketed and drugs at the clinical trial stage for treating fibrosis.

Objective: To analyze the temporal changes in lipid levels in patients following acute pancreatitis(AP) and explore the factors associated with post-AP serum triglyceride( TG) level changes. Methods: Patients diag- nosed with AP were included in this study. Clinical data were collected retrospectively , and lipid profile data from follow-up visits after discharge were tracked. Kaplan-Meier(K-M) curves were used to stratify follow-up duration ,iodine content detection. Thyroid volume was measured using a fully digital ultrasound imaging system , and goiter prevalence was calculated. Results: A total of 141 patients with 306 follow⁃up visits were included. Spearman correlation analysis showed a mild increase in lipid levels over time post⁃discharge : TG( r = 0. 159 , P = 0. 005) , total cholesterol(TC)( r = 0. 231 , P < 0. 000 1) , high⁃density lipoprotein cholesterol( HDL⁃C) ( r = 0. 181 , P = 0. 002) , and apolipoproteinA1 ( ApoA1) ( r = 0. 371 , P <0. 000 1) . In the univariate linear mixed model , male gender(β = 0. 160 ,P = 0. 007) , body mass index(BMI) (β= 0. 017 , P = 0. 007) , diabetes history(β = 0. 138 , P = 0. 030) , smoking history(β = 0. 166 ,P = 0. 004) , and recurrent AP(β = 0. 119 , P = 0. 029) were significantly associated with Lg(TG) levels (P < 0. 05) . In the multivariate model , BMI( β = 0. 019 , P = 0. 042) , smoking history ( β = 0. 155 , P = 0. 049 ) , and recurrent AP( β =0. 148 , P = 0. 032) remained significantly positively correlated with changes in Lg(TG) levels after AP , albeit with a low correlation strength (r < 0. 200) . Conclusion Lipid levels , including TG , TC , HDL⁃C and ApoA1 , tend to increase over time in AP patients after discharge , with this trend being more pronounced in those with hypertriglyceridemic acute pancreatitis. Post⁃AP TG levels are significantly influenced by BMI at the time of onset , smoking history and recurrent AP.

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.

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.

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.

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.