BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and aggressive malignancy. Although most cases are sporadic, hereditary pancreatitis (HP) represents an important predisposing condition. The substantial overlap in clinical symptoms and imaging findings between chronic pancreatitis and early PDAC often leads to diagnostic delay and missed opportunities for timely intervention. CASE SUMMARY A 53-year-old woman with genetically confirmed HP experienced recurrent episodes of pancreatitis and underwent multiple endoscopic retrograde cholangiopancreatography procedures. She was later admitted for evaluation of a markedly elevated carbohydrate antigen 19-9 level and diagnosed with PDAC. Surgical management included distal pancreatectomy, sigmoid colectomy, and total splenectomy, followed by six cycles of adjuvant chemotherapy. Postoperatively, tumor markers normalized, and clinical recovery was achieved. CONCLUSION For individuals with HP, lifelong surveillance and early intervention before malignant progression are strongly recommended.

Chronic and acute pancreatitis (CP and AP, respectively) are debilitating conditions with significant morbidity and mortality, necessitating a comprehensive understanding of their underlying mechanisms. This study provides a high-resolution, multi-omics investigation into the genetic and immune cell underpinnings of pancreatitis, integrating rare familial CP with a large cohort of patients with AP. Utilizing an integrative approach that combined whole-exome sequencing (WES) from two pediatric CP patients and their family members with single-cell RNA sequencing (scRNA-seq) and bulk transcriptomics from a public AP cohort (n = 119), we identified a shared molecular and cellular pathology. WES of the CP family revealed heterozygous mutations in 12 novel genes, including EXOC4, ATG2A, and UNC80. Functional enrichment analysis highlighted autophagy, cell adhesion, and vesicle-mediated transport as the key biological processes implicated in the pathophysiology of both conditions. Single-cell profiling of peripheral blood mononuclear cells (PBMCs) from the CP family revealed a marked increase in the proportion of naive B cells and an altered activity of CD8+ T cells, suggesting a dysregulated B-cell-mediated immune response. This observation was corroborated in the AP cohort, where CIBERSORT analysis revealed a significant increase in both naive B cells and CD8+ T cells correlating with the disease severity. Weighted gene co-expression network analysis (WGCNA) on the AP cohort uncovered 14 gene modules associated with disease progression. These modules were significantly enriched for pathways central to the innate immune response, including complement-dependent cytotoxicity and neutrophil degranulation, providing a molecular link to the observed immune cell infiltration. An artificial intelligence (AI)-driven model incorporating 110 CP family-related genes (GTCPFs) demonstrated exceptional predictive capability (average AUC > 0.84) for AP severity, highlighting the translational potential of our findings. The model identified a robust signature of 17 genes, including ATG2A, EXOC4, and TNS1, which may serve as novel diagnostic and prognostic biomarkers. Our findings provide a unified view of the pathogenesis of pancreatitis, linking novel genetic variants to specific immune cell and transcriptomic signatures. This integrative approach underscores the critical importance of both genetic and immune factors in CP and AP, identifying potential biomarkers and therapeutic targets and paving the way for personalized medicine in the management of these challenging conditions.

INTRODUCTION:Chronic pancreatitis (CP), characterized by progressive pancreatic fibrosis and irreversible tissue damage, lacks definitive therapies. Chaihu Shuyi Formula (CHSYF), a traditional Chinese medicine containing constituents with anti-inflammatory and anti- fibrotic phytochemicals, demonstrates therapeutic potential for CP; however, the therapeutic effects and mechanisms underlying its modulation of the microbiota remain incompletely characterized. METHODS:This study evaluated the therapeutic effects of CHSYF on caerulein-induced CP in mice through histopathological analysis and high-throughput 16S rRNA sequencing of gut microbiota. RESULTS:CHSYF treatment significantly alleviated inflammatory symptoms in CP mice, as evidenced by increased body and pancreatic weights, reduced levels of ALT, AST, IL-6, and TNF- α, and decreased pathological damage, including fibrotic lesions in pancreatic tissues. Analysis of the gut microbiota revealed that CHSYF altered the microbial structure, reduced species richness, and improved gut microbiota imbalance in CP mice. Treatment with CHSYF led to significant decreases in Odoribacter, Faecalibaculum, and Alloprevotella, and a shift in the dominant bacterial communities toward norank_f__Oscillospiraceae, Parabacteroides, Alistipes, and Muribaculum. The gut microbiota of CHSYF-treated mice primarily participate in the endocannabinoid and lysine metabolic pathways. Conversely, the gut microbiota of mice with CP was more involved in pathways such as apelin signaling and calcium signaling. CONCLUSION:CHSYF modulated the gut microbiota in mice with caerulein-induced CP, thereby attenuating pancreatic injury. This study provides novel insights into the application of CHSYF for the treatment of CP.

BACKGROUND:Pediatric chronic pancreatitis (CP) is associated with significant morbidity and nutritional challenges, yet the impact of endoscopic retrograde cholangiopancreatography (ERCP) on clinical and nutritional outcomes in children remains incompletely defined. This study aimed to evaluate age associated outcomes following ERCP in children. METHODS:We conducted a retrospective cohort study of 154 pediatric patients who underwent 360 ERCP procedures between 2019 and 2024 with age-stratified analyses. The primary outcomes included the rate of pre-discharge pain relief, defined as a discharge Visual Analogue Scale (VAS) score <4, the incidence of post-ERCP pancreatitis (PEP), and changes in body mass index (BMI). Nutritional status was assessed using BMI, weight-for-age Z-scores, and vitamin D levels. Follow-up data were available for 134 patients (87%) at ≥2 years. Secondary outcomes included recurrent pancreatitis within 2 years after ERCP, nutritional evolution, and pancreatic function. RESULTS:High rates of nutritional abnormalities were observed, including vitamin D deficiency (61.2%), undernutrition (18%), and overweight/obesity (5.2% & 5.2%). ERCP technical success was 99.17%. In this chronic pancreatitis-only cohort, PEP occurred after 111 of 360 procedures (30.8%) and was more frequent in preschool-aged than school-aged children (35.13% vs. 27.8%, P = 0.023). School-aged children showed a higher pre-discharge pain relief rate and significant VAS score reduction, whereas preschool-aged children had higher PEP rates and less statistically evident VAS score improvement. BMI showed an increasing trend mainly in school-aged children, with no significant change in preschool-aged children. CONCLUSIONS:ERCP appears feasible in pediatric CP, with high technical success and predominantly mild complications. Age was associated with differences in pain relief and PEP risk. Nutritional findings should be interpreted cautiously as a limited longitudinal signal rather than definitive improvement. IMPACT:Patient age was associated with differences in ERCP-related outcomes in pediatric chronic pancreatitis. School-aged children showed a higher pre-discharge pain relief rate, whereas preschool-aged children showed higher PEP rates and less statistically evident VAS score improvement, suggesting the need for careful age-specific risk assessment. To our knowledge, this is one of the largest age-stratified studies evaluating ERCP-related clinical and nutritional outcomes in pediatric chronic pancreatitis. These findings may support age-specific risk assessment, closer monitoring of younger children, and more individualized nutritional follow-up after ERCP.

The main treatments for biliary dilatation (BD) are surgical resection and choledochojejunostomy. However, various factors lead to the postponement of early surgical intervention in pediatric BD patients. This study aimed to analyze the effectiveness and limitations of endoscopic retrograde cholangiopancreatography (ERCP) in BD pediatric patients. Data on patients with BD treated at two centers from June 2018 to June 2022 were retrospectively collected. Patients were categorized into five groups according to Todani classification. Clinical features, ERCP processes, ERCP-related complications, ERCP effectiveness and its limitations were reviewed. A cohort of 77 symptomatic BD patients was evaluated, with pancreaticobiliary malformation (PBM) identified in 68.8

BACKGROUND:Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas.PURPOSE:To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas.STUDY DESIGN:This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China.METHODS:Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression.RESULTS:Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18).CONCLUSION:Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.

Background and AimsMounting evidence highlights a strong association between chronic pancreatitis (CP) and type 2 diabetes (T2D), although the exact mechanism of interaction remains unclear. This study aimed to investigate the crosstalk genes and pathogenesis between CP and T2D.MethodsTranscriptomic gene expression profiles of CP and T2D were extracted from Gene Expression Omnibus, respectively, and the common differentially expressed genes (DEGs) were subsequently identified. Further analysis, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction, transcription factors (TFs), microRNA (miRNAs), and candidate chemicals identification, was performed to explore the possible common signatures between the two diseases.ResultsIn total, we acquired 281 common DEGs by interacting CP and T2D datasets, and identified 10 hub genes using CytoHubba. GO and KEGG analyses revealed that endoplasmic reticulum stress and mitochondrial dysfunction were closely related to these common DEGs. Among the shared genes, EEF2, DLD, RAB5A, and SLC30A9 showed promising diagnostic value for both diseases based on receiver operating characteristic curve and precision-recall curves. Additionally, we identified 16 key TFs and 16 miRNAs that were strongly correlated with the hub genes, which may serve as new molecular targets for CP and T2D. Finally, candidate chemicals that might become potential drugs for treating CP and T2D were screened out.ConclusionThis study provides evidence that there are shared genes and pathological signatures between CP and T2D. The genes EEF2, DLD, RAB5A, and SLC30A9 have been identified as having the highest diagnostic efficiency and could be served as biomarkers for these diseases, providing new insights into precise diagnosis and treatment for CP and T2D.

ETHNOPHARMACOLOGICAL RELEVANCE:Jianpi Jiedu Formula (JPJDF) is a traditional Chinese medicinal decoction clinically used for its anti-cancer properties, particularly in colorectal cancer (CRC). AIM OF THE STUDY:This study aims to investigate the therapeutic effects of JPJDF on CRC and elucidate its potential molecular mechanisms, with a focus on its impact on hypoxia-inducible factor 1 alpha (HIF1α) and cancer-associated fibroblasts (CAFs) both in vitro and in vivo. MATERIALS AND METHODS:UPLC-Q-TOF-MS was used to identify the constituents of JPJDF. A chemical-induced colorectal cancer model was established and treated with JPJDF to evaluate its effects. Tumor size was measured, and histopathological analyses were performed to examine JPJDF's regulatory potential on CRC. The functional mechanism of JPJDF was predicted through network pharmacology, molecular docking, and transcriptomics. Co-culture techniques involving CRC cells and CCD-18Co fibroblasts were used to assess JPJDF's impact on fibroblast activation. The effects of HIF1α on CAFs were evaluated using CCK-8 proliferation, clonal formation, and apoptotic assays, with differential marker expression quantified via qPCR and Western blotting. RESULTS:Pharmacodynamic assessment demonstrated that JPJDF reduced tumor size without affecting body weight, indicating its safety in the chemical-induced murine CRC model. Network pharmacology analysis, combined with molecular docking and transcriptomics, revealed that JPJDF regulates HIF-1 signaling pathways and identified HIF1α as a potential target for JPJDF's anti-CRC effect. JPJDF effectively suppressed CRC growth in vivo by attenuating fibroblast activation, reducing α-SMA expression and POSTN secretion through HIF1α inhibition. HIF1α knockdown in CRC cells inhibited fibroblast proliferation and clonal formation, while overexpression promoted these processes. Additionally, downregulating HIF1α suppressed α-SMA and POSTN expression in fibroblasts, whereas overexpression enhanced fibroblast activation. CONCLUSION:JPJDF emerges as a promising therapeutic candidate for inhibiting CAFs activation by targeting HIF1α, offering potential avenues for modulating fibroblast activation towards CAFs in CRC therapy.

BackgroundPatients with colorectal cancer commonly experience disturbances in coagulation homeostasis. Activation of the coagulation system contributes to cancer-associated thrombosis as the second risk factor for death in cancer patients. This study intended to discover coagulation-related genes and construct a risk model for colorectal cancer patients' prognosis.MethodsCoagulation-related genes were identified by searching coagulation-related pathways in the Molecular Signatures Database. Transcriptomic data and clinical data were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Univariate Cox and backward stepwise regression were utilized to identify prognosis-related genes and construct a predictive risk model for the training cohort. Next, survival analysis determines the risk model's predictive power, correlation with clinicopathological characteristics, and nomogram. Additionally, we characterized the variances in immune cell infiltration, somatic mutations, immune checkpoint molecules, biological functions, and drug sensitivity between the high- and low-score patients.ResultEight hundred forty-five genes were obtained by searching the theme term "coagulation" after de-duplication. After univariate regression analysis, 69 genes correlated with prognosis were obtained from the Cancer Genome Atlas dataset. A signature consisting of 17 coagulation-related genes was established through backward stepwise regression. The Kaplan-Meier curve indicated a worse prognosis for high-score patients. Time-dependent receiver operating characteristic curve analysis demonstrated high accuracy in predicting overall survival. Further, the results were validated by two independent datasets (GSE39582 and GSE17536). Combined with clinicopathological characteristics, the risk model was proven to be an independent prognostic factor to predict poor pathological status and worse prognosis. Furthermore, high-score patients had significantly higher stromal cell infiltration. Low-score patients were associated with high infiltration of resting memory CD4+ T cells, activated CD4+ T cells, and T follicular helper cells. The low-score patients exhibited increased expression of immune checkpoint genes, and this might be relevant to their better prognosis. High-score patients exhibited lower IC50 values of Paclitaxel, Rapamycin, Temozolomide, Cyclophosphamide, etc. The differential signaling pathways mainly involve the calcium signaling pathway and the neuroactive ligand-receptor interaction. Lastly, a nomogram was constructed and showed a good prediction.ConclusionThe prognostic signature of 17 coagulation-related genes had significant prognostic value for colorectal cancer patients. We expect to improve treatment modalities and benefit more patients through research on molecular features.

慢性胰腺炎是发生胰腺癌的独立危险因素,高度重视慢性胰腺炎"炎-癌转化"并进行干预具有重要意义.基于李东垣的阴火理论,认为阴火主要是指脾胃气虚所致的气郁郁火及湿热之邪,是慢性胰腺炎"炎-癌转化"的关键.从阴火理论出发探讨中医药干预慢性胰腺炎"炎-癌转化",需把握其动态变化,紧扣阴火这一核心环节,健脾益气、因势利导、攻伐有道,才能取得临床效益的最大化.

2022 年初上海市 SARS-CoV-2 奥密克戎变异株流行,上海中医药大学附属曙光医院西院院区作为 SARS-CoV-2 感染患者定点医院开展了相关确诊病例的急诊内镜诊疗工作.目前 SARS-CoV-2 感染的暴发流行期已过去,但仍存在后续再度流行的可能,并且 SARS-CoV-2 仍有变异可能,内镜操作中的防护工作仍需继续提高警惕,因此本文总结定点医院的内镜诊疗实践工作,参考国家卫生健康委员会最新发布的文件,结合国家有关 SARS-CoV-2 感染防控期间消化内镜操作的防控措施的规范,梳理并总结了相关经验和体会,以供内镜及相关临床工作者参考.

There is a high incidence of Diabetes mellitus and vitamin D deficiency seen among Hepatitis C patients. The effect of the simultaneous occurrence of DM and low levels of 25-Hydroxy Vitamin D on HCV related liver disease remains unclear. In this study

胰胆管汇合异常(pancreaticobiliary maljunction,PBM)是一种胰胆管发育异常的先天性疾病.胰腺分裂症(pancreas divisum,PD)是胰腺最常见的先天性解剖异常,由胚胎发育时期腹侧胰管与背侧胰管融合失败所致.二者临床均不常见,合并概率更低,诊疗难度较大.本文报道1 例6 岁患儿通过内镜下逆行胰胆管造影(Endoscopic Retrograde Cholangio Pancreatography,ERCP)诊断PBM合并PD并解除胰管梗阻的案例,给临床医师提供参考.

BACKGROUND:Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective.AIM:To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP.METHODS:From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared.RESULTS:The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication.CONCLUSION:ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

BACKGROUND:Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children.AIM:To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children.METHODS:This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated.RESULTS:A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed.CONCLUSION:External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.

目的 探讨SpyGlass内镜直视系统在原位肝移植术后复杂胆道并发症中的应用效果.方法 回顾性分析 369 例因成人原位肝移植术后胆道并发症首次行内镜逆行胰胆管造影术(ERCP)治疗患者的临床资料.分析接受SpyGlass治疗患者的术前情况、术中表现、治疗转归及并发症.结果 56 例患者接受SpyGlass治疗,主要术前体征包括腹部不适 38 例、发热 8 例、黄疸 6 例、皮肤瘙痒 4 例.18 例患者行超声检查,提示胆总管狭窄,肝内胆管明显扩张.56例患者术前均行磁共振胰胆管成像(MRCP)检查,其中胆总管狭窄合并结石36例、单纯胆总管狭窄 16 例、考虑肿瘤可能 4 例,均具有明确的SpyGlass治疗指征.56 例接受SpyGlass治疗患者中,吻合口狭窄合并结石 34 例、单纯吻合口狭窄 12 例、单纯胆道结石 1 例、肿瘤 4 例.48 例SpyGlass操作成功者术后 48 h丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转移酶、碱性磷酸酶、总胆红素水平均较术前下降(均为P<0.05).56 例经SpyGlass治疗患者未出现严重并发症.结论 SpyGlass在肝移植术后复杂胆道并发症治疗中能够明显提高治疗成功率,安全性较高,值得推广应用.

肿瘤微环境是指围绕在肿瘤细胞周围的细胞和理化成分,其改变与肿瘤的侵袭、转移及耐药有关.与肿瘤细胞相比,肿瘤微环境中的非肿瘤成分具有更好的遗传稳定性.水飞蓟宾能够在肿瘤的不同阶段发挥抗肿瘤作用,在结直肠癌的研究中引起了广泛关注.从血管生成、炎症反应、免疫细胞、细胞外基质以及肿瘤相关成纤维细胞等方面综述水飞蓟宾对结直肠癌肿瘤微环境的靶向作用,以期为结直肠癌的治疗提供参考.