Pancreatic cancer is characterized by high malignancy and difficult early diag-nosis, with the majority of patients presenting at advanced, unresectable stages at the time of initial diagnosis. The efficacy of conventional treatments, including surgery, radiotherapy, and chemo-therapy, has reached a therapeutic plateau. The concept of precision medicine has gradually infiltrated the diagnosis and treatment of pancreatic cancer, driving the advancement of individua-lized therapies. Large-scale, multi-center studies have significantly advanced the molecular classifica-tion of pancreatic cancer, providing a basis for personalized treatment. Minimally invasive surgery, especially robotic surgery, has seen significant development and is increasingly entering clinical practice. The development of personalized drug screening, targeted therapy, and immunotherapy has paved new avenues for precision treatment. The authors review the latest research progress both domestically and internationally, discussing the application of precision medicine in the treat-ment of pancreatic cancer, aiming to improve patient prognosis.

Pancreatic cancer is characterized by high malignancy and difficult early diag-nosis, with the majority of patients presenting at advanced, unresectable stages at the time of initial diagnosis. The efficacy of conventional treatments, including surgery, radiotherapy, and chemo-therapy, has reached a therapeutic plateau. The concept of precision medicine has gradually infiltrated the diagnosis and treatment of pancreatic cancer, driving the advancement of individua-lized therapies. Large-scale, multi-center studies have significantly advanced the molecular classifica-tion of pancreatic cancer, providing a basis for personalized treatment. Minimally invasive surgery, especially robotic surgery, has seen significant development and is increasingly entering clinical practice. The development of personalized drug screening, targeted therapy, and immunotherapy has paved new avenues for precision treatment. The authors review the latest research progress both domestically and internationally, discussing the application of precision medicine in the treat-ment of pancreatic cancer, aiming to improve patient prognosis.

Pancreatic surgery is one of the most challenging specialties in general surgery. Due to the variety of pancreatic diseases, the difficulty of surgery, and the differences in diagnosis and treatment among different diseases, treatment strategies for these diseases remain controversial. From the aspects of surgical treatment such as pancreatitis, pancreatic cystic neoplasms, pancreatic neuroendocrine neoplasms, and pancreatic cancer, as well as neoadjuvant therapy, adjuvant therapy, immunotherapy, and targeted therapy. We review and summarize the frontier progress of clinical and translational research in pancreatic surgery in 2023, in order to further standardize the diagnosis and treatment of pancreatic surgery.

Pancreatic cancer is a common malignant tumor in the digestive tract, and the difficulty of early diagnosis and the lack of effective treatment means are the main reasons for the poor prognosis of pancreatic cancer. In recent years, multidisciplinary treatment (MDT) has become an important means to break through the bottleneck of diagnosis and treatment of pancreatic cancer and improve clinical prognosis. Besides providing patients with high-quality diagnosis and treatment services, this treatment model helps to improve the clinical diagnosis and treatment level of specialists and cultivate high-quality compound medical talents. It also highlights clinical research groups and high-quality case resource sharing, and promotes the clinical application of innovative drugs and new diagnostic and therapeutic technologies, which plays an essential role in increasing the core competence of hospitals. This paper reviews and summarizes the origin, status quo, and deficiencies of the MDT diagnosis and treatment model of pancreatic cancer in China, and examines the prospects for future development, with the aim to provide reference for domestic and foreign counterparts.

To investigate the differences in postoperative short-term complications and long-term prognosis of pancreatic cancer(PC) patients after total pancreatectomy(TP) and pancreaticoduodenectomy(PD).

As pancreatic cancer (PC) is highly malignant, its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies. First-line chemotherapies for PC, according to current guidelines, include fluoropyrimidine- and gemcitabine-based regimens. Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC, especially those involving glycolysis and glutamine metabolism, are highly associated with chemoresistance. Additionally, lipid metabolism is a major factor in chemoresistance. However, emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance. This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

Pancreatic cystic neoplasm (PCN) is characterized by cystic degeneration with a low incidence. With the development of imaging technology and the popularization of screening, the detection rate of this disease has been increasing in recent years, especially in the elderly population. Due to the multiple subtypes of PCN, difficult differential diagnosis, and the potential risk of malig-nant transformation, the formulation of reasonable diagnosis and treatment strategy is the key to treat PCN. Although many clinical guidelines have been released, the diagnosis and treatment strategies of PCN are still controversial. Elderly patients are generally weak, some with serious comorbidities, and have poor tolerance to surgery. In the process of diagnosis and treatment, clinicians need to pay special attention, carefully evaluate and weigh the advantages and disadvantages, so as to make the best plan for treatment. Based on the current guidelines and clinical experience, the authors summarize the diagnosis, surgical indications, and the whole-course management strategies of elderly patients with PCN, in order to provide suggestions for the diagnosis and treatment of this disease.

Objective:The effect of intermedin (IMD) on ATP-induced activation of inflammatory bodies and pyroptosis of cells and its mechanism were studied using lipopolysaccharide (LPS)-sensitized mouse macrophage line RAW 264.7.Methods:The cells were divided into the control groups, the LPS groups, LPS+IMD groups, and LPS+IMD+LY294002 groups. The expression of interleukin (IL)-1β and IL-18 and the activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory cells were detected by real-time PCR and western blotting, and the pyroptosis of cells was detected by propidium iodide (PI) staining. The measurement data was represented by MS± SD, and the inter-group difference was compared with ANOVA calculations, and P<0.05 represented the difference with statistical significance. Results:Compared with the control group [(0.83±0.09) vs (0.49±0.04)], the ratio of phosphorylated phosphatidylinositol-3-kinase, p-PI3K)/phosphatidylinositol-3-kinase (PI3K) (0.44±0.05) and p-Akt/Akt (0.27±0.06) in the LPS group was significantly decreased. The ratios of p-PI3K/PI3K (1.22±0.18) and pAkt/Akt (0.83±0.09) in LPS+IMD group was significantly increased ( F=31.40, P<0.001; F=50.88, P<0.001). Compared with the control group, the mRNA and protein expressions of IL-1β, IL-18 and NLRP3 inflammasome (NLRP3, caspase-1, ASC) in RAW264.7 cells were up-regulated in the LPS group (LPS and ATP). Compared with LPS group, IMD treatment inhibited the expression of inflammatory cytokines IL-1β, IL-18 and NLRP3 inflammasome, which was blocked by LY294002, a blocker of PI3K/Akt pathway. The results of real-time PCR showed that the relative expression of IL-1β mRNA was (1.00±0.11) in the control group, (8.32±0.61) in the LPS group, (8.32±0.55) in the LPS+IMD group, and (7.23±0.41) in the LPS+IMD+LY group ( F=15.42, P<0.001). The relative expression of IL-18 mRNA in the control group was (1.00±0.17), (1.82±0.21) in the LPS group, (1.14±0.15) in the LPS+IMD group, and (1.53±0.11) in the LPS+IMD+LY group respectively ( F=18.16, P<0.001). The relative expression of NLRP3 mRNA in the control group was (1.00±0.13), (2.58±0.18) in the LPS group, (1.07±0.17) in the LPS+IMD group, and (1.33±0.32) in the LPS+IMD+LY group respectively ( F=15.98, P< 0.001); The relative expression of caspase-1 mRNA in the control group was (1.00±0.09), (6.20±0.19) in the LPS group, (3.43±0.06) in the LPS+IMD group, and (5.50±0.45) in the LPS+IMD+LY group respectively ( F=18.39, P<0.001). The relative expression of ASC mRNA in the control group was (1.00±0.21), (4.58±0.48) in the LPS group, (2.07±0.51) in the LPS+IMD group, and (3.33±0.32) in the LPS+IMD+LY group respectively ( F=15.19, P<0.001). Western blotting results showed that the relative expression of IL-1β protein was as follows: (100%) in the control group, [(188±14)%] in the LPS group, [(112±11)%] in the LPS+IMD group, and [(171±27)%] in the LPS+IMD+LY group respectively ( F=21.25, P<0.001). The relative expression of IL-18 protein in the control group was 100%, [(183±16)%] in the LPS group, [(115±19)%] in the LPS+IMD group, and [(179±23)%] in the LPS+IMD+LY group respectively ( F=19.62, P<0.001). The relative expression of NLRP3 protein was 100% in the control group, [(149±15)%] in the LPS group, [(106±10)%] in the LPS+IMD group, and [(144±15)%] in LPS+IMD+LY group respectively ( F=14.35, P<0.001). The relative expression of ASC protein was 100% in the control group, [(188±12)%] in the LPS group, [(110±18)%] in the LPS+IMD group, and [(192±8)%] in the LPS+IMD+LY group ( F=15.79, P<0.001). Conclusion:IMD inhibits the activation of NLRP3 inflammasome and cell pyroptosis by regulating PI3K/Akt activity.

ObjectiveTo observe the therapeutic effect of Yiyuan Qiwei pills （YYQW） on diabetes mellitus-induced induced erectile dysfunction （DMED） in rats and explore its regulation on the nitric oxide （NO）-cyclic guanosine monophosphate （cGMP） signaling pathway. MethodFifty-five healthy SD male rats of clean grade aged 2-3 months underwent intraperitoneal injection of streptozotocin （STZ） to induce the DMED model， and another 10 healthy SD male rats of clean grade aged 2-3 months were assigned to the control group. The model rats were randomly divided into a model group， a sildenafil group （5 mg·kg^-1， ig）， and low-， medium-， and high-dose YYQW groups （1.5， 3.0， 6.0 g·kg^-1， ig）. The rats in the model group and the control group were given normal saline by gavage at 10 mL·kg^-1， once a day for two months. After intervention， the penile erectile function of rats in each group was measured by a pressure detection system. The pathological changes and ultrastructure of penile corpus cavernosum were observed by hematoxylin-eosin （HE） staining and transmission electron microscopy， respectively. The level of NO in the corpus cavernosum was detected by nitrate reductase. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of cGMP and advanced glycation end products （AGEs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of endothelial nitric oxide synthase （eNOS）， neurogenic nitric oxide synthase （nNOS）， total nitric oxide synthase （NOS）， and phosphodiesterase type5 （PDE5） in rat penile tissues. The expression of above proteins was detected by Western blot. ResultCompared with the control group， the model group showed decreased intracavernous pressure （ICP）， NO， and cGMP levels， reduced mRNA and protein expression of nNOS and NOS， and increased PDE5 mRNA and protein expression （P<0.05）. Compared with the model group， the sildenafil group and the YYQW groups displayed increased ICP， NO， and cGMP levels， elevated mRNA and protein expression levels of nNOS and NOS， and reduced PDE5 mRNA and protein expression levels （P<0.05）. There were no pathological changes in the tissues and cell ultrastructure of the corpus cavernosum in the control group， while serious pathological changes were observed in the model group. Additionally， the sildenafil group and the YYQW groups were superior to the model group， the optimal effect was observed in the high-dose YYQW group. ConclusionYYQW can improve the penile erectile function of DMED rats and reduce the pathological damage of corpus cavernosum. The mechanism may be related to the promotion of nNOS and NOS expression， the inhibition of PDE5 expression， and the activation of the NO/cGMP signaling pathway.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to limited therapeutic options. This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets. We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness. HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4. Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC (log-rank P = 0.036; HR = 1.60, 95% CI = 1.03-2.47). We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency. Furthermore, Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC (log-rank P = 0.022; HR = 0.31, 95% CI = 0.14-0.68) but not in patients with SMAD4-normal PDAC. Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway. These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.