Pancreatic neuroendocrine neoplasms represent a highly heterogeneous group of malignancies exhibiting a broad spectrum of biological behaviors ranging from indolent to highly aggressive. The formulation of therapeutic strategies requires a comprehensive consideration of patient condition and tumor biological characteristics. Neoadjuvant therapy has demonstrated promising efficacy in tumor downstaging,enhancing R0 resection rates,and improving prognoses across various solid tumors,yet its application in pancreatic neuroendocrine neoplasms remains underexplored with limited clinical evidence. This review systematically examines critical issues in neoadjuvant management of pancreatic neuroendocrine neoplasms based on contemporary guidelines and emerging literature,encompassing patient selection criteria,regimen optimization,response evaluation,and optimal surgical timing. Current challenges persist in standardizing neoadjuvant approaches,necessitating multicenter prospective studies to establish high-level evidence. Future advancements in artificial intelligence and precision medicine hold potential to revolutionize personalized therapeutic paradigms,ultimately improving patient survival outcomes.

Pancreatic neuroendocrine neoplasms represent a highly heterogeneous group of malignancies exhibiting a broad spectrum of biological behaviors ranging from indolent to highly aggressive. The formulation of therapeutic strategies requires a comprehensive consideration of patient condition and tumor biological characteristics. Neoadjuvant therapy has demonstrated promising efficacy in tumor downstaging,enhancing R0 resection rates,and improving prognoses across various solid tumors,yet its application in pancreatic neuroendocrine neoplasms remains underexplored with limited clinical evidence. This review systematically examines critical issues in neoadjuvant management of pancreatic neuroendocrine neoplasms based on contemporary guidelines and emerging literature,encompassing patient selection criteria,regimen optimization,response evaluation,and optimal surgical timing. Current challenges persist in standardizing neoadjuvant approaches,necessitating multicenter prospective studies to establish high-level evidence. Future advancements in artificial intelligence and precision medicine hold potential to revolutionize personalized therapeutic paradigms,ultimately improving patient survival outcomes.

Objective:To investigate the clinicopathological characteristics and prognosis of pancreatic cancer (PC) patients with fatty pancreas (FP).Methods:The retrospective cohort study was conducted. The clinicopathological data of 116 patients with PC who underwent surgery at Qilu Hospital of Shandong University from January 2013 to January 2022 were collected. There were 85 males and 31 females, aged 60(54,65)years. Observation indicators: (1) clinicopathological characteristics of PC patients with FP; (2) influencing factors for FP in PC patients; (3) prognosis of PC patients with FP. Comparison of count data between groups was conducted using the Pearson chi-square test. Multivariate analysis was conducted using the Logistic regression model. The Kaplan-Meier method was used to plot survival curve and calculate survival rate, and Cox proportional hazard model was used for survival analysis.Results:(1) Clinicopathological characteristics of PC patients with FP. Of the 116 PC patients, there were 43 cases with FP and 73 cases without FP. Cases with tumor location at pancreatic head were 36 in PC patients with FP and 46 in PC patients without FP. Cases with tumor location at pancreatic body or tail were 7 in PC patients with FP and 27 in PC patients without FP. Cases with high-density lipoprotein cholesterol ≥1.04 mmol/L were 14 in PC patients with FP and 34 in PC patients without FP. Cases with dyslipidemia were 33 in PC patients with FP and 36 in PC patients without FP. There were significant differences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP ( χ2=5.600, 4.588, 5.165, P<0.05). (2) Influencing factors for FP in PC patients. Results of multivariate analysis showed that no correlation was found between tumor location, high-density lipoprotein cholesterol, plasma lipid and FP in PC patients ( P>0.05). (3) Prognosis of PC patients with FP. Eighty of the 116 PC patients were followed up for 30.8(15.1,57.5)months, with the median overall survival time of 24.0 months. Among them, 54 patients with FP had a median overall survival time of 19.5 months, 26 patients without FP had a median overall survival time of 24.6 months, showing no significant difference in survival between them ( hazard ratio=1.031, P>0.05). Conclusions:There are differ-ences in tumor location, high-density lipoprotein cholesterol and plasma lipid between PC patients with and without FP, but no correlation is found between the above indicators and FP in PC patients. There is no significant difference in prognosis between patients with and without FP.

Objective Exploring the therapeutic mechanism of Yishen Jiangzhuo Granules(YSJZG)on chronic kidney disease(CKD)based on mitochondrial dynamics and apoptosis of renal tubular epithelial cells.Methods The CKD model of rats with 5/6 nephrectomy was adopted and divided into 6 groups according to random number table:sham operation control group,model group,emodin group(500 mg/kg/d),Yishen Jiangzhuo granule low,middle and high dose groups.After 8 weeks of treatment with YSJZG,serum creatinine(SCR)and urea nitrogen(BUN),pathological changes of renal cortex,mitochondrial morphology and ultrastructure were detected,and mitochondrial kinetic protein in renal tubular epithelial cells was detected by immunohistochemistry(Drp1,Fis1)and fusion proteins(Opa1,Mfn1)were detected by Western blot,and apoptotic proteins(CytC,Bax)in cytoplasm and mitochondria were detected by real-time PCR.Results Renal injury:Compared with the model group,YSJZG groups significantly reduced the levels of SCR and BUN,renal tubular degeneration and necrosis,and mitochondrial structural damage in rats.Renal tubule mitochondrial dynamic protein:Compared with the model group,the expression of division proteins Drp1 and Fis1 was downregulated,the expression of fusion proteins Opa1 and Mfn1 was upregulated,and transmission electron microscopy observed that the mitochondrial fragmentation changes were relatively mild.Apoptosis related indicators and mtDNA copy number of renal tubular cells:Compared with the model group,the content of Bax protein in renal tubular epithelial cells of YSJZG groups increased significantly in cytoplasm(P<0.05)and decreased significantly in mitochondria(P<0.05).The content of CytC protein decreased significantly in cytoplasm(P<0.05)and increased significantly in mitochondria(P<0.05).The copy number of mtDNA increased significantly(P<0.05),and the total levels of SMAC,CytC and Bax mRNA decreased significantly(P<0.05).Correlation between mitochondrial dynamic protein and apoptosis in renal tubular cells:Pearson correlation analysis showed that the expression of Drp1 and Fis1 was negatively correlated with the expression of CytC in mitochondria,and positively correlated with the expression of CytC in cytoplasm.The expression levels of fusion proteins Opa1 and Mfn1 showed a significant positive correlation with CytC expression in mitochondria,and a significant negative correlation with CytC expression in cytoplasm.Conclusion YSJZG can significantly delay the progression of CKD,and its mechanism may be achieved by regulating mitochondrial dynamics of renal tubular epithelial cells,thereby inhibiting endogenous cell apoptosis pathway.

Objective:To establish a rat model of vulvovaginal candidiasis (VVC) and to directly observe the histopathological and ultrastructural characteristics of vaginal mucosal barrier after Candida albicans infection and treatment with Lactobacillus crispatus.Methods:Female unmated SD rats were used to establish the VVC model and divided into three groups (normal group, VVC group, and Lactobacillus group; n=6 per group). Lactobacillus group received intravaginal administration of Lactobacillus crispatus suspension, while rats in VVC group and normal group were infused with phosphate buffered solution instead. Vaginal tissues were collected on day 4 post-treatment for HE staining and transmission electron microscopy (to observe ultrastructural pathological changes). Results:The results of HE staining revealed the disruption and desquamation of vaginal epithelium, necrotic epithelial tissues, neutrophil infiltration in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal structure (mucosal layers and thickness) to normal levels, mucosal layers of Lactobacillus group and normal group were 9.50±1.38 vs 10.67±1.03 ( P=0.226), mucosal thickness of Lactobacillus group and normal group were (116.50±12.14) vs (130.33±13.91) μm ( P=0.211). The results of transmission electron microscopy revealed intercellular desmosome rupture, loss of microvilli and glycocalyx on superficial cells, and mitochondrial swelling in Candida albicans-infected rats. Lactobacillus crispatus intervention restored the damaged vaginal mucosal ultrastructures (mitochondria and intercellular connections, etc.) to normal levels. Conclusions:Fungal infection severely disrupte the vaginal mucosal barrier in rats. Lactobacillus crispatus could restore the vaginal mucosal barrier and epithelial ultrastructures.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective:To explore the effect of ginsenoside Rg1 on spermatogenic dysfunction in mice caused by diabetes and its mechanism of action.Methods:Eighteen male C57BL mice were randomly divided into control group, the model group and the ginsenoside Rg1 group by completely random method, with 6 mice in each group. Type 2 diabetes models were established in the model group and the ginsenoside Rg1 group by a high-fat diet combined with intraperitoneal injection of streptozotocin, while control group was injected with the same amount of normal saline. After successful modeling, control group was given a regular diet for 8 weeks, while the model group and ginsenoside Rg1 group were given a high-fat diet for 8 weeks. The ginsenoside Rg1 group was also treated with ginsenoside Rg1 medication. Reproductive hormone levels were detected by enzyme-linked immunosorbent assay test kits, and Western blotting was used to detect the expressions of apoptosis-related proteins (Bcl2 protein, Caspase-3 protein, Bax protein), autophagy-related proteins (P62, LC3Ⅰ, LC3Ⅱ, Beclin1), β-Catenin protein, mTOR protein, LAMP1 protein and transcription factor EB. The body weight, blood glucose levels, testicular index of mice in each group were compared, as well as the testicular injury status.Results:The body weight [(18.77±1.14) g], testosterone level [(141.07±8.47) ng/L], follicle-stimulating hormone level [(9.19±0.74) U/L], and luteinizing hormone level [(1 497.91±99.57) pg/L] of mice in the model group were significantly lower than those in the control [(31.57±2.35) g, P<0.001; (171.50±11.76) ng/L, P<0.001; (12.46±1.54) U/L, P<0.001; (1 807.29±92.76) pg/L, P<0.001]; fasting blood glucose level [(20.82±1.11) mmol/L], glycosylated hemoglobin (12.67%±1.03%), the testis index (0.65%±0.03%) were significantly higher than those in the control [(6.40±1.34) mmol/L, P<0.001; 5.17%±1.17%, P<0.001; 0.48%±0.04%, P<0.001]. Compared with the model group, the body weight [(22.62±0.92) g, P=0.023], testosterone level [(172.63±9.20) ng/L, P<0.001], follicle-stimulating hormone level [(12.37±1.15) U/L, P<0.001], and luteinizing hormone level [(1 847.80±108.80) pg/L, P<0.001] of mice in the ginsenoside Rg1 group increased significantly, fasting blood glucose level [(18.63±1.14) mmol/L, P=0.017], glycosylated hemoglobin (8.50%±1.05%, P<0.001) and testicular index (0.54%±0.02%, P<0.001) decreased significantly. Compared with the control, the expressions of P62 ( P=0.039), LC3Ⅱ/LC3Ⅰ( P<0.001), Beclin1 ( P=0.002) and mTOR ( P=0.036) in the testicular tissue of mice in the model group all increased, the expression of β-Catenin ( P<0.001), LAMP1 ( P=0.005), transcription factor EB ( P<0.001) all decreased. Compared with the model group, the expressions of autophagy-related proteins P62 ( P=0.048), LC3Ⅱ/LC3Ⅰ( P<0.001) , Beclin1 ( P=0.023) and mTOR ( P=0.005) in the ginsenoside Rg1 group all decreased, while the expression of β-Catenin ( P=0.001), LAMP1 ( P=0.011) and transcription factor EB ( P=0.022) all increased. Transmission electron microscopy detected a decrease in the number of autophagosomes in the testicles of mice in the model group, and it improved after drug intervention. The HE staining showed that the testes of mice in the model group exhibited phenotypes such as the shedding and disorganization of spermatogenic cells, while ginsenoside Rg1 was able to improve these phenotypes. Conclusion:Ginsenoside Rg1 can improve testicular injury caused by diabetes in mice by regulating autophagy.

Objective:To study the efficiency and biosafety of Electrochemical advanced oxidation processes(EAOP)in dental bleaching,and conduct preliminary application.Methods:Indigo carmine and coffee were used as the indicator to assess the effi-cacy of EAOP.High resistance meter was used to measure the resistance of the tooth to verify the safety of the working voltage.Twenty wisdom teeth after tooth extraction were collected,dyed and bleached in vitro to verify the bleaching efficiency.Subsequent-ly,the bleached teeth were examined by scanning electron microscopy,hardness testing,and bacterial adhesion experiments to as-sess surface damage.To determine its cytotoxicity,cells were co-cultured with electrolyte.Initial samples of bleaching tray was prepared,and its durability were verified.Results:The EAOP could bleach indigo carmine within 10 min and coffee within 90 min at an operating voltage of 8 V.The resistance at the groove of the tooth socket was(3.4±1.2)MΩ,and the theoretical calculated current was less than 3 μA.The efficiency of EAOP tooth bleaching was slightly lower than that of traditional office bleaching and higher than that of home bleaching.Compared with the traditional bleaching method,scanning electron microscopy showed that EAOP had less demineralization effect on tooth surface.The tooth hardness before and after bleaching had no statistical difference(P=0.912).The bacterial adhesion test after tooth bleaching showed that EAOP method could reduce about 60％bacterial adhe-sion(P＜0.001).The cytotoxicity test showed that EAOP electrolyte had no obvious toxic effect.The durability test shows that the bleached denture still has good bleaching effect after 20 h of use.Conclusion:Compared with the traditional bleaching method,EAOP bleaching had excellent tooth bleaching effect,little effect on tooth damage,high safety,and the related bleaching devices had good durability.

Parkinson's disease(PD)is a common progressive neurodegenerative disease mainly affecting the motor system.Various genetic factors and cellular mechanisms underlying PD have recently been discovered.Emerging evidence suggests that epigenetic modifications play a very important role in the pathogenesis,prevention,and treatment of PD.Epigenetic modification mediates genetic and environmental interactions mainly through complex interactions of DNA methylation,histone modification,and non-coding RNA,thereby affecting expression in the absence of changes in DNA sequence.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.In this review,we summarize the epigenetic modification mechanisms involved in the pathogenesis of Parkinson's disease.Recent studies have found that traditional Chinese medicine can participate in the regulation of abnormal epigenetic modifications in the treatment of PD.Traditional Chinese medicine benefits from its multi-level and multi-target regulatory effects,and various traditional Chinese medicine monomers,compound prescriptions,and techniques have been evaluated,confirming that this is a promising approach for improving symptoms in PD.This review summarizes the mechanisms by which epigenetic modifications contribute to P D,explores the role of traditional Chinese medicine,and provides new ideas for clinical treatment and drug development in PD through epigenetic intervention.