Pancreatic cancer （PC）， a highly malignant tumor of the digestive system， is characterized by extremely high incidence and mortality rates， imposing a severe burden on the healthcare system. Despite significant advancements in comprehensive therapeutic strategies for PC， clinical benefits for patients remain limited due to the high heterogeneity and unique microenvironment of the tumor. Therefore， further elucidating the molecular mechanisms underlying PC progression and developing novel， effective therapeutic strategies have become an urgent necessity in the current research. Programmed cell death （PCD） is a genetically orchestrated process of autonomous cell demise that is crucial for maintaining cellular homeostasis. Recent studies have demonstrated that tumor cells can remodel the tumor microenvironment by modulating various PCD pathways—including apoptosis， autophagy， pyroptosis， and ferroptosis—thereby driving tumor proliferation， invasion， and drug resistance. Traditional Chinese medicine （TCM） possesses unique advantages in anti-tumor therapy， characterized by multi-component， multi-target， and multi-pathway regulation. Accumulating evidence suggests that TCM formulas and their natural active compounds can effectively delay the malignant progression of PC by modulating PCD in tumor cells. This article systematically summarizes the molecular mechanisms of PCD in PC progression and reviews the mechanisms by which TCM formulas and natural active compounds intervene in PC through PCD modulation. This review aims to provide theoretical support and future research directions for the prevention and treatment of PC with TCM.

AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

AIM:To investigate the effect of Jianpi-Huayu decoction(JPHYD)combined with gemcitabine(GEM)on ferroptosis of pancreatic cancer PANC-1 cells and its mechanism.METHODS:PANC-1 cells were cultured in vitro,and CCK8 method was used to detect the cell viability after different concentrations of JPHYD and GEM,and ap-propriate concentrations were selected for follow-up experiments.EDU assay and clonogenesis assay were used to detect cell proliferation.The apoptosis rate was detected by flow cytometry.Intracellular reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescent probe and lipid peroxidation was detected by BODIPY 581/591C11 staining.The contents of glutathione(GSH),ferrous ion(Fe2+)and malondialdehyde(MDA)in the cells were detected by the kit.The mRNA levels and protein expression levels of Nrf2,HO-1,SLC7A11,GPX4,TFR1 and ACSL4 were detected by RT-qPCR and Western blot.RESULTS:Compared with the control group,the cell viability of PANC-1 treated with JPHYD and GEM was significantly decreased in a concentration-dependent manner.And the combined use of the two can significantly im-prove the cytotoxic effect of GEM and have a synergistic effect;Compared with control group,JPHYD group,GEM group and JPHYD+GEM group can significantly reduce EDU positive efficiency,colony formation numbers and promote cell apoptosis,and the combined group has the most obvious effect.After adding JPHYD+GEM into the cells,the cells be-came rounded and the cell viability decreased.The addition of ferrostatin-1(Fer-1),an inhibitor of ferroptosis,had no significant effect on cell morphology and viability,and the co-treatment with JPHYD+GEM and Fer-1 could reverse the ef-fects of JPHYD+GEM on cell morphology and viability.Compared with control group and GEM group,JPHYD+GEM group can significantly increase the levels of intracellular reactive oxygen species(ROS)and lipid peroxidation,increase the levels of Fe2+and MDA,decrease the levels of GSH,further promote lipid peroxidation and induce ferroptosis.JPHYD+GEM also significantly down-regulated the mRNA and protein expressions of Nrf2,HO-1,SLC7A11 and GPX4,and up-regulated the mRNA and protein expressions of TFR1 and ACSL4.The addition of Fer-1 significantly reversed the activation of iron death in the combined treatment group and reversed its efficacy,and the difference was statistically signif-icant.CONCLUSION:Jianpi Huayu decoction and gemcitabine may induce ferroptosis of PANC-1 cells by inhibiting Nrf2/SLC7A11/GPX4 axis in vitro,thus playing a synergistic anticancer role.

Objective:To investigate the effects of lezumab adjuvant therapy on the degree of retinal vasculopathy and immune response in the treatment of macular central diabetic retinopathy (DR).Methods:From July 2022 to December 2023, 120 patients with DR in macular central who received treatment in the Xi′an People′s Hospital (Xi′an Fourth Hospital) were retrospectively selected and divided into two groups according to the treatment methods: the observation group (60 cases, lezumab combined with sitagliptin), and the control group (60 cases, sitagliptin). Patients′glucose metabolism, visual acuity, degree of retinopathy, inflammation [tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-10 (IL-10)] and angiogenesis related factors [serum vascular endothelial growth factor (VEGF), midkine (MK), 5′-nucleotidase (CD73)] were evaluated, and the curative efficacy of the two groups was compared. The security of the two schemes was compared.Results:Compared with the control group, the serum concentrations of MK, CD73, TNF-α and VEGF were lower in the observation group after treatment: (1.44 ± 0.06) ng/L vs. (1.67 ± 0.11) ng/L, (1.10 ± 0.27) ng/L vs. (1.31 ± 0.26) ng/L, (11.62 ± 0.89) ng/L vs. (15.96 ± 4.42) ng/L, (84.07 ± 27.07) ng/L vs. (100.72 ± 16.05) ng/L, while the concentration of IL-10 was higher: (65.65 ± 8.68) ng/L vs. (60.02 ± 5.07) ng/L, with statistically significant differences ( P<0.05). There were no statistically significant differences in fasting blood glucose (FBG) and 2 h postprandial blood glucose between two groups before and after treatment ( P>0.05). After treatment, the macular thickness and visual field gray value in the observation group were lower than those in the control group: (302.81 ± 77.08) μm vs. (336.44 ± 10.35) μm, (1.55 ± 0.43)% vs. (2.09 ± 0.51)% ( P<0.05). After 3 months of treatment, the visual acuity in the observation group was higher than that in the control group: 0.493 ± 0.103 vs. 0.439 ± 0.084 ( P<0.05). No serious adverse reactions occurred in both groups. Conclusions:Lezumab assisted sitagliptin has a significant effect in the treatment of DR, which can reduce the degree of lesions, improve vision, and reduce the levels of inflammation and angiogenesis related factors.

Objective:To analyze the effects of parental adverse childhood experiences on their offspring's prosocial behaviors,as well as to examine the moderating role of parental positive childhood experiences.Methods:A total of 3 090 parents of preschool children were selected to participate in this study.The Adverse Childhood Ex-periences International Questionnaire(ACE-IQ)and Benevolent Childhood Experiences Scale(BCEs)were used to examine parental adverse childhood experiences(i.e.,abuse,neglect,and dysfunctional households,etc)and posi-tive childhood experiences(i.e.,internal and external perceived safety,support,and positive personality traits,etc),Children Strength and Difficulties Question(SDQ)were performed to test offspring prosocial behaviors.Results:Parents'ACE-IQ scores were negatively correlated with offspring SDQ scores(r=-0.15)and parents'BCEs scores moderated(β=0.19)the relationship between parental ACE-IQ scores and offspring SDQ scores(β=-0.12).Conclusion:The study suggests that parental adverse childhood experiences are negatively associated with offspring pro-social behavior.Additionally,it indicates that an increase in positive childhood experiences can en-hance the relationships of parents'adverse childhood experiences.

AIM:To investigate the effect of Jianpi-Huayu decoction(JPHYD)combined with gemcitabine(GEM)on ferroptosis of pancreatic cancer PANC-1 cells and its mechanism.METHODS:PANC-1 cells were cultured in vitro,and CCK8 method was used to detect the cell viability after different concentrations of JPHYD and GEM,and ap-propriate concentrations were selected for follow-up experiments.EDU assay and clonogenesis assay were used to detect cell proliferation.The apoptosis rate was detected by flow cytometry.Intracellular reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescent probe and lipid peroxidation was detected by BODIPY 581/591C11 staining.The contents of glutathione(GSH),ferrous ion(Fe2+)and malondialdehyde(MDA)in the cells were detected by the kit.The mRNA levels and protein expression levels of Nrf2,HO-1,SLC7A11,GPX4,TFR1 and ACSL4 were detected by RT-qPCR and Western blot.RESULTS:Compared with the control group,the cell viability of PANC-1 treated with JPHYD and GEM was significantly decreased in a concentration-dependent manner.And the combined use of the two can significantly im-prove the cytotoxic effect of GEM and have a synergistic effect;Compared with control group,JPHYD group,GEM group and JPHYD+GEM group can significantly reduce EDU positive efficiency,colony formation numbers and promote cell apoptosis,and the combined group has the most obvious effect.After adding JPHYD+GEM into the cells,the cells be-came rounded and the cell viability decreased.The addition of ferrostatin-1(Fer-1),an inhibitor of ferroptosis,had no significant effect on cell morphology and viability,and the co-treatment with JPHYD+GEM and Fer-1 could reverse the ef-fects of JPHYD+GEM on cell morphology and viability.Compared with control group and GEM group,JPHYD+GEM group can significantly increase the levels of intracellular reactive oxygen species(ROS)and lipid peroxidation,increase the levels of Fe2+and MDA,decrease the levels of GSH,further promote lipid peroxidation and induce ferroptosis.JPHYD+GEM also significantly down-regulated the mRNA and protein expressions of Nrf2,HO-1,SLC7A11 and GPX4,and up-regulated the mRNA and protein expressions of TFR1 and ACSL4.The addition of Fer-1 significantly reversed the activation of iron death in the combined treatment group and reversed its efficacy,and the difference was statistically signif-icant.CONCLUSION:Jianpi Huayu decoction and gemcitabine may induce ferroptosis of PANC-1 cells by inhibiting Nrf2/SLC7A11/GPX4 axis in vitro,thus playing a synergistic anticancer role.

Objective:To analyze the effects of parental adverse childhood experiences on their offspring's prosocial behaviors,as well as to examine the moderating role of parental positive childhood experiences.Methods:A total of 3 090 parents of preschool children were selected to participate in this study.The Adverse Childhood Ex-periences International Questionnaire(ACE-IQ)and Benevolent Childhood Experiences Scale(BCEs)were used to examine parental adverse childhood experiences(i.e.,abuse,neglect,and dysfunctional households,etc)and posi-tive childhood experiences(i.e.,internal and external perceived safety,support,and positive personality traits,etc),Children Strength and Difficulties Question(SDQ)were performed to test offspring prosocial behaviors.Results:Parents'ACE-IQ scores were negatively correlated with offspring SDQ scores(r=-0.15)and parents'BCEs scores moderated(β=0.19)the relationship between parental ACE-IQ scores and offspring SDQ scores(β=-0.12).Conclusion:The study suggests that parental adverse childhood experiences are negatively associated with offspring pro-social behavior.Additionally,it indicates that an increase in positive childhood experiences can en-hance the relationships of parents'adverse childhood experiences.

Objective:To investigate the effects of lezumab adjuvant therapy on the degree of retinal vasculopathy and immune response in the treatment of macular central diabetic retinopathy (DR).Methods:From July 2022 to December 2023, 120 patients with DR in macular central who received treatment in the Xi′an People′s Hospital (Xi′an Fourth Hospital) were retrospectively selected and divided into two groups according to the treatment methods: the observation group (60 cases, lezumab combined with sitagliptin), and the control group (60 cases, sitagliptin). Patients′glucose metabolism, visual acuity, degree of retinopathy, inflammation [tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-10 (IL-10)] and angiogenesis related factors [serum vascular endothelial growth factor (VEGF), midkine (MK), 5′-nucleotidase (CD73)] were evaluated, and the curative efficacy of the two groups was compared. The security of the two schemes was compared.Results:Compared with the control group, the serum concentrations of MK, CD73, TNF-α and VEGF were lower in the observation group after treatment: (1.44 ± 0.06) ng/L vs. (1.67 ± 0.11) ng/L, (1.10 ± 0.27) ng/L vs. (1.31 ± 0.26) ng/L, (11.62 ± 0.89) ng/L vs. (15.96 ± 4.42) ng/L, (84.07 ± 27.07) ng/L vs. (100.72 ± 16.05) ng/L, while the concentration of IL-10 was higher: (65.65 ± 8.68) ng/L vs. (60.02 ± 5.07) ng/L, with statistically significant differences ( P<0.05). There were no statistically significant differences in fasting blood glucose (FBG) and 2 h postprandial blood glucose between two groups before and after treatment ( P>0.05). After treatment, the macular thickness and visual field gray value in the observation group were lower than those in the control group: (302.81 ± 77.08) μm vs. (336.44 ± 10.35) μm, (1.55 ± 0.43)% vs. (2.09 ± 0.51)% ( P<0.05). After 3 months of treatment, the visual acuity in the observation group was higher than that in the control group: 0.493 ± 0.103 vs. 0.439 ± 0.084 ( P<0.05). No serious adverse reactions occurred in both groups. Conclusions:Lezumab assisted sitagliptin has a significant effect in the treatment of DR, which can reduce the degree of lesions, improve vision, and reduce the levels of inflammation and angiogenesis related factors.

Objective:To improve a device and fixation method for ventricular catheterization in rats,which is mini-mally invasive,has a short stress period,and allows delayed drug administration or cerebrospinal fluid collection.Methods:Healthy adult male SD rats were divided into a Regular method group,Modified method group and Control group.In the Regular method group,commercially available cannula needles with internal cores were used for catheter-ization,fixed to the skull using dental cement along with fixing screws;in Modified method group an improved catheter-ization device was used along with its corresponding fixation technique;no treatment was given in Control group.Senso-ry function and motor function of rats were assessed by using hot plate test and footprint analysis respectively at 4 and 7 days after insertion;HE staining was used to observe the damage of brain tissue around the needle tract at 7 days of catheterization,and immunofluorescence staining was used to detect change in Iba-1 expression near the catheter needle tract.Results:The sensory and motor function impairments in the Modified method group were milder than those in the Regular method group(P＜0.05);HE staining showed that the needle tract in the Modified method group was signifi-cantly narrower than that in the Regular method group;immunofluorescence staining revealed a significantly higher num-ber of Iba-1 positive cells near the needle tract in the Regular method group compared to the Modified method group(P＜0.05).Conclusion:The modified catheterization device and fixation method described in this article result in minimal brain injury,shorter stress period,and can be used for delayed intraventricular drug administration or cerebro-spinal fluid collection.