Objective To explore the biological behavior and mechanism of isovitexin(Isov)on pancreatic cancer cells.Methods Isov was used to treat the human normal pancreatic ductal epithelial cells HPDE and PC cell lines,and CCK-8 was used to detect the cell proliferation and calculate the half inhibitory concentration(IC50).The PC cell line PANC-1 cells were grouped into the control group,the Isov group,the Isov+in-miR-NC group,the Isov+in-miR-339-5p group,the Isov+in-miR-339-5p+si-NC group and the Isov+in-miR-339-5p+si-HSPA8 group.The survival,migration and invasion of PANC-1 cells were detected by CCK-8,scratch healing assay and Transwell assay.Real time fluorescence quantitative PCR was used to detect the mRNA expression of miR-339-5p and heat shock protein family A member 8(HSPA8)in PANC-1 cells.Western blot assay was used to detect protein HSPA8 expression in various groups of cells.Dual luciferase reporter gene was used to detect the targeting effect of miR-339-5p and HSPA8.A xenograft nude mouse model was used to determine the in vivo anticancer effects of Isov.Results Isov inhibited PC cell proliferation but had little cytotoxicity to HPDE cells.Isov could obviously reduce the survival rate and scratch healing rate of PANC-1 cells,reduce the number of invasive cells,up-regulate miR-339-5p expression and down-regulate HSPA8 mRNA and protein levels(P＜0.05),while these effects were blocked by down-regulated miR-339-5p(P＜0.05).In addition,HSPA8 was the target gene of miR-339-5p,and knockdown of HSPA8 reversed the regulatory effect of Isov on the malignant biological behavior of PANC-1 cells.In vivo studies confirmed that after Isov treatment,the tumor volume and weight of nude mice decreased,the expression of miR-339-5p was increased and the expression of HSPA8 mRNA was decreased(P＜0.05).Conclusion Isov may inhibit the proliferation,migration and invasion of PC cells through the miR-339-5p/HSPA8 axis.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective Evaluate the effects of different solvent extracts from Jujing Pills on improving retinal damage in kidney Yang deficiency aging mice and explore the underlying mechanism.Methods A composite modeling method of subcutaneous injection of D-galactose and hind limb injection of hydrocortisone was used to establish a kidney Yang deficiency type aging mouse model,and various solvent extract of Jujing Pills were given for intervention treatment.The improvement effect of different solvent extracts of Jujing Pills on aging mice with kidney Yang deficiency was evaluated by observing physical signs,measuring serum oxidative stress marker levels,and cyclic nucleotide levels.Optical coherence tomography(OCT)was used to detect the condition of the mouse retina,HE staining was used to detect the degree of retinal cell damage,TUNEL staining was used to detect retinal cell apoptosis,assay kit was used to detect oxidative stress factor expression,enzyme-linked immunosorbent assay was used to detect the expression of ciliary neurotrophic factor(CNTF),brain-derived neurotrophic factor(BDNF),and nerve growth factor(NGF)in the mouse eyeball,and Western blotting(WB)was used to quantitatively analyze the expression levels of apoptosis and neurotrophic pathway related proteins in the mouse retina tissue.Results Compared with the control group,the model group mice showed slow weight gain,reduced activity,decreased expression of antioxidant factors such as superoxide dismutase(SOD)and glutathione(GSH)in serum(P<0.01),and decreased cAMP/cGMP ratio(P<0.01).Different solvent extracts of Jujing Pills significantly increased the expression of antioxidant factors such as SOD and GSH(P<0.05),reduced the production of oxidative product malondialdehyde(MDA)(P<0.01),and increased the cAMP/cGMP ratio(P<0.01);Significantly increased the retinal thickness of model mice(P<0.01),improved retinal damage and inhibited retinal cell apoptosis(P<0.01),and significantly downregulated the ratio expression levels of Cleaved Caspase-3 and Caspase-3(P<0.01);The expression of CNTF,BDNF,and NGF was upregulated by water extracted medicinal residue alcohol extract,water extracted alcohol sediment,and total extract(P<0.01).The phosphorylation levels of CREB and ERK in the eyeball were significantly upregulated by water extracted medicinal residue alcohol extract and total extract(P<0.05).Conclusion Different solvent extracts of Jujing Pills can exert different pharmacological effects on improving retinal damage in aging mice with kidney yang deficiency model.Its mechanism of action is related to improving retinal apoptosis caused by oxidative stress and increasing the expression of nutritional factors.

Objective To explore the biological behavior and mechanism of isovitexin(Isov)on pancreatic cancer cells.Methods Isov was used to treat the human normal pancreatic ductal epithelial cells HPDE and PC cell lines,and CCK-8 was used to detect the cell proliferation and calculate the half inhibitory concentration(IC50).The PC cell line PANC-1 cells were grouped into the control group,the Isov group,the Isov+in-miR-NC group,the Isov+in-miR-339-5p group,the Isov+in-miR-339-5p+si-NC group and the Isov+in-miR-339-5p+si-HSPA8 group.The survival,migration and invasion of PANC-1 cells were detected by CCK-8,scratch healing assay and Transwell assay.Real time fluorescence quantitative PCR was used to detect the mRNA expression of miR-339-5p and heat shock protein family A member 8(HSPA8)in PANC-1 cells.Western blot assay was used to detect protein HSPA8 expression in various groups of cells.Dual luciferase reporter gene was used to detect the targeting effect of miR-339-5p and HSPA8.A xenograft nude mouse model was used to determine the in vivo anticancer effects of Isov.Results Isov inhibited PC cell proliferation but had little cytotoxicity to HPDE cells.Isov could obviously reduce the survival rate and scratch healing rate of PANC-1 cells,reduce the number of invasive cells,up-regulate miR-339-5p expression and down-regulate HSPA8 mRNA and protein levels(P＜0.05),while these effects were blocked by down-regulated miR-339-5p(P＜0.05).In addition,HSPA8 was the target gene of miR-339-5p,and knockdown of HSPA8 reversed the regulatory effect of Isov on the malignant biological behavior of PANC-1 cells.In vivo studies confirmed that after Isov treatment,the tumor volume and weight of nude mice decreased,the expression of miR-339-5p was increased and the expression of HSPA8 mRNA was decreased(P＜0.05).Conclusion Isov may inhibit the proliferation,migration and invasion of PC cells through the miR-339-5p/HSPA8 axis.

Objective Evaluate the effects of different solvent extracts from Jujing Pills on improving retinal damage in kidney Yang deficiency aging mice and explore the underlying mechanism.Methods A composite modeling method of subcutaneous injection of D-galactose and hind limb injection of hydrocortisone was used to establish a kidney Yang deficiency type aging mouse model,and various solvent extract of Jujing Pills were given for intervention treatment.The improvement effect of different solvent extracts of Jujing Pills on aging mice with kidney Yang deficiency was evaluated by observing physical signs,measuring serum oxidative stress marker levels,and cyclic nucleotide levels.Optical coherence tomography(OCT)was used to detect the condition of the mouse retina,HE staining was used to detect the degree of retinal cell damage,TUNEL staining was used to detect retinal cell apoptosis,assay kit was used to detect oxidative stress factor expression,enzyme-linked immunosorbent assay was used to detect the expression of ciliary neurotrophic factor(CNTF),brain-derived neurotrophic factor(BDNF),and nerve growth factor(NGF)in the mouse eyeball,and Western blotting(WB)was used to quantitatively analyze the expression levels of apoptosis and neurotrophic pathway related proteins in the mouse retina tissue.Results Compared with the control group,the model group mice showed slow weight gain,reduced activity,decreased expression of antioxidant factors such as superoxide dismutase(SOD)and glutathione(GSH)in serum(P<0.01),and decreased cAMP/cGMP ratio(P<0.01).Different solvent extracts of Jujing Pills significantly increased the expression of antioxidant factors such as SOD and GSH(P<0.05),reduced the production of oxidative product malondialdehyde(MDA)(P<0.01),and increased the cAMP/cGMP ratio(P<0.01);Significantly increased the retinal thickness of model mice(P<0.01),improved retinal damage and inhibited retinal cell apoptosis(P<0.01),and significantly downregulated the ratio expression levels of Cleaved Caspase-3 and Caspase-3(P<0.01);The expression of CNTF,BDNF,and NGF was upregulated by water extracted medicinal residue alcohol extract,water extracted alcohol sediment,and total extract(P<0.01).The phosphorylation levels of CREB and ERK in the eyeball were significantly upregulated by water extracted medicinal residue alcohol extract and total extract(P<0.05).Conclusion Different solvent extracts of Jujing Pills can exert different pharmacological effects on improving retinal damage in aging mice with kidney yang deficiency model.Its mechanism of action is related to improving retinal apoptosis caused by oxidative stress and increasing the expression of nutritional factors.

Objective To observe the clinical efficacy of artificial liver plasma bilirubin adsorption for treatment of patients with severe viral hepatitis B (HBV). Methods A retrospective study was conducted, the 120 patients with severe HBV B and their historical data of having undergone treatment of artificial liver plasma bilirubin adsorption admitted to Department of Respiration of Mianyang Central Hospital from August 2015 to August 2017 were collected, and there were 68 cases in the cirrhotic group and 52 cases in the non-cirrhotic group. The indexes of liver function and coagulation function before and after the treatment of artificial liver plasma bilirubin adsorption were collected; the differences of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein (TP), albumin (Alb), globulin (Glo), prothrombin time (PT), prothrombin activity (PTA), total bilirubin (TBil) and indirect bilirubin (IBil), total bile acid (TBA), etc were compared between cirrhotic group and the severe hepatitis B non-cirrhotic group. Results The levels of ALT, AST, ALP, LDH after artificial liver plasma bilirubin adsorption therapy were lower than those before the treatment [ALT (U/L): 138.8±26.2 vs. 993.4±185.2, AST (U/L): 121.7±119.9 vs. 798.7±226.8, ALP (U/L): 129.7±8.1 vs. 178.9±14.1, LDH (μmol·L-1·s-1·L-1): 4.50±0.32 vs. 8.15 ±1.75, all P < 0.05], PTA was higher than that before the treatment [(43.2±25.6)% vs. (30.0±16.1)%, P < 0.05]. After the treatment, the decline rate of ALP, TBil, and TBA of non-cirrhotic group was higher than those in cirrhotic group (ALP: 34.20% vs. 17.80%, TBil: 39.10% vs. 18.10%, TBA:30.70% vs. 5.00%, P < 0.05), the elevation rate of PTA in non-cirrhotic group was also higher than that in cirrhotic group (52.50% vs. 25.10%, P < 0.05). Conclusion Artificial liver plasma bilirubin adsorption therapy is effective for treatment of patients with severe HBV B, particularly the effect being good on the early severe viral HBV B non-cirrhotic group.

Objective To analyze of the relationship between level of anxiety and depression before surgery and anus exhausting time for patients after gynecological abdominal surgery.Methods A descriptive study was conducted with a survey of 100 cases of patients with gynecological abdominal surgery where the level of anxiety and depression before surgery and post-anus exhausting time were analyzed to explore the correlation between them.Results In the 88 valid questionnaires,the incidences of stress and anxiety before surgery were respectively 38.64％(34/84) and 19.32％(17/88) and the average anus exhausting time after surgery was (44.55 ± 13.90) hours;the anus exhausting time of anxious patients was significantly longer than that of non-anxious patients [(48.35±12.84) hours vs.(42.50±14.13) hours,t=-2.12,P＜0.05] and bivariate Logistic regression analysis suggested that preoperative level of anxiety had a significant effect on anus exhausting time after surgery.Conclusions Stress,anxiety and other negative emotions can affect anus exhausting time after surgery and level of anxiety could be used as one predictor of the delay of anus exhausting time after surgery.

Objective To observe the effect of single and low dose propofol administered near the end of surgery on the cardiovascular and adverse response during extnhation in patients undergoing ovarian cancer operation. Methods Fifty ASA Ⅰ - Ⅱ patients undergoing selective ovarian cancer operation were randomly allocated into group S and group P,with 25 patients in each group. In group S, inhalation of sevoflurane was discontinued at about 2 minutes before the end of operation. In group P, inhalation of sevoflurane was discontinued at about 5 minutes before the end of operation,and at the same time,0.5 mg/kg of propofol was administered intravenously. The systolic blood pressure (SBP),diastolic blood pressure (DBP),heart rate (HR) and recovery time of consciousness were recorded at 5 min before extubation (t_1),during extubation (t_2), 1 min after extubation (t_3), and 5 rain after extubation (t_4). The incidence of agitatian,bucking,nausea and vomiting were recorded by an observer who was blind to this study. Results There were statistical differences in HR,SBP,DBP at t_2-t_4 between two groups. The recovery time was (10.39 ± 1.26) min in group P,and(9.57 ± 1.25) min in group S,there was significant difference between group P (2 cases) and group S (9 cases)(P< 0.05). There was significant difference in the incidence of agitation between two groups (P< 0.05). Conclusion Low dose propofol before extubation can inhibit stress and cardiovascular response and decrease the incidence of agitation, bucking, nausea and vomiting.