Objective: To investigate the potential of bortezomib in inhibiting the malignant biological behaviors and liver metastasis of pancreatic cancer cells. Methods : KPC and Panc02 cell lines were used as a couple of working cells in this study. The CCK-8 assay was used to assess the effect of bortezomib on cell viability in murine pancreatic cancer cells, and the half inhibitory concentration(IC50) values were calculated. The EdU assay was performed to evaluate the impact of bortezomib on the proliferation of these two cell lines. Apoptosis assays were conducted to investigate the pro-apoptotic effects of bortezomib on pancreatic cancer cells. Colony formation, scratch wound healing, and Transwell assays were used to examine the effects of bortezomib on the proliferation, migration, and invasion of pancreatic cancer cells. QRT-PCR and Western blot were employed to assess the impact of bortezomib on the expression of epithelial-mesenchymal transition(EMT) related markers, includingCdh1,Cdh2,VimandSnailgene and E-cadherin protein, N-cadherin protein, Vimentin protein and Snail protein. Anin vivospleen-to-liver metastasis model was established to evaluate the therapeutic value of bortezomib in inhibiting pancreatic cancer liver metastasis. Results : The CCK-8 assay showed that bortezomib significantly reduced the viability of KPC and Panc02 cells(P<0.000 1), with IC50values of approximately 118.70 nmol/L and 34.16 nmol/L, respectively. The EdU assay showed that bortezomib markedly inhibited the proliferative capacity of pancreatic cancer cells(P<0.01). Apoptosis assays showed that bortezomib promoted both early and late apoptosis in pancreatic cancer cells(P<0.05). Colony formation, scratch wound healing, and Transwell assays showed that bortezomib effectively suppressed colony formation, migration, and invasion(P<0.01) of pancreatic cancer cells. qRT-PCR and Western blot analyses showed that bortezomib altered the expression of EMT-related markers at both the mRNA(the expression level ofCdh1gene increased, while the expression levels ofCdh2,VimandSnailgenes decreased)(P<0.000 1) and protein(the expression level of E-cadherin protein increased, while the expression levels of N-cadherin protein, Vimentin protein and Snail protein decreased) levels in pancreatic cancer cells. Thein vivospleen-to-liver metastasis model demonstrated that bortezomib significantly inhibited pancreatic cancer liver metastasis(P<0.01). Conclusion Bortezomib can inhibit the malignant biological behaviors of pancreatic cancer cells, suggesting it might be a potential anti-cancer drug in pancreatic cancer.

Objective To compare the therapeutic effects of modified Shenqi Maiwei Dihuang Decoction combined with Buzhong Yiqi Pill and Buzhong Yiqi pill alone in the patients with cold and heat mixed type di-abetic foot.Methods A total of 123 patients with cold and heat mixed type diabetic foot receiving the treat-ment in this hospital from April 2022 to December 2023 were selected and divided into the modified Shenqi Mai-Dihuang Decoction and Buzhong Yiqi Pill group(combined group,60 cases)and Buzhong Yiqi Pill group(monotherapy group,63 cases).The wound healing,mean blood flow amount of foot dorsal artery,blood glu-cose and changes in vascular diameter,inflammatory factors and vascular endothelial growth factor after 2 courses of treatment were compared betweeb the 2 groups.Results The ulcer reduction rate in the combina-tion group was significantly higher than that in the monotherapy group(P=0.001).The fasting blood glu-cose and 2 h postprandial blood glucose after treatment in the combination group all were lower than those in the monotherapy group(P=0.001).The average blood flow of foot dorsal artery after treatment in combina-tion group was higher than that in the monotherapy group,and the difference was statistically significant(P=0.013).There were 34 cases of Wagner grade 3 in the combined group and 33 cases of Wagner grade 3 in the monotherapy subgroup respectively.There was statistically significant difference in the CRP level between the two subgroups(P=0.045).Conclusion Shenqi Maiwei Dihuang Decoction combined with Buzhong Yiqi Pill in treating diabetic foot ulcer is more effective than Buzhong Yiqi Pill alone,moreover the safety is high.

Objective To establish a risk model of rivaroxaban-related bleeding events in elderly patients with non-valvular atrial fibrillation(NVAF)based on gene polymorphism.Methods A total of 268 elderly NVAF patients receiving rivaroxaban treatment in Department of General Practice of the First Affiliated Hospital of Shihezi University from January 2021 to July 2023 were enrolled in this study.According to whether bleeding events occurred in 12 months'follow-up,they were divided into a bleeding group(47 cases)and a non-bleeding group(221 cases).The clinical data and results of gene polymorphism were compared between the two groups.Multivari-ate logistic regression was adopted to construct a risk prediction model of bleeding events based on gene polymorphism,and the predictive performance was verified.Results Significantly ad-vanced age and lower creatinine level were observed in the bleeding group than the non-bleeding group(P＜0.01).The bleeding group had obviously lower GG genotype frequency at the rs1128503 locus and TT genotype frequency at the rs4148738 of ATP-binding cassette,sub-family B member 1(ABCB1),and lower AC genotype frequency at the rs1057910 locus of cytochrome P450 2C9(CYP2C9)than the non-bleeding group(P＜0.05).Multivariate logistic regression analy-sis showed that age(OR=1.136,95％CI:1.031-1.251),and AA genotype(OR=15.407,95％CI:4.259-55.741)and GA genotype(OR=6.990,95％CI:1.599-30.546)of ABCB1 rs1 128503 were risk factors for rivaroxaban-related bleeding events in elderly NVAF patients(P＜0.01).Creatinine(OR=0.943,95％CI:0.899-0.989),TT genotype at ABCB1 rs4148738(OR=0.048,95％CI:0.009-0.242)and AC genotype of CYP2C9 rs1057910(OR=0.092,95％CI:0.021-0.408)were protective factors for the risk(P＜0.05).ROC curve analysis indicated that the AUC value of the risk model based on gene polymorphism was 0.827(95％CI:0.776-0.870),the spe-cificity was 81.90％,and the sensitivity was 76.60％.Conclusion Our risk model of rivaroxaban-related bleeding events based on ABCB1 gene and CYP2C9 gene has high application value for elderly NVAF patients.

Objective To establish a risk model of rivaroxaban-related bleeding events in elderly patients with non-valvular atrial fibrillation(NVAF)based on gene polymorphism.Methods A total of 268 elderly NVAF patients receiving rivaroxaban treatment in Department of General Practice of the First Affiliated Hospital of Shihezi University from January 2021 to July 2023 were enrolled in this study.According to whether bleeding events occurred in 12 months'follow-up,they were divided into a bleeding group(47 cases)and a non-bleeding group(221 cases).The clinical data and results of gene polymorphism were compared between the two groups.Multivari-ate logistic regression was adopted to construct a risk prediction model of bleeding events based on gene polymorphism,and the predictive performance was verified.Results Significantly ad-vanced age and lower creatinine level were observed in the bleeding group than the non-bleeding group(P＜0.01).The bleeding group had obviously lower GG genotype frequency at the rs1128503 locus and TT genotype frequency at the rs4148738 of ATP-binding cassette,sub-family B member 1(ABCB1),and lower AC genotype frequency at the rs1057910 locus of cytochrome P450 2C9(CYP2C9)than the non-bleeding group(P＜0.05).Multivariate logistic regression analy-sis showed that age(OR=1.136,95％CI:1.031-1.251),and AA genotype(OR=15.407,95％CI:4.259-55.741)and GA genotype(OR=6.990,95％CI:1.599-30.546)of ABCB1 rs1 128503 were risk factors for rivaroxaban-related bleeding events in elderly NVAF patients(P＜0.01).Creatinine(OR=0.943,95％CI:0.899-0.989),TT genotype at ABCB1 rs4148738(OR=0.048,95％CI:0.009-0.242)and AC genotype of CYP2C9 rs1057910(OR=0.092,95％CI:0.021-0.408)were protective factors for the risk(P＜0.05).ROC curve analysis indicated that the AUC value of the risk model based on gene polymorphism was 0.827(95％CI:0.776-0.870),the spe-cificity was 81.90％,and the sensitivity was 76.60％.Conclusion Our risk model of rivaroxaban-related bleeding events based on ABCB1 gene and CYP2C9 gene has high application value for elderly NVAF patients.

Objective To investigate the correlation between peripheral blood eosinophil(EOS)and left ventricular hypertrophy(LVH)in elderly patients with hypertension.Methods A retrospec-tive cross-section analysis was conducted on 711 elderly hypertensive patients admitted to our de-partment from January to December 2023.According to their EOS count,they were divided into Group 1(＜100×106/L),Group 2[(100-190)× 106/L]and Group 3(＞190 × 106/L).The gen-eral clinical data,biochemical indicators,and echocardiographic parameters were compared among the three groups.The correlation between EOS and each indicator was analyzed by using Spearman correlation analysis.Logistic regression analysis was employed to identify the influential factors for hypertension complicated with LVH.Results Smoking history,TG and UA levels,and lymphocyte counts were gradually increased,while HDL-C level was gradually decreased in the three groups with the increment of EOS count(P＜0.05,P＜0.01).The proportions of usingβ-blockers,calcium channel blockers and statins were gradually increased in the three groups(P＜0.05,P＜0.01),so were the values of LVM,LVMI,IVST,LVEDD and LVPWT in them(P＜0.01).EOS count was positively correlated with the values of LVM,LVMI,IVST,LVEDD and LVPWT,smoking history,TG and UA levels,WBC,lymphocyte and monocyte counts,and ratios of using β-blockers,calcium channel blockers and statins,but negatively with HDL-C level(P＜0.05,P＜0.01).Binary logistic regression analysis showed that female and HDL-C were protective factors for LVH in hypertensive patients,while age and EOS count were risk factors(OR=0.149,95％CI:0.096-0.230;OR=0.632,95％CI:0.399-0.999;OR=1.034,95％CI:1.007-1.062;OR=1.956,95％CI:1.446-2.645).Conclusion In elderly hypertensive patients with LVH,female and HDL-C are the protective factors,while age and EOS are the risk factors.EOS has a certain correlation with the occurrence of LVH in elderly hypertensive patients.

Objective To investigate the correlation between peripheral blood eosinophil(EOS)and left ventricular hypertrophy(LVH)in elderly patients with hypertension.Methods A retrospec-tive cross-section analysis was conducted on 711 elderly hypertensive patients admitted to our de-partment from January to December 2023.According to their EOS count,they were divided into Group 1(＜100×106/L),Group 2[(100-190)× 106/L]and Group 3(＞190 × 106/L).The gen-eral clinical data,biochemical indicators,and echocardiographic parameters were compared among the three groups.The correlation between EOS and each indicator was analyzed by using Spearman correlation analysis.Logistic regression analysis was employed to identify the influential factors for hypertension complicated with LVH.Results Smoking history,TG and UA levels,and lymphocyte counts were gradually increased,while HDL-C level was gradually decreased in the three groups with the increment of EOS count(P＜0.05,P＜0.01).The proportions of usingβ-blockers,calcium channel blockers and statins were gradually increased in the three groups(P＜0.05,P＜0.01),so were the values of LVM,LVMI,IVST,LVEDD and LVPWT in them(P＜0.01).EOS count was positively correlated with the values of LVM,LVMI,IVST,LVEDD and LVPWT,smoking history,TG and UA levels,WBC,lymphocyte and monocyte counts,and ratios of using β-blockers,calcium channel blockers and statins,but negatively with HDL-C level(P＜0.05,P＜0.01).Binary logistic regression analysis showed that female and HDL-C were protective factors for LVH in hypertensive patients,while age and EOS count were risk factors(OR=0.149,95％CI:0.096-0.230;OR=0.632,95％CI:0.399-0.999;OR=1.034,95％CI:1.007-1.062;OR=1.956,95％CI:1.446-2.645).Conclusion In elderly hypertensive patients with LVH,female and HDL-C are the protective factors,while age and EOS are the risk factors.EOS has a certain correlation with the occurrence of LVH in elderly hypertensive patients.

This paper discusses the application of MRN combined with 3D printing in SNM in neurogenic bladder patients with special comorbidities. In this study, 21 cases of neurogenic bladder patients with special comorbidities involved, including 14 cases into the control group and 7 cases in the experimental group. Traditional X-ray guidance was used in the control group, while the MRN combined with 3D printing navigation template positioning was used in the experimental group. Compared with those in the control group, the X-ray fluoroscopy, number of punctures, puncture time, intraoperative adjustment and testing time were significantly decreased in the experimental group. The difference of implantable pulse generator implantation rates between the two groups was statistically significant.

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis,abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects.However,the role of herb-drug interaction between indomethacin and A.officinarum based on pharmacokinetic,tissue distribution and excretion still remains unknown.In this study,an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS)method was developed for simultaneous determina-tion of indomethacin and its three metabolites,O-desmethylindomethacin(ODI),deschlor-obenzoylindomethacin(NDI)and indomethacin acyl-β-D-glucuronide(IDAβG)by oral administration of indomethacin solution with and without the ethanolic extract of A.officinarum and applied to comparative pharmacokinetic,tissue distribution and excretion studies.Our results clarified that oral administration of A.officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin.And the pharmacokinetic interaction between indomethacin and A.officinarum reduced the systemic exposure of indomethacin and increased its elimination.Tissue distribution results demonstrated that co-administration of A.Officinarum could not reduce the accumulation of indo-methacin in the target tissue of the stomach,but could accelerate the excretions of indomethacin and its three metabolites including ODI,NDI and IDAβG in the bile and feces of rats in the excretion study.Therefore,A.Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

The hinge structure, also known as hinge region or bend, is a special structure found in some antimicrobial peptides. Most studies on antimicrobial peptides focused on the standard secondary structure of α-helix and β-sheet, while the hinge structure and its functions were rarely studied. The hinge structure confers the antimicrobial peptides an improved structural flexibility, which may promote their disruptive effect on bacterial membrane or their binding efficiency to the intracellular targets, thus resulting in a higher antibacterial activity. Meanwhile, the hinge structure may reduce the structural rigidity, which may eliminate the cytotoxicity of antimicrobial peptides to eukaryotic cells. This article reviews the structural characteristics of the hinge structure, its effects on the biological activity of antimicrobial peptides and application in the molecular design, with the aim to provide a reference for the design and development of new antimicrobial peptides.
Anti-Bacterial Agents/pharmacology* ; Anti-Infective Agents/pharmacology* ; Antimicrobial Cationic Peptides/pharmacology* ; Pore Forming Cytotoxic Proteins ; Protein Structure, Secondary

Objective To investigate the function of JAK2-STAT3 signaling pathway in pancreatic injury and systematic inflammatory response in rats with acute necrotizing pancreatitis ( ANP) . Methods SD rats were randomly divided into the ANP group (n=48), ANP+JAK2 inhibitor Ruxolitinib group (ANP+R group, n=48), ANP+STAT3 inhibitot Stattic group (ANP+S group, n=48), ANP+Ruxolitinib+Stattic group (ANP+R+S group, n=48), and sham operation group (SO group, n=48). 5％ sodium taurocholate injection via retrograde pancreatobiliary duct was used to establish ANP model. Blood samples from abdominal aorta and pancreatic tissue were collected after 3 h, 6 h, 12 h and 18 h after modeling. Serum amylase (AMY) and tumor necrosis factor-α(TNF-α) and interleukin-4 (IL-4) were tested. JAK2 and STAT3 mRNA expression and protein expression of p-JAK2 and p-STAT3 in pancreas were examined by RT qPCR and western blot, respectively. Results AMY, TNF-α and IL-4 in plasma, and JAK2 mRNA, STAT3 mRNA, p-JAK2 protein and p-STAT3 protein at different time points in ANP group were all obviously higher than those in SO group(P<0. 05). Serum AMY, TNF-αand IL-4 in ANP+R group, ANP+S group and ANP+R+S group at different time points were lower than those in ANP group [12 h (5391 ± 1009),(6130 ± 1227),(4818 ± 992)U/L vs (8524 ± 1360) U/L;(147.25 ± 27.85),(156.25 ± 23.17),(127.87 ± 21.39) ng/L vs (187.58 ±20.09)ng/L;(45.89 ±16.95),(50.19 ±15.87),(38.87 ±14.03)ng/L vs (58.85 ±9.34)ng/L] . JAK2 mRNA and p-JAK2 protein,STAT3 mRNA and p-STAT3 protein in ANP+R group and ANP+R+S group at different time points were obviously lower than those in ANP group (12 h 0. 357 ± 0. 091 vs 0. 597 ± 0. 121,1. 115 ± 0. 203 vs 1. 217 ± 0. 213,0. 361 ± 0. 089 vs 0. 489 ± 0. 097,0. 965 ± 0. 189 vs 1. 128 ± 0. 217, 0. 362 ± 0. 092 vs 0. 597 ± 0. 121,1. 107 ± 0. 212 vs 1. 217 ± 0. 213,0. 297 ± 0. 087 vs 0. 489 ± 0. 097,0. 713 ± 0. 184 vs 1. 128 ± 0. 217). STAT3 mRNA and p-STAT3 protein in ANP+S group were obviously lower than those in ANP group(0. 319 ± 0. 107 vs 0. 489 ± 0. 097,0. 849 ± 0. 177 vs 1. 128 ± 0. 217), and the difference was statistically different (P<0.05). Conclusions The activation of JAK2-STAT3 signaling pathway in pancreas may play a key role in the pathogenesis of systematic inflammatory response in ANP.