Objective:To explore the biological efficacy and molecular mechanism of the new 6449Da active peptide against gastric adenocarcinoma.Methods:Effect 6449Da active peptides on SGC-7901 gastric adenocarcinoma cells line was studied and mRNA and protein expression levels of key factors relating to apoptosis, proliferation and notch signaling pathway was detcted.Results:The 6449Da functional fragment WSGC peptide located on the cell membrane relatively specifically inhibited the growth of gastric adenocarcinoma cells, but had a weak effect on normal gastric mucosal cells [cell doubling time , SGC-7901, 1.2 μmol/ml: (38.22±6.80) h vs. 0 μmol/ml: (25.65±1.82) h, P<0.05; GES-1, 1.2 μmol/ml: (33.37±3.15) h vs. 0 μmol/ml: (29.25±1.26) h, P>0.05].After treatment of SGC-7901 cells by IC80 (48 h),the cell apoptosis rate was higher than that in the control group (IC80: 0.421±0.036 vs. control group: 0.028±0.004, P<0.001), while the cell proliferation coefficient,number of transmembrane invasive cells and relative migration rate were all lower than those of the control group (all P<0.01).Compared with the control group, the mRNA and protein expression levels of Bax and Caspase-3 were higher than those in the control group(all P<0.01).Compared with the control group, the mRNA and protein expression levels of Ki67, PCNA, NOTCH1,Jagged 1, MAML3, CSL and HES1 were significantly lower than those in the control group (all P<0.01).After treatment with WSGC bioactive peptides, tumor weight was significantly lower than that of the control group [40 nmol/g: (0.463±0.031) g, 80 nmol/g: (0.340±0.040) g vs. control group: (1.667±0.373) g, all P<0.01]. Conclusion:6449Da functional fragment WSGC active peptide relatively specifically interferes with the growth of gastric adenocarcinoma cells by inhibiting the Notch signaling pathway, and has the biological effects of promoting apoptosis,inhibiting proliferation, transmembrane invasion and migration.

Objective:To explore the biological efficacy and molecular mechanism of the new 6449Da active peptide against gastric adenocarcinoma.Methods:Effect 6449Da active peptides on SGC-7901 gastric adenocarcinoma cells line was studied and mRNA and protein expression levels of key factors relating to apoptosis, proliferation and notch signaling pathway was detcted.Results:The 6449Da functional fragment WSGC peptide located on the cell membrane relatively specifically inhibited the growth of gastric adenocarcinoma cells, but had a weak effect on normal gastric mucosal cells [cell doubling time , SGC-7901, 1.2 μmol/ml: (38.22±6.80) h vs. 0 μmol/ml: (25.65±1.82) h, P<0.05; GES-1, 1.2 μmol/ml: (33.37±3.15) h vs. 0 μmol/ml: (29.25±1.26) h, P>0.05].After treatment of SGC-7901 cells by IC80 (48 h),the cell apoptosis rate was higher than that in the control group (IC80: 0.421±0.036 vs. control group: 0.028±0.004, P<0.001), while the cell proliferation coefficient,number of transmembrane invasive cells and relative migration rate were all lower than those of the control group (all P<0.01).Compared with the control group, the mRNA and protein expression levels of Bax and Caspase-3 were higher than those in the control group(all P<0.01).Compared with the control group, the mRNA and protein expression levels of Ki67, PCNA, NOTCH1,Jagged 1, MAML3, CSL and HES1 were significantly lower than those in the control group (all P<0.01).After treatment with WSGC bioactive peptides, tumor weight was significantly lower than that of the control group [40 nmol/g: (0.463±0.031) g, 80 nmol/g: (0.340±0.040) g vs. control group: (1.667±0.373) g, all P<0.01]. Conclusion:6449Da functional fragment WSGC active peptide relatively specifically interferes with the growth of gastric adenocarcinoma cells by inhibiting the Notch signaling pathway, and has the biological effects of promoting apoptosis,inhibiting proliferation, transmembrane invasion and migration.

Objective:To investigate the biofilm genes and quorum sensing genes of carbapenem resistant Acinetobacter baumannii (CRAB) in the wounds of diabetic foot patients. Methods:This study was a retrospective observational study. The 233 strains of Acinetobacter baumannii were cultured from 177 inpatients (128 males and 49 females, aged (56±10) years) with diabetic foot admitted to the Department of Diabetic Foot of Tianjin Medical University Chu Hsien-I Memorial Hospital from October 2020 to September 2023. Two hundred and thirty-three Acinetobacter baumannii strains were detected by bacterial culture from the diabetic foot wounds of the aforementioned patients. All Acinetobacter baumannii strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, followed by analysis of their resistance rate using kinetic turbidimetric assay by a fully automated microbiological analysis system. Ten CRAB strains (from 10 patients, 9 males and 1 female, aged (63±13) years) and 10 carbapenem sensitive Acinetobacter baumannii (CSAB; from 10 patients, 8 males and 2 females, aged (63±9) years) strains were randomly selected, and the whole DNA genome was extracted and sequenced. The antibiotic resistance genes were annotated using a comprehensive antibiotic resistance gene database, and a phylogenetic tree was drawn to analyze the homologous relationship between CRAB and CSAB. The 7 housekeeping genes of Acinetobacter baumannii was entered into the PubMLST website to analyze the multi-locus sequence typing of CRAB and CSAB. All the measured genes were put into the PubMLST website to search for the biofilm genes bap, csuA, csuB, csuA/B, csuC, csuD, csuE, pgaA, pgaB, pgaC, pgaD, bfmR, bfmS, ompA carried by each Acinetobacter baumannii, as well as the quorum sensing genes abaI and abaR, and flagellar gene pilA. The differences in carrying these genes between CRAB and CSAB were compared. The biofilm genes and quorum sensing genes carried by CRAB and CSAB carrying oxacillinase (OXA) resistance gene blaOXA were analyzed. Gross observation was performed to check if there was gel-like membrane-like substance in the diabetic foot wounds infected with CRAB and CSAB, and if so, the microstructure was observed by scanning electron microscope. Results:Among the detected Acinetobacter baumannii, the positive detection rates of CSAB, CRAB, multi-drug resistant Acinetobacter baumannii, and pan-drug resistant Acinetobacter baumannii were 16.7% (39/233), 83.3% (194/233), 95.3% (222/233), and 34.3% (80/233), respectively, and no fully drug-resistant Acinetobacter baumannii was detected. Among 233 strains of Acinetobacter baumannii, the resistance rate to carbapenem antibiotics exceeded 80%; the resistance rate of cefoperazone/sulbactam was relatively low, at 37%; the resistance rates to the other cephalosporin antibiotics (cefotaxime, ceftazimide, cefotetan, and cefuroxime) were more than 80%; the resistance rates to all penicillin antibiotics were greater than 80%; the resistance rates to quinolone antibiotics were all over 60%; the resistance rate to minocycline was only 12%; the resistance rates to tigecycline and colistin did not exceed 1%. The phylogenetic tree showed that 10 CRAB strains were highly homologous, while 10 CSAB strains had low homology. The analysis of multi-locus sequence typing showed that 10 CRAB strains were all the same type; among the 10 CSAB strains, except 1 strain without typing, the remaining 9 CSAB strains had 7 types. Eight of 10 CRAB strains contained complete biofilm genes and quorum sensing genes. The biofilm genes from the strains of CSAB were incomplete and none carried the bap gene. Neither CRAB nor CSAB carried the flagellar gene pilA. Compared with that carried by CRAB, biofilm genes bap, csuA, csuC, and csuD and quorum sensing genes abaI and abaR carried by CSAB were significantly decreased ( P<0.05). The main blaOXA categories carried by CRAB were blaOXA-23-like (specifically BlaOXA-167) and blaOXA-51-like (specifically blaOXA-66), both of which had carbapenase activity. Eight of 10 CRAB strains carried both blaOXA-66 and blaOXA-167, and all of them had relatively complete quorum sensing genes and biofilm genes. The main blaOXA categories carried by CSAB were blaOXA-51-like and blaOXA-213-like. Although they had carbapenemase activity, clinical drug sensitivity test showed that they were all sensitive to carbapenem antibiotics. Gel-like and membrane-like substance could be seen in wounds infected with CRAB, which were biofilm; no gel-like and membrane-like substance was found in the wound infected with CSAB. Conclusions:CRAB and CSAB in diabetic foot wounds are significantly different in terms of multi-locus sequence typing, carrying biofilm genes, quorum sensing genes, and blaOXA gene, leading to differences in antibiotic resistance between the two.

Objective:To investigate the biofilm genes and quorum sensing genes of carbapenem resistant Acinetobacter baumannii (CRAB) in the wounds of diabetic foot patients. Methods:This study was a retrospective observational study. The 233 strains of Acinetobacter baumannii were cultured from 177 inpatients (128 males and 49 females, aged (56±10) years) with diabetic foot admitted to the Department of Diabetic Foot of Tianjin Medical University Chu Hsien-I Memorial Hospital from October 2020 to September 2023. Two hundred and thirty-three Acinetobacter baumannii strains were detected by bacterial culture from the diabetic foot wounds of the aforementioned patients. All Acinetobacter baumannii strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, followed by analysis of their resistance rate using kinetic turbidimetric assay by a fully automated microbiological analysis system. Ten CRAB strains (from 10 patients, 9 males and 1 female, aged (63±13) years) and 10 carbapenem sensitive Acinetobacter baumannii (CSAB; from 10 patients, 8 males and 2 females, aged (63±9) years) strains were randomly selected, and the whole DNA genome was extracted and sequenced. The antibiotic resistance genes were annotated using a comprehensive antibiotic resistance gene database, and a phylogenetic tree was drawn to analyze the homologous relationship between CRAB and CSAB. The 7 housekeeping genes of Acinetobacter baumannii was entered into the PubMLST website to analyze the multi-locus sequence typing of CRAB and CSAB. All the measured genes were put into the PubMLST website to search for the biofilm genes bap, csuA, csuB, csuA/B, csuC, csuD, csuE, pgaA, pgaB, pgaC, pgaD, bfmR, bfmS, ompA carried by each Acinetobacter baumannii, as well as the quorum sensing genes abaI and abaR, and flagellar gene pilA. The differences in carrying these genes between CRAB and CSAB were compared. The biofilm genes and quorum sensing genes carried by CRAB and CSAB carrying oxacillinase (OXA) resistance gene blaOXA were analyzed. Gross observation was performed to check if there was gel-like membrane-like substance in the diabetic foot wounds infected with CRAB and CSAB, and if so, the microstructure was observed by scanning electron microscope. Results:Among the detected Acinetobacter baumannii, the positive detection rates of CSAB, CRAB, multi-drug resistant Acinetobacter baumannii, and pan-drug resistant Acinetobacter baumannii were 16.7% (39/233), 83.3% (194/233), 95.3% (222/233), and 34.3% (80/233), respectively, and no fully drug-resistant Acinetobacter baumannii was detected. Among 233 strains of Acinetobacter baumannii, the resistance rate to carbapenem antibiotics exceeded 80%; the resistance rate of cefoperazone/sulbactam was relatively low, at 37%; the resistance rates to the other cephalosporin antibiotics (cefotaxime, ceftazimide, cefotetan, and cefuroxime) were more than 80%; the resistance rates to all penicillin antibiotics were greater than 80%; the resistance rates to quinolone antibiotics were all over 60%; the resistance rate to minocycline was only 12%; the resistance rates to tigecycline and colistin did not exceed 1%. The phylogenetic tree showed that 10 CRAB strains were highly homologous, while 10 CSAB strains had low homology. The analysis of multi-locus sequence typing showed that 10 CRAB strains were all the same type; among the 10 CSAB strains, except 1 strain without typing, the remaining 9 CSAB strains had 7 types. Eight of 10 CRAB strains contained complete biofilm genes and quorum sensing genes. The biofilm genes from the strains of CSAB were incomplete and none carried the bap gene. Neither CRAB nor CSAB carried the flagellar gene pilA. Compared with that carried by CRAB, biofilm genes bap, csuA, csuC, and csuD and quorum sensing genes abaI and abaR carried by CSAB were significantly decreased ( P<0.05). The main blaOXA categories carried by CRAB were blaOXA-23-like (specifically BlaOXA-167) and blaOXA-51-like (specifically blaOXA-66), both of which had carbapenase activity. Eight of 10 CRAB strains carried both blaOXA-66 and blaOXA-167, and all of them had relatively complete quorum sensing genes and biofilm genes. The main blaOXA categories carried by CSAB were blaOXA-51-like and blaOXA-213-like. Although they had carbapenemase activity, clinical drug sensitivity test showed that they were all sensitive to carbapenem antibiotics. Gel-like and membrane-like substance could be seen in wounds infected with CRAB, which were biofilm; no gel-like and membrane-like substance was found in the wound infected with CSAB. Conclusions:CRAB and CSAB in diabetic foot wounds are significantly different in terms of multi-locus sequence typing, carrying biofilm genes, quorum sensing genes, and blaOXA gene, leading to differences in antibiotic resistance between the two.

Objective:To investigate the efficacy and safety of a novel modified Blumgart pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy (LPD).Methods:Between May 2021 and January 2022, 13 successive cases from Lihuili Hospital Affiliated to Ningbo University who underwent LPD were enrolled in this retrospective study. The study retrospectively analyzed the demographic characteristics, perioperative outcomes, and pathological results of these cases.Results:Twenty patients underwent LPD success-fully and one required conversion to open surgery. The operative time was (308.6 ± 61.7) min. The duration for PJ was (26.7 ± 4.3) min. The estimated blood loss was (188.1 ± 94.2) ml. The postoperative hospital stay was (14.2 ± 3.5) d. There was one case of biochemical leakage and no case of grade B or grade C pancreatic fistula.Conclusions:The new method is safe, simple and feasible. The novel method could reduce the incidence of pancreatic fistula and other complications after LPD.

Objective:To explore the effect of nursing based on enhanced recovery after surgery (ERAS) in the perioperative period of children with hydronephrosis who underwent robot-assisted laparoscopic pyeloplasty.Methods:From March 2020 to March 2021, convenience sampling was used to select 60 children with hydronephrosis who underwent robot-assisted laparoscopic pyeloplasty in the First Affiliated Hospital of Zhengzhou University as the research object. According to the random number table method, the children were divided into the control group and the observation group, 30 cases in each group. The control group was given routine perioperative nursing. On this basis, the observation group conducted nursing based on ERAS. The postoperative recovery and postoperative complications of the two groups were compared.Results:The time of first eating after surgery, the time of extubation of wound drainage tube after surgery, and the average hospital stay of the observation group were shorter than those of the control group, and the differences were statistically significant ( P<0.01) . The total incidence of postoperative complications in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The nursing based on ERAS can effectively reduce the incidence of postoperative complications in children with hydronephrosis after robot-assisted laparoscopic pyeloplasty, and promote the postoperative recovery of children, which is worthy of clinical promotion.

Objective:To investigate the expression of CXC chemokine ligand 11 (CXCL11) in gallbladder cancer (GBC) and its effect on cell proliferation and invasion.Methods:The surgically resected specimens of 47 GBC patients were collected in Lihuili Hospital Affiliated to Ningbo University from January 2017 to December 2020. There were 26 females and 21 males, with the age (62.0±8.2) years. The expression of CXCL11 protein in GBC tissues and corresponding paracancer tissues was detected by immunohistochemistry. Associations between CXCL11 expression and clinicopathological features were analyzed. After co-culturing of GBC-SD cells with exogenous CXCL11, cell counting kit-8 (CCK-8) and Transwell assays were performed to detect cell proliferation and invasion ability. The expression and phosphorylation level of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (Akt) were also detected by Western blot.Results:The positive expression rate of CXCL11 in GBC tissues was significantly higher than that in adjacent paracancerous tissues [63.8% (30/47) vs 31.9% (15/47), χ 2=9.59, P=0.002]. Furthermore, CXCL11 expression was significantly associated with tumor stage (χ 2=6.64, P=0.010) and lymph nodal metastasis (χ 2=7.86, P=0.005). CCK-8 assay revealed that the proliferation ability of GBC-SD cells in CXCL11-treated group significantly increased than that in the control group (absorbance value: 0.59±0.06 vs 0.32±0.04, t=9.64, P<0.001). Transwell assay showed that the cell invasion ability in CXCL11-treated group significantly increased than that in the control group [number of transmembrane cells: (133.4±12.3) cells vs (38.6±4.4) cells, t=16.21, P<0.001]. Western blot analysis showed that the relative expression levels of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) in CXCL11-treated group (0.88±0.06 and 0.83±0.04) were significantly higher than those in the control group (0.17±0.04 and 0.23±0.06), and the differences were statistically significant ( t=18.54, P<0.001 and t=15.21, P<0.001). Conclusion:CXCL11 is highly expressed in GBC and closely related to tumor progression. CXCL11 can promote the proliferation and invasion of GBC cells via PI3K/Akt signaling pathway.

Objective:To evaluate the effect of laparoscopic-assisted anorectoplasty in the treatment of children′s congenital anal atresia.Methods:In this study , 49 children undergoing laparoscopic-assisted anorectoplasty between Mar 2009 and Mar 2015 were compared in terms of outcomes with 42 children under going posterior sagittal anorectoplasty during this period.The post-operative complications, bowel functions and courses were evaluated.Results:The ratio of primary healing in laparoscopic-assisted anorectoplasty was higher than posterior sagittal anorectoplasty(22 % vs. 10%, χ 2=4.306, P=0.038), the age of sequential operation in the former was lower than control group [(9.9±6.5) d vs. (13.4±5.1) d, t=2.823, P=0.003]. The perioperative complications were lower than that in the control group(20% vs. 50%, χ 2=8.817, P=0.003), the bowel function was better than control group(χ 2=7.419, P=0.025). Conclusions:Perioperative complications in laparoscopic-assisted anorectoplasty is lower than posterior sagittal anorectoplasty, with better bowel function and higher primary healing rate.

Cell death plays important roles in living organisms and is a hallmark of numerous disorders such as cardiovascular diseases, sepsis and acute pancreatitis. Moreover, cell death also plays a pivotal role in the treatment of certain diseases, for example, cancer. Noninvasive visualization of cell death contributes to gained insight into diseases, development of individualized treatment plans, evaluation of treatment responses, and prediction of patient prognosis. On the other hand, cell death can also be targeted for the treatment of diseases. Although there are many ways for a cell to die, only apoptosis and necrosis have been extensively studied in terms of cell death related theranostics. This review mainly focuses on molecular imaging and therapeutic strategies directed against necrosis. Necrosis shares common morphological characteristics including the rupture of cell membrane integrity and release of cellular contents, which provide potential biomarkers for visualization of necrosis and necrosis targeted therapy. In the present review, we summarize the updated joint efforts to develop molecular imaging probes and therapeutic strategies targeting the biomarkers exposed by necrotic cells. Moreover, we also discuss the challenges in developing necrosis imaging probes and propose several biomarkers of necrosis that deserve to be explored in future imaging and therapy research.

The aim of this study was to synthesize and evaluate the necrosis avidity of MRI contrast agent based on rhein and linked by ether. The novel ligand 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(DO3A-Ether-Rhein, E1)was synthesized by two steps of acylation and deprotection reaction. The paramagnetic gadolinium 10-{［6-(1, 8-dihydroxyanthraquinone-3-carboxamido)ethoxyethyl］amino}carbonylmethyl-1, 4, 7, 10-tetraazacyclododecan-1, 4, 7-triacetic acid(Gd-DO3A-Ether-Rhein, GdE1)was obtained by coordination of Gd3+ with the above ligand. We examined the necrotic avidity of GdE1 in human hepatocellular carcinoma HepG2 cell necrosis induced by hyperthermia in vitro and in rat model with muscular necrosis induced by microwave ablation in vivo by MRI. The MRI was implemented before administration of GdE1 and during 0-9 h after administration of GdE1(0. 1 mmol/kg), and Gd-DOTA(gadolinium 1, 4, 7, 10-tetraacetic acid-1, 4, 7, 10-tetraazacyclo dodecane)was used as control. The signal intensity of necrotic cells(4 369±70)was significantly higher than that of normal cells(2 555±84)(P< 0. 05). Similarly, the contrast ratio between necrotic and normal muscle at 3 h after administration of GdE1(2. 00±0. 12)was remarkblely higher than that at 0 h after administration of GdE1(1. 27±0. 03)(P< 0. 05). Therefore, GdE1 presents good necrosis affinity and has the potential to be used in the diagnosis of necrosis-related diseases.