Objective:To explore whether perioperative oral probiotic therapy reduces infectious complications following pancreaticoduodenectomy (PD), aiming to obtain higher-level evidence for clinical practice.Methods:A total of 81 participants undergoing PD at the Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital & Affiliated Hospital of Medical School, Nanjing University, from May 2024 to December 2024 were enrolled in this single-center, prospective, randomized controlled trial. The participants were randomly divided into a probiotic treatment group and a control group (receiving conventional treatment without probiotics) using a random number method. The primary outcomes included the incidence of postoperative infectious complications and intra-abdominal infection, and the secondary outcomes were the recovery of gastrointestinal function, postoperative hospital stay, and duration and costs of antibiotic use. The hematological indicators including inflammation and immune markers on postoperative days (POD) 1, 3, 5, and 7 were also compared between these two groups.Results:Finally 72 cases (39 males and 33 females) were analyzed, with 36 patients in the probiotic treatment group and 36 patients in the control group. Compared to the control group, the probiotic treatment group showed statistically significant reductions in the incidence of infectious complications (33.3% vs. 66.7%, P=0.029), intra-abdominal infection (27.8% vs. 58.3%, P=0.030), and incidence of delayed gastric emptying (0 vs. 16.7%, P=0.033). Also, the probiotic treatment group exhibited significantly faster recovery in postoperative bowel movements and shorter time to defecation, liquid diet, and semi-liquid diet (all P<0.05). Additionally, the probiotic treatment group had significantly shorter hospital stay, reduced duration of antibiotic use, and lower antibiotic costs (all P<0.05). Finally, the probiotic treatment group had significantly higher lymphocyte counts on POD 1 ( P<0.05) and showed a significant downward trend in inflammatory markers such as interleukin-6 on PODs 3 and 5 and C-reactive protein on POD 7 (all P<0.05). Conclusions:Perioperative application of probiotic preparations in PD may reduce the incidence of postoperative infectious complications, especially intra-abdominal infection. Additionally, it can prevent delayed gastric emptying, promote the recovery of postoperative gastrointestinal function, shorten hospital stay, and reduce the use of antibiotics. These benefits may be related to the improvement of postoperative inflammatory status.

Objective To compare the application value of coronary computed tomography angiography(CCTA)based plaque characteristics and computed tomography(CT)derived parameters in predicting future major adverse cardiovascular events(MACE)between patients with and without diabetes mellitus.Methods A total of 425 patients who underwent CCTA in Shunde Hospital Affiliated to Southern Medical University from June 2016 to November 2016 were retrospectively analyzed.Patients were divided into DM group(n=120)and non-DM group(n=305)for follow-up.According to the occurrence of MACE during follow-up,patients were divided into DM group(n=81),DM+MACE group(n=39),non-DM group(n=39),non-DM group(n=244)and non-DM+MACE group(n=61).The differences in general characteristics,biochemical index and parameters in imaging were compared among the four groups.Cox proportional hazards regression analysis was used to analyze the influencing factors for MACE in the two populations.The receiver operating characteristic(ROC)curve was used to analyze the difference in the predictive value of different plaque characteristics and CT-derived parameters for MACE.Results The levels of coronary artery calcification score(CACS),and the proportion of low-attenuation plaque(LAP)were higher in the DM+MACE group than in the DM group(P<0.05).The levels of positive reconstruction(PR),the proportion of antihypertensive drugs,CAD-RADS,CACS,residual cholesterol and apolipoprotein B were higher in the non-DM+MACE group than in the non-DM group(P<0.05).Cox proportional hazards regression analysis showed that CACS≥100(HR 2.151,95%CI 1.128～4.102,P=0.020)and LAP(HR 2.337,95%CI 1.032～5.290,P=0.042)were the influencing factors for MACE in patients with DM.PR(HR 124.305,95%CI 42.883～360.326,P<0.001)was the influencing factor for MACE in patients without DM.ROC curve analysis showed that the AUC of CACS combined with LAP were 0.606,0.609 and 0.660 for predicting MACE in DM patients within 1,3 and 5 years respectively.The AUC of PR for predicting MACE were 0.862,0.927,and 0.806 in the non-DM population within 1,3,and 5 years respectively.The predictive value of CACS and LAP for MACE in the DM patients was stable during the 5 years,while the predictive value of PR for MACE in the non-DM population decreased significantly after 4 years.Conclusions The predictive values of different plaque characteristics and CT derived parameters for future MACE are different between population with and without diabetes.The combination of CACS and low-attenuation plaques can effectively evaluate the risk of MACE in diabetic patients,while PR has a higher predictive value for MACE in non-diabetic patients.

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

Objective To compare the application value of coronary computed tomography angiography(CCTA)based plaque characteristics and computed tomography(CT)derived parameters in predicting future major adverse cardiovascular events(MACE)between patients with and without diabetes mellitus.Methods A total of 425 patients who underwent CCTA in Shunde Hospital Affiliated to Southern Medical University from June 2016 to November 2016 were retrospectively analyzed.Patients were divided into DM group(n=120)and non-DM group(n=305)for follow-up.According to the occurrence of MACE during follow-up,patients were divided into DM group(n=81),DM+MACE group(n=39),non-DM group(n=39),non-DM group(n=244)and non-DM+MACE group(n=61).The differences in general characteristics,biochemical index and parameters in imaging were compared among the four groups.Cox proportional hazards regression analysis was used to analyze the influencing factors for MACE in the two populations.The receiver operating characteristic(ROC)curve was used to analyze the difference in the predictive value of different plaque characteristics and CT-derived parameters for MACE.Results The levels of coronary artery calcification score(CACS),and the proportion of low-attenuation plaque(LAP)were higher in the DM+MACE group than in the DM group(P<0.05).The levels of positive reconstruction(PR),the proportion of antihypertensive drugs,CAD-RADS,CACS,residual cholesterol and apolipoprotein B were higher in the non-DM+MACE group than in the non-DM group(P<0.05).Cox proportional hazards regression analysis showed that CACS≥100(HR 2.151,95%CI 1.128～4.102,P=0.020)and LAP(HR 2.337,95%CI 1.032～5.290,P=0.042)were the influencing factors for MACE in patients with DM.PR(HR 124.305,95%CI 42.883～360.326,P<0.001)was the influencing factor for MACE in patients without DM.ROC curve analysis showed that the AUC of CACS combined with LAP were 0.606,0.609 and 0.660 for predicting MACE in DM patients within 1,3 and 5 years respectively.The AUC of PR for predicting MACE were 0.862,0.927,and 0.806 in the non-DM population within 1,3,and 5 years respectively.The predictive value of CACS and LAP for MACE in the DM patients was stable during the 5 years,while the predictive value of PR for MACE in the non-DM population decreased significantly after 4 years.Conclusions The predictive values of different plaque characteristics and CT derived parameters for future MACE are different between population with and without diabetes.The combination of CACS and low-attenuation plaques can effectively evaluate the risk of MACE in diabetic patients,while PR has a higher predictive value for MACE in non-diabetic patients.

Objective:To explore whether perioperative oral probiotic therapy reduces infectious complications following pancreaticoduodenectomy (PD), aiming to obtain higher-level evidence for clinical practice.Methods:A total of 81 participants undergoing PD at the Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital & Affiliated Hospital of Medical School, Nanjing University, from May 2024 to December 2024 were enrolled in this single-center, prospective, randomized controlled trial. The participants were randomly divided into a probiotic treatment group and a control group (receiving conventional treatment without probiotics) using a random number method. The primary outcomes included the incidence of postoperative infectious complications and intra-abdominal infection, and the secondary outcomes were the recovery of gastrointestinal function, postoperative hospital stay, and duration and costs of antibiotic use. The hematological indicators including inflammation and immune markers on postoperative days (POD) 1, 3, 5, and 7 were also compared between these two groups.Results:Finally 72 cases (39 males and 33 females) were analyzed, with 36 patients in the probiotic treatment group and 36 patients in the control group. Compared to the control group, the probiotic treatment group showed statistically significant reductions in the incidence of infectious complications (33.3% vs. 66.7%, P=0.029), intra-abdominal infection (27.8% vs. 58.3%, P=0.030), and incidence of delayed gastric emptying (0 vs. 16.7%, P=0.033). Also, the probiotic treatment group exhibited significantly faster recovery in postoperative bowel movements and shorter time to defecation, liquid diet, and semi-liquid diet (all P<0.05). Additionally, the probiotic treatment group had significantly shorter hospital stay, reduced duration of antibiotic use, and lower antibiotic costs (all P<0.05). Finally, the probiotic treatment group had significantly higher lymphocyte counts on POD 1 ( P<0.05) and showed a significant downward trend in inflammatory markers such as interleukin-6 on PODs 3 and 5 and C-reactive protein on POD 7 (all P<0.05). Conclusions:Perioperative application of probiotic preparations in PD may reduce the incidence of postoperative infectious complications, especially intra-abdominal infection. Additionally, it can prevent delayed gastric emptying, promote the recovery of postoperative gastrointestinal function, shorten hospital stay, and reduce the use of antibiotics. These benefits may be related to the improvement of postoperative inflammatory status.

Objective:To explore the effects of consecutively repeated application of emergency contraception pills (ECPs) containing levonorgestrel (LNG) on the female fertility and the health outcomes of F1 generation rats.Methods:Female SPF rats were intragastric administered with LNG-ECPs consecutively for 3 (P-3), 6 (P-6) and 12 (P-12) estrous cycles (three times in each estrous cycle), respectively. Under each administration schedule, rats were randomly divided into 2 groups according to body weight stratification using random numbers generated in Excel, i.e. LNG-ECPs group and solvent control group, administered with 0.12 mg/kg LNG-ECPs and corresponding volumes of 0.5% CMC-Na, respectively. Four hours after the last dosing, half of the animals (12-18) in each group were allotted randomly for dissection (6-9) and mating (6-9), respectively. The remaining half (12-18) were recovered for 3 estrous cycles, and then were randomly allocated for dissection (6-9) and mating (6-9). Organ coefficients were calculated. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, anti-Müllerian hormone (AMH) and free thyroid hormone 3 (fT3) were examined by enzyme linked immunosorbent assay (ELISA). Ovarian tissues were sectioned and stained with hematoxylin and eosin (HE) for follicle counting. In addition, the pregnancy rate and litter size of the female rats were recorded, and the growth indexes and behavioral parameters of the cubs were measured. Moreover, RNA sequencing (RNA-seq) of the ovarian tissues was performed to establish the differential expression gene profile of ovarian injury induced by LNG-ECPs. Then gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed.Results:1) After consecutive administration for 3 and 6 estrous cycles, LNG-ECPs showed no significant impact on the serum hormone levels and female fertility (all P>0.05), and the growth indexes and behavioral parameters of the F1 generation (all P>0.05). 2) After consecutive administration for 12 estrous cycles, the serum levels of FSH [(0.21±0.17) U/L], LH [(0.27±0.08) U/L] and progesterone [(0.68±0.23) μg/L] in LNG-ECPs group decreased significantly compared with those in solvent control group [(1.00±0.82) U/L, P=0.043; (1.00±0.50) U/L, P=0.006; (1.00±0.20) μg/L, P=0.027], while the level of estradiol [(2.24±1.03) μg/L] and testosterone [(1.25±0.25) μg/L] increased noticeably compared with those in solvent control group [(1.00±0.35) μg/L, P=0.019; (1.00±0.07) μg/L, P=0.044]. The number of primordial follicles (4.88±2.36) lost distinctly, while the number of atretic follicles (24.38±5.01) increased markedly in LNG-ECPs group compared with those in solvent control group (16.13±9.36, P=0.005; 19.13±2.30, P=0.018). In addition, the weight-loaded swimming (WLS) time of the F1 generation rats from the LNG-ECPs group [(157.13±32.29) s] reduced obviously compared with those from the solvent control group [(198.06±40.01) s, P=0.003]. Moreover, after recovering for 3 estrous cycles, LNG-ECPs significantly increased the levels of FSH [(2.48±1.18) U/L], LH [(1.60±0.41) U/L], testosterone [(1.37±0.23) μg/L] and the ratio of FSH/LH (1.61±0.41) compared with those in solvent control group [(1.00±0.67) U/L, P=0.024; (1.00±0.27) U/L, P=0.014; (1.00±0.18) μg/L, P=0.011; 1.00±0.49, P=0.042], respectively. Additionally, the serum levels of estradiol [(0.49±0.15) μg/L] and AMH [(0.79±0.15) μg/L] were significantly lower than those in solvent control group [(1.00±0.37) μg/L, P=0.011; (1.00±0.10) μg/L, P=0.016]. In addition, the number of primordial follicles in rats of LNG-ECPs group (6.25±5.06) were obviously less than that in solvent control group (12.00±5.56, P=0.048). Furthermore, the total distance in open field [(89.85±36.98) m] and the swimming time in WLS [(112.00±29.52) s] in rats treated with LNG-ECPs both decreased distinctly compared with those in solvent control group [(147.55±23.13) m, P<0.001; (137.69±25.85) s, P=0.014]. 3) According to transcriptomic analysis, Cd5, Cxcr1, Lexm, Fga, Mybphl and Gstm5 were the significant differential expressed genes (DEGs) in the ovarian tissues of rats. These DEGs were involved in pathways related to steroid hormone biosynthesis, including terpenoid backbone biosynthesis, ovarian steroidogenesis, cortisol synthesis and secretion. Additionally, these genes were involved in metabolic processes, such as carbon metabolism, butanoate metabolism, cysteine and methionine metabolism. And the genes were also involved in immunoregulatory processes including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptors. Conclusion:Consecutively repeated administering LNG-ECPs to the female rats in a short-term period (<12 cycles) did not demonstrate significant adverse effects on female fertility and the growth and development and the behaviors of their F1 generation cubs. However, long-term repeated treatment with LNG-ECPs (12 cycles) caused ovarian injury on female rats and showed negative impacts on the health of the F1 generation cubs, and no significant improvement was observed after recovering for 3 estrous cycles.

Objective To analyze the clinical characteristics,drug resistance and risk factors for poor prognosis in children patients with carbapenem resistant Klebsiella pneumoniae(CRKP)infection.Methods The samples of CRKP isolated from the children inpatients in this hospital from August 5,2016 to December 31,2020 were collected.The clinical data and drug resistance of CRKP in the patients with CRKP positive were analyzed.The risk factors in the poor prognosis group and good prognosis group of children pa-tients with CRKP infection conducted the correlation analysis.Results A total of 106 strains of non-repeti-tive CRKP were collected,which were mainly isolated from the patients ≤ 1 year old.The department distri-bution was dominated by the neonatal ICU and comprehensive ICU.CRKP showed the high resistance to mul-tiple antibacterial drugs,and its resistance rates to amikacin,levofloxacin,gentamicin,ciprofloxacin,minocy-cline and chloramphenicol were less than 30％.The poor prognosis rate in the children patients with CRKP in-fection reached 27.4％.The logistic multivariate regression analysis results showed that the multiple organ dysfunction and anemia were the independent risk factors for poor prognosis in the children patients with CRKP infection(P＜0.05).Conclusion The children CRKP infection is mainly the infants ≤1 years old,and CRKP shows the high resistance to multiple antibacterial drugs,the independent risk factors of poor prognosis include the multiple organ dysfunction and anemia

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl₄） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl₄ was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg^-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G₀/G₁ phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G₀/G₁ phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G₀/G₁ phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Objective To investigate the mechanism of Sini San Formula in the treatment of ulcerative colitis and depression through"homotherapy for heteropathy"based on network pharmacology and molecular docking.Methods The TCMSP database was used to obtain the potential active components and their related targets;GeneCards,CTD,and TTD databases were used to screen the disease-related targets of ulcerative colitis and depression;the intersection of the predicted targets of the active components and the disease-related targets was used to obtain the potential targets(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,and Cytoscape 3.7.2 software to construct a"Chinese medicinals-active components-diseases-common targets"network to analyze the core components;importing the common targets into the STRING database,constructing a common protein-protein interaction(PPI)network.The GO function and KEGG pathway enrichment of the shared targets were analyzed by DAVID database,and molecular docking between the core components and the key targets was verified.Results A total of 136 active components of Sini San Formula were obtained,and 220 potential targets of action(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,involving 657 biological processes,70 cellular components,147 molecular functions and 133 signaling pathways.The screening yielded core active compounds such as quercetin,kaempferol,lignans,naringenin,7-methoxy-2-methylisoflavone,key target proteins such as JUN,MAPK3,STAT3,AKT1,and MAPK1,as well as signaling pathways such as TNF,IL-17,Th17 cellular differentiation,HIF-1,and Toll-like receptor.Five potential key targets have strong binding activity to quercetin,kaempferol,lignans and naringenin.Conclusion Sini San Formula may act on key targets such as JUN,MAPK3,STAT3,AKT1,MAPK1,etc.through active components such as quercetin,kaempferol,lignocerotonin,naringenin,etc.,and play the role of"homotherapy for heteropathy"for ulcerative colitis and depression through the signaling pathways such as TNF,IL-17,HIF-1,Toll-like receptor and Th17 cell differentiation.

AIM: To investigate the effects of hypobaric hypoxia in plateau on tear indexes and related anatomical structures in rabbits.METHODS: A total of 18 healthy New Zealand rabbits were selected and randomly divided into plateau group and control group, with 9 rabbits(18 eyes)in each group. The plateau group was housed in the Simulated Climate Cabin for Special Environment of Northwest of China, simulating hypobaric hypoxia at an altitude of 6 000 m. The control group was housed in a clean animal room with atmospheric pressure and oxygen. Changes in the tear meniscus height and non-invasive tear break-up time were detected by using RHCT-1 corneal topographer dry eye comprehensive analysis system, changes in tear secretion was measured by Schirmer Ⅰ test, before intervention and on the 3, 7 d, 2 and 4 wk. Meanwhile, the changes in tear composition before and after intervention in the plateau environment were analyzed using Raman Spectroscopy. The histopathological changes of the lower lid conjunctiva, cornea, lacrimal gland, and Hardarian gland were observed by hematoxylin-eosin(HE)staining after 4 wk of intervention, and the expression of mucin 5AC(MUC5AC)in conjunctiva was detected by immunohistochemistry.RESULTS: Compared with the control group, Schirmer Ⅰ test, tear meniscus height, first and average non-invasive tear break-up time in the plateau group decreased significantly since 3 d, and the difference was significant with the extension of observation time(P<0.05). The above indexes increased from 2 wk. After 4 wk of intervention, the protein and lipid content of the tear composition of rabbits in the plateau group increased, and the nucleic acid content decreased compared with the pre-intervention period. Compared with the control group, rabbits in the plateau group showed thickening of corneal stromal edema, an increase in the number of conjunctival cup cells, increase in the level of expression of MUC5AC, an increase in the level of expression of MUC5AC, an atrophy and flattening of cytoplasm in lacrimal epithelial cells, an enlargement of glandular lumen, and no obvious destructive changes in the Hardarian glands.CONCLUSION: Acute plateau environment can destroy the homeostasis of rabbit ocular surface, so that the tear secretion and the tear film stability decreases, but within a certain period of time, rabbits undergo compensation with the habituation to the hypobaric hypoxia environment, which can increase the tear secretion to a certain extent and restore the tear film stability.