Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

BACKGROUND: Endoscopic sphincterotomy (EST) is widely used to treat common bile duct stones (CBDS); however, long-term studies have revealed the increasing incidence of recurrent CBDS after EST. Loss of sphincter of Oddi function after EST was the main cause of recurrent CBDS. Reparation of the sphincter of Oddi is therefore crucial. This study aims to investigate the effectiveness and safety of endoclip papilloplasty (ECPP) for repairing the sphincter of Oddi and elucidate its mechanism. METHODS: Eight healthy Bama minipigs were randomly divided into the EST group and the ECPP group at a 1:1 ratio, and bile samples were collected before endoscopy and 6 months later. All minipigs underwent transabdominal biliary ultrasonography for the diagnosis of cholelithiasis 6 months after endoscopy. The biliary microbiota composition and alpha and beta diversity were analyzed by 16S ribosomal RNA gene sequencing. Differential metabolites were analyzed by bile acid metabolomics to explore the predictive indicators of cholelithiasis. RESULTS: Three minipigs were diagnosed with cholelithiasis in the EST group, while none in the ECPP group showed cholelithiasis. The biliary Firmicutes/Bacteroidota (F/B) ratio was increased after EST and decreased after ECPP. The Chao1 and observed species index significantly decreased 6 months after EST ( P  = 0.017 and 0.018, respectively); however, the biliary α-diversity was similar before and 6 months after ECPP. The β-diversity significantly differed in the EST group before and 6 months after EST, as well as in the ECPP group before and 6 months after ECPP (analysis of similarities [ANOSIM]: R  = 0.917, P  = 0.040; R  = 0.740, P  = 0.035; respectively). Glycolithocholic acid (GLCA) and taurolithocholic acid (TLCA) accumulated in bile 6 months after EST. CONCLUSIONS ECPP has less impact on the biliary microenvironment than EST and prevents duodenobiliary reflux by repairing the sphincter of Oddi. The bile levels of GLCA and TLCA may be used to predict the risk of cholelithiasis.
Animals ; Swine, Miniature ; Swine ; Cholelithiasis/prevention & control* ; Sphincterotomy, Endoscopic/methods* ; Sphincter of Oddi/surgery* ; Female ; Male

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

To systematically construct a guideline to provide a methodological guide for researchers to develop patient decision aids.

Information construction helps hospitals to accurately manage the blood glucose levels of hospitalized patients and improve the quality and safety of medical care. In July 2022, a large tertiary public hospital launched an information management of perioperative patient blood glucose. By establishing a multidisciplinary support and information management team, building an information-based blood glucose management system, establishing standardized management processes, implementing automatic hierarchical blood glucose warning, blood glucose critical value warning and control, abnormal blood glucose consultation, and insulin pump management, the hospital had achieved the information sharing of blood glucose perioperative patients, as well as timely warning and handling of abnormal blood glucose, ensuring patient safety. As of June 2023, the hospital had deployed a total of 364 intelligent blood glucose meters in clinical departments, and monitored blood glucose levels for 12 216 perioperative patients. The blood glucose compliance rate of perioperative patients increased from 81.81% in July 2022 to 82.95% in June 2023. This practice brought convenience to the work of clinical departments, improved the overall quality of medical services in hospitals, and could provide references for other hospitals to carry out blood glucose information management.

AIM: To analyze the chemical ingredients of Qingxin-zishen prescription decoction (QZPD) and predict its main pharmacodynamic substances and mechanism in the prevention and treatment of menopause syndrome (MPS) with the help of high performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF/MS) combined with network pharmacology. METHODS: The chemical ingredients of QZPD were identified after analyzing the retention time, exact mass, secondary mass spectrometry fragmentation and other information obtained from HPLC-Q-TOF/MS and comparing them with the established chemical ingredients database and the literatures. The targets of ingredients in QZPD were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction database. The disease targets of MPS were obtained through Online Mendelian Inheritance in Man (OMIM) and GeneCards Database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of potential targets were analyzed with the Metascape database. Cytoscape 3.7.2 software was used to construct the network of active components-key targets-pathways. AutoDockTools 4.2.5 software was applied in the molecular docking verification between the key active components and key targets. RESULTS: A total of 83 components were identified in QZPD and 847 drug targets were predicted. After intersection them with 3 050 disease targets, 395 common targets were obtained. After network topology analysis, 74 key targets were obtained, involving mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), transforming growth factor-β (TGF-β) and other signaling pathways. Molecular docking analysis results indicated that 23 key active components, such as berberine, epiberberine, coptisine, geissoschizine methyl ether, liensinine, norcoclaurine, palmatine, quercetin, and luteolin, had good binding activity with several of the key targets. CONCLUSION: This study preliminarily identifies the potential effective chemical ingredients of QZPD, predicts its targets in the prevention and treatment of MPS, which provides supporting information for the further study of the pharmacodynamic substances and mechanisms of QZPD.

Objective: To elucidate the clinicopathological characters and prognostic factors of invasive micropapillary carcinoma of the breast (IMPC) by compared with invasive ductal carcinoma, not otherwise specified of the breast (IDC). Methods: The retrospective study was performed with female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy from June 2008 to April 2016 in Breast Center of Beijing Hospital. Forty-seven mixed or pure IMPC patients and 93 pure IDC patients(admitted in the same center from October 2008 to January 2016 ) were matched for tumor stage, nodal status and age. Follow-up was done every 3 to 6 months postoperatively. The deadline was July 31, 2016. The curves of disease free survival and overall survival were drawn by the Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables that were identified on univariate analysis were analyzed with Cox′s proportional hazards regression model for multivariate analysis. The χ² test or Fisher′s exact test was used to compare distributions across 2 groups and the Mann-Whitney U test or t test was used to analyze the medians or means of 2 groups. Results: With exact matches, the rates of lymphovascular invasion (LVI) (29.8% vs. 12.9%, χ²=5.885, P=0.015)and histological grade 3 (40.4% vs. 21.5%, χ²=-2.690, P=0.007) were both significantly higher in patients with IMPC than that in IDC group, but the survival between the two pathological types were not significantly different (all P>0.05). The percent of IMPC component didn′t influence the clinicopathologic characters (all P >0.05), but a significantly longer median disease free survival (χ²=11.731, P=0.001) when the patients had more than 50% of IMPC component was found. Conclusions Higher rates of LVI and histological grade 3 were found in IMPC than that in IDC, but the survival was comparable between the two groups. A longer DFS occurred in patients with IMPC component more than 50%.

Objective To evaluate the hemostatic effect of hemocoagulase agkistrodon on surgical wound in breast cancer surgery. Methods Totally 60 patients undergoing breast cancer surgery were enrolled in this prospective,randomized,double-blinded,and controlled study. All the patients met the inclusion and exclusion criteria and signed the informed consent. Hemocoagulase agkistrodon (2 U) was injected 20 minutes before surgery and 4 and 24 hours after surgery in the intervention group (n=30),whereas normal saline was used instead in the control group (n=30). The volume of intraoperative bleeding,wound drainage volume 1-3 days after surgery,and total drainage volume were recorded. Meanwhile,the change of blood coagulation function,treatment safety,and clinical outcomes were observed. Results The intra-operative hemorrhage volume of the intervention group [(95.0±48.3)g] was significantly lower than that of the control group [(144.8±105.4)g] (t=-2.07,P=0.044). The volume of total drainage of the intervention group [(166.7±71.2)g] was significantly lower than that of the control group [(251.4±166.3)g] (t=-2.29,P=0.029). The hemoagglutination indicators were similar in the two groups and no complication such as thrombosis occurred. The length of hospital stay of the intervention group [(15.00±3.53)d] was similar to that of the control group [(15.92±2.32)d] (t=-1.057,P=0.297). No research drug-related adverse event was occurred in our study. Conclusion Hemocoagulase agkistrodon has good hemostatic effect for patients undergoing breast cancer surgery without increasing the risk of thrombosis.

Objective To investigate the therapeutic outcomes of unilateral adrenalectomy for Cushing syndrome in patients with adrenocorticotropic hormone (ACTH) independent bilateral macronodular adrenal hyperplasia.Methods 22 patients diagnosed with Cushing syndrome caused by ACTH independent bilateral macronodular adrenal hyperplasia from January 2005 to December 2015 were retrospectively concluded.There are 17 male patients and 5 female patients with the median age of 46.5 years.All patients were presented with Cushing syndrome such as moon face, buffalo hump and other typical symptoms of Cushing syndrome.The laboratory tests showed disappearance of cortisol rhythm, elevated 24-hour urinary free cortisol, suppressed or normal ACTH and unsuppressed low dose dexamethasone suppressing test.CT scan showed bilateral macronodular adrenal hyperplasia in all patients.Results All the patients received unilateral adrenalectomy.Pathological results showed adrenal cortex nodular hyperplasia.16 patients had reexamination in the endocrine department.The median follow-up time was 26 (17-118)months for these 16 patients.In the follow-up between 3 to 9 months after surgery, laboratory test showed serum and urinary cortisol level returned to normal range and Cushing syndrome also disappeared in these 16 patients.CT scan showed no recurrence.And no adrenal insufficiency occurred.One patient had recurrence one year after surgery and two patients turned better after surgery but had recurrence at 3 years and 10 years after surgery.Two patients received contralateral adrenalectomy and cortisol hormone replacement therapy after surgery.Another patient with recurrence refused second surgery.No recurrence was observed in other patients.Four patients were followed up by telephone, and all recovered well after surgery.18 patients had hypertension before surgery and their blood pressure significantly decreased after surgery.Among them 13 cases blood pressure returned to normal range.5 patients had elevated blood glucose before surgery, and 3 patients' blood glucose returned to normal range.Conclusions Unilateral adrenalectomy for Cushing syndrome in patients with ACTH independent bilateral macronodular adrenal hyperplasia is safe and effective.