Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

Molecularly Imprinted Electrochemical Sensors Based on Ti3C2Tx-MXene and Graphene Composite Modifications for Ultrasensitive Cortisol Detection.

The increasing pressure and unhealthy lifestyle are gradually eroding the physical and mental health of modern people. As a key hormone responsible for maintaining the normal functioning of human systems, cortisol plays a vital role in regulating physiological activities. Moreover, cortisol can serve as a marker for monitoring psychological stress. The development of cortisol detection sensors carries immense potential, as they not only facilitate timely adjustments and treatments by detecting abnormal physiological indicators but also provide comprehensive data for conducting research on the correlation between cortisol and several potential diseases. Here, we report a molecularly imprinted polymer (MIP) electrochemical biosensor that utilizes a porous composite (MXG) modified electrode. MXG composite is prepared by combining Ti3C2Tx-MXene sheets and graphene (Gr). MXG composite material with high conductive properties and large electroactive surface area promotes the charge transfer capability of the electrode surface, expands the effective surface area of the sensor, and increases the content of cortisol-imprinted cavities on the electrode, thereby improving the sensing ability of the sensor. By optimizing the preparation process, the prepared sensor has an ultralow lower limit of detection of 0.4 fM, a wide detection range of 1 fM-10 µM, and good specificity for steroid hormones and interfering substances with similar cortisol structure. The ability of the sensor to detect cortisol in saliva was also confirmed experimentally. This highly sensitive and selective cortisol sensor is expected to be widely used in the fields of physiological and psychological care.

Relationship between SUVmax on 18F-FDG PET and PD-L1 expression in liver metastasis lesions after colon radical operation.

PURPOSE: Our study was to investigate the correlation correlation between FDG uptake and PD-L1 expression of liver metastasis in patients with colon cancer, and to determine the value of FDG-PET in predicting PD-L1 expression in liver metastasis of colon cancer. METHODS: A total of 72 patients with confirmed liver metastasis of colon cancer were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of liver metastasis lesions were assessed using 18 F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis. RESULTS: PD-L1 expression was significantly correlated with FDG uptake (SUVmax), tumor size, differentiation, survival and cytotoxic T cells infiltration in liver metastasis of colon cancer (P < 0.05). And liver metastases with high counts of infiltrating cytotoxic T cells showed greater FDG uptake than those with low counts of infiltrating cytotoxic T cells. The SUVmax of liver metastases and the degree of differentiation of metastases were closely related to PD-L1 expression, and were independent risk factors.The combined assessment of SUVmax values and tthe degree of differentiation of metastase can help determine PD-L1 expression in liver metastasis of colon cancer. CONCLUSIONS: FDG uptake in liver metastasis of colon cancer was positively correlated with the PD-L1 expression and the number of cytotoxic T cells infiltration. The joint evaluation of two parameters, SUVmax and degree of differentiation, can predict PD-L1 expression in liver metastases.

Sperm-borne small RNAs improve the developmental competence of pre-implantation cloned embryos in rabbit.

The low efficiency of somatic cell nuclear transfer (SCNT) greatly limits its application. Compared with the fertilized embryo, cloned embryos display abnormal epigenetic modification and other inferior developmental properties. In this study, small RNAs were isolated, and miR-34c and miR-125b were quantified by real-time PCR; results showed that these micro-RNAs were highly expressed in sperm. The test sample was divided into three groups: one was the fertilized group, one was the SCNT control group (NT-C group), and the third group consisted of SCNT embryos injected with sperm-borne small RNA (NT-T group). The level of tri-methylation of lysine 9 on histone H3 (H3K9me3) at the 8-cell stage was determined by immunofluorescence staining, and the cleavage ratio, blastocyst ratio, apoptotic cell index of the blastocyst and total cell number of blastocysts in each group were analyzed. Results showed that the H3K9me3 level was significantly higher in the NT-C group than in the fertilized group and the NT-T group. The apoptosis index of blastocysts in the NT-C group was significantly higher than that in the fertilized group and the NT-T group. The total cell number of SCNT embryos was significantly lower than that of fertilized embryos, and injecting sperm-borne small RNAs could significantly increase the total cell number of SCNT blastocysts. Our study not only demonstrates that sperm-borne small RNAs have an important role in embryo development, but also provides a new strategy for improving the efficiency of SCNT in rabbit.

Preoperative Fibrinogen Albumin Ratio is an Effective Biomarker for Prognostic Evaluation of Gallbladder Carcinoma After Radical Resection: A 10-Year Retrospective Study at a Single Center.

Background: To explore and screen preoperative serum immune response level-related biomarkers with better prognostic ability and developed a prognostic model for decision-making in clinical practice for gallbladder carcinoma (GBC) patients. Methods: A total of 427 patients who underwent radical resection for GBC in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Time-dependent receiver operating characteristic (time-ROC) was performed to determine the prognostic predictive power of preoperative biomarkers. A nomogram survival model was established and validated. Results: Time-ROC indicated that the preoperative fibrinogen-to-albumin ratio (FAR) had a better predictive ability for overall survival among preoperative serum immune response level-related biomarkers. Multivariate analysis indicated that FAR was an independent risk factor (P<0.05). The proportion of clinicopathological characteristics of poor prognosis (such as advanced T stage, and N1-2 stage) was significantly higher in high FAR group (P<0.05). Subgroup analyses indicate the prognostic discrimination ability of FAR depended on CA19-9, CA125, liver involvement, major vascular invasion, perineural invasion, T stage, N stage, and TNM stage (all P <0.05). A nomogram model was established based on the prognostic independent risk factors with the C-index of 0.803 (95% CI:0.771~0.835) and 0.774 (95% CI:0.696~0.852) in the training and testing sets, respectively. The decision curve analysis indicated the nomogram model had a better predictive ability than the FAR and TNM staging system in the training and testing sets. Conclusion: Preoperative serum FAR has a better predictive ability for overall survival among preoperative serum immune response level-related biomarkers, and it can be used for survival assessment of GBC and guide clinical decision-making.

Textbook outcome in gallbladder carcinoma after curative-intent resection: a 10-year retrospective single-center study.

BACKGROUND: Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients. METHODS: A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO. RESULTS: Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 µmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05). CONCLUSION: Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.

The clinical impact of early recurrence and its recurrence patterns in patients with gallbladder carcinoma after radical resection.

BACKGROUND: It is common for patients with gallbladder carcinoma (GBC) to develop recurrence shortly after radical resection. We aimed to investigate the risk factors of early recurrence (ER) and its recurrence patterns and further analyze the effect of adjuvant chemotherapy (ACT) on ER and non-ER patients for decision-making in clinical practice. METHODS: A total of 276 patients who underwent radical resection for GBC were retrospectively analyzed. Factors associated with overall survival (OS) and recurrence free survival (RFS) were identified using the Cox proportional hazard regression model, whereas ER was investigated using univariate and multivariable logistic regression models. RESULTS: The results indicated that 23.2% (64/276) of GBC patients developed ER after radical resection. ER was determined to be an independent risk factor for OS in patients with GBC after resection (P < 0.05). CA125, liver invasion, T stage, and N stage were independently associated with ER (P < 0.05). N1/N2 stage disease was an independent risk factor for OS, RFS and ER, and had a better predictive value in identifying ER than the other three variables associated with ER (P < 0.05). The liver and lymph nodes were the main first recurrence sites, and ER patients had a higher proportion of multisite recurrence. The prognosis of GBC patients with ER after radical resection differed significantly depending on whether ACT was provided, with ACT demonstrated to improve their prognosis (P < 0.05). CONCLUSIONS: Early recurrence after radical resection indicates a very poor prognosis in GBC and can be used to identify those who will benefit from ACT.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Induced Colon Injury by Disrupting the Intestinal Bacterial Composition and Lipid Metabolic Pathways in Rats.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the most abundant heterocyclic amines, is a common carcinogen produced in thermally processed protein-rich foods. Studies have demonstrated that PhIP could induce colon tumors in rodents, leaving mechanisms uncovered. This study aims to investigate the mechanism of PhIP-induced colon injury in a rat model. The results of 16S rRNA gene sequencing and metabolomics showed that PhIP disrupted intestinal bacterial composition and affected the glycerophospholipid metabolism and linoleic acid metabolism. Simultaneously, the lipid metabolism function in the intestinal flora was inhibited by PhIP. Notably, transcriptomics revealed that PhIP remarkably inhibited the expression of gene sets associated with steroid hormone biosynthesis, fatty acid elongation, fatty acid degradation, and glycerolipid metabolism pathways in the colon. The results provide new perspectives to study the mechanism of PhIP-induced colon injury and theoretical bases for further understanding the toxicity of PhIP.

Intervention with the crude polysaccharides of Physalis pubescens L. mitigates colitis by preventing oxidative damage, aberrant immune responses, and dysbacteriosis.

In this study, a colitis mouse model induced by dextran sulfate sodium (DSS) was used to investigate the mechanisms of action of an extract of crude polysaccharides (POL) from Physalis pubescens L. as a dietary intervention for colitis. Our results showed that the administration of POL prior to DSS-induced colitis protected the colon mucosal layer; maintained intestinal barrier integrity; alleviated oxidative damage; and lowered neutrophil infiltration by downregulating intercellular cell adhesion molecule-1 and monocyte chemoattractant protein-1 expression. More importantly, POL pretreatment reduced the expression of the proinflammatory factors tumor necrosis factor-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), thereby modulating the nuclear factor-κB/iNOS-COX-2 signal transduction pathway. In addition, POL reversed DSS-induced gut dysbiosis, accompanied by reducing the relative abundance of Helicobacter, Mucispirillum, and Erysipelatoclostridium. In conclusion, POL ameliorated DSS-induced intestinal injury in mice, indicating that POL could be a useful dietary nutrient to protect against colitis. PRACTICAL APPLICATION: Physalis pubescens L. is an edible fruit. The results of this study show that the intervention with Physalis pubescens L. crude polysaccharides may help prevent ulcerative colitis.

Platelet-derived microvesicles are involved in cardio-protective effects of remote preconditioning.

The ischemia-protective mechanism of remote precondition has been a mystery for a long time. Little was known about details of the inter-organ cardio-protective. Microvesicles, also known as microparticles (MPs), are small membrane-vesicles budding from the plasma membrane of cell. Recent studies have indicated MPs to be an important messenger in various biological processes. Our research mainly examined the hypothesis that remote ischemic conditioning can attenuate heart infarction in a rat after they were subjected to 30 min ischemia and 180 min reperfusion (I/R) by MPs. MPs were extracted from three groups of rat: 1) healthy rats, 2) healthy rats that underwent hindlimb ischemia-reperfusion preconditioning (RIPC) immediately, 3) healthy rats that underwent RIPC in 6 hours. Isolated MPs were transfused into rats that had undergone I/R without RIPC. The transfusion of MPs from rats that underwent RIPC immediately resulted in an increase in platelet-derived MPs in blood and reduction in infarction size, confirmed by 2-3-5-triphenyltetrazolium chloride staining. We further observed the contractile function in hearts after they were subjected to different treatments. However, no significant difference was observed in transfusion of MPs from rats that underwent RIPC in 6 hours. RIPC induces an increase in MPs, and platelet-derived MPs may confer at least part of the remote protective effect against cardiac ischemic-reperfusion injury.

Overexpression of SMAR1 Enhances Radiosensitivity in Human Breast Cancer Cell Line MCF7 via Activation of p53 Signaling Pathway.

This study sought to investigate the effect of overexpression of SMAR1 (scaffold/matrix-associated region-binding protein 1) on cell radiosensitivity in breast cancer, as well as elucidate its regulatory mechanism. We constructed a lentiviral expression system to successfully overexpress SMAR1 in human breast cancer cell line MCF7. In addition, overexpression of SMAR1 in MCF7 cells enhanced the radiosensitivity to (89)SrCl2. Moreover, overexpression of SMAR1 significantly induced cell apoptosis rate and G2/M phase arrest under the irradiation of (89)SrCl2. In addition, Western blot analysis showed that overexpression of SMAR1 in MCF cells significantly increased the expression levels of pP53 (ser15), pP53 (ser20), acP53, and p21 and obviously decreased the expression of MDM2 under the irradiation of (89)SrCl2. Notably, these expression changes could be neutralized by PFTα, an inhibitor of p53 signaling pathway that could inhibit p53-dependent transactivation of p53-responsive genes. Therefore, overexpression of SMAR1 may increase radiosensitivity to (89)SrCl2 in breast cancer cell line MCF7 by p53-dependent G2/M checkpoint arrest and apoptosis. Enhanced expression of SMAR1 in tumors will help to improve the clinical efficiency of radiation therapy.

Radiosensitizing effects of arsenic trioxide on MCF-7 human breast cancer cells exposed to 89 strontium chloride.

The aim of this study was to investigate the radiosensitizing effects of arsenic trioxide (As2O3) on MCF-7 human breast cancer cells irradiated with 89 strontium chloride (89SrCl2). The 50% inhibitory concentration (IC50) was calculated from results of an MTT assay. The concentration of As2O3 less than 20% IC50 was selected for subsequent experiments. Cells were treated with As2O3 and 89SrCl2. Morphological changes of cells were observed under an inverted microscope. The radiosensitivity enhancing ratio (SER) was computed based on a clone formation assay. Cell cycle distribution and apoptosis were measured by flow cytometry (FCM). Expression of Bcl-2 and Bax at both the mRNA and protein levels was assessed by RT-PCR and western blotting. The IC50 of As2O3 at 24 h was 11.7 µM. Doses of As2O3 (1 and 2 µM) were used in combination treatments and SER values were 1.25 and 1.79, respectively. As2O3 significantly suppressed cell growth, caused G2/M arrest, enhanced cell death and apoptosis induced by 89SrCl2 and decreased expression of the Bcl-2 gene. Since expression of Bax was unchanged following treatment, As2O3 effectively reduced the Bcl-2/Bax ratio. As2O3 (1-2 µM) enhances the cytotoxic effects of 89SrCl2 on the MCF-7 human breast cancer cell line by inducing G2 phase delay and promoting apoptosis through the reduction of the Bcl-2/Bax ratio.