DR10627, a Novel Dual Glucagon­like Peptide­1 and Gastric Inhibitory Polypeptide Receptor Agonist for the Treatment of Obesity and Type 2 Diabetes Mellitus.

Introduction: Diabetes and obesity are momentous risk factors threatening people's lives and health. Currently available incretin analogue glucagon-like peptide 1 (GLP-1) possesses huge hypoglycemic effect with the unsatisfactory effect of weight loss. Co-agonists targeting GLP-1R plus glucagon receptor (GCGR) or gastric inhibitory polypeptide receptor (GIPR) show synergistic benefits in glycaemic control and weight loss. Here, we describe a novel dual GIP and GLP-1 receptor agonist, DR10627, and performed a preclinical assessment of it. Methods: The agonistic ability of DR10627 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary (CHO) cells transfected with GLP-1R or GIPR in vitro. The plasma pharmacokinetics of DR10627 were analysed in cynomolgus monkeys. The OGTTs were performed in Sprague­Dawley (SD) rats. The glucose lowering effects were evaluated by repeated administration of DR10627 in diabetic (db/db) mice for 4 weeks. The effects of anti-obesity and improving metabolism of DR10627 were evaluated by repeated administration of DR10627 in diet-induced obesity (DIO) mice for 57 days. Results: DR10627 had the capacity to activate both GLP-1R and GIPR in vitro. The terminal half-life of DR10627 was found to be approximately 4.19-5.8 h in cynomolgus monkeys. DR10627 had a great improvement in oral glucose tolerance in SD rats. Moreover, DR10627 had a potent glucose-lowering effect in db/db mice, and the hypoglycemic effect of 18 nmol/kg DR10627 was better than that of 50 nmol/kg liraglutide. In addition, 10 and 30 nmol/kg DR10627 possessed the ability of potentiating the weight-loss, lipid-lowing efficacy and improving metabolism to a greater extent than 80 nmol/kg liraglutide. Conclusion: Preclinical assessment demonstrated that administration of DR10627 resulted in glucose lowering in SD rats and db/db mice, and substantial body weight reduction and metabolism improvement in DIO mice. DR10627 is a promising agent deserving further investigation for the treatment of type 2 diabetes and obesity.

Preparation of HA-MAO coatings on ß-type alloys and its corrosion resistance in high glucose environments.

Aim to provide practical clinical guidance for the treatment of implants in diabetic patients, this study investigated the corrosion mechanism of bionic coatings containing different Ca/P ratios in diabetic environments. The bionic coatings were prepared in ß-titanium alloys using micro-arc oxidation (MAO) technology and evaluated for corrosion mechanism, biocompatibility, and safety by cytotoxicity, electrochemical corrosion, and coating bonding force experiments. Ca and P from the electrolyte were integrated into the coating during MAO discharge process to form hydroxyapatite. The coating Ca/P ratio initially increased and then decreased with the electrolyte Ca/P ratio. In vitro cellular experiments demonstrated that increasing the porosity of HA-containing coatings would be beneficial to the growth of cells adhering to their surfaces. Corrosion tests revealed that the corrosion tendency of the coating at higher sugar content was more severe, and a proper elevation of the Ca/P ratio was better for the corrosion resistance of the coating. The bonding analysis of the coatings before and after corrosion showed that an increase in the Ca/P ratio would improve the bonding of the MAO coatings in higher glucose content environments, thus improving the safety of the implants in diabetic patients.

Influence of stress-specific interventions on biomarker levels and cognitive function in cancer patients: Systematic review and meta-analysis.

PURPOSE: Cancer patients' psycho-physiological health is seriously affected by long-term exposure to stress. Many studies have explored the impact of stress-specific interventions on cancer patients' biomarker levels and cognitive functions. However, the current research findings are inconsistent, and their statistical power is limited by the small samples. Therefore, we conducted this meta-analysis to verify the effect of stress-specific interventions on cancer patients. METHODS: The literature involved nine databases from the inception until January 13, 2024, extracted 19 randomized controlled trials (RCTs). Review Manager (RevMan) 5.4 software was used to perform a meta-analysis, and the revised Cochrane risk of bias tool (RoB2) was utilized for quality evaluation. RESULTS: Nine RCTs were assessed as having a low risk of bias, and others had a moderate risk. The results showed that stress-specific interventions had beneficial effects on patients' subjective cognition but uncertain impacts on their executive function, tumour necrosis factor-α level, morning cortisol level, and no effect on cortisol at other times, interleukin (IL)-10, IL-8, IL-6, IL-1, and C-reactive protein. CONCLUSION: More rigorous studies are required to elucidate the influence of stress-specific interventions on biomarker levels. The potential mechanism by which stress-specific interventions affect the cancer patient's cognitive function remains unclear.

NRG2 family members of Arabidopsis and maize regulate nitrate signalling and promote nitrogen use efficiency.

Nitrogen (N) is an essential nutrient for plant growth, and most plants absorb it as nitrate. AtNRG2 has been reported to play an important role in nitrate regulation. In this study, we investigated the functions of AtNRG2 family members of Arabidopsis thaliana and maize in nitrate signalling and metabolism. Our results showed that both AtNRG2.10 and AtNRG2.15 regulated nitrate signalling and metabolism. Overexpression of AtNRG2.11 (AtNRG2) could promote plant growth and improve nitrogen use efficiency (NUE). In addition, the maize genome harbors 23 ZmNRG2 members. We detected the expression of these genes treated with nitrate and the expression of four genes was strongly induced with ZmNRG2.7 having the highest levels. Overexpression of ZmNRG2.7 in the atnrg2 mutant could restore the defects of atnrg2, suggesting that ZmNRG2.7 is involved in nitrate signalling and metabolism. Moreover, the overexpression lines of ZmNRG2.7 showed increased biomass and NUE. These findings demonstrate that at least a part of NRG2 family genes in Arabidopsis and maize regulate nitrate signalling and provide a molecular basis for improving the NUE of crops.

The diagnostic, prognostic, drug sensitivity and ceRNA internet of PPP4R1 in liver hepatocellular carcinoma (LIHC).

Background: Recent studies have reported a role of protein phosphatase 4 regulatory subunit 1 (PPP4R1) in cancer development. However, its expression, diagnostic significance, prognostic value and biological function in liver hepatocellular carcinoma (LIHC) are not known. Methods: The expression level of PPP4R1 in pan-cancer was evaluated by analyzing publicly accessible data from the University of California Santa Cruz (UCSC) Xena database. The diagnostic value of PPP4R1 for tumors was assessed using receiver operating characteristic (ROC) curves, whereas the impact of PPP4R1 on tumor prognosis was determined using Kaplan-Meier survival curves, and a prognostic model for LIHC was established using cox regression analysis. In addition, analysis of the correlation between PPP4R1 and anti-cancer drugs using Spearman's correlation coefficient was carried out. Four databases, miRWalk (mRNA-miRNA interactions), MicroT-CDS (mRNA-miRNA interactions), LncBase (miRNA-lncRNA interactions) and Encyclopedia of RNA Interactomes (ENCORI), were used to predict the competitive endogenous RNA (ceRNA) regulatory network of PPP4R1. Finally, the expression of PPP4R1 protein levels was verified using experiments. Results: The findings indicated that the PPP4R1 expression level in cancerous tissues was notably greater than in adjacent tissues (P<0.05). PPP4R1 showed diagnostic significance for 14 tumors based on the ROC curves results area under the curve >0.7. Furthermore, the Kaplan-Meier survival plots demonstrated that PPP4R1 exhibited prognostic significance for all five tumors (P<0.05). According to the cox regression analysis, LIHC patients' prognosis was independently influenced by pathological stage, M stage, and PPP4R1 (P<0.05). The drug sensitivity analysis revealed a positive correlation between the expression level of PPP4R1 and the half maximal inhibitory concentration (IC50) of fludarabine. Additionally, the ceRNA network prediction indicated that the FGD5 antisense RNA 1 (FGD5-AS1)-hsa-miR-22-3p-PPP4R1 ceRNA network could potentially contribute to the progression of LIHC. The experimental results showed that the expression level of PPP4R1 protein was higher in cancer tissues than in paracancerous tissues. Conclusions: PPP4R1 has diagnostic value in most cancers, and high expression of PPP4R1 is associated with poor prognosis, drug resistance and natural killer cell-mediated toxicity, particularly in LIHC. Therefore, PPP4R1 may be a prognostic biomarker and a potential target for immunotherapy in LIHC.

Potential source and health risks of black carbon based on MERRA-2 reanalysis data in a typical industrial city of North China Plain.

Black carbon (BC) significantly affects climate, environmental quality, and human health. This study utilised Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2), which can compensate for the shortcomings of ground BC monitoring in spatial-temporal distribution to study the pollution characteristics of BC and potential pollution sources in a typical industrial city (Xinxiang) with serious air pollution in northern China. The results showed that average daily ground observation and MERRA-2 concentration of BC of 7.33 µg m-3 and 9.52 µg m-3. The mean BC concentration derived from MERRA-2 reanalysis data was higher than ground measurement due to resolution limitations and pollution from the northern regions. The reliability of the MERRA-2 data was confirmed through correlation analysis. Consideration of the spatial distribution of BC from MERRA-2 and incorporating the potential source contribution function (PSCF), concentration-weighted trajectory (CWT), and emission inventory, other possible source areas and primary sources of BC in Xinxiang were investigated. The results indicated that implementing transportation and residential emission control measures in Henan Province and its surrounding provinces, such as Hebei Province, will effectively decrease the BC level in Xinxiang City. A passively smoked cigarettes model was used to evaluate the risk of BC exposure. The percentage of lung function decrement (PLFD) was the highest in school-age children, while the impact on lung cancer (LC) health risk was comparatively lower. Notably, the BC health risk in Xinxiang was lower than in most cities across Asia.

Development and validation of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy: A study protocol.

AIM: This study aims to develop and validate a clinical nutrition risk screening tool to predict nutrition risk in home for the patients with gastric cancer after surgery at home so that high-risk patients can be targeted for preventive nutrition care. DESIGN: The development of self-screening tool for nutrition risk in patients with gastric cancer after gastrectomy (SNRSGC) through literature review, expert panel ratings and cognitive interview; the validation of SNRSGC is evaluated through prospective research on participants. METHODS: This research is divided into four parts: Step 1, Identification of a potential referred nutritional risk screening; Step 2, Item generation and scoring are selected through literature review methods to screen sensitive indicators which can reflect the nutritional characteristics of patients after gastric cancer surgery, establish the frame and update according to the latest guidelines; Step 3, Item reduction is determined by the rating of SNRSGC items by an expert panel and cognitive interview; Step 4, During the validation stage, we conducted research design based on the Consensus-based Standards for the selection of health Measurement Instruments checklist to evaluate the validity, reliability, interpretability and acceptability of SNRSGC. RESULTS: SNRSGC is the first screening tool specifically to predict nutrition risk for stay-at-home postoperative patients with gastric cancer, which can help patients at home detect nutritional risks at home in time and guide patients to seek medical treatment as soon as possible to improve their nutritional status.

Effects of interventions for enhancing resilience in cancer patients: A systematic review and network meta-analysis.

BACKGROUND: Various interventions appear to enhance cancer patients' resilience. However, the best intervention options are still unknown. This systematic review and network meta-analysis aimed to examine the impact of different interventions on resilience and identify the most effective interventions. METHODS: Nine major English and Chinese databases were systematically retrieved for randomized controlled trials (RCTs) published from inception to 13 November 2023. The outcome was resilience. The analysis was conducted using Software Review Manager 5.4, R 4.2.3, and STATA 14.0. RESULTS: The network meta-analysis included 32 RCTs and evaluated 12 interventions. Regarding effectiveness, compared to routine care, the relative effect sizes of attention and interpretation therapy, cyclic adjustment training, cognitive intervention, expressive therapy, positive psychological intervention, social support intervention, and work-environment therapy had statistically significant enhancing resilience, with the SMD (95%CI) of 1.42 (0.75, 2.07), 1.97 (0.76, 3.18), 1.26 (0.76, 1.77), 0.93 (0.08, 1.78), 1.02 (0.55, 1.50), 1.01 (0.48, 1.56), 1.65 (0.94, 2.37), respectively. Considering the rank probability, statistical power, and efficacy, the most effective interventions for improving resilience were attention and interpretation therapy, cognitive intervention, and positive psychological intervention. With the limited quantity of RCTs, the effectiveness of cyclic adjustment training and work-environment therapy still needs to be explored. CONCLUSIONS: Attention and interpretation therapy was the first best choice for boosting resilience out of the 12 interventions. Cognitive intervention and positive psychological intervention were also better choices for improving cancer patients' resilience. Due to the low quality and quantity of included RCTs, the need for multi-center, higher-quality trials with larger samples should be carried out. PROSPERO ID: CRD42023434223. The study did not receive funding support.

α-Conotoxin recombinant protein ImI-AFP3 efficiently inhibits the growth and migration of lung cancer cells.

α-Conotoxin ImI is a selective antagonist of alpha7 nicotinic acetylcholine receptor (α7 nAChR) that is involved in cancer development. Human alpha fetoprotein domain 3 (AFP3) is a prototype of anticancer agents. In an effort to design drugs for anticancer treatments, we fused the ImI peptide to AFP3 as a fusion protein for testing. The fusion protein (ImI-AFP3) was highly expressed in the insect Bac-to-Bac system. The purified fusion protein was found to have improved anticancer activity and synergized with the drug gefitinib to inhibit the growth and migration of A549 and NCI-H1299 lung cancer cells. Our data have demonstrated that the recombinant protein ImI-AFP3 is a promising candidate for drug development to suppress lung cancer cell growth, especially to suppress hepatoid adenocarcinoma of the lung (HAL) cell growth.

RNA-Seq analysis of long non-coding RNA in human intestinal epithelial cells infected by Shiga toxin-producing Escherichia coli.

BACKGROUND: The Shiga toxin-producing Escherichia coli (STEC) infects animals and induces acute intestinal inflammation. Long non-coding RNAs (lncRNAs) are known to play crucial roles in modulating inflammation response. However, it is not clear whether lncRNAs are involved in STEC-induced inflammation. METHODS AND RESULTS: To understand the association of lncRNAs with STEC infection, we used RNA-seq technology to analyze the profiles of lncRNAs in Mock-infected and STEC-infected human intestinal epithelial cells (HIECs). We detected a total of 702 lncRNAs differentially expressed by STEC infection. 583 differentially expressed lncRNAs acted as competitive microRNAs (miRNAs) binding elements in regulating the gene expression involved in TNF signaling pathway, IL-17 signaling pathway, PI3K-Akt signaling pathway, and apoptosis pathways. We analyzed 3 targeted genes, TRADD, TRAF1 and TGFB2, which were differentially regulated by mRNA-miRNA-lncRNA interaction network, potentially involved in the inflammatory and apoptotic response to STEC infection. Functional analysis of up/downstream genes associated with differentially expressed lncRNAs revealed their role in adheres junction and endocytosis. We also used the qRT-PCR technique to validate 8 randomly selected differentially expressed lncRNAs and mRNAs in STEC-infected HIECs. CONCLUSION: Our results, for the first time, revealed differentially expressed lncRNAs induced by STEC infection of HIECs. The results will help investigate the molecular mechanisms for the inflammatory responses induced by STEC.

A systematic review and meta-analysis of interventions to reduce perceived stress in breast cancer patients.

PURPOSE: Breast cancer (BC) patients commonly face stress that causes severe psychological and physiological problems. The main objective of the review was to confirm the effect of interventions on breast cancer patients' perceived stress, and the secondary objective was to explore the impact of interventions on anxiety, depression, and inflammatory markers. METHODS: A systematic and comprehensive search for randomized controlled trials (RCTs) that reported interventions' effects on perceived stress in breast cancer patients was performed in nine databases. RESULTS: Twenty-four RCTs, including 1887 participants, met the inclusion criteria, summarizing six categories for the intervention group: mindfulness and yoga, exercise, cognitive-behavioral stress management, self-regulation, relaxation training, and acupuncture. Compared with usual care or other types of care, mindfulness and yoga had excellent effects against perceived stress, anxiety, and depression; self-regulation could reduce perceived stress and anxiety; exercise could reduce perceived stress; acupuncture could reduce the level of depression; mindfulness could improve the TNF-α level, and yoga can reduce the level of salivary cortisol and DNA damage. CONCLUSION: This systematic review indicated that nondrug interventions, such as mindfulness and yoga, effectively reduce perceived stress, anxiety, and depression. Rigorous studies with large sample sizes are needed to address the limitations of small sample sizes and shortcomings in methodology in this area.

Effects of the Novel Coronavirus Pandemic on the Identification and Care of Critically Ill Emergency Patients Not Infected with COVID-19.

Objective: To clarify variations of diagnosis and treatment in the emergency care of critically ill patients not infected with novel coronavirus (COVID-19) prior to and amidst the COVID-19 pandemic. Methods: A retrospective cohort study was conducted to compare and analyze the diagnosis and treatment data of critically ill patients with non-COVID-19 infection who were admitted to the emergency department of the Fourth Medical Center of Chinese PLA General Hospital from January 2019 to November 2022. The variations in emergency care of the pandemic were summarized, and the influence of the pandemic on emergency care was assessed. Results: A total of 6634 critically ill patients with non-COVID-19 infection were included in this study. These patients were elderly, high incidence of chronic diseases, and extended emergency duration during the pandemic. Notably, the proportion of patients requiring intensive care was twofold higher compared to the period before the pandemic. Throughout the pandemic, patients experienced prolonged emergency durations, increased overall costs and daily expenses per patient. Further investigation revealed that elderly patients exhibited worse medical conditions, requiring lengthier emergency treatment and incurring escalated healthcare expenses. However, the presence of pre-existing chronic diseases did not appear to influence disease severity, nor extended emergency durations or heightened healthcare expenditures. Irrespective of the pandemic phase-be it short-term, medium-term, or long-term emergency care-greater healthcare spending was necessary. Conclusion: There was no difference in the disease spectrum of emergency critical ill patients with non-COVID-19 infection prior to and amidst the COVID-19 pandemic, nor the duration and expenditure in prior chronic illness patients. However, the disease severity and emergency duration have led to an increase in the total cost and economic intensity of emergency care for all patients during the epidemic. Especially, elderly patients required longer emergency duration, greater healthcare spending, and more inpatient medical resources than usual.

Association between self-perception of aging and cognitive function in Chinese older adults: The mediation effect of health behaviors.

OBJECTIVE: To investigate the association between self-perception of aging (SPA) and cognitive function in Chinese older adults, and to explore the mediating role of health behaviors. METHODS: This study included 5,445 Chinese older adults from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Correlation, linear regression and mediation effect analysis were employed to evaluate the association. RESULTS: SPA is significantly related to the health behaviors (r = 0.160, P < 0.01) and cognition (r = 0.086, P < 0.01), and health behaviors exhibited a positive correlation with cognition (r = 0.179, P < 0.01). SPA and health behaviors significantly impacted cognition (ß = 0.032, P = 010; ß = 0.103, P < 0.001). Health behaviors partially mediated the effect of SPA on cognitive function, accounting for 27.12 % of the total effect. CONCLUSION: Health behaviors mediate the association between SPA and cognitive function. Healthcare providers should prioritize addressing SPA of older adults and encourage them to engage in health behaviors for cognitive health.

Nursing student learning of evidence-based nursing through case-based learning and flipped learning: A mixed study.

AIM: To evaluate a teaching experience in evidence-based nursing learning through case-based learning (CBL) and flipped learning (FL). DESIGN: Embedded mixed methods study. METHODS: In the first phase, a questionnaire on utility, satisfaction and perceived competency development is used to collect quantitative data, and the open question instrument is used to collect qualitative data. After the first phase, an in-depth semi-structured interview is used. RESULTS: Five themes are identified: the enhancement of learning content, knowledge integration and transfer, the development of teamwork competency, the didactic support of FL and the difficulties and challenges faced by students. Regarding utility, 'combine theory and practice' and 'select the best evidence from what is found in the search' have the highest values. The most developed skills are communication and critical thinking ability. Finally, most participants are satisfied. CONCLUSIONS: The combination of CBL and FL is an innovative strategy for learning evidence-based nursing courses. No Patient or Public Contribution.

Glucose metabolism reprogramming promotes immune escape of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a complex process that plays an important role in its progression. Abnormal glucose metabolism in HCC cells can meet the nutrients required for the occurrence and development of liver cancer, better adapt to changes in the surrounding microenvironment, and escape the attack of the immune system on the tumor. There is a close relationship between reprogramming of glucose metabolism and immune escape. This article reviews the current status and progress of glucose metabolism reprogramming in promoting immune escape in liver cancer, aiming to provide new strategies for clinical immunotherapy of liver cancer.

Modelling the case-based learning preferences of undergraduate nursing students using a discrete choice experiment in China.

PURPOSE: To investigate the preferences for case-based learning programmes among undergraduate nursing students. METHOD: A questionnaire was designed based on a discrete choice experiment, and 227 undergraduate nursing students were investigated. In STATA 15.0 software, the data were statistically analysed using a mixed logit model. RESULT: All attributes in our study were found to have a significant influence on undergraduate nursing students' preferences for case-based learning programmes. The students' preference for the CBL programme was influenced by the clinical internship experience and type of university. Furthermore, the most ideal scenario was found to be video case modality, unfolding delivery, provided by academic experts and clinical instructors, group size 9-11, adequate feedback, and fragmented case content. CONCLUSION: The undergraduate nursing students' preferences for case-based learning programmes were affected by the provider, case modality, modality, group size, feedback, and case content. Our results can provide useful information for nursing educators to gain insight into student preferences and formulate case-based learning programs.

The devastating oomycete phytopathogen Phytophthora cactorum: Insights into its biology and molecular features.

Phytophthora cactorum is one of the most economically important soilborne oomycete pathogens in the world. It infects more than 200 plant species spanning 54 families, most of which are herbaceous and woody species. Although traditionally considered to be a generalist, marked differences of P. cactorum isolates occur in degree of pathogenicity to different hosts. As the impact of crop loss caused by this species has increased recently, there has been a tremendous increase in the development of new tools, resources, and management strategies to study and combat this devastating pathogen. This review aims to integrate recent molecular biology analyses of P. cactorum with the current knowledge of the cellular and genetic basis of its growth, development, and host infection. The goal is to provide a framework for further studies of P. cactorum by highlighting important biological and molecular features, shedding light on the functions of pathogenicity factors, and developing effective control measures. TAXONOMY: P. cactorum (Leb. & Cohn) Schröeter: kingdom Chromista; phylum Oomycota; class Oomycetes; order Peronosporales; family Peronosporaceae; genus Phytophthora. HOST RANGE: Infects about 200 plant species in 154 genera representing 54 families. Economically important host plants include strawberry, apple, pear, Panax spp., and walnut. DISEASE SYMPTOMS: The soilborne pathogen often causes root, stem, collar, crown, and fruit rots, as well as foliar infection, stem canker, and seedling damping off.

Case-based learning interventions for undergraduate nursing students in a theoretical course: A review of design, implementation, and outcomes.

BACKGROUND: Case-based learning (CBL) is a contextualized learning and teaching method that can facilitate active and reflective learning to develop critical thinking and problem-solving skills. However, nursing educators have some difficulty in creating a CBL environment that matches the diverse professional nursing curriculum and students' needs, including developing relevant cases and appropriate CBL implementation processes. OBJECTIVE: To summarize the case design, implementation process, and their relationship with CBL effectiveness. METHODS: Electronic databases of PubMed, Embase, Web of Science, CINAHL, China National Knowledge Infrastructure (CNKI) and Wanfang Data (a Chinese database) were searched from inception until January 2022. Study quality was assessed using the Mixed Methods Appraisal Tool. A qualitative synthesis was then conducted to summarize the study findings. RESULTS: The systematic mixed studies review included twenty-one quantitative studies, five qualitative studies and two mixed methods studies. The case design and implementation process were indispensable parts of each study, but the application process of CBL in each study was slightly different, basically including case design, preparation, small-group interaction and exploration, collaborative efforts, teacher summary, assignment and teacher feedback. There were three themes in this review that indicate the effect of CBL on students, namely, knowledge, competence and attitude. CONCLUSION: The present review analyzes the available literature and suggests that there is no common format for the case design and CBL implementation process, but demonstrates that they are an indispensable part of each study. This review provides conceptual procedures for nurse educators to design and implement CBL in nursing theoretical courses to improve the effectiveness of CBL.

A novel approach of intraoperative cholangiography in laparoscopic left lateral sectionectomy in living donor liver transplantation.

BACKGROUND: Accurate division of bile duct during laparoscopic donor hepatectomy in living donor liver transplantation is essential. We here present a novel approach to achieve cholangiography via the bile duct stump of segment IV (B4 stump) during laparoscopic donor hepatectomy in adult-to-pediatric living donor liver transplantation. PATIENTS AND METHODS: Donors who underwent laparoscopic left lateral sectionectomy (LLLS) from January 2022 to April 2022 in our liver transplant center were retrospectively analyzed. A total of 32 donors were eventually enrolled into this study. Cholangiography via the B4 stump was performed in 11 donors (B4 group) while indocyanine green (ICG) fluorescence guiding was performed in 21 donors (ICG group). Perioperative data were collected and compared between groups. RESULTS: Cholangiography by catheterizing the B4 stump was successfully performed in all 11 donors in the B4 group. The mean time of this procedure was 12.82 ± 9.11 min. Compared to the ICG group, it was more likely to acquire single bile duct orifice on graft in the B4 group (B4: 10/11, 90.91% vs ICG: 9/21, 42.86%) and it was significantly different (p = 0.030). The donors' complications (Clavien-Dindo grade III-IV) were not significantly different. There was one donor developed intraperitoneal effusion in B4 group, while two donors (one bile leakage and one biliary stricture) developed biliary tract related complications in the ICG group. A Roux-en-Y was performed to solve the biliary stricture in the ICG group. The recipients' outcomes were not significantly different between groups. CONCLUSIONS: Cholangiography via the B4 stump catheterization is feasible and safe in identifying the bifurcation of bile duct during LLLS.

Alpha fetoprotein promotes polarization of macrophages towards M2-like phenotype and inhibits macrophages to phagocytize hepatoma cells.

Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains unclear. In the present study, we explored the correlation between AFP regulation of macrophage function and the possible regulatory mechanisms. Human mononuclear leukemia cells (THP-1) and monocytes from healthy donors were used to analyze the effect of AFP on the macrophages' phenotype and phagocytosis. THP-1 cells and healthy human donor-derived monocytes were polarized into M0 macrophages induced by phorbol ester (PMA), and M0 macrophages were polarized into M1 macrophages induced by lipopolysaccharide(LPS) and interferon-γ(IFN-γ). Interleukin-4(IL-4) and interleukin-13(IL-13) were used to induce M0 macrophage polarization into M2 macrophages. Tumor-derived AFP(tAFP) stimulated M0 macrophage polarization into M2 macrophages and inhibited M1 macrophages to phagocytize HCC cells. The role of AFP in promoting macrophage polarization into M2 macrophages and inhibiting the M1 macrophages to phagocytize HCC cells may be involved in activating the PI3K/Akt signaling pathway. AFP could also enhanced the migration ability of macrophages and inhibited the apoptosis of HCC cells when co-cultured with M1-like macrophages. AFP is a pivotal cytokine that inhibits macrophages to phagocytize HCC cells.