Icariin upregulates methyltransferase-like 14-mediated prolyl 4-hydroxylase beta subunit m6A modification to promote osteogenic differentiation of bone marrow stem cells.

Prolyl 4-hydroxylase beta subunit (P4HB) plays a vital role in bone formation. This study intends to clarify the role of P4HB in the therapeutic effect of Icariin (ICA) on osteoporosis. Herein, in vivo and in vitro models were constructed by performing ovariectomy (OVX) in rats and inducing osteogenic differentiation in bone marrow stem cells (BMSCs), respectively. Hematoxylin and eosin staining and micro-computed tomography analysis were performed to evaluate osteoporosis in OVX rats. Alizarin Red staining, alkaline phosphatase staining, and the ALP activity test were employed to assess osteogenesis. m6A dot blotting and methylated RNA immunoprecipitation were used to determine m6A modification. We found that P4HB was downregulated in bone tissues of patients with osteoporosis and OVX rats. P4HB facilitated osteogenic differentiation of BMSCs. What's more, ICA upregulated P4HB expression, promoted osteogenic differentiation of BMSCs, and alleviated osteoporosis in OVX rats, which were reversed by knocking down P4HB. ICA enhanced the stability and m6A modification of P4HB. METTL14 mediated m6A modification of P4HB mRNA. In addition, METTL14 knockdown overturned the promotive effects of ICA on P4HB m6A level and BMSC osteogenic differentiation. To sum up, ICA elevated the METTL14-mediated m6A modification of P4HB to facilitate BMSC osteogenic differentiation.

Functional roles and engineering strategies to improve the industrial functionalities of lactic acid bacteria during food fermentation.

In order to improve the flavor profiles, food security, probiotic effects and shorten the fermentation period of traditional fermented foods, lactic acid bacteria (LAB) were often considered as the ideal candidate to participate in the fermentation process. In general, LAB strains possessed the ability to develop flavor compounds via carbohydrate metabolism, protein hydrolysis and amino acid metabolism, lipid hydrolysis and fatty acid metabolism. Based on the functional properties to inhibit spoilage microbes, foodborne pathogens and fungi, those species could improve the safety properties and prolong the shelf life of fermented products. Meanwhile, influence of LAB on texture and functionality of fermented food were also involved in this review. As for the adverse effect carried by environmental challenges during fermentation process, engineering strategies based on exogenous addition, cross protection, and metabolic engineering to improve the robustness and of LAB were also discussed in this review. Besides, this review also summarized the potential strategies including microbial co-culture and metabolic engineering for improvement of fermentation performance in LAB strains. The authors hope this review could contribute to provide an understanding and insight into improving the industrial functionalities of LAB.

Role of Hydrophobic Modification in Spermine-Based Poly(ß-amino ester)s for siRNA Delivery and Their Spray-Dried Powders for Inhalation and Improved Storage.

After RNAi was first discovered over 20 years ago, siRNA-based therapeutics are finally becoming reality. However, the delivery of siRNA has remained a challenge. In our previous research, we found that spermine-based poly(ß-amino ester)s are very promising for siRNA delivery. However, the role of hydrophobic modification in siRNA delivery of spermine-based poly(ß-amino ester)s is not fully understood yet. In the current work, we synthesized spermine-based poly(ß-amino ester)s with different percentages of oleylamine side chains, named P(SpOABAE). The chemical structures of the polymers were characterized by 1H NMR. The polymers showed efficient siRNA encapsulation determined by SYBR Gold assays. The hydrodynamic diameters of the P(SpOABAE) polyplexes from charge ratio N/P 1 to 20 were 30-100 nm except for aggregation phenomena observed at N/P 3. Morphology of the polyplexes was visualized by atomic force microscopy, and cellular uptake was determined by flow cytometry in H1299 cells, where all the polyplexes showed significantly higher cellular uptake than hyperbranched polyethylenimine (25 kDa). The most hydrophobic P(SpOABAE) polyplexes were able to achieve more than 90% GFP knockdown in H1299/eGFP cells. The fact that gene silencing efficacy increased with hydrophobicity but cellular uptake was affected by both charge and hydrophobic interactions highlights the importance of endosomal escape. For pulmonary administration and improved storage stability, the polyplexes were spray-dried. Results confirmed the maintained siRNA activity after storage for 3 months at room temperature, indicating potential for dry powder inhalation.

Gualou-Xiebai-Banxia-Tang regulates liver-gut axis to ameliorate Metabolic Syndrome in HFD-fed mice.

BACKGROUND: Metabolic syndrome (MetS), characterized by obesity, hyperglycemia, and abnormal blood lipid levels, is the pathological basis of many cardiovascular diseases. Gualou-Xiebai-Banxia-Tang decoction (GT) was first described in the Synopsis of the Golden Chamber, the earliest traditional Chinese medicine (TCM) monograph on diagnosis and treatment of miscellaneous diseases in China. According to TCM precepts, based on its ability to activate yang to release stagnation, activate qi to reduce depression, remove phlegm, and broaden the chest, GT has been used for more than 2,000 years to treat cardiovascular ailments. However, the molecular bases of its therapeutic mechanisms remain unclear. PURPOSE: The aim of this study was to identify lipid- and glucose-related hepatic genes differentially regulated by GT, and to assess GT impact on gut microbiota composition, in mice with high-fat diet (HFD)-induced MetS. STUDY DESIGN AND METHODS: ApoE-/- mice were fed with an HFD for 24 weeks, with or without concurrent GT supplementation, to induce MetS. At the study's end, body weight, visceral fat weight, blood lipid levels, and insulin sensitivity were measured, and histopathological staining was used to evaluate hepatosteatosis and intestinal barrier integrity. Liver transcriptomics was used for analysis of differentially expressed genes in liver and prediction of relevant regulatory pathways. Hepatic lipid/glucose metabolism-related genes and proteins were detected by RT-qPCR and western blotting. Gut microbial composition was determined by 16S rRNA gene sequencing. RESULTS: GT administration reduced MetS-related liver steatosis and weight gain, promoted insulin sensitivity and lipid metabolism, and beneficially modulated gut microbiota composition by decreasing the relative abundance of g_Lachnospiraceae_NK4A136_group and increasing the relative abundance of g_Alistipes. Liver transcriptomics revealed that GT regulated the expression of genes related to lipid and glucose metabolism (Pparγ, Igf1, Gpnmb, and Trem2) and of genes encoding chemokines/chemokine receptors (e.g. Cxcl9 and Cx3cr1). Significant, positive correlations were found for Ccr2, Ccl4, Ccr1, and Cx3cr1 and the g_Lachnospiraceae_NK4A136_group, and between Cxcl9, Ccr2, Ccl4, and Cx3cr1 and g_Desulfovibrio. GT treatment downregulated the protein expressions of SCD1 and CX3CR1 and upregulated the expression of PCK1 protein. CONCLUSION: GT supplementation alleviates HFD-induced MetS in mice by improving hepatic lipid and glucose metabolism. The anti-metabolic syndrome effects of GT may be related to the regulation of the gut-liver axis.

Excess multi-cause mortality linked to influenza virus infection in China, 2012-2021: a population-based study.

Objectives: The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations. Methods: Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death. Results: There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year. Conclusion: Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.

Isl Identifies the Extraembryonic Mesodermal/Allantois Progenitors and is Required for Placenta Morphogenesis and Vasculature Formation.

The placenta links feto-maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process and maintenance. The allantois and mesodermal components of amnion, chorion, and yolk sac are derived from extraembryonic mesoderm (Ex-Mes), however, the mechanisms contributing to distinct components of the placenta and regulation the interactions between allantois and epithelium during chorioallantoic fusion and labyrinth formation remains unclear. Isl1 is expressed in progenitors of the Ex-Mes and allantois the Isl1 mut mouse line is analyzed to investigate contribution of Isl1+ Ex-Mes / allantoic progenitors to cells of the allantois and placenta. This study shows that Isl1 identifies the Ex-Mes progenitors for endothelial and vascular smooth muscle cells, and most of the mesenchymal cells of the placenta and umbilical cord. Deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion, and placenta vessel morphogenesis. RNA-seq and CUT&Tag analyses revealed that Isl1 promotes allantoic endothelial, inhibits mesenchymal cell differentiation, and allantoic signals regulated by Isl1 mediating the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. This study above reveals that Isl1 plays roles in regulating multiple genetic and epigenetic pathways of vascular morphogenesis, provides the insight into the mechanisms for placental formation, highlighting the necessity of Isl1 for placenta formation/pregnant maintenance.

Micro- and Nanoengineered Metal Additively Manufactured Surfaces for Enhanced Anti-Frosting Applications.

The greater geometrical design freedom offered by additive manufacturing (AM) as compared to the conventional manufacturing method has attracted increasing interest in AM to develop innovative and complex designs for enhanced performance. However, the difference in material composition and surface properties from conventional alloys has made surface micro-/nanostructuring of AM metals challenging. Frost accretion is a safety hazard in numerous engineering applications. To expand the application of AM, this study experimentally investigates the antifrosting performance of superhydrophobic and slippery lubricant-infused porous surfaces (SLIPSs) generated on AM alloy, AlSi10Mg. By strategically utilizing the subgrain structure in the metallography of the AM alloy, the functionalized superhydrophobic AM surface featuring hierarchical structures was shown to greatly reduce frost formation as compared to functionalized single-tier structured surfaces, hierarchical structures formed on conventional aluminum alloy surfaces, and SLIPSs. Optical observation of frost propagation demonstrated that the mechanism of frost delay is governed by the inhibition of spontaneous droplet freezing through exceptional Cassie state stability during condensation frosting. The Cassie stability results from the unique AM structure morphology, which creates a higher structural energy barrier to prevent condensate from infiltrating the cavities. This phenomenon also enables the formation of a high surface-to-droplet thermal resistance, which eliminates spontaneous droplet freezing down to a -15 °C surface temperature. Our work demonstrates a scalable structuring method for AM metals, which can result in delayed frost formation, and it also provides guidelines for the development of engineered surfaces requiring the antifrosting function for several industries.

Evaluation of the American College of Surgeons risk calculator in hepatectomy for metastatic colorectal cancer in a Southeast Asian population.

PURPOSE: This study evaluated the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) calculator in predicting outcomes after hepatectomy for colorectal cancer (CRC) liver metastasis in a Southeast Asian population. METHODS: Predicted and actual outcomes were compared for 166 patients undergoing hepatectomy for CRC liver metastasis identified between 2017 and 2022, using receiver operating characteristic curves with area under the curve (AUC) and Brier score. RESULTS: The ACS-NSQIP calculator accurately predicted most postoperative complications (AUC > 0.70), except for surgical site infection (AUC = 0.678, Brier score = 0.045). It also exhibited satisfactory performance for readmission (AUC = 0.818, Brier score = 0.011), reoperation (AUC = 0.945, Brier score = 0.002), and length of stay (LOS, AUC = 0.909). The predicted LOS was close to the actual LOS (5.9 vs. 5.0 days, P = 0.985). CONCLUSION: The ACS-NSQIP calculator demonstrated generally accurate predictions for 30-day postoperative outcomes after hepatectomy for CRC liver metastasis in our patient population.

Evaluating the economic efficiency of open, laparoscopic, and robotic distal pancreatectomy: an updated systematic review and network meta-analysis.

BACKGROUND: This study compared the cost-effectiveness of open (ODP), laparoscopic (LDP), and robotic (RDP) distal pancreatectomy (DP). METHODS: Studies reporting the costs of DP were included in a literature search until August 2023. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, mean difference (MD), odds ratio (OR), and 95% credible intervals (CrIs) were calculated for outcomes of interest. Cluster analysis was performed to examine the similarity and classification of DP approaches into homogeneous clusters. A decision model-based cost-utility analysis was conducted for the cost-effectiveness analysis of DP strategies. RESULTS: Twenty-six studies with 29,164 patients were included in the analysis. Among the three groups, LDP had the lowest overall costs, while ODP had the highest overall costs (LDP vs. ODP: MD - 3521.36, 95% CrI - 6172.91 to - 1228.59). RDP had the highest procedural costs (ODP vs. RDP: MD - 4311.15, 95% CrI - 6005.40 to - 2599.16; LDP vs. RDP: MD - 3772.25, 95% CrI - 4989.50 to - 2535.16), but incurred the lowest hospitalization costs. Both LDP (MD - 3663.82, 95% CrI - 6906.52 to - 747.69) and RDP (MD - 6678.42, 95% CrI - 11,434.30 to - 2972.89) had significantly reduced hospitalization costs compared to ODP. LDP and RDP demonstrated a superior profile regarding costs-morbidity, costs-mortality, costs-efficacy, and costs-utility compared to ODP. Compared to ODP, LDP and RDP cost $3110 and $817 less per patient, resulting in 0.03 and 0.05 additional quality-adjusted life years (QALYs), respectively, with positive incremental net monetary benefit (NMB). RDP costs $2293 more than LDP with a negative incremental NMB but generates 0.02 additional QALYs with improved postoperative morbidity and spleen preservation. Probabilistic sensitivity analysis suggests that LDP and RDP are more cost-effective options compared to ODP at various willingness-to-pay thresholds. CONCLUSION: LDP and RDP are more cost-effective than ODP, with LDP exhibiting better cost savings and RDP demonstrating superior surgical outcomes and improved QALYs.

Evaluating the surgical trainee ergonomic experience during minimally invasive abdominal surgery (ESTEEMA study).

Minimally invasive abdominal surgery (MAS) can exert a physical cost. Surgical trainees spend years assisting minimally-invasive surgeries, increasing the risk of workplace injury. This prospective questionnaire-based cohort study was conducted amongst general surgery residents in Singapore. Residents assisting major MAS surgery were invited to complete anonymous online survey forms after surgery. The Phase 1 survey assessed physical discomfort scores and risk factors. Intraoperative measures to improve ergonomics were administered and evaluated in Phase 2. During Phase 1 (October 2021 to April 2022), physical discomfort was reported in at least one body part in 82.6% (n = 38) of respondents. Over a third of respondents reported severe discomfort in at least one body part (n = 17, 37.0%). Extremes of height, training seniority, longer surgical duration and operative complexity were significant risk factors for greater physical discomfort. In Phase 2 (October 2022 to February 2023), the overall rate of physical symptoms and severe discomfort improved to 81.3% (n = 52) and 34.4% (n = 22) respectively. The ergonomic measure most found useful was having separate television monitors for the primary surgeon and assistants, followed by intraoperative feedback on television monitor angle or position. Close to 20% of survey respondents felt that surgeon education was likely to improve physical discomfort.

Short-chain fatty acids: Important components of the gut-brain axis against AD.

Alzheimer's disease (AD) comprises a group of neurodegenerative disorders with some changes in the brain, which could lead to the deposition of certain proteins and result in the degeneration and death of brain cells. Patients with AD manifest primarily as cognitive decline, psychiatric symptoms, and behavioural disorders. Short-chain fatty acids (SCFAs) are a class of saturated fatty acids (SFAs) produced by gut microorganisms through the fermentation of dietary fibre ingested. SCFAs, as a significant mediator of signalling, can have diverse physiological and pathological roles in the brain through the gut-brain axis, and play a positive effect on AD via multiple pathways. Firstly, differences in SCFAs and microbial changes have been stated in AD cases of humans and mice in this paper. And then, mechanisms of three main SCFAs in treating with AD have been summarized, as well as differences of gut bacteria. Finally, functions of SCFAs played in regulating intestinal flora homeostasis, modulating the immune system, and the metabolic system, which were considered to be beneficial for the treatment of AD, have been elucidated, and the key roles of gut bacteria and SCFAs were pointed out. All in all, this paper provides an overview of SCFAs and gut bacteria in AD, and can help people to understand the importance of gut-brain axis in AD.

Leptomeningeal metastasis of breast cancer during neo-adjuvant chemotherapy in a 38-year-old woman: a case report.

Background: Breast cancer accounts for 5% of the population who develop central nervous system metastasis, which is only second to the lung cancer. Breast cancer metastasis to the brain including parenchymal brain metastasis (BM) and leptomeningeal metastasis (LM). Compared with BM, LM is a more rare but aggressive metastatic diagnosis with poor outcome. Case Description: We reported a 38-year-old woman presented to the neurology department due to progressive headache for 1 month, accompanied with dizziness, nausea, vomiting and neck pain. During hospitalization, she experienced paroxysmal loss of consciousness twice. Five months prior to this visit, her first visit was diagnosed with breast cancer on the right side which was of triple-negative subtype and with homolateral axillary lymph node involvement by biopsy. After the clinician assessment she had received six cycles of TCb (docetaxel/carboplatin) neo-adjuvant chemotherapy. During the period of neo-adjuvant chemotherapy, she did not report the presence of severe neurological symptoms. Twenty days ago, she underwent right breast-conserving surgery and the postoperative evaluation was ypT1N3M0 stage and Miller-Payne grade 2. Head computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging (MRI) didn't find typical brain imaging changes. No other signs of metastasis were seen in the CT examinations of the patient's chest and abdomen. Finally, lumbar puncture with cerebrospinal fluid (CSF) analysis showed the presence of malignant cells. Given the patient's clinical history and new neurologic symptoms, the diagnosis was LM from breast cancer. Various treatment modalities including intrathecal thiotepa, oral temozolomide (TMZ) and whole-brain radiation therapy (WBRT) had been used, but none of them showed significant benefit for survival. Conclusions: Breast cancer metastasis to the brain, especially LM, should be given sufficient vigilance and attention at the beginning of the diagnosis and treatment, particularly in triple-negative breast cancer patients who are at high risk. Symptoms of LM may be masked by the chemotherapy adverse effects. The results of MRI and CT may show negative results, thus lumbar puncture with CSF should be done promptly if LM is highly suspected in clinical practice. Early prevention, early detection and timely treatment are crucial according to the poor prognosis.

Comparative cost-effectiveness of open, laparoscopic, and robotic liver resection: A systematic review and network meta-analysis.

BACKGROUND: This study evaluated the cost-effectiveness of open, laparoscopic, and robotic liver resection. METHODS: A comprehensive literature review and Bayesian network meta-analysis were conducted. Surface under cumulative ranking area values, mean difference, odds ratio, and 95% credible intervals were calculated for all outcomes. Cluster analysis was performed to determine the most cost-effective clustering approach. Costs-morbidity, costs-mortality, and costs-efficacy were the primary outcomes assessed, with postoperative overall morbidity, mortality, and length of stay associated with total costs for open, laparoscopic, and robotic liver resection. RESULTS: Laparoscopic liver resection incurred the lowest total costs (laparoscopic liver resection versus open liver resection: mean difference -2,529.84, 95% credible intervals -4,192.69 to -884.83; laparoscopic liver resection versus robotic liver resection: mean difference -3,363.37, 95% credible intervals -5,629.24 to -1,119.38). Open liver resection had the lowest procedural costs but incurred the highest hospitalization costs compared to laparoscopic liver resection and robotic liver resection. Conversely, robotic liver resection had the highest total and procedural costs but the lowest hospitalization costs. Robotic liver resection and laparoscopic liver resection had a significantly reduced length of stay than open liver resection and showed less postoperative morbidity. Laparoscopic liver resection resulted in the lowest readmission and liver-specific complication rates. Laparoscopic liver resection and robotic liver resection demonstrated advantages in costs-morbidity efficiency. While robotic liver resection offered notable benefits in mortality and length of stay, these were balanced against its highest total costs, presenting a nuanced trade-off in the costs-mortality and costs-efficacy analyses. CONCLUSION: Laparoscopic liver resection represents a more cost-effective option for hepatectomy with superior postoperative outcomes and shorter length of stay than open liver resection. Robotic liver resection, though costlier than laparoscopic liver resection, along with laparoscopic liver resection, consistently exceeds open liver resection in surgical performance.

Analysis of the Efficacy of Polyenyl Phosphatidylcholine in Combination with Liraglutide in Nonalcoholic Fatty Liver Disease and the Effect of Omentin-1 and Vaspin Expression.

Objective: To evaluate the efficacy of combining polyene phosphatidylcholine (PPC) with liraglutide in the treatment of nonalcoholic fatty liver disease (NAFLD) and investigate its impact on adipokine expression, specifically omentin-1 and vaspin. Methods: One hundred twenty NAFLD patients were randomly assigned to either the observation group (n = 60) or the control group (n = 60). The control group received single-dose PPC treatment, while the observation group received a combination of PPC and liraglutide for 12 weeks. Clinical efficacy, adipose-related factors (omentin-1, vaspin, serum fibroblast growth factor 21 (FGF21)), liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT)), and adverse reaction rates were compared between the two groups before and after treatment. Results: In the observation group, the clinical effectiveness rate (95.00%) was significantly higher than that in the control group (83.33%) (P < .05). Before treatment, there were no significant differences in omentin-1, vaspin, FGF21, ALT, AST, and GGT between the two groups (P > .05). After treatment, both groups showed decreased levels of vaspin, FGF21, ALT, AST, and GGT, along with increased omentin-1 levels. However, levels of vaspin, FGF21, ALT, AST, and GGT were lower in the observation group compared to the control group, while omentin-1 levels were higher (P < .05). Adverse reaction rates did not significantly differ between the two groups (10.00% vs. 6.67%) (P > .05). Conclusions: The combination therapy of PPC and liraglutide demonstrates efficacy in treating NAFLD, improving adipose-related factors, and reducing liver enzyme activity with high safety. This approach warrants broader clinical implementation.

The trends of pediatric duodenal ulcer and predictors of recurrence.

BACKGROUND: Duodenal ulcer (DU) causes various symptoms in children. The prevalence of Helicobacter pylori (Hp)-associated DU has been reducing in some regions, yet the updated trend in Taiwan is unknown. Risk factors of DU recurrence have not been comprehensively investigated in children. METHODS: This retrospective study included children diagnosed with DU to evaluate the demographics, symptoms, diagnostics, treatment, and outcomes. Specific populations (infant, surgery required) were sorted for subgroup analysis. Predictors of DU recurrence was analyzed in patients who received endoscopic follow-ups. RESULTS: A total of 488 children were included. Most patients were male (72.5%), school-aged (11.3 ± 4.8 years old), and with varied underlying diseases in one-fifth. The annual incidences were around 3-5%, with a declining trend of case numbers and the Hp-positive proportion. Hp infection, concurrent gastric ulcer, perforation, and mortality were noted in 32.7%, 16%, 1.6%, and 1% of patients. Patients with or without Hp infection showed different clinical features but similar outcomes. The characteristics of subpopulations were depicted respectively. Male sex, lower Hb level, and perforation were independent risk factors associated with recurrence. CONCLUSIONS: Hp-positive DU seems to wane. Patients with male sex, lower Hb level, or perforation at diagnosis carried a higher risk of recurrence, which may warrant active surveillance and endoscopic follow-up.

Interactions between MDSCs and the Autonomic Nervous System: Opportunities and Challenges in Cancer Neuroscience.

Myeloid-derived suppressor cells (MDSC) are a population of heterogeneous immune cells that are involved in precancerous conditions and neoplasms. The autonomic nervous system (ANS), which is composed of the sympathetic nervous system and the parasympathetic nervous system, is an important component of the tumor microenvironment that responds to changes in the internal and external environment mainly through adrenergic and cholinergic signaling. An abnormal increase of autonomic nerve density has been associated with cancer progression. As we discuss in this review, growing evidence indicates that sympathetic and parasympathetic signals directly affect the expansion, mobilization, and redistribution of MDSCs. Dysregulated autonomic signaling recruits MDSCs to form an immunosuppressive microenvironment in chronically inflamed tissues, resulting in abnormal proliferation and differentiation of adult stem cells. The two components of the ANS may also be responsible for the seemingly contradictory behaviors of MDSCs. Elucidating the underlying mechanisms has the potential to provide more insights into the complex roles of MDSCs in tumor development and lay the foundation for the development of novel MDSC-targeted anticancer strategies.

Twenty years' experience of midgut malrotation and volvulus in a tertiary center in northern Taiwan: A retrospective study.

BACKGROUND: Early diagnosis and surgical intervention for midgut malrotation with bowel obstruction are crucial. We aimed to identify risk factors for adverse outcomes in infants with midgut malrotation and to develop a prediction model. METHODS: We reviewed the operation records of infants surgically diagnosed with midgut malrotation at Chang Gung Children's Medical Center between January 2000 and December 2020. Patients were classified into the poor-outcome group (PO) if they underwent bowel resection or experienced mortality; all others were categorized as the favorable-outcome group (FO). Data on demographics, initial presentations, laboratory results, radiographic or sonographic findings, maternal conditions, and outcomes were collected and analyzed. Fisher's exact test, the independent sample t-test, and the Mann-Whitney test were utilized for comparative analysis when suitable. RESULTS: The study included 103 infants. Eleven were in the PO group, and 92 were in the FO group. Initial presentations such as respiratory distress, poor activity, and shock status were notably more prevalent in the PO group. The INR, hemoglobin, HCO3, base excess, and aspartate transaminase values showed significant variation between the two groups. Multivariate analysis identified that lower hemoglobin (OR 0.677, p = 0.043) and higher AST (OR 1.036, p = 0.044) were independent predictors of adverse outcomes. An AST/Hb ratio of <3.78 demonstrated a high negative predictive value (98.6%) for an adverse outcome in midgut malrotation. CONCLUSIONS: Prompt diagnosis and surgical treatment of midgut malrotation are vital to prevent bowel resection or mortality. The independent predicting factors for poor outcomes include low hemoglobin and elevated AST levels.

Lung adenocarcinoma with EGFR L858R-K860I and L858R-L861F doublet mutations from which the L858R mutation is undetectable through the cobas EGFR mutation test v2.

In East Asia, epidermal growth receptor factor (EGFR) mutations are the most prevalent and important biomarkers for treating patients with advanced lung cancer. However, as L858R doublet mutations are rare, commercially available EGFR tests may yield false-negative results. To determine whether the L858R mutation of the L858R-K860I and L858R-L861F doublet mutations could be identified using different types of EGFR detection tests and to describe the clinical response of patients with lung cancer with L858R doublet mutations to EGFR tyrosine kinase inhibitors (TKI). Information and samples from four patients with L858R doublet mutations, including three with L858R-K860I and one with L858R-L861F, were retrospectively collected from the archives of our department. For each case, the clinical response to EGFR-TKI was retrieved from the medical records. Archived formalin-fixed paraffin-embedded blocks were subjected to Sanger sequencing, the cobas and Idylla EGFR tests, the IntelliPlex-LCP-DNA assay, and AmoyDx PLC panel. L858R mutations were all detected by Sanger sequencing and the Idylla EGFR test but missed by the cobas assay. The AmoyDx PLC detected L858R only in cases with L858R-K860I while the IntelliPlex-LCP-DNA assay detected L858R in the case with L858R-L861F. Additionally, three of the patients, who had measurable tumors, showed partial responses to afatinib and osimertinib. The L858R mutation associated with L858R-K860I and L858R-L861F doublet mutations could be detected using Idylla but not cobas EGFR tests. Using next-generation sequencing analysis should be considered after initial negative reports from the cobas test, because patients with L858R doublet mutations may benefit from EGFR-TKIs.

Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

In situ fast self-assembled preparation of dandelion-like Cu(OH)2@Cu3(HHTP)2 with core-shell heterostructure arrays for electrochemical sensing of formaldehyde in food samples.

Formaldehyde is known to harm the respiratory, nervous, and digestive systems of people. In this paper, a novel dandelion-like electrocatalyst with core-shell heterostructure arrays were fast self-assembled prepared in situ using copper foam (CF) as support substrate and 2,3,6,7,10,11 hexahydroxy-triphenyl (HHTP) as ligand (Cu(OH)2@Cu3(HHTP)2/CF) by a simple two-step hydrothermal reaction. The 1D Cu(OH)2 nanorods "core" and the 2D π-conjugated conducting metal-organic frameworks (Cu3(HHTP)2cMOF) "shell" with remote delocalized electrons give the dandelion-like heterogeneous catalysts excellent electrochemical activity such as a large specific surface area, high conductivity and a fast electron transfer rate. The Cu(OH)2@Cu3(HHTP)2/CF exhibited excellent electrocatalytic performance for formaldehyde under alkaline conditions with a linear range of 0.2 µmol/L - 125 µmol/L and 125 µmol/L - 8 mmol/L, a detection limit as low as 15.9 nmol/L (S/N = 3), as well as good accuracy, consistency, and durability, and it effectively identified FA in food.