Development of esophagogastroduodenoscopy in China: results from the national census in 2013 and 2020.

Background: Given the significant burden of upper digestive diseases, there has been a substantial increase in the utilization of esophagogastroduodenoscopy (EGD) in China from 2012 to 2019. The objective of this study is to investigate the development, practice, and factors influencing the widespread use of EGD during this period. Methods: Two national censuses were conducted among all hospitals in mainland China that perform gastrointestinal endoscopy. These censuses aimed to extract information on the infrastructure, volume, and quality of EGD. The analysis of potential factors influencing EGD practice was based on real-world data from open access sources. Results: From 2012 to 2019, the number of hospitals performing EGD in mainland China increased from 1,518 to 2,265 (1.49-fold) in tertiary hospitals and from 3,633 to 4,097 (1.12-fold) in secondary hospitals, respectively. The national utilization rate of EGD also increased from 1,643.53 to 2,018.06 per 100,000 inhabitants, indicating a 1.23-fold increase. Regions with more endoscopists per 100,000 inhabitants (OR 9.61, P<0.001), more tertiary hospitals performing EGD per million inhabitants (OR 2.43, P<0.001), higher incidence of esophageal and gastric cancer (OR 2.09, P=0 016), and higher number of hospitals performing EGD per million inhabitants (OR 1.77, P=0.01) tended to provided more numerous and qualitied EGD. And hospital grading, regional GDP, incidence of esophageal and gastric cancer and the volume of EGD were observed as the significantly relevant factors of malignant dictation rate (MDR) (P<0.05), but not the number and educational background of endoscopists. Conclusion: Over the past seven years, China has made significant progress in EGD. However, challenges persist in terms of quality and inequality.

Inhibition of CIRBP represses the proliferation and migration of vascular smooth muscle cells via inhibiting Rheb/mTORC1 axis.

The excessive migration and proliferation of vascular smooth muscle cells (VSMCs) plays a vital role in vascular intimal hyperplasia. CIRBP is involved in the proliferation of various cancer cells. This study was aimed to explore the role of CIRBP in the proliferation and migration of VSMCs. Adenovirus was used to interfere with cold-inducible RNA-binding protein (CIRBP) expression, while lentivirus was used to overexpress Ras homolog enriched in brain (Rheb). Western blotting and qRT-PCR were used to evaluate the expression of CIRBP, Rheb, and mechanistic target of rapamycin complex 1 (mTORC1) activity. The cell proliferation was determined by Ki67 immunofluorescence staining and CCK-8 assay. The wound healing assay was performed to assess cell migration. Additionally, immunohistochemistry was conducted to explore the role of CIRBP in intimal hyperplasia after vascular injury. We found that silencing CIRBP inhibited the proliferation and migration of VSMCs, decreased the expression of Rheb and mTORC1 activity. Restoration of mTORC1 activity via insulin or overexpression of Rheb via lentiviral transfection both attenuated the inhibitory effects of silencing CIRBP on the proliferation and migration of VSMCs. Moreover, Rheb overexpression abolished the inhibitory effect of silencing CIRBP on mTORC1 activity in VSMCs. CIRBP was upregulated in the injured carotid artery. Silencing CIRBP ameliorated intimal hyperplasia after vascular injury. In the summary, silencing CIRBP attenuates mTORC1 activity via reducing Rheb expression, thereby supressing the proliferation and migration of VSMCs and intimal hyperplasia after vascular injury.

Comprehensive prognostic and immunological analysis of Cullin2 in pan-cancer and its identification in hepatocellular carcinoma.

BACKGROUND: As a member of the Cullin family, Cullin2 (CUL2) is involved in the development and spread of different types of cancers. However, the precise role of CUL2 in human cancer remains largely elusive. METHODS: In this study, various databases were applied to observe the CUL2 expression. Kaplan-Meier and Spearman correlation analyses were employed to investigate the potential links between CUL2 level, patient prognosis, and the infiltration of immune cells. In addition, the association between CUL2 and the efficacy of immunotherapy in an immunotherapy cohort was investigated. Moreover, the expression and distribution of CUL2 in cells were observed using the Human Protein Atlas (THPA) database. Finally, clinical tissue specimens and in vitro function assays were conducted to validate the expressions and effects of CUL2 on the biological functions in hepatocellular carcinoma (HCC) cells. RESULTS: While there are variations in CUL2 expression across different organs and cell types, it is notably upregulated in a majority of tumor tissues. In addition, CUL2 gene mutations are common in multiple cancers with low mutation rates and CUL2 is closely related to the prognosis of some cancer's patients, some immune regulatory factors, TMB, MSI, MMR genes, and DNA methylation. Further, our results found that downregulating CUL2 inhibits the proliferation, and migration abilities. CONCLUSIONS: The expression of CUL2 has an impact on the prognosis of various tumors, and this correlation is particularly noteworthy due to its significant association with the infiltration of immune cells within tumors. CUL2 was an oncogene contributing to the progression of HCC.

Decoding Gastric Cancer: Machine Learning Insights Into the Significance of COMMDs Family in Immunotherapy and Diagnosis.

Copper, an indispensable trace element for the human body, serves not only as a crucial auxiliary factor in redox reactions within the organism but also as a significant constituent of numerous key metabolic enzymes. The COMMD family plays a vital role in regulating copper at both the cellular and systemic levels, particularly in the realm of tumor research, an area notably deficient in gastric cancer investigations. With the advancement of precision medical techniques, individualized and precise screening and treatment have become paramount considerations in the contemporary medical landscape for gastric cancer therapy. In light of this, we meticulously scrutinized existing transcriptomic datasets for gastric cancer, validating the expression levels and prognostic value of COMMD family genes. Simultaneously, employing the ssGSEA algorithm, we devised the COMMDs score. Enrichment analysis, gene mutations, and clinical features were incorporated into the assessment of this score. Furthermore, we contextualized the COMMDs score within the framework of the immune microenvironment, evaluating the relationship between the COMMDs family and immune factors as well as immune cells. The results suggest a correlation between the COMMDs score and various immune-related features. Based on this foundation, multiple machine learning approaches indicated Logistic Regression, with a remarkable ROC of 0.972, as the optimal diagnostic model. To accentuate the translational medical value of the COMMDs family, we selected COMMD10 as a differential gene in gastric cancer for further validation. Functional experiments revealed a decline in the proliferative and migratory capabilities of gastric cancer cells upon silencing COMMD10. Additionally, through pathway intervention, we unveiled the PI3K-AKT pathway as a potential mechanism through which COMMD10 influences gastric cancer activity. In summary, our study affirms the prospective role of the COMMDs family as potential markers for the diagnosis and treatment of gastric cancer in the future.

A safe and effective endoscopic treatment method for simple hepatic cysts (with video).

Background and study aims Symptomatic simple hepatic cysts require treatment, with several guidelines recommending laparoscopic deroofing. However, cysts located in the posterosuperior segments are considered poor candidates for this procedure. Gastrointestinal endoscopes are more flexible and able to reach less accessible areas than laparoscopes. This study aimed to evaluate the utility of endoscopic transgastric hepatic cyst deroofing (ETGHCD) for treatment of simple hepatic cysts. Patients and methods Seven patients with simple hepatic cysts were evaluated between June 2021 and October 2023. The success rate, procedure time, post-procedure length of hospital stays, complications, pathologic diagnosis, and efficacy were recorded. Results Eleven cysts in seven patients (5 men; mean age 65.5 (standard deviation [SD] 8.5) years) were successfully treated without any complications. The mean procedure time was 65.6 minutes (SD 17.2). Mean post-procedure hospitalization was 4.4 days (SD 1.0). The pathologic diagnosis of 11 cysts showed simple hepatic cysts. The size of the cysts was significantly decreased from 337.0 cm 3 (SD 528.8) to 5.2 cm 3 (SD 6.3) 1 month after ETGHCD. During the median 12.7-month follow-up in seven patients, the cysts showed a 99.6% reduction with no recurrence. Conclusions ETGHCD provided a feasible, safe, effective, and minimal invasive alternative approach for the treatment of simple hepatic cysts.

Diagnostic Efficacy of a Novel Rotating Brush for Endoscopic Sampling of Malignant Biliary Strictures: A Multicenter Prospective Study.

INTRODUCTION: Although cytologic examination of biliary stricture brushings obtained by endoscopic retrograde cholangiopancreatography is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBS detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs involving biliary stricture brushings obtained using our RIS brush. The historical control group consisted of the 30-brushing arm of our previous randomized trial (patient inclusion, 2018-2020) that used the study design in the same centers and with the same endoscopists as were used in this study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs by cytologic evaluation of biliary stricture brushings between the 2 groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in the RIS brush group than in the conventional brush group (0.75 vs 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBS detection. No significant differences were observed in procedure-related complications between the 2 groups. DISCUSSION: The RIS brush was a promising tool for effective and safe MBS sampling and diagnosis. Further randomized studies are warranted to confirm our results (Chictr.org.cn, identifier: ChiCTR2100047270).

Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data.

BACKGROUND: Pyroptosis impacts the development of malignant tumors, yet its role in colorectal cancer (CRC) prognosis remains uncertain. AIM: To assess the prognostic significance of pyroptosis-related genes and their association with CRC immune infiltration. METHODS: Gene expression data were obtained from The Cancer Genome Atlas (TCGA) and single-cell RNA sequencing dataset GSE178341 from the Gene Expression Omnibus (GEO). Pyroptosis-related gene expression in cell clusters was analyzed, and enrichment analysis was conducted. A pyroptosis-related risk model was developed using the LASSO regression algorithm, with prediction accuracy assessed through K-M and receiver operating characteristic analyses. A nomogram predicting survival was created, and the correlation between the risk model and immune infiltration was analyzed using CIBERSORTx calculations. Finally, the differential expression of the 8 prognostic genes between CRC and normal samples was verified by analyzing TCGA-COADREAD data from the UCSC database. RESULTS: An effective pyroptosis-related risk model was constructed using 8 genes-CHMP2B, SDHB, BST2, UBE2D2, GJA1, AIM2, PDCD6IP, and SEZ6L2 (P < 0.05). Seven of these genes exhibited differential expression between CRC and normal samples based on TCGA database analysis (P < 0.05). Patients with higher risk scores demonstrated increased death risk and reduced overall survival (P < 0.05). Significant differences in immune infiltration were observed between low- and high-risk groups, correlating with pyroptosis-related gene expression. CONCLUSION: We developed a pyroptosis-related prognostic model for CRC, affirming its correlation with immune infiltration. This model may prove useful for CRC prognostic evaluation.

A clinical study on gastric cancer patients administered EN and PN versus PN alone in enhanced recovery after surgery.

Background and objectives: Enhanced recovery after surgery (ERAS) recommends avoiding enteral nutrition (EN) due to undesirable sequelae such as pulmonary aspiration and infections. Not using of EN in nongastric resections under ERAS pathways is often successful. However, parenteral nutrition (PN) alone followed by early postoperative oral feeding in gastric cancer patients, recommended by the ERAS guidelines, has unclear benefit and is only adopted after gastric resection. This study aimed to compute the postoperative outcomes of EN and PN compared to those of the ERAS-recommended nutritional pathway. Our secondary objective was to compare postoperative complications between the two groups. Materials and methods: Of 173 gastrectomy patients, 116 patients were in the combined group (EN and PN), whereas 57 patients were in the PN alone group. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) version 26.0.0 software. The data were analyzed by one-way ANOVA, the independent sample t-test, or, in the case of several independent samples, by the Kruskal-Wallis test. Categorical data were analyzed by Pearson's χ2 test or Fisher's exact test. Results: The observed indices included C-reactive protein (CRP), platelet (PLT), white blood cells (WBC), hemoglobin (Hb), albumin, and PRE-albumin. The secondary outcomes included length of hospital stay (LOS), cost, incidence of pulmonary infection, and total incidence of infection. Conclusion: The combined mode of nutrition is feasible and is not associated with postoperative complications in gastric cancer patients under ERAS.

Self-Catalyzed Synthesis of Length-Controlled One-Dimensional Nickel Oxide@N-Doped Porous Carbon Nanostructures from Metal Ion Modified Nitrogen Heterocycles for Efficient Lithium Storage.

Transition metal oxides with the merits of high theoretical capacities, natural abundance, low cost, and environmental benignity have been regarded as a promising anodic material for lithium ion batteries (LIBs). However, the severe volume expansion upon cycling and poor conductivity limit their cycling stability and rate capability. To address this issue, NiO embedded and N-doped porous carbon nanorods (NiO@NCNR) and nanotubes (NiO@NCNT) are synthesized by the metal-catalyzed graphitization and nitridization of monocrystalline Ni(II)-triazole coordinated framework and Ni(II)/melamine mixture, respectively, and the following oxidation in air. When applied as an anodic material for LIBs, the NiO@NCNR and NiO@NCNT hybrids exhibit a decent capacity of 895/832 mA h g-1 at 100 mA g-1, high rate capability of 484/467 mA h g-1 at 5.0 A g-1, and good long-term cycling stability of 663/634 mA h g-1 at 600th cycle at 1 A g-1, which are much better than those of NiO@carbon black (CB) control sample (701, 214, and 223 mA h g-1). The remarkable electrochemical properties benefit from the advanced nanoarchitecture of NiO@NCNR and NiO@NCNT, which offers a length-controlled one-dimensional porous carbon nanoarchitecture for effective e-/Li+ transport, affords a flexible carbon skeleton for spatial confinement, and forms abundant nanocavities for stress buffering and structure reinforcement during discharge/charging processes. The rational structural design and synthesis may pave a way for exploring advanced metal oxide based anodic materials for next-generation LIBs.

Xanthene-based near-infrared chromophores for high-contrast fluorescence and photoacoustic imaging of dipeptidyl peptidase 4.

Near-infrared (NIR) chromophores with analyte tunable emission and absorption properties are highly desirable for developing activatable fluorescence and photoacoustic (PA) probes for bioimaging and disease diagnosis. Here we engineer a class of new chromophores by extending the π-conjugation system of a xanthene scaffold at position 7 with different electron withdrawing groups. It is demonstrated that these chromophores exhibit pH-dependent transition from a spirocyclic "closed" form to a xanthene "open" form with remarkable changes in spectral properties. We further develop fluorescence and PA probes by caging the NIR xanthene chromophores with a dipeptidyl peptidase 4 (DPPIV) substrate. In vitro and live cell studies show that these probes allow activatable fluorescence and PA detection and imaging of DPPIV activity with high sensitivity, high specificity and fast response. Moreover, these two probes allow high-contrast and highly specific imaging of DPPIV activity in a tumour-bearing mouse model in vivo via systemic administration. This study highlights the potential of a xanthene scaffold as a versatile platform for developing high-contrast fluorescence and PA molecular probes.

Effects of the enhanced recovery after surgery (ERAS) protocol on the postoperative stress state and short-term complications in elderly patients with colorectal cancer.

OBJECTIVE: The aim of this study was to evaluate the feasibility and necessity of enhanced recovery after surgery in elderly patients with colorectal cancer by observing inflammatory markers and postoperative complications. METHODS: Hospitalized colorectal cancer patients from the Affiliated Hospital of Jiangsu University from January 2021 to September 2022 were included in the study and divided into two groups: Enhanced Recovery After Surgery (ERAS) and non-ERAS. Data on postoperative inflammatory markers and complications were also collected. RESULTS: A total of 313 patients with colorectal cancer were included: 182 in the ERAS group and 131 in the non-ERAS group. The patients in the ERAS group had significantly shorter days of postoperative hospitalization, urinary catheter and drainage tube withdrawal times, and recovery of bowel function (P < .05) than those of the non-ERAS group. Moreover, the ERAS group had lower hospitalization expenses than those of the non-ERAS group (P < .05). However, the procalcitonin and tumor necrosis factor (TNF)-α levels in the ERAS group was significantly lower than those in the non-ERAS group on postoperative days 1 and 3 (P < .05), and the interleukin (IL)-6 and IL-10 levels in the ERAS group were significantly lower than those in the non-ERAS group on the 1st, 3rd, and 5th postoperative days (P < .05). The C-reactive protein (CRP) and white blood cell (WBC) levels in the ERAS group were lower than those in the non-ERAS group on postoperative days 3 and 5 (P < .05). However, the hemoglobin levels did not differ significantly (P > .05). The albumin levels did not differ significantly between the two groups before surgery (P > .05); however, the albumin level in the ERAS group was higher than that in the non-ERAS group on postoperative days 3 and 5 (P < .05). The ERAS patients had lower albumin levels after surgery than those of the non-ERAS patients (P < .05). CONCLUSION: ERAS leads to a series of perioperative optimization measures, thereby reducing the postoperative stress response in elderly patients with colorectal cancer and the occurrence of perioperative complications.

The adverse association of animal zinc intake with cardio-cerebrovascular and metabolic risk factors.

Background: The effect of zinc intake on cardio-cerebrovascular and metabolic diseases has always been controversial. Aims: We hoped to evaluate the associations of the daily dietary estimate (DDE) of zinc intake with cardio-cerebrovascular and metabolic risk factors. Methods: Baseline data from the Study of Women's Health Across the Nation (SWAN) were obtained. Multivariable linear regression analysis was used to examine associations of the DDE of zinc intake with cardio-cerebrovascular and metabolic risk factors. Results: The smooth curve demonstrated positive associations of the DDE of animal zinc intake with low-density lipoprotein-cholesterol (LDL-C), triglycerides, total cholesterol, fasting blood glucose, insulin, systolic blood pressure (BP) and diastolic BP and an inverse association of the DDE of animal zinc intake with high-density lipoprotein-cholesterol (HDL-C). Consistently, multivariable linear regression models also showed that an increased DDE of animal zinc intake was closely related to a higher risk of cardio-cerebrovascular and metabolic risk factors [systolic BP: 0.37 (0.13, 0.61); diastolic BP: 0.17 (0.02, 0.33); fasting blood glucose: 1.13 (0.67, 1.59); insulin: 0.26 (0.05, 0.47); LDL-C: 0.82 (0.34, 1.29), triglycerides: 1.65 (0.75, 2.55), total cholesterol: 0.91 (0.38, 1.43) and HDL-C: -0.24 (-0.45, -0.03)] when age, race/ethnicity, total family income, smoking status, alcohol consumption and menopausal status were controlled for. Importantly, stratified analysis supported that the independent associations between the DDE of animal zinc intake and risk factors for cardio-cerebrovascular and metabolic diseases were hardly affected by age and body mass index (BMI). Conclusion: We found that an increased DDE of animal zinc intake was associated with higher cardiovascular and metabolic risks among middle-aged women, which did not support the benefit of zinc intake in reducing cardiovascular and metabolic risks. The association seems to be incongruous with the anti-inflammation and antioxidation physiological functions of zinc. Thus, additional well-designed and prospective studies are needed to confirm this association.

Calpain Inhibitor Calpeptin Improves Pancreatic Fibrosis in Mice with Chronic Pancreatitis by Inhibiting the Activation of Pancreatic Stellate Cells.

BACKGROUND: Pancreatic fibrosis is a hallmark feature of chronic pancreatitis (CP), resulting in persistent damage to the pancreas. The sustained activation of pancreatic stellate cells (PSCs) plays a pivotal role in the progression of pancreatic fibrosis and is a major source of extracellular matrix (ECM) deposition during pancreatic injury. METHODS: Calpain is a calcium-independent lysosomal neutral cysteine endopeptidase and was found to be correlated to various fibrotic diseases. Studies have revealed that calpeptin, a calpain inhibitor, can improve the fibrosis process of multiple organs. This study investigated the effect of the calpain inhibitor, calpeptin, on fibrosis in experimental CP and activation of cultured PSCs in mice. CP was induced in mice by repeated injections of cerulein for four weeks in vivo, and the activation process of mouse PSCs was isolated and cultured in vitro. Then, the inhibitory effect of calpeptin on pancreatic fibrosis was confirmed based on the histological damage of CP, the expression of α-smooth muscle actin (α-SMA) and collagen-Iα1(Col1α1), and the decrease in mRNA levels of calpain-1 and calpain-2. RESULTS: In addition, it was revealed that calpeptin can inhibit the activation process of PSCs and induce significant PSCs apoptosis by downregulating the expression of calpain-1, calpain-2 and TGF-ß1, and the expression and phosphorylation of smad3 in vitro. CONCLUSION: These results suggest that the calpain inhibitor, calpeptin, plays a key role in the regulation of PSC activation by inhibiting the TGF-ß1/smad3 signaling pathway, which supports the potential of calpeptin as an inhibitor of pancreatic fibrosis in mice by interfering with calpain.

Qing Xia Jie Yi Formula granules alleviated acute pancreatitis through inhibition of M1 macrophage polarization by suppressing glycolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulas from Traditional Chinese Medicine are common and well-established practice for treating acute pancreatitis (AP) patients. However, little is known about their bioactive ingredients and mechanisms, such as their targets and pathways to inhibit inflammation. AIM OF THE STUDY: This study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and discuss the molecular mechanisms involved. MATERIALS AND METHODS: Major compounds in QXJYF granules were identified using UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). The effect of QXJYF granules on experimental AP models both in vitro and in vivo, and detailed mechanisms were clarified. Two AP models were induced in mice by intraperitoneally injections of caerulein or L-arginine, and QXJYF granules were used to treat AP mice in vivo. Histological evaluation of pancreas and lung, serum amylase and lipase levels, serum inflammatory cytokines, inflammatory cell infiltration and macrophage phenotype were assessed. Bone marrow derived macrophages (BMDMs) were cultured and treated with QXJYF granules in vitro. BMDM phenotype and glycolysis levels were measured. Lastly, clinical effect of QXJYF granules on AP patients was verified. Predicted severe AP (pSAP) patients eligible for inclusion were assessed for enrollment. RESULTS: Nine major compounds were identified in QXJYF granules. Data showed that QXJYF granules significantly alleviated AP severity both in caerulein and L-arginine-induced AP models in vivo, pancreatic injury and inflammatory cell infiltration, systematic inflammation, lung injury and inflammatory cell infiltration were all improved after QXJYF treatment. QXJYF granules significantly reduced M1 macrophages during AP both in vivo and in vitro; besides, the mRNA expression levels of M1 genes such as inos, Tnfα, Il1ß and Il6 were significantly lower after QXJYF treatment in M1 macrophages. Mechanistically, we found that HK2, PFKFB3, PKM, LDHα levels were increased in M1 macrophages, but significantly decreased after QXJYF treatment. Clinical data indicated that QXJYF granules could significantly reduce CRP levels and shorten the duration of organ failure, thereby reducing the incidence of SAP and preventing pSAP patients from progressing to SAP. CONCLUSION: QXJYF granules alleviated AP through the inhibition of M1 macrophage polarization by suppressing glycolysis.

Copper homeostasis and cuproptosis in cancer immunity and therapy.

Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), which correlates to the mitochondrial tricarboxylic acid (TCA) cycle, resulting in proteotoxic stress and eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts an indispensable role in cancer progression, which is considered a promising strategy for cancer therapy. Cancer immunotherapy has gained extensive attention owing to breakthroughs in immune checkpoint blockade; furthermore, cuproptosis is strongly connected to the modulation of antitumor immunity. Thus, a thorough recognition concerning the mechanisms involved in the modulation of copper metabolism and cuproptosis may facilitate improvement in cancer management. This review outlines the cellular and molecular mechanisms and characteristics of cuproptosis and the links of the novel regulated cell death modality with human cancers. We also review the current knowledge on the complex effects of cuproptosis on antitumor immunity and immune response. Furthermore, potential agents that elicit cuproptosis pathways are summarized. Lastly, we discuss the influence of cuproptosis induction on the tumor microenvironment as well as the challenges of adding cuproptosis regulators to therapeutic strategies beyond traditional therapy.

Urocortin2 attenuates diabetic coronary microvascular dysfunction by regulating macrophage extracellular vesicles.

Diabetic patients develop coronary microvascular dysfunction (CMD) and exhibit high mortality of coronary artery disease. Methylglyoxal (MGO) largely accumulates in the circulation due to diabetes. We addressed whether macrophages exposed to MGO exhibited damaging effect on the coronary artery and whether urocortin2 (UCN2) serve as protecting factors against such diabetes-associated complication. Type 2 diabetes was induced by high-fat diet and a single low-dose streptozotocin in mice. Small extracellular vesicles (sEV) derived from MGO-treated macrophages (MGO-sEV) were used to produce diabetes-like CMD. UCN2 was examined for a protective role against CMD. The involvement of arginase1 and IL-33 was tested by pharmacological inhibitor and IL-33-/- mice. MGO-sEV was capable of causing coronary artery endothelial dysfunction similar to that by diabetes. Immunocytochemistry studies of diabetic coronary arteries supported the transfer of arginase1 from macrophages to endothelial cells. Mechanism studies revealed arginase1 contributed to the impaired endothelium-dependent relaxation of coronary arteries in diabetic and MGO-sEV-treated mice. UCN2 significantly improved coronary artery endothelial function, and prevented MGO elevation in diabetic mice or enrichment of arginase1 in MGO-sEV. Diabetes caused a reduction of IL-33, which was also reversed by UCN2. IL-33-/- mice showed impaired endothelium-dependent relaxation of coronary arteries, which can be mitigated by arginase1 inhibition but can't be improved by UCN2 anymore, indicating the importance of restoring IL-33 for the protection against diabetic CMD by UCN2. Our data suggest that MGO-sEV induces CMD via shuttling arginase1 to coronary arteries. UCN2 is able to protect against diabetic CMD via modulating MGO-altered macrophage sEV cargoes.

Validation and update of a clinical score model to predict technical difficulty of colorectal endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).

Enhancing wound healing and adhesion through dopamine-assisted gelatin-silica hybrid dressings.

Gelatin, widely employed in hydrogel dressings, faces limitations when used in high fluid environments, hindering effective material adhesion to wound sites and subsequently reducing treatment efficacy. The rapid degradation of conventional hydrogels often results in breakdown before complete wound healing. Thus, there is a pressing need for the development of durable adhesive wound dressings. In this study, 3-glycidoxypropyltrimethoxysilane (GPTMS) was utilized as a coupling agent to create gelatin-silica hybrid (G-H) dressings through the sol-gel method. The coupling reaction established covalent bonds between gelatin and silica networks, enhancing structural stability. Dopamine (DP) was introduced to this hybrid (G-H-D) dressing to further boost adhesiveness. The efficacy of the dressings for wound management was assessed through in-vitro and in-vivo tests, along with ex-vivo bioadhesion testing on pig skin. Tensile bioadhesion tests demonstrated that the G-H-D material exhibited approximately 2.5 times greater adhesion to soft tissue in wet conditions compared to pure gelatin. Moreover, in-vitro and in-vivo wound healing experiments revealed a significant increase in wound healing rates. Consequently, this material shows promise as a viable option for use as a moist wound dressing.

Identification of driving genes of familial adenomatous polyposis by differential gene expression analysis and weighted gene co-expression network analysis.

BACKGROUND: Despite the advancement of new screening strategies and the advances in pharmacological therapies, the cancerization rates of familial adenomatous polyposis (FAP) are stable and even increased in the last years. Therefore, it necessitates additional research to characterize and understand the underlying mechanisms of FAP. OBJECTIVE: To determine the genes that drive the pathogenesis of familial adenomatous polyposis (FAP). METHODS: We performed on a cohort (GSE111156) gene profile, which consist of four group of gene expressions (the gene expressions of cancer, adenoma and normal tissue of duodenal cancer from patients with FAP were defined as Case N, Case A and Case C respectively, while that of adenoma tissue from patients with FAP who did not have duodenal cancer was Ctrl A). Tracking Tumor Immunophenotype (TIP) website was applied to reveal immune infiltration profile and signature genes of FAP. We merged the genes of key module (pink and midnight module) with signature genes to obtained the biomarkers related with FAP pathogenesis. The expression of these five biomarkers in FAP intratumoral region (IT) and tumor rim (TR) was detected with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: In total, 220, 23 and 63 DEGs were determined in Cases C, A and N, in comparison to Ctrl A. In total, 196 and 10 DEGs were determined in Cases C and A, separately, as compared to Case N. A total of four biomarkers including CCL5, CD3G, CD2 and TLR3 were finally identified associated with pink module, while only one biomarker (KLF2) associated with midnight module was identified. All biomarkers were evidently raised in FAP IT tissues utilizing qRT-PCR. CONCLUSION: We identified five potential biomarkers for pathogenesis of FAP to understand the fundamental mechanisms of FAP progression and revealed some probable targets for the diagnosis or treatment of FAP.

Erratum: Shikonin induces apoptosis and necroptosis in pancreatic cancer via regulating the expression of RIP1/RIP3 and synergizes the activity of gemcitabine.

[This corrects the article on p. 5507 in vol. 9, PMID: 29312502.].