Developing a Prognostic Model for Primary Biliary Cholangitis Based on a Random Survival Forest Model.

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease with few effective treatments and a poor prognosis, and its incidence is on the rise. There is an urgent need for more targeted treatment strategies to accurately identify high-risk patients. The use of stochastic survival forest models in machine learning is an innovative approach to constructing a prognostic model for PBC that can improve the prognosis by identifying high-risk patients for targeted treatment. Method: Based on the inclusion and exclusion criteria, the clinical data and follow-up data of patients diagnosed with PBC-associated cirrhosis between January 2011 and December 2021 at Taizhou Hospital of Zhejiang Province were retrospectively collected and analyzed. Data analyses and random survival forest model construction were based on the R language. Result: Through a Cox univariate regression analysis of 90 included samples and 46 variables, 17 variables with p-values <0.1 were selected for initial model construction. The out-of-bag (OOB) performance error was 0.2094, and K-fold cross-validation yielded an internal validation C-index of 0.8182. Through model selection, cholinesterase, bile acid, the white blood cell count, total bilirubin, and albumin were chosen for the final predictive model, with a final OOB performance error of 0.2002 and C-index of 0.7805. Using the final model, patients were stratified into high- and low-risk groups, which showed significant differences with a P value <0.0001. The area under the curve was used to evaluate the predictive ability for patients in the first, third, and fifth years, with respective results of 0.9595, 0.8898, and 0.9088. Conclusion: The present study constructed a prognostic model for PBC-associated cirrhosis patients using a random survival forest model, which accurately stratified patients into low- and high-risk groups. Treatment strategies can thus be more targeted, leading to improved outcomes for high-risk patients.

Qualitative study on the perception of good death in patients with end-stage cancer in oncology nurses.

OBJECTIVE: To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. METHOD: In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi's analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULT: Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients' quality of life. CONCLUSION: The nurses in the department of oncology have a low level of knowledge about the "good death", and the correct understanding and view of the "good death" is the premise of the realization of " good death". The ability of nursing staff to improve the "good death", attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of "good death".

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling.

Nonalcoholic steatohepatitis (NASH) could progress to hepatic fibrosis in the absence of effective control. The purpose of our experiment was to investigate the protective effect of drinking water with a high concentration of hydrogen, namely, hydrogen-rich water (HRW), on mice with nonalcoholic fatty liver disease to elucidate the mechanism underlying the therapeutic action of molecular hydrogen. The choline-supplemented, l-amino acid-defined (CSAA) or the choline-deficient, l-amino acid-defined (CDAA) diet for 20 wk was used to induce NASH and fibrosis in the mice model and simultaneously treated with the high-concentration 7-ppm HRW for different periods (4 wk, 8 wk, and 20 wk). Primary hepatocytes were stimulated by palmitate to mimic liver lipid metabolism during fatty liver formation. Primary hepatocytes were cultured in a closed vessel filled with 21% O2 + 5% CO2 + 3.8% H2 and N2 as the base gas to verify the response of primary hepatocytes in a high concentration of hydrogen gas in vitro. Mice in the CSAA + HRW group had lower serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and milder histological damage. The inflammatory cytokines were expressed at lower levels in the HRW group than in the CSAA group. Importantly, HRW reversed hepatocyte fatty acid oxidation and lipogenesis as well as hepatic inflammation and fibrosis in preexisting hepatic fibrosis specimens. Molecular hydrogen inhibits the lipopolysaccharide-induced production of inflammation cytokines through increasing heme oxygenase-1 (HO-1) expression. Furthermore, HRW improved hepatic steatosis in the CSAA + HRW group. Sirtuin 1 (Sirt1) induction by molecular hydrogen via the HO-1/adenosine monophosphate activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα)/peroxisome proliferator-activated receptor γ (PPAR-γ) pathway suppresses palmitate-mediated abnormal fat metabolism. Orally administered HRW suppressed steatosis induced by CSAA and attenuated fibrosis induced by CDAA, possibly by reducing oxidative stress and the inflammation response.NEW & NOTEWORTHY The mRNA expression of inflammatory cytokines in the HRW group was lower than in the CSAA group. HRW reversed hepatocyte apoptosis as well as hepatic inflammation and fibrosis in NASH specimens. Molecular hydrogen inhibits LPS-induced inflammation via an HO-1/interleukin 10 (IL-10)-independent pathway. HRW improved hepatic steatosis in the CSAA + HRW group. Sirt1 induction by molecular hydrogen via the HO-1/AMPK/PPARα/PPARγ pathway suppresses palmitate-mediated abnormal fat metabolism.

A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice.

OBJECTIVE: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. METHODS: A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically. RESULTS: Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. CONCLUSIONS: The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.

Trifocal diffractive intraocular lens implantation in patients after previous corneal refractive laser surgery for myopia.

BACKGROUND: With the difficulties in IOL power calculation and the potential side effects occurring postoperatively, multifocal IOL implantation after previous corneal refractive surgery are rarely reported especially for the trifocal IOL. Herein we report the clinical observation of trifocal IOL implantation in patients with previous myopia excimer laser correction. In this study, a multi-formula average method was performed for the IOLs power calculation to improve the accuracy. Visual and refractive outcomes were analyzed, and the subjective quality of patients' life was evaluated by questionnaires survey. METHODS: This retrospective case series included patients with previous myopia excimer laser correction who underwent femtosecond laser assisted phacoemulsification and trifocal IOL (AT LISA tri 839 MP) implantation. Follow-up was done at 1-day, 1-month and 3-month to assess the visual outcomes. Outcome measures were uncorrected distance, intermediate and near visual acuity (UDVA, UIVA, UNVA), manifest refraction, defocus curve, and subjective quality of vision. RESULTS: Twenty-one Eyes from sixteen patients (14 eyes with previous laser in situ keratomileusis and 7 eyes with previous photorefractive keratectomy) were included. Mean postoperative spherical equivalent (SE) at 3-month was - 0.56 D ± 0.49 SD, wherein, 10 eyes (47.6%) were within ±0.50 D of the desired emmetropia and 19 eyes (90.5%) were within ±1.0 D. Mean monocular UDVA, UIVA and UNVA (logMAR) at last visit were 0.02 ± 0.07, 0.10 ± 0.10, and 0.15 ± 0.11 respectively. Three patients (19%) reported halos and glare in postoperative 3 months, two of them needed to use spectacles to improve the intermediate visual acuity. Fifteen patients (94%) reported a satisfaction score of ≥3.5 out of 4.0, without any difficulty in daily activity. Thirteen patients (81%) did not need spectacles at all distances, while the other 3 patients (19%) used spectacles for near-distance related visual activity. Mean composite score of the VF-14 questionnaire was 95.00 ± 7.29 out of 100. CONCLUSIONS: Trifocal IOL implantation after myopia excimer laser correction could restore good distance, intermediate visual acuity and acceptable near visual acuity, and provide accurate refractive outcomes as well as high spectacles independence rate.

NLRP1 deficiency attenuates diabetic retinopathy (DR) in mice through suppressing inflammation response.

Diabetic retinopathy (DR) is the common cause of diabetic vascular complications. The NOD-like receptor (NLR) family, pyrin domain containing 1 (NLRP1), also known as NALP1, inflammasome is the first member of the NLR family to be discovered, playing an important role in inflammatory response. However, its effect on DR development has not been reported. In the study, the wild type (WT) and NLRP1-/- mice were injected with streptozotocin (STZ) to induce DR. The results indicated that NLRP1-/- significantly increased bodyweight reduction and decreased blood glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRP1 in retinas. NLRP1-/- ameliorated retinal abnormalities in DR mice using H&E staining. In addition, attenuated avascular areas and neovascular tufts were also observed in NLRP1-/-/DR mice. The levels of pro-inflammatory cytokines in serum and retinas were highly induced in WT/DR mice, whereas being markedly reduced by NLRP1-/-. In addition, vascular endothelial growth factor (VEGF) and Iba1 expressions induced by STZ in serum or retinas were significantly down-regulated in NLRP1-/-/DR mice. Consistently, NLRP1-/- attenuated ASC and Caspase-1 expressions in retinas of DR mice. Compared to WT/DR group, NLRP1-/- markedly decreased retina p-nuclear factor-κB (NF-κB), interleukin-1ß (IL-1ß) and IL-18 levels. And similar results were confirmed in vitro that suppressing NLRP1/ASC inflammasome ameliorated inflammatory response in fructose-treated retinal ganglion cells. The results above indicated that the modulation of NLRP1 inflammasome might be a promising strategy for DR therapy.

Expression of p38 mitogen-activated protein kinase (p38MAPK) and pathological change in intussusception.

BACKGROUND: The aim of this study was to develop a mouse model and further assess the pathological changes associated with the expression of p38mitogen-activated protein kinase (p38MAPK) in intussusception. METHODS: Sixty-two adult Balb/C mice were used. A longitudinal incision was made in the middle rectus muscle in the body cavity. The ileum was intussuscepted into the colon. Measurements were taken at the onset of intussusception and at 5, 15, 30, 60, and 120 min. Mucosal impairment was assessed on microscopy. Ten of the intussuscepted mice were used as an ischemia-reperfusion (I/R) model. Immunohistochemistry was used to assess expression of p38MAPK in the I/R model and pediatric patients specimens of intussusception. RESULTS: The intussusception model was successfully established in 46 mice. After 15 min, vascular compromise became visible in these 46 mice. Over time, vascular function worsened. There were significant differences in microscopy injury score in the intestinal mucosa between the 15 min and 30 min groups (P = 0.0006), 30 min and 60 min groups (P = 0.0046), and the 60 min and 120 min groups (P = 0.0050). There was no significant difference between the 5 min and 15 min groups (P = 0.0597). p38MAPK was expressed strongly in pediatric specimens of intussusception. Immunostained sections of intestinal epithelium had significantly higher mean quick score for p38MAPK in the intussusception I/R model group than in the intussusception group and controls (P = 0.0130). On each two-group comparison there was a significant difference between groups (all P < 0.01; Fig. ). CONCLUSIONS: The present mouse model can be used to assess the dynamic pathological changes associated with intussusception. I/R is associated with upregulation of p38MAPK in intussusception.

A Good Prognosis of Patients with Acute Pancreatitis Combined with Pulmonary Embolism: Early Identification and Intervention.

BACKGROUND: Pulmonary embolism (PE) is a relatively rare vascular complication of acute pancreatitis (AP), and its mortality rate is high. To our knowledge, relevant literature reports still need to be summarized. In this study, we analyzed the clinical characteristics, treatment, and prognosis of five patients with AP complicated by PE and summarized and reviewed the relevant literature. METHODS: Clinical data of patients with AP complicated by PE treated in Taizhou Hospital of Zhejiang Province between January 2017 and September 2022 were retrospectively collected. Combined with the relevant literature, the clinical characteristics, treatment, and prognoses of patients with AP combined with PE were analyzed and summarized. RESULTS: Five patients were eventually enrolled in this study. Among the five patients with AP complicated by PE, all (100%) had symptoms of malaise, primarily chest tightness, shortness of breath, and dyspnea. All patients (100%) had varied degrees of elevated D-dimer levels and a significant decrease in the pressure of partial oxygen (PO2) and pressure of arterial oxygen to fractional inspired oxygen concentration ratio (PaO2/FiO2). Computed tomographic angiography (CTA) or pulmonary ventilation/perfusion imaging revealed a pulmonary artery filling defect in these patients. One patient (20%) had left calf muscular venous thrombosis before the occurrence of PE. Four patients (80%) were treated with lowmolecular- weight heparin (LMWH), and one patient (20%) was treated with rivaroxaban during hospitalization; all continued oral anticoagulant therapy after discharge. All patients (100%) were cured and discharged. No patients showed recurrence of AP or PE. CONCLUSION: PE is a rare but life-threatening complication of AP. However, once diagnosed, early treatment with anticoagulation or radiological interventional procedures is effective, and the prognosis is good. Core Tips: Pulmonary embolism (PE) is a rare but life-threatening complication of acute pancreatitis (AP). Its early diagnosis and timely anticoagulation or radiological intervention can reduce mortality. However, only nine cases have been reported in the English literature thus far, and they are all case reports. Our study is the first systematic analysis of patients with AP combined with PE with a review of the relevant literature. Our patients and those reported in the literature were discharged with good prognoses under treatment such as anticoagulation and vascular intervention. These cases remind clinicians that, in patients with AP, especially those with risk factors for venous thrombosis, it is necessary to monitor the D-dimer level dynamically. Clinicians should pay attention to AP patients' symptoms and related examinations to reduce the chance of a missed diagnosis or misdiagnosis of PE.

Pancreatic islet transplantation: current advances and challenges.

Diabetes is a prevalent chronic disease that traditionally requires severe reliance on medication for treatment. Oral medication and exogenous insulin can only temporarily maintain blood glucose levels and do not cure the disease. Most patients need life-long injections of exogenous insulin. In recent years, advances in islet transplantation have significantly advanced the treatment of diabetes, allowing patients to discontinue exogenous insulin and avoid complications.Long-term follow-up results from recent reports on islet transplantation suggest that they provide significant therapeutic benefit although patients still require immunotherapy, suggesting the importance of future transplantation strategies. Although organ shortage remains the primary obstacle for the development of islet transplantation, new sources of islet cells, such as stem cells and porcine islet cells, have been proposed, and are gradually being incorporated into clinical research. Further research on new transplantation sites, such as the subcutaneous space and mesenteric fat, may eventually replace the traditional portal vein intra-islet cell infusion. Additionally, the immunological rejection reaction in islet transplantation will be resolved through the combined application of immunosuppressant agents, islet encapsulation technology, and the most promising mesenchymal stem cells/regulatory T cell and islet cell combined transplantation cell therapy. This review summarizes the progress achieved in islet transplantation, and discusses the research progress and potential solutions to the challenges faced.

Relationship between the microenvironment and survival in kidney transplantation: a bibliometric analysis from 2013 to 2023.

Background: Kidney transplantation is considered the most effective treatment for end-stage renal failure. Recent studies have shown that the significance of the immune microenvironment after kidney transplantation in determining prognosis of patients. Therefore, this study aimed to conduct a bibliometric analysis to provide an overview of the knowledge structure and research trends regarding the immune microenvironment and survival in kidney transplantation. Methods: Our search included relevant publications from 2013 to 2023 retrieved from the Web of Science core repository and finally included 865 articles. To perform the bibliometric analysis, we utilized tools such as VOSviewer, CiteSpace, and the R package "bibliometrix". The analysis focused on various aspects, including country, author, year, topic, reference, and keyword clustering. Results: Based on the inclusion criteria, a total of 865 articles were found, with a trend of steady increase. China and the United States were the countries with the most publications. Nanjing Medical University was the most productive institution. High-frequency keywords were clustered into 6 areas, including kidney transplantation, transforming growth factor ß, macrophage, antibody-mediated rejection, necrosis factor alpha, and dysfunction. Antibody mediated rejection (2019-2023) was the main area of research in recent years. Conclusion: This groundbreaking bibliometric study comprehensively summarizes the research trends and advances related to the immune microenvironment and survival after kidney transplantation. It identifies recent frontiers of research and highlights promising directions for future studies, potentially offering fresh perspectives to scholars in the field.

Anoikis-related signature identifies tumor microenvironment landscape and predicts prognosis and drug sensitivity in colorectal cancer.

Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer. Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as "Cibersort" and "ssGSEA". We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. We incorporated clinical traits to build a nomogram. Additionally, the quantitative real-time PCR was employed to investigate the mRNA expression of selected anoikis-associated genes. Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. And SIRT3, PIK3CA, ITGA3, DAPK1, and CASP3 increased in CRC group through the PCR assay. Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated.

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Development of the hepatitis E vaccine: from bench to field.

Along with the improvement of diagnostic techniques, hepatitis E has attracted increasing awareness in recent years. Hepatitis E virus infection leads to high mortality in pregnant women and patients with underlying liver disease. Several hepatitis E vaccine candidates have been designed and have proved their efficacy in animal models; two candidates have successfully undergone clinical trials. Having proved safe and effective in a large phase III trials, an Escherichia coli expressed particulate protein, HEV 239, has been registered in China and is now available for use in China.

Hepatitis E virus: neutralizing sites, diagnosis, and protective immunity.

There have been increased attentions on HEV and its associated diseases in recent years as a result of an increased number of reports on autochthonous patients from many developed countries. Vaccine development and better disease management are expected from protective immunity with increased knowledge on the pathogenesis and virology of HEV. This review summarizes the current understanding of the HEV virology, the key neutralization sites (epitopes) on the surface of the viral capsid, the host humoral immune responses for HEV infection, and the protective immunity conferred by natural infection and vaccination. Recombinant VLPs were prepared to mimic the protective and neutralizing epitopes on the virion surface, thus being capable of eliciting protective immunity when injected to nonhuman primates or human volunteers during preclinical tests and clinical trials. Four markers-viral RNA, anti-HEV IgM, anti-HEV IgG, and low avidity of anti-HEV IgG-are important in the diagnosis of HEV infection, particularly for patients presenting with acute hepatitis symptoms. This toolbox of genomic and immunological assays is valuable in furthering our understanding of the time course of HEV infection and the subsequent hepatitis during preclinical and clinical development of an efficacious vaccine. Two vaccine candidates had shown good tolerability, high immunogenicity, and high efficacy against symptomatic and/or asymptomatic HEV infection. One of them has been licensed in China recently. However, many issues need to be resolved before new technological progresses can benefit the people who need them most.

Challenges and opportunities in the islet transplantation microenvironment: a comprehensive summary of inflammatory cytokine, immune cells, and vascular endothelial cells.

It is now understood that islet transplantation serves as a ß-cell replacement therapy for type 1 diabetes. Many factors impact the survival of transplanted islets, especially those related to the microenvironment. This review explored microenvironmental components, including vascular endothelial cells, inflammatory cytokines, and immune cells, and their profound effects on post-islet transplantation survival rates. Furthermore, it revealed therapeutic strategies aimed at targeting these elements. Current evidence suggests that vascular endothelial cells are pivotal in facilitating vascularization and nutrient supply and establishing a new microcirculation network for transplanted islets. Consequently, preserving the functionality of vascular endothelial cells emerges as a crucial strategy to enhance the survival of islet transplantation. Release of cytokines will lead to activation of immune cells and production and release of further cytokines. While immune cells hold undeniable significance in regulating immune responses, their activation can result in rejection reactions. Thus, establishing immunological tolerance within the recipient's body is essential for sustaining graft functionality. Indeed, future research endeavors should be directed toward developing precise strategies for modulating the microenvironment to achieve higher survival rates and more sustained transplantation outcomes. While acknowledging certain limitations inherent to this review, it provides valuable insights that can guide further exploration in the field of islet transplantation. In conclusion, the microenvironment plays a paramount role in islet transplantation. Importantly, we discuss novel perspectives that could lead to broader clinical applications and improved patient outcomes in islet transplantation.

Role of ferroptosis in colorectal cancer.

Colorectal cancer (CRC) is the second deadliest cancer and the third-most common malignancy in the world. Surgery, chemotherapy, and targeted therapy have been widely used to treat CRC, but some patients still develop resistance to these treatments. Ferroptosis is a novel non-apoptotic form of cell death. It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer drugs. This review summarizes recent advances in the prognostic role of ferroptosis in CRC and the mechanism of action in CRC.

The Effects of Programmed Cell Death of Mesenchymal Stem Cells on the Development of Liver Fibrosis.

Mesenchymal stem cells have shown noticeable potential for unlimited self-renewal. They can differentiate into specific somatic cells, integrate into target tissues via cell-cell contact, paracrine effects, exosomes, and other processes and then regulate the target cells and tissues. Studies have demonstrated that transplantation of MSCs could decrease the expression and concentration of collagen in the liver, thereby reducing liver fibrosis. A growing body of evidence indicates that apoptotic MSCs could inhibit harmful immune responses and reduce inflammatory responses more effectively than viable MSCs. Accumulating evidence suggests that mitochondrial transfer from MSCs is a novel strategy for the regeneration of various damaged cells via the rescue of their respiratory activities. This study is aimed at reviewing the functions of MSCs and the related roles of the programmed cell death of MSCs, including autophagy, apoptosis, pyroptosis, and ferroptosis, as well as the regulatory pathogenic mechanisms of MSCs in liver fibrosis. Research has demonstrated that the miR-200B-3p gene is differentially expressed gene between LF and normal liver samples, and that the miR-200B-3p gene expression is positively correlated with the degree of liver fibrosis, suggesting that MSCs could inhibit liver fibrosis through pyroptosis. It was confirmed that circulating monocytes could deliver MSC-derived immunomodulatory molecules to different sites by phagocytosis of apoptotic MSCs, thereby achieving systemic immunosuppression. Accordingly, it was suggested that characterization of the programmed cell death-mediated immunomodulatory signaling pathways in MSCs should be a focus of research.

Quantum computer-aided design for advanced superconducting qubit: Plasmonium.

Complex quantum electronic circuits can be used to design noise-protected qubits, but their complexity may exceed the capabilities of classical simulation. In such cases, quantum computers are necessary for efficient simulation. In this work, we demonstrate the use of variational quantum computing on a transmon-based quantum processor to simulate a superconducting quantum electronic circuit and design a new type of qubit called "Plasmonium", which operates in the plasmon-transition regime. The fabricated Plasmonium qubits show a high two-qubit gate fidelity of 99.58(3)%, as well as a smaller physical size and larger anharmonicity compared to transmon qubits. These properties make Plasmonium a promising candidate for scaling up multi-qubit devices. Our results demonstrate the potential of using quantum computers to aid in the design of advanced quantum processors.

New hope for esophageal stricture prevention: A prospective single-center trial on acellular dermal matrix.

BACKGROUND: Given the high incidence of esophageal cancer in China, an increasing number of patients there are undergoing endoscopic mucosal dissection (ESD). Although the 5-year survival rate after ESD can exceed 95%, esophageal stricture, the most common and serious postoperative complication, affects the long-term prognosis of patients and the quality of life. Autologous mucosal grafts have proven to be successful in preventing stricture after ESD for early esophageal cancer. AIM: To examine the viability of acellular dermal matrix (ADM) as an alternative to autologous mucosa for the prevention of stricture after ESD. METHODS: This is a prospective, single-center, controlled study. Consecutive patients who underwent ESD surgery and were willing to undergo autologous mucosal transplantation were recruited between January 1 and December 31, 2017. Consecutive patients who underwent ESD surgery and were willing to undergo ADM transplantation were recruited between January 1 to December 31, 2019. A final three-year follow-up of patients who received transplants was conducted. RESULTS: Based on the current incidence of esophageal stricture, the sample size required for both the autologous mucosal graft group and the ADM group was calculated to be 160 cases. Due to various factors, a total of 20 patients with autologous mucosal grafts and 25 with ADM grafts were recruited. Based on the inclusion exclusion and withdrawal criteria, 9 patients ultimately received autologous mucosal grafts and completed the follow-up, while 11 patients received ADM grafts and completed the follow-up. Finally, there were 2 cases of stenosis in the autologous mucosal transplantation group with a stenosis rate of 22.22% and 2 cases of stenosis in the ADM transplantation group with a stenosis rate of 18.18%, with no significant difference noted between the groups (P = 0.94). CONCLUSION: In this prospective, single-center, controlled trial, we compared the effectiveness of autologous mucosa transplantation and ADM for the prevention of esophageal stricture. Due to certain condition limitations, we were unable to recruit sufficient subjects meeting our target requirements. However, we implemented strict inclusion, exclusion, and withdrawal criteria and successfully completed three years of follow-up, resulting in valuable clinical insights. Based on our findings, we hypothesize that ADM may be similarly effective to autologous mucosal transplantation in the prevention of esophageal stricture, offering a comparable and alternative approach. This study provides a new therapeutic idea and direction for the prevention of esophageal stricture.