Evaluation of tumor budding with virtual panCK stains generated by novel multi-model CNN framework.

As the global incidence of cancer continues to rise rapidly, the need for swift and precise diagnoses has become increasingly pressing. Pathologists commonly rely on H&E-panCK stain pairs for various aspects of cancer diagnosis, including the detection of occult tumor cells and the evaluation of tumor budding. Nevertheless, conventional chemical staining methods suffer from notable drawbacks, such as time-intensive processes and irreversible staining outcomes. The virtual stain technique, leveraging generative adversarial network (GAN), has emerged as a promising alternative to chemical stains. This approach aims to transform biopsy scans (often H&E) into other stain types. Despite achieving notable progress in recent years, current state-of-the-art virtual staining models confront challenges that hinder their efficacy, particularly in achieving accurate staining outcomes under specific conditions. These limitations have impeded the practical integration of virtual staining into diagnostic practices. To address the goal of producing virtual panCK stains capable of replacing chemical panCK, we propose an innovative multi-model framework. Our approach involves employing a combination of Mask-RCNN (for cell segmentation) and GAN models to extract cytokeratin distribution from chemical H&E images. Additionally, we introduce a tailored dynamic GAN model to convert H&E images into virtual panCK stains, integrating the derived cytokeratin distribution. Our framework is motivated by the fact that the unique pattern of the panCK is derived from cytokeratin distribution. As a proof of concept, we employ our virtual panCK stains to evaluate tumor budding in 45 H&E whole-slide images taken from breast cancer-invaded lymph nodes . Through thorough validation by both pathologists and the QuPath software, our virtual panCK stains demonstrate a remarkable level of accuracy. In stark contrast, the accuracy of state-of-the-art single cycleGAN virtual panCK stains is negligible. To our best knowledge, this is the first instance of a multi-model virtual panCK framework and the utilization of virtual panCK for tumor budding assessment. Our framework excels in generating dependable virtual panCK stains with significantly improved efficiency, thereby considerably reducing turnaround times in diagnosis. Furthermore, its outcomes are easily comprehensible even to pathologists who may not be well-versed in computer technology. We firmly believe that our framework has the potential to advance the field of virtual stain, thereby making significant strides towards improved cancer diagnosis.

Genetic causality between modifiable risk factors and the risk of rheumatoid arthritis: Evidence from Mendelian randomization.

OBJECTIVES: Emerging research has investigated the potential impact of several modifiable risk factors on the risks of rheumatoid arthritis (RA), but the findings did not yield consistent results. This study aimed to comprehensively explore the genetic causality between modifiable risk factors and the susceptibility of RA risk using the Mendelian randomization (MR) approach. METHODS: Genetic instruments for modifiable risk factors were selected from several genome-wide association studies at the genome-wide significance level (p < 5 × 10-8), respectively. Summary-level data for RA were sourced from a comprehensive meta-analysis. The causal estimates linking modifiable risk factors to RA risk were assessed using MR analysis with inverse variance weighting (IVW), MR-Egger, weighted, and weighted median methods. RESULTS: After Bonferroni correction for multiple tests, we found the presence of causality between educational attainment and RA, where there were protective effects of educational attainment (college completion) (odds ratio [OR] = 0.50, 95% CI = 0.36, 0.69, p = 2.87E-05) and educational attainment (years of education) (OR = 0.93, 95% CI = 0.90, 0.96, p = 4.18E-06) on the lower RA risks. Nevertheless, smoking initiation was observed to be associated with increased RA risks (OR = 1.27, 95% CI = 1.09, 1.47, p = .002). Moreover, there was no indication of horizontal pleiotropy of genetic variants during causal inference between modifiable risk factors and RA. CONCLUSIONS: Our study reveals the genetic causal impacts of educational attainment and smoking on RA risks, suggesting that the early monitoring and recognition of modifiable risk factors would be beneficial for the preventive counseling/treatment strategies for RA.

Inhibitory Effects of Royal Jelly and Its Functional Components on the Proliferation of MKN-28 Gastric Cancer Cells.

Royal jelly (RJ) is a natural food product with nutritional value and anticancer activity. However, their effects on gastric cancer are unclear. Here, we show that treatment with 5-320 µg/mL of RJ, ethanol extract (RJEE), and protein hydrolyzate (RJPH) decreased the viability of MKN-28 gastric cancer cells, with a half-maximal inhibitory concentration of 123.22 µg/mL for RJEE. RJ, RJEE, and RJPH increase the lactate dehydrogenase release rate and change the morphology of the cells, resulting in cell shrinkage, nucleoplasm condensation, and the formation of apoptotic bodies. RJ and its functional components stagnated the cell cycle in the G0/G1 phase, accompanied by the accumulation of reactive oxygen species, decreased mitochondrial membrane potential, and increased expression levels of p53 and p21 proteins, caspase-3 activation, and apoptosis. Therefore, RJ, RJEE, and RJPH have potential inhibitory effects on the proliferation of gastric cancer cells.

Merging Natural Product Structures with Pharmaceutical Leads: Unnatural Enantiomers of Estranes as Glucocorticoid Receptor Modulators That Suppress TNF-α and IL-6 Release.

Natural products are widely recognized as valuable starting points for the development of therapeutics, with synthetic tetracyclic triterpenoids (e.g., steroids) being the most well represented among the drugs approved by the Food and Drug Administration. Here, recently developed synthetic tools for concise, asymmetric, and convergent construction of steroidal systems are leveraged to drive a program aimed at identifying novel glucocorticoid receptor (GR) modulators. While glucocorticoids have been extensively used as anti-inflammatory agents, they are plagued by severe side effects that include bone loss, muscle wasting, and metabolic disease. Ultimately, a program targeting the unnatural enantiomers of estranes (ent-estranes) that are practically inaccessible from natural product derivatization (semisynthesis) has resulted in the identification of a new class of potent dissociated GR modulators. We identify several leads with >99% efficacy as antagonists of GR trans-activation (potency within 10-fold of that of mifepristone) and further characterize examples that also inhibit release of pro-inflammatory cytokines IL-6 and TNF-α.

Self-management interventions for chronic widespread pain including fibromyalgia: a systematic review and qualitative evidence synthesis.

ABSTRACT: Supporting behavioural self-management is increasingly important in the care for chronic widespread pain (CWP), including fibromyalgia. Understanding peoples' experiences of these interventions may elucidate processes and mechanisms that lead to or hinder their intended impact. We conducted a systematic review and thematic synthesis of qualitative studies exploring peoples' experiences of self-management interventions for CWP, including fibromyalgia. MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science were searched. Primary qualitative or mixed-methods studies were included if they explored people's self-management intervention experiences for their CWP, including fibromyalgia. Screening, data extraction, and critical appraisal were conducted by 2 reviewers. Data analysis was conducted through thematic synthesis. Twenty-three studies were included, mostly were rated as high or moderate quality. We developed 4 analytic themes: A multifaceted experience of the intervention, potential for transformative experience of group cohesion, a new outlook, and striving for change after the loss of support. Broadly, personalisation was perceived as beneficial and people experienced a range of emotional experiences. These appeared to support positive behavioural and cognitive changes. For most, group activities promoted acceptance and support, fostering new perspectives and improved self-management, although some found aspects of group contexts challenging. Lack of on-going support after interventions led to challenges in applying behavioural strategies, and some struggled without social support from the group. The experiences of self-management interventions for CWP reflect a complex, multifaceted process. Although many reported positive experiences, addressing issues with integration of physical activity, group dynamics and postintervention support may improve effectiveness for a broader range of people.

Cystathionine-ß-synthase expression correlates with tumour progression and adverse prognosis in patients with colon cancer.

OBJECTIVE: To investigate the levels of cystathionine-ß-synthase (CBS) in colon cancer tissues compared with adjacent control tissues; and to examine the relationship between CBS level and clinical characteristics and prognosis. METHODS: This retrospective study enrolled patients with primary colon cancer. Paraffin-embedded specimens were used to create pathological tissue microarrays. Immunohistochemistry was performed on the microarray to detect the levels of CBS in colon cancer tissues and normal adjacent tissues. Analyses were undertaken to examine the relationship between the level of CBS and clinical characteristics and prognosis. RESULTS: A total of 216 patients (107 males and 109 females) were included in the study. The level of CBS in cancer tissues was found to be significantly increased compared with normal adjacent control tissues. There were significant differences in tumour location, tumour-node-metastasis stage and survival rate between the CBS-negative and CBS-positive groups. Positive CBS immunostaining was associated with decreased survival in colon cancer patients. The results of multivariate Cox regression analysis revealed that tumour location and positive CBS immunostaining were independent prognostic factors for survival. CONCLUSION: Positive CBS immunostaining was closely associated with colon cancer and high levels of CBS might accelerate tumour development and affect patient prognosis in colon cancer.

Nuclear receptor coactivator 7 (NCOA7) protects cancer cells from oxidative damage through its ERbd domain.

Oxidative stress causes damage to cancer cells and plays an important role in cancer therapy. Antagonizing oxidative stress is crucial for cancer cells to survive during the oxidation-based therapy. In this study, we defined the role of nuclear receptor co-activator 7 (NCOA7) in anti-oxidation in lung cancer cells and found that NCOA7 protects lung cancer A549 cells from the oxidative damage caused by hydrogen peroxide. Knockdown of NCOA7 in A549 cells significantly enhanced the hydrogen peroxide-caused inhibition of cell proliferation and migration, and markedly increased the damage effect of hydrogen peroxide on F-actin and focal adhesion structure, suggesting that NCOA7 protects F-actin and focal adhesion structure, thus the cell proliferation and migration, from oxidation-caused damage. Mechanistically, the anti-oxidation effect of NCOA7 is mediated by its nuclear receptor binding domain, the ERbd domain, suggesting that the anti-oxidation function of NCOA7 is dependent on its nuclear receptor co-activator activity. Our studies identified NCOA7 as an anti-oxidative protein through its nuclear receptor co-activator function and revealed the mechanism underlying the anti-oxidative effect of NCOA7 on cancer cell proliferation and migration.

Bone morphogenetic protein 4 ameliorates bleomycin-induced pulmonary fibrosis in mice by repressing NLRP3 inflammasome activation and epithelial-mesenchymal transition.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and deadly lung disease with limited therapeutic options. Bone morphogenetic protein 4 (BMP4), a multifunctional growth factor that belongs to the transforming growth factor-ß superfamily, is able to relieve pulmonary fibrosis in mice; nevertheless, the potential mechanism of action remains largely unknown. Growing evidence supports the notion that reiterant damage to the alveolar epithelial cells (AECs) is usually the "prime mover" for pulmonary fibrosis. Here, we examined the effect and mechanisms of BMP4 on bleomycin (BLM)-induced activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and epithelial-mesenchymal transition (EMT) in vivo and in vitro. Methods: The in vivo impact of BMP4 was investigated in a BLM mouse model. Histopathologic changes were analyzed by hematoxylin-eosin (H&E) and Masson's trichrome staining. The NLRP3 inflammasome activation was determined by quantitative real time polymerase chain reaction (qRT-PCR) and immunofluorescence staining. Biomarkers of EMT were measured by qRT-PCR, Western blot and immunofluorescence staining. The in vitro impact of BMP4 on BLM-induced NLRP3 inflammasome activation and EMT was explored in A549 AECs. We also evaluated whether BMP4 inhibited BLM-activated ERK1/2 signaling to address the possible molecular mechanisms. Results: BMP4 was significantly downregulated in the mouse lungs from BLM-induced pulmonary fibrosis. BMP4+/- mice presented with more severe lung fibrosis in response to BLM, and accelerated NLRP3 inflammasome activation and EMT process compared with that in BMP4+/+ mice. Whereas overexpression of BMP4 by injecting adeno-associated virus (AAV) 9 into mice attenuated BLM-induced fibrotic changes, NLRP3 inflammasome activation, and EMT in the mouse lungs, thus exerting protective efficacy against lung fibrosis. In vitro, BMP4 significantly reduced BLM-induced activation of NLRP3 inflammasome and EMT in human alveolar epithelial A549 cells. Mechanically, BMP4 repressed BLM-induced activation of ERK1/2 signaling in vivo and in vitro, suggesting that ERK1/2 inactivation contributes to BMP4-induced effects on BLM-induced activation of NLRP3 inflammasome and EMT. Conclusions: Our findings suggest that BMP4 can suppress NLRP3 inflammasome activation and EMT in AECs via inhibition of ERK1/2 signaling pathway, thus has a potential for the treatment of pulmonary fibrosis.

Circ_0005397 inhibits ferroptosis of pancreatic cancer cells by up-regulating PCBP2 through KAT6A/H3K9Ac.

Pancreatic cancer is a highly aggressive and lethal carcinoma. Circular RNAs (circRNAs) serve key regulatory functions in pancreatic cancer. Ferroptosis was induced by erastin treatment and analyzed by examining malondialdehyde (MDA), iron, Fe2+ and glutathione (GSH). C11-BODIPY 581/591 was used to stain cells for analyzing lipid peroxidation. RNA immunoprecipitation, pull-down and chromatin immunoprecipitation assays were applied to evaluate intermolecular interaction. Mice received subcutaneous injection of pancreatic cancer cells as a model of subcutaneous tumor for in vivo tests. Circ_0005397 was abundantly expressed in pancreatic cancer, and its upregulation was associated with low survival of patients with pancreatic cancer. Circ_0005397 expression was induced by EIF4A3. PCBP2 was highly expressed in pancreatic cancer, and circ_0005397 and PCBP2 were positively correlated in patients with pancreatic cancer. Circ_0005397 knockdown sensitized pancreatic carcinoma cells to ferroptosis via downregulating PCBP2. Circ_0005397 promoted PCBP2 transcription via facilitating the binding of KAT6A and H3K9ac to PCBP2 promoter. Silencing of circ_0005397 reduced tumor growth by enhancing erastin-induced ferroptosis in vivo. EIF4A3-induced circ_0005397 inhibited erastin-induced ferroptosis in pancreatic cancer by promoting PCBP2 expression through KAT6A and H3K9ac.

Chronic abdominal distention caused by diffuse nodular ileal and mesenteric lipomatosis: A case report.

RATIONALE: Diffuse intestinal and mesenteric lipomatosis is a rare condition characterized by the overgrowth of adipose tissue in the intestines and mesentery. This case report aims to highlight the rare occurrence of chronic abdominal distention caused by this disease and its unique invasion into the muscle layer, which has not been previously reported. PATIENT CONCERNS: A 36-year-old woman with a 7-year history of abdominal distension was admitted to our hospital's Department of Gastrointestinal Surgery. DIAGNOSE: Abdominal and pelvic computed tomography revealed diffuse small intestinal lipomatosis. INTERVENTIONS: The patient underwent surgery. We performed an open-field ilectomy involving removal of all lipomatous intestines (250 cm). OUTCOMES: During the surgery, diffuse nodular ileal and mesenteric lipomatosis was confirmed, characterized by the presence of multiple nodular lipomas within the submucosal and muscular layers. The surgical intervention involved the resection of 250 cm of the affected ileum, followed by jejunoileal anastomosis. Postoperative pathology confirmed the diagnosis, with lesions observed in both the submucosa and muscle layers. The patient showed significant improvement in symptoms, with normal intestinal function and weight gain observed over a 10-month follow-up period, and no signs of recurrence. LESSONS: Diffuse intestinal and mesenteric lipomatosis can lead to long-term abdominal distension. Additionally, it may be involved in the muscle layer of the intestinal wall. Surgery is the primary treatment option for symptomatic intestinal lipomatosis.

Bariatric surgery and diabetes: Current challenges and perspectives.

Diabetes mellitus (DM) and obesity have become public issues of global concern. Bariatric surgery for the treatment of obesity combined with type 2 DM has been shown to be a safe and effective approach; however, there are limited studies that have systematically addressed the challenges of surgical treatment of obesity combined with DM. In this review, we summarize and answer the most pressing questions in the field of surgical treatment of obesity-associated DM. I believe that our insights will be of great help to clinicians in their daily practice.

Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Development and validation of a nomogram for predicting occurrence of severe case in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era.

Background: The significant rebound of influenza A (H1N1) virus activity, particularly among children, with rapidly growing number of hospitalized cases is of major concern in the post-COVID-19 era. The present study was performed to establish a prediction model of severe case in pediatric patients hospitalized with H1N1 infection during the post-COVID-19 era. Methods: This is a multicenter retrospective study across nine public tertiary hospitals in Yunnan, China, recruiting pediatric H1N1 inpatients hospitalized at five of these centers between February 1 and July 1, 2023, into the development dataset. Screening of 40 variables including demographic information, clinical features, and laboratory parameters were performed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression to determine independent risk factors of severe H1N1 infection, thus constructing a prediction nomogram. Receiver operating characteristic (ROC) curve, calibration curve, as well as decision curve analysis (DCA) were employed to evaluate the model's performance. Data from four independent cohorts comprised of pediatric H1N1 inpatients from another four hospitals between July 25 and October 31, 2023, were utilized to externally validate this nomogram. Results: The development dataset included 527 subjects, 122 (23.1 %) of whom developed severe H1N1 infection. The external validation dataset included 352 subjects, 72 (20.5 %) of whom were eventually confirmed as severe H1N1 infection. The LASSO regression identified 19 candidate predictors, with logistic regression further narrowing down to 11 independent risk factors, including underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, neutrophil-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). By integrating these 11 factors, a predictive nomogram was established. In terms of prediction of severe H1N1 infection, excellent discriminative capacity, favorable accuracy, and satisfactory clinical usefulness of this model were internally and externally validated via ROC curve, calibration curve, and DCA, respectively. Conclusion: Our study successfully established and validated a novel nomogram model integrating underlying conditions, prematurity, fever duration, wheezing, poor appetite, leukocyte count, NLR, ESR, LDH, IL-10, and TNF-α. This nomogram can effectively predict the occurrence of serious case in pediatric H1N1 inpatients during the post-COVID-19 era, facilitating the early recognition and more efficient clinical management of such patients.

Near-infrared-responsive Prussian blue nanocages loaded with 5-fluorouracil for combined chemotherapy and photothermal therapy in tumor treatment.

Nanodrug delivery systems (NDDS) have been proposed to improve the targeting and bioavailability of chemotherapy drugs. The approach of drug loading via physical adsorption is facile to operate; however, there exists a risk of premature leakage. Coupling the drug molecules with the carrier through chemical reactions can guarantee the stability of the drug delivery process, yet the preparation procedure is relatively intricate. In this research, a kind of Prussian blue nanocage (PB Cage) was fabricated, and the phase change material, 1-pentadecanol, was used as the gating material to solidify 5-fluorouracil (5-FU) inside the nanocage. Upon irradiation with near-infrared (NIR) light, the temperature of the PB Cage can rise rapidly. When the temperature exceeds 43 °C, 1-pentadecanol undergoes a solid-liquid phase transition and subsequently releases 5-FU to inhibit DNA synthesis. Meanwhile, the photothermal therapy (PTT) mediated by the PB Cage is also capable of ablating tumor cells. The NDDS constructed based on PB has achieved the precise release of 5-FU triggered by NIR light, which may avoid side effects on normal tissues. Moreover, the combination of chemotherapy and photothermal therapy can efficaciously suppress the proliferation of tumor cells.

TPE-embedded butterfly bis-crown ether with controllable conformation and supramolecular chiroptical property.

Understanding how subtle structural differences between macrocyclic conformational isomers impact their properties and separation has garnered increasing attention in the field of supramolecular synthetic chemistry. In this work, a series of tetraphenylene (TPE)-embedded butterfly bis-crown ether macrocycles (BCE[n], n = 4-7), comprising two crown ether side rings and a TPE core, are synthesized through intramolecular McMurry coupling. Unexpectedly, the presence of flexible oligoethylene chains with varying lengths are found to influence molecular conformation via multiple intramolecular interactions, resulting in the formation of two stabilized conformers with specific semi-rigid symmetric/asymmetric structures (sym-BCE[n] and asym-BCE[n], n = 5, 6). Moreover, it is noteworthy that neither symmetric nor asymmetric conformers are present in the more rigid BCE[4] or the more flexible BCE[7]. Interestingly, these conformers display distinct fluorescence properties and host-guest binding abilities, and only sym-BCE[5] can serve as a host for chiral polymer binding, resulting in the formation of chiral supramolecular assemblies through host-guest interaction induced chirality. Moreover, both circular dichroism and circularly polarized luminescence signals of the obtained assemblies can be switched off by the addition of sodium ion, suggesting potential applications in the field of dynamic chiral materials.

Zn2+ chelating peptide GFLGSP: Characterization of structure/Zn2+ chelating mode and the potential mechanisms for promoting Zn2+ transport in Caco-2 cells.

This study focused on exploring the Zn2+ chelating peptide GFLGSP: the characterization of structure/Zn2+ chelating mode and the potential mechanisms for promoting Zn2+ transport in Caco-2 cells. The findings revealed the bidentate chelating between Zn2+ and carboxyl oxygen atom in Pro6 residue. Thereafter, the secondary structure of GFLGSP remained unchanged, but there was an increase in zeta potential and particle size. Notably, the GFLGSP-Zn2+ complex enhanced the Zn2+ transport rate and modulated ZIP4 and ZNT1 expression in a Caco-2 cells monolayer model. As revealed by molecular docking analysis, GFLGSP interacted with ZIP4 through intermolecular hydrogen bonds as well as Van der Waals forces. The Zn2+ transport mechanisms of the GFLGSP-Zn2+ complex encompassed ZIP4 (vital channel), endocytosis (primary pathway) and paracellular transport (supplementary pathway). Based on these results, the tilapia skin collagen-derived GFLGSP hold promise as the potential dietary Zn2+ supplement.

Association of peripheral eosinophil count with chronic kidney disease progression risk: a retrospective cohort study in Chinese population.

BACKGROUND: The role of peripheral eosinophils in chronic kidney disease (CKD) requires further evaluation. We aimed to determine whether an eosinophil count increase is related to the occurrence of end-stage renal disease (ESRD). METHODS: This single-center, observational, retrospective cohort study was conducted between January 2016 and December 2018 in Hangzhou, China, and included 3163 patients, categorized into four groups according to peripheral eosinophil count (PEC) quartile values. The main outcome was ESRD development during follow-up. We evaluated the relationship between the serum eosinophil count, demographic and clinical information, and ESRD incidence. Cox proportional hazards models and Kaplan-Meier survival curves were used. RESULTS: A total of 3163 patients with CKD were included in this cohort, of whom 1254 (39.6%) were females. The median (interquartile range [IQR]) age was 75 [64, 85] years, and the median (IQR) estimated glomerular filtration rate was 55.16 [45.19, 61.19] mL/min/1.73 m2. The median PEC was 0.1224 × 109/L (IQR, 0.0625-0.212). Among the 3163 patients with CKD, 273 (8.6%) developed ESRD during a median follow-up time of 443.8 [238.8, 764.9] days. Individuals in the highest PEC quartile had a 66.2% higher ESRD risk than those in the lowest quartile (hazard ratio, 1.662; 95% confidence interval, 1.165-2.372). The results from the Kaplan-Meier survival curves confirmed the conclusion. CONCLUSIONS: Alongside traditional risk factors, patients with CKD and an elevated PEC are more likely to develop ESRD. Therefore, more attention should be paid to those patients with CKD who have a high PEC.

"Hepatic hilum area priority, liver posterior first": An optimized strategy in laparoscopic resection for type III-IV hilar cholangiocarcinoma.

BACKGROUND: In recent years, pure laparoscopic radical surgery for Bismuth-Corlette type III and IV hilar cholangiocarcinoma (HCCA) has been preliminarily explored and applied, but the surgical strategy and safety are still worthy of further improvement and attention. AIM: To summarize and share the application experience of the emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types III and IV. METHODS: The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types III and IV who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed. RESULTS: Among the 6 patients, 4 were males and 2 were females. The average age was 62.2 ± 11.0 years, and the median body mass index was 20.7 (19.2-24.1) kg/m2. The preoperative median total bilirubin was 57.7 (16.0-155.7) µmol/L. One patient had Bismuth-Corlette type IIIa, 4 patients had Bismuth-Corlette type IIIb, and 1 patient had Bismuth-Corlette type IV. All patients successfully underwent pure laparoscopic radical resection following the strategy of "hepatic hilum area dissection priority, liver posterior separation first". The operation time was 358.3 ± 85.0 minutes, and the intraoperative blood loss volume was 195.0 ± 108.4 mL. None of the patients received blood transfusions during the perioperative period. The median length of stay was 8.3 (7.0-10.0) days. Mild bile leakage occurred in 2 patients, and all patients were discharged without serious surgery-related complications. CONCLUSION: The emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types III and IV. This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA, shortens the learning curve, and is worthy of further clinical application.

A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

Association of textbook outcomes with improved survival in pancreatic ductal adenocarcinoma following pancreaticoduodenectomy: a retrospective study.

Background: Assessing the perioperative outcomes of pancreaticoduodenectomy (PD) based solely on individual complications is not comprehensive, and the association between perioperative outcomes and the long-term prognosis of individuals diagnosed with pancreatic ductal adenocarcinoma (PDAC) remains uncertain. Our study is designed to evaluate the impact of a novel composite indicator, textbook outcomes (TO), on the long-term prognosis of patients undergoing PD for PDAC. Methods: This study conducted a retrospective analysis of 139 patients who underwent PD for pathologically confirmed PDAC at our hospital between January 2018 and December 2021. After applying exclusion criteria, a total of 111 patients were included in the subsequent analysis. These patients were categorized into two groups: the non-TO group (n=42) and the TO group (n=69). The Kaplan-Meier survival curve was employed to describe the relationship between TO and disease-free survival (DFS) and overall survival (OS). Cox regression was employed to assess the impact of achieving TO on long-term survival. Logistic regression was employed to investigate the risk factors affecting the achievement of TO. Results: Out of the 111 PDAC patients, 69 (62.2%) achieved TO following PD. The achievement of TO significantly improved the OS of PDAC patients [P=0.03; hazard ratio (HR) =0.60; 95% confidence interval (CI): 0.37-0.83]. Cox regression analysis indicated that achieving TO was a protective factor for OS (P=0.04; HR =4.08; 95% CI: 1.07-15.61). Logistic regression analysis indicated that high amylase in drainage fluid on the third day after surgery (>1,300 U/L) was detrimental to achieve TO [odds ratio (OR) =0.10; 95% CI: 0.02-0.58; P=0.01], longer surgery durations (≥6.25 hours) was detrimental to achieve TO (OR =0.19; 95% CI: 0.06-0.54; P=0.002), and soft pancreatic texture was detrimental to achieve TO (OR =0.31; 95% CI: 0.10-0.93, P=0.04). Conclusions: Achievement of TO significantly improves the OS of PDAC patients and has the potential to serve as a robust prognostic indicator. Looking ahead, it is highly necessary for TO to become a standard surgical quality control measure in hospitals.