Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

[Prospective comparative study of breast reconstruction with dual plane prosthesis implantation and anterior pectoralis prosthesis implantation under endoscopy].

Objective: To discuss the effectiveness of breast reconstruction with dual plane prosthesis implantation or anterior pectoralis prosthesis implantation under endoscopy by using prospective comparative study, in order to provide a reference for clinical surgical selection. Methods: A total of 54 female patients with breast cancer admitted between January 2023 and December 2023 and met the selection criteria were selected as research subjects. According to the random number table, 54 patients were divided into trial group and control group with 27 cases in each. The patients in the trial group and control group were treated with dual plane prosthesis implantation and anterior pectoralis prosthesis implantation for breast reconstruction after glandular resection under endoscopy, respectively. There was no significant difference between the two groups ( P>0.05) in the terms of age, body mass index, affected side, breast clinical stages, molecular typing, disease duration, breast volume of healthy side, breast ptosis of affected side, and preoperative Breast-Q score (social mental health, sexual health, breast satisfaction, chest somatic health). The operation-related indicators (operation time, total volume of drainage within 7 days after operation, extubation time, and hospital stay), occurrence of complications, breast reconstruction efficacy related indicators (transverse and longitudinal distance difference), and the pre- and post-operative differences (change values) of Breast-Q scores for each item were compared between the two groups. Results: There was no significant difference in operation time, total volume of drainage within 7 days after operation, extubation time, and hospital stay between the two groups ( P>0.05). All patients of the two groups were followed up 3-12 months (mean, 6.3 months). Three patients (11.11%) in trial group and 5 patients (18.52%) in control group experienced complications, and there was no significant difference in the occurrence of complications ( P>0.05). At 7 days after operation, the transverse and longitudinal distance differences were significantly less in trial group than in control group ( P<0.05). The Breast-Q scores of the two groups at 7 days after operation were significantly higher in all items than those before operation ( P<0.05), but there was no significant difference in all change values between the two groups ( P>0.05). Conclusion: For patients with breast cancer, comparison of breast reconstruction with anterior pectoralis prosthesis implantation, breast reconstruction with dual plane prosthesis implantation has better breast reconstruction effectiveness and higher safety.

Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions: an intravascular ultrasound study.

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial.

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

Synergistic Copper-Aminocatalysis for Direct Tertiary α-Alkylation of Ketones with Electron-Deficient Alkanes.

In this study, a novel approach for the tertiary α-alkylation of ketones using alkanes with electron-deficient C─H bonds is presented, employing a synergistic catalytic system combining inexpensive copper salts with aminocatalysis. This methodology addresses the limitations of traditional alkylation methods, such as the need for strong metallic bases, regioselectivity issues, and the risk of over alkylation, by providing a high reactivity and chemoselectivity without the necessity for pre-functionalized substrates. The dual catalytic strategy enables the direct functionalization of C(sp3)─H bonds, demonstrating remarkable selectivity in the presence of conventional C(sp3)─H bonds that are adjacent to heteroatoms or π systems, which are typically susceptible to single-electron transfer processes. The findings contribute to the advancement of alkylation techniques, offering a practical and efficient route for the construction of C(sp3)─C(sp3) bonds, and paving the way for further developments in the synthesis of complex organic molecules.

Stereotactic central/core ablative radiation therapy: results of a phase I study of a novel strategy to treat bulky tumor.

Purpose: Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART. Methods and materials: We defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV's border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents. Results: 21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14-85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009). Conclusion: SCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

A multi-kingdom collection of 33,804 reference genomes for the human vaginal microbiome.

The human vagina harbours diverse microorganisms-bacteria, viruses and fungi-with profound implications for women's health. Genome-level analysis of the vaginal microbiome across multiple kingdoms remains limited. Here we utilize metagenomic sequencing data and fungal cultivation to establish the Vaginal Microbial Genome Collection (VMGC), comprising 33,804 microbial genomes spanning 786 prokaryotic species, 11 fungal species and 4,263 viral operational taxonomic units. Notably, over 25% of prokaryotic species and 85% of viral operational taxonomic units remain uncultured. This collection significantly enriches genomic diversity, especially for prevalent vaginal pathogens such as BVAB1 (an uncultured bacterial vaginosis-associated bacterium) and Amygdalobacter spp. (BVAB2 and related species). Leveraging VMGC, we characterize functional traits of prokaryotes, notably Saccharofermentanales (an underexplored yet prevalent order), along with prokaryotic and eukaryotic viruses, offering insights into their niche adaptation and potential roles in the vagina. VMGC serves as a valuable resource for studying vaginal microbiota and its impact on vaginal health.

Geometric Understanding of Discriminability and Transferability for Visual Domain Adaptation.

To overcome the restriction of identical distribution assumption, invariant representation learning for unsupervised domain adaptation (UDA) has made significant advances in computer vision and pattern recognition communities. In UDA scenario, the training and test data belong to different domains while the task model is learned to be invariant. Recently, empirical connections between transferability and discriminability have received increasing attention, which is the key to understand the invariant representations. However, theoretical study of these abilities and in-depth analysis of the learned feature structures are unexplored yet. In this work, we systematically analyze the essentials of transferability and discriminability from the geometric perspective. Our theoretical results provide insights into understanding the co-regularization relation and prove the possibility of learning these abilities. From methodology aspect, the abilities are formulated as geometric properties between domain/cluster subspaces (i.e., orthogonality and equivalence) and characterized as the relation between the norms/ranks of multiple matrices. Two optimization-friendly learning principles are derived, which also ensure some intuitive explanations. Moreover, a feasible range for the co-regularization parameters is deduced to balance the learning of geometric structures. Based on the theoretical results, a geometry-oriented model is proposed for enhancing the transferability and discriminability via nuclear norm optimization. Extensive experiment results validate the effectiveness of the proposed model in empirical applications, and verify that the geometric abilities can be sufficiently learned in the derived feasible range.

When Invariant Representation Learning Meets Label Shift: Insufficiency and Theoretical Insights.

As a crucial step toward real-world learning scenarios with changing environments, dataset shift theory and invariant representation learning algorithm have been extensively studied to relax the identical distribution assumption in classical learning setting. Among the different assumptions on the essential of shifting distributions, generalized label shift (GLS) is the latest developed one which shows great potential to deal with the complex factors within the shift. In this paper, we aim to explore the limitations of current dataset shift theory and algorithm, and further provide new insights by presenting a comprehensive understanding of GLS. From theoretical aspect, two informative generalization bounds are derived, and the GLS learner are proved to be sufficiently close to optimal target model from the Bayesian perspective. The main results show the insufficiency of invariant representation learning, and prove the sufficiency and necessity of GLS correction for generalization, which provide theoretical supports and innovations for exploring generalizable model under dataset shift. From methodological aspect, we provide a unified view of existing shift correction frameworks, and propose a kernel embedding-based correction algorithm (KECA) to minimize the generalization error and achieve successful knowledge transfer. Both theoretical results and extensive experiment evaluations demonstrate the sufficiency and necessity of GLS correction for addressing dataset shift and the superiority of proposed algorithm.

Formic acid enhances whole-plant mulberry silage fermentation by boosting lactic acid production and inhibiting harmful bacteria.

Mulberry has also been regarded as a valuable source of forage for ruminants. This study was developed to investigate the impact of four additives and combinations thereof on fermentation quality and bacterial communities associated with whole-plant mulberry silage. Control fresh material (FM) was left untreated, while other groups were treated with glucose (G, 20 g/kg FM), a mixture of Lactobacillus plantarum and L. buchneri (L, 106 CFU/g FM), formic acid (A, 5 mL/kg FM), salts including sodium benzoate and potassium sorbate (S, 1.5 g/kg FM), a combination of G and L (GL), a combination of G and A (GA), or a combination of G and S (GS), followed by ensiling for 90 days. Dry matter content in the A, S, GA, and GS groups was elevated relative to the other groups (p < 0.01). Relative to the C group, all additives and combinations thereof were associated with reductions in pH and NH3-N content (p < 0.01). The A groups exhibited the lowest pH and NH3-N content at 4.23 and 3.27 g/kg DM, respectively (p < 0.01), whereas the C groups demonstrated the highest values at 4.43 and 4.44 g/kg DM, respectively (p < 0.01). The highest levels of lactic acid were observed in the GA and A groups (70.99 and 69.14 g/kg DM, respectively; p < 0.01), followed by the GL, L, and GS groups (66.88, 64.17 and 63.68 g/kg DM, respectively), with all of these values being higher than those for the C group (53.27 g/kg DM; p < 0.01). Lactobacillus were the predominant bacteria associated with each of these samples, but the overall composition of the bacterial community was significantly impacted by different additives. For example, Lactobacillus levels were higher in the G, A, and GA groups (p < 0.01), while those of Weissella levels were raised in the L, GL, and GS groups (p < 0.01), Pediococcus levels were higher in the A and GA groups (p < 0.01), Enterococcus levels were higher in the G and S groups (p < 0.01), and Lactococcus levels were raised in the S group (p < 0.01). Relative to the C group, a reduction in the levels of undesirable Enterobacter was evident in all groups treated with additives (p < 0.01), with the greatest reductions being evident in the A, S, GA, and GS groups. The additives utilized in this study can thus improve the quality of whole-plant mulberry silage to varying extents through the modification of the associated bacterial community, with A and GA addition achieving the most efficient reductions in pH together with increases in lactic acid content and the suppression of undesirable bacterial growth.

Exploration and Optimization of the Polymer-Modified NiOx Hole Transport Layer for Fabricating Inverted Perovskite Solar Cells.

The recombination of charge carriers at the interface between carrier transport layers such as nickel oxide (NiOx) and the perovskite absorber has long been a challenge in perovskite solar cells (PSCs). To address this issue, we introduced a polymer additive poly(vinyl butyral) into NiOx and subjected it to high-temperature annealing to form a void-containing structure. The formation of voids is confirmed to increase light transmittance and surface area of NiOx, which is beneficial for light absorption and carrier separation within PSCs. Experimental results demonstrate that the incorporation of the polymer additive helped to enhance the hole conductivity and carrier extraction of NiOx with a higher Ni3+/Ni2+ ratio. This also optimized the energy levels of NiOx to match with the perovskite to raise the open-circuit voltage to 1.01 V. By incorporating an additional NiOx layer beneath the polymer-modified NiOx, the device efficiency was further increased as verified from the dark current measurement of devices.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

High-Pressure Molecular Sieving of High-Humidity C2H4/C2H6 Mixture by a Hydrophobic Flexible Metal-Organic Framework.

Molecular sieving is an ideal separation mechanism, but controlling pore size, restricting framework flexibility, and avoiding strong adsorption are all very challenging. Here, we report a flexible adsorbent showing molecular sieving at ambient temperature and high pressure, even under high humidity. While typical guest-induced transformations are observed, a high transition pressure of 16.6 atm is observed for C2H4 at 298 K because of very weak C2H4 adsorption (~16 kJ mol-1). Also, C2H6 is completely excluded below the pore-opening pressure of 7.7 atm, giving single-component selectivity of ca. 300. Quantitative high-pressure column breakthrough experiments using 1 : 1 C2H4/C2H6 mixtures at 10 atm as input confirm molecular sieving with C2H4 adsorption of 0.73 mmol g-1 or 32 cm3(STP) cm-3 and negligible C2H6 adsorption of 0.001(2) mmol g-1, and the adsorbent can be completely regenerated by inert gas purging. Furthermore, it is highly hydrophobic with negligible water adsorption, and the C2H4/C2H6 separation performance is unaffected at high humidity.

L0 Gradient-Regularization and Scale Space Representation Model for Cartoon and Texture Decomposition.

In this paper, we consider decomposing an image into its cartoon and texture components. Traditional methods, which mainly rely on the gradient amplitude of images to distinguish between these components, often show limitations in decomposing small-scale, high-contrast texture patterns and large-scale, low-contrast structural components. Specifically, these methods tend to decompose the former to the cartoon image and the latter to the texture image, neglecting the scale features inherent in both components. To overcome these challenges, we introduce a new variational model which incorporates an L0 -based total variation norm for the cartoon component and an L2 norm for the scale space representation of the texture component. We show that the texture component has a small L2 norm in the scale space representation. We apply a quadratic penalty function to handle the non-separable L0 norm minimization problem. Numerical experiments are given to illustrate the efficiency and effectiveness of our approach.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Retrospective study of 189 cases of acute perforated peptic ulcer: safety and efficacy of over-the-scope-clip based endoscopic closure.

BACKGROUND: To compare the clinical outcomes in patients with acute perforated peptic ulcer (PPU) treated with over-the-scope clip (OTSC), non-surgical, and surgical interventions, and to explore the effectiveness and safety of OTSC closure. METHODS: Hospital stay, antibiotic use, diet resumption time, and mortality rate were analyzed retrospectively. Binary Logistic regression analysis was used to identify the risk factors influencing PPU complicated with sepsis. RESULTS: Patients were divided into three treatment groups: OTSC (n = 62), non-surgical (n = 72), and surgical (n = 55) groups. The median time (IQR) from symptom onset to admission was 9.0 (4-23) h. 88.71% (55/62) of the patients in In the OTSC group underwent OTSC closure within 24 h (median [IQR] time: 14.5 [7.00-30.25] h). The perforation diameters in the OTSC and surgical groups were 9.87 mm ± 5.97 mm and 8.55 mm ± 6.17 mm, respectively. The median (IQR) hospital stays in the OTSC (9.50 [7.00-12.25] days) and non-surgical group (9.00[7.00-13.00]days) were similar (p > 0.05), but shorter than that in surgical group (12.00[10.00-16.00]days), (p < 0.05). The median duration of antibiotic use was shorter in the OTSC group (7.00[3.00-10.00]) than in the non-surgical group (9.00[7.00-11.00]) and surgical group (11.00[9.00-13.00]) ( p < 0.05); and the time to resume oral feeding was shorter in the OTSC group (4.00[2.00-5.25]) than in the non-surgical group (7.00[6.13-9.00]) and surgical group (8.00[6.53-10.00]), respectively ( p < 0.05). No mortality difference among groups (p = 0.109) was found. Lower albumin level at admission, older age, and elevated creatinine levels were associated with increased sepsis risk, with OR(95%CI) of 0.826 (0.687-0.993), 1.077 (1.005-1.154), and 1.025 (1.006-1.043), respectively (all p < 0.05). CONCLUSION: OTSC closure improves clinical outcomes of acute PPU patients without sepsis. Age, hypoalbuminemia, and baseline renal dysfunction increase the risk of sepsis, while mortality was associated with sepsis and multiorgan dysfunction.

Dynamic natural components and morphological changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome and mild chronic kidney disease at the 1-year follow-up and clinical significance at the 5-year follow-up.

INTRODUCTION: The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. METHODS: A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. RESULTS: Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). CONCLUSIONS: Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. TRIAL REGISTRATION: Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection.

The treatment of severe acute pancreatitis (SAP), with high mortality rates, poses a significant clinical challenge. Investigating the pathological changes associated with SAP using animal models can aid in identifying potential therapeutic targets and exploring novel treatment approaches. Previous studies primarily induced pancreatic injury through retrograde bile duct injection of sodium taviaurocholate, but the impact of surgical damage on the quality of the animal model remains unclear. In this study, we employed various frequencies of intraperitoneal Caerulein injections combined with different doses of LPS to induce pancreatic injury in C57BL/6J mice and compared the extent of injury across five intraperitoneal injection protocols. Regarding inducing acute pancreatitis in mice, an intraperitoneal injection protocol is proposed that results in a mortality rate as high as 80% within 5 days. Specifically, mice received ten daily intraperitoneal injections of Caerulein (50 µg/kg), followed by an injection of LPS (15 mg/kg) one hour after the last Caerulein administration. By adjusting the frequency and dosage of injected medications, one can manipulate the severity of pancreatic injury effectively. This model exhibits strong controllability and has a short replication cycle, making it feasible for completion by a single researcher without requiring expensive equipment. It conveniently and accurately simulates key disease characteristics observed in human SAP while demonstrating a high degree of reproducibility.

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty.

OBJECTIVE: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term target vessel failure (TVF) outcome in patients with in-stent restenosis (ISR) by using drug-coated balloon (DCB) treatment after a long-term follow-up. METHODS: This was a retrospective study. A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled. The QFR of the entire target vessel was measured offline. The primary endpoint was TVF, including target vessel-cardiac death (TV-CD), target vessel-myocardial infarction (TV-MI), and clinically driven-target vessel revascularization (CD-TVR). RESULTS: The follow-up time was 3.09±1.53 years, and 50 patients had TVF. The QFR immediately after percutaneous coronary intervention (PCI) was significantly lower in the TVF group than in the no-TVF group. Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up [hazard ratio (HR): 5.15×10-5 (6.13×10-8-0.043); P<0.01]. Receiver-operating characteristic (ROC) curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925 (area under the curve: 0.886, 95% confidence interval: 0.834-0.938; sensitivity: 83.40%, specificity: 88.00; P<0.01). In addition, QFR≤0.925 post-PCI was strongly correlated with the TVF, including TV-MI and CD-TVR (P<0.01). CONCLUSION: The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty. A lower QFR immediately after PCI was associated with a worse TVF outcome.

Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.