Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Influence of motor capacity of the lower extremity and mobility performance on foot plantar pressures in community-dwelling older women.

Objectives: To investigate the associations of motor capacity of the lower extremity and mobility performance in daily physical activities with peak foot plantar pressures during walking among older women. Methods: Using the data collected among 58 community-dwelling older women (68.66 ± 3.85 years), Pearson correlation and multiple linear regression analyses were performed to analyze the associations of motor capacity of the lower extremity (the 30-s chair stand test, the timed one-leg stance with eyes closed, and the Fugl-Meyer assessment of lower extremity), mobility performance in daily physical activities (the average minutes of moderate to vigorous physical activity every day and the metabolic equivalents), and foot plantar pressures (peak force and peak pressure) with the age and body fat percentage as covariates. Results: (1) The motor capacity of the lower extremity has higher explanatory power for peak foot plantar pressures compared with the mobility performance in daily physical activities. (2) Higher body fat percentage was positively associated with peak force and pressure, while a lower score on the Fugl-Meyer assessment of lower extremity was negatively associated with both of them. (3) The metabolic equivalents were positively associated with the peak force, while the 30-s chair stand test was negatively associated with it. Conclusions: Mobility performance in daily physical activities can be significant predictors for peak foot plantar pressures among older women. The significant predictor variables include the Fugl-Meyer assessment of lower extremity, the 30-s chair stand test, and metabolic equivalents.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis.

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Effect of radiation cross-linked collagen scaffold in alveolar ridge preservation of extraction socket.

This study aimed to evaluate the properties of radiation cross-linked collagen scaffold (RCS) and its efficacy for alveolar ridge preservation (ARP). RCS was prepared from collagen dispersion by electron beam irradiation and freeze-drying. The microstructure, swelling ratio, area alteration and mechanical properties of RCS were characterized. Fifty-four New Zealand rabbits performing incisor extraction on maxilla and mandible were randomly assigned into positive, sham operation or treatment groups. Micro-computed tomography (micro-CT) scans, performed after 1, 4, and 12 weeks of surgery, were to assess changes in ridge height at buccal and palatal side, in ridge width and in micromorphological parameters. Histological analysis accessed socket microarchitecture. The results showed that RCS had stable mechanical properties and morphologic features that provided a reliable physical support for ARP. Dimensional changes in treatment group revealed significantly greater vertical height at buccal (5.32 [3.37, 7.26] mm, p < .0001) and palatal (4.37 [2.66, 6.09] mm, p < .0001) side, and horizontal width at the maxilla (0.16 [0.04, 0.28] mm, p < .01) and mandible (0.33 [0.11, 0.54] mm, p < .01) than those in sham operation group after 12 weeks. The treatment group had advantage than positive group in vertical height preservation, quantitatively. The order and density of bone trabeculae were improved in treatment group. These findings indicated that RCS had the potential to serve as an effective scaffold for ARP.

Highly efficient field-free switching of perpendicular yttrium iron garnet with collinear spin current.

Yttrium iron garnet, a material possessing ultralow magnetic damping and extraordinarily long magnon diffusion length, is the most widely studied magnetic insulator in spintronics and magnonics. Field-free electrical control of perpendicular yttrium iron garnet magnetization with considerable efficiency is highly desired for excellent device performance. Here, we demonstrate such an accomplishment with a collinear spin current, whose spin polarization and propagation direction are both perpendicular to the interface. Remarkably, the field-free magnetization switching is achieved not only with a heavy-metal-free material, Permalloy, but also with a higher efficiency as compared with a typical heavy metal, Pt. Combined with the direct and inverse effect measurements, we ascribe the collinear spin current to the anomalous spin Hall effect in Permalloy. Our findings provide a new insight into spin current generation in Permalloy and open an avenue in spintronic devices.

Development of generic metabolic Raman calibration models using solution titration in aqueous phase and data augmentation for in-line cell culture analysis.

This study presents a novel approach for developing generic metabolic Raman calibration models for in-line cell culture analysis using glucose and lactate stock solution titration in an aqueous phase and data augmentation techniques. First, a successful set-up of the titration method was achieved by adding glucose or lactate solution at several different constant rates into the aqueous phase of a bench-top bioreactor. Subsequently, the in-line glucose and lactate concentration were calculated and interpolated based on the rate of glucose and lactate addition, enabling data augmentation and enhancing the robustness of the metabolic calibration model. Nine different combinations of spectra pretreatment, wavenumber range selection, and number of latent variables were evaluated and optimized using aqueous titration data as training set and a historical cell culture data set as validation and prediction set. Finally, Raman spectroscopy data collected from 11 historical cell culture batches (spanning four culture modes and scales ranging from 3 to 200 L) were utilized to predict the corresponding glucose and lactate values. The results demonstrated a high prediction accuracy, with an average root mean square errors of prediction of 0.65 g/L for glucose, and 0.48 g/L for lactate. This innovative method establishes a generic metabolic calibration model, and its applicability can be extended to other metabolites, reducing the cost of deploying real-time cell culture monitoring using Raman spectroscopy in bioprocesses.

Single-cell transcriptome landscape elucidates the cellular and developmental responses to tomato chlorosis virus infection in tomato leaf.

Plant viral diseases compromise the growth and yield of the crop globally, and they tend to be more serious under extreme temperatures and drought climate changes. Currently, regulatory dynamics during plant development and in response to virus infection at the plant cell level remain largely unknown. In this study, single-cell RNA sequencing on 23 226 individual cells from healthy and tomato chlorosis virus-infected leaves was established. The specific expression and epigenetic landscape of each cell type during the viral infection stage were depicted. Notably, the mesophyll cells showed a rapid function transition in virus-infected leaves, which is consistent with the pathological changes such as thinner leaves and decreased chloroplast lamella in virus-infected samples. Interestingly, the F-box protein SKIP2 was identified to play a pivotal role in chlorophyll maintenance during virus infection in tomato plants. Knockout of the SlSKIP2 showed a greener leaf state before and after virus infection. Moreover, we further demonstrated that SlSKIP2 was located in the cytomembrane and nucleus and directly regulated by ERF4. In conclusion, with detailed insights into the plant responses to viral infections at the cellular level, our study provides a genetic framework and gene reference in plant-virus interaction and breeding in the future research.

Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

Swim bladder-derived biomaterials: structures, compositions, properties, modifications, and biomedical applications.

Animal-derived biomaterials have been extensively employed in clinical practice owing to their compositional and structural similarities with those of human tissues and organs, exhibiting good mechanical properties and biocompatibility, and extensive sources. However, there is an associated risk of infection with pathogenic microorganisms after the implantation of tissues from pigs, cattle, and other mammals in humans. Therefore, researchers have begun to explore the development of non-mammalian regenerative biomaterials. Among these is the swim bladder, a fish-derived biomaterial that is rapidly used in various fields of biomedicine because of its high collagen, elastin, and polysaccharide content. However, relevant reviews on the biomedical applications of swim bladders as effective biomaterials are lacking. Therefore, based on our previous research and in-depth understanding of this field, this review describes the structures and compositions, properties, and modifications of the swim bladder, with their direct (including soft tissue repair, dural repair, cardiovascular repair, and edible and pharmaceutical fish maw) and indirect applications (including extracted collagen peptides with smaller molecular weights, and collagen or gelatin with higher molecular weights used for hydrogels, and biological adhesives or glues) in the field of biomedicine in recent years. This review provides insights into the use of swim bladders as source of biomaterial; hence, it can aid biomedicine scholars by providing directions for advancements in this field.

Synthesis of N-H Aziridines from Unactivated Olefins Using Hydroxylamine-O-Sulfonic Acids as Aminating Agent.

Herein, we presented a practical methodology for the intermolecular aziridination of alkenes, using HOSA as the aminating agent, alongside pyridine or piperidine as the base, within HFIP solvent system. Notably, this approach showcases excellent reactivity, especially with nonactivated alkenes, and facilitates the transformation of various alkenes substrates, including mono-, di-, tri, and tetra-substituted alkenes, into aziridines with moderate to excellent yield. This method presents a promising avenue for synthesizing aziridines from a wide range of alkenes, featuring the benefits of straightforward operation, mild reaction conditions, extensive substrate compatibility, and scalability.

Improving Soluble Phenolic Profile and Antioxidant Activity of Grape Pomace Seeds through Fungal Solid-State Fermentation.

Grape pomace seeds contain abundant phenolic compounds, which are also present in both soluble and insoluble forms, similar to many other plant matrices. To further increase the extractable soluble phenolics and their antioxidant activities, grape pomace seeds were fermented with different fungi. Results showed that solid-state fermentation (SSF) with Aspergillus niger, Monascus anka, and Eurotium cristatum at 28 °C and 65% humidity had a significantly positive impact on the release of soluble phenolics in grape pomace seeds. Specifically, SSF with M. anka increased the soluble phenolic contents by 6.42 times (calculated as total phenolic content) and 6.68 times (calculated as total flavonoid content), leading to an overall improvement of antioxidant activities, including DPPH (increased by 2.14 times) and ABTS (increased by 3.64 times) radical scavenging activity. Furthermore, substantial changes were observed in the composition and content of individual phenolic compounds in the soluble fraction, with significantly heightened levels of specific phenolics such as chlorogenic acid, syringic acid, ferulic acid, epicatechin gallate, and resveratrol. Notably, during M. anka SSF, positive correlations were identified between the soluble phenolic content and hydrolase activities. In particular, there is a strong positive correlation between glycosidase and soluble phenols (r = 0.900). The findings present an effective strategy for improving the soluble phenolic profiles and bioactivities of grape pomace seeds through fungal SSF, thereby facilitating the valorization of winemaking by-products.

Zhilong Huoxue Tongyu capsule improves myocardial ischemia/reperfusion injury via the PI3K/AKT/Nrf2 axis.

INTRODUCTION: Zhilong Huoxue Tongyu Capsule (ZL) is a Chinese medicine used for the treatment of cardio-cerebral diseases. However, the pharmacological mechanisms underlying its regulation of myocardial ischemia/reperfusion injury (MI/RI) remain unclear. PURPOSE: This study aims to investigate the effects and mechanisms of ZL on MI/RI in mice. MATERIALS AND METHODS: C57BL/6J mice were randomly assigned to four groups: Sham group, I/R group, ZL group, and ZLY group. The MI/RI mouse model was established by ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 120 minutes to restore blood perfusion. Cardiac function was evaluated using cardiac ultrasound. Histopathological changes and myocardial infarction area were assessed using Hematoxylin and eosin (H&E) staining and triphenyltetrazolium chloride (TTC) staining. The changes in oxidative stress- and ferroptosis-related markers were detected. RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of ZL in improving MI/RI. RESULTS: Our findings demonstrated that ZL exerted a protective effect against MI/RI by inhibiting ferroptosis, evidenced by the upregulation of antioxidant enzymes such as GSH and GPX4, coupled with the downregulation of ACSL4, a pro-ferroptosis factor. Furthermore, ZL positively impacted the PI3K/AKT/Nrf2 pathway by promoting ATPase activities and enhancing the relative protein expression of its components. Notably, the administration of a PI3K/AKT inhibitor reversed the antioxidant and anti-ferroptosis effects of ZL to some extent, suggesting a potential role for this pathway in mediating ZL's protective effects. CONCLUSIONS: ZL protects against MI/RI-induced ferroptosis by modulating the PI3K/AKT signaling pathway, leading to increased Nrf2 expression and activation of the HO-1/GPX4 pathway. These findings shed light on the potential therapeutic mechanisms of ZL in the context of cardiovascular diseases.

Exercise intervention in middle-aged and elderly individuals with insomnia improves sleep and restores connectivity in the motor network.

Exercise is a potential treatment to improve sleep quality in middle-aged and elderly individuals. Understanding exercise-induced changes in functional plasticity of brain circuits that underlie improvements in sleep among middle-aged and older adults can inform treatment of sleep problems. The aim of the study is to identify the effects of a 12-week exercise program on sleep quality and brain functional connectivity in middle-aged and older adults with insomnia. The trial was registered with Chinese Clinical Trial Register (ChiCTR2000033652). We recruited 84 healthy sleepers and 85 individuals with insomnia. Participants with insomnia were assigned to receive either a 12-week exercise intervention or were placed in a 12-week waitlist control condition. Thirty-seven middle-aged and older adults in the exercise group and 30 in the waitlist group completed both baseline and week 12 assessments. We found that middle-aged and older adults with insomnia showed significantly worse sleep quality than healthy sleepers. At the brain circuit level, insomnia patients showed decreased connectivity in the widespread motor network. After exercise intervention, self-reported sleep was increased in the exercise group (P < 0.001) compared to that in the waitlist group. We also found increased functional connectivity of the motor network with the cerebellum in the exercise group (P < 0.001). Moreover, we observed significant correlations between improvement in subjective sleep indices and connectivity changes within the motor network. We highlight exercise-induced improvement in sleep quality and functional plasticity of the aging brain.

Enhancing oncolytic virus efficiency with methionine and N-(3-aminoprolil)methacrylamide modified acrylamide cationic block polymer.

Oncolytic virus ablation of tumor cells has the advantages of high tumor selectivity, strong immunogenicity, and low side effects. However, the recognition and clearance of oncolytic viruses by the immune system are the main factors limiting their anti-tumor efficiency. As a highly biosafe and highly modifiable oncolytic virus vector, acrylamide can improve the long-term circulation of oncolytic viruses. Still, it is limited in its uptake efficiency by tumor cells. Herein, we constructed an N-hydroxymethyl acrylamide-b-(N-3-aminopropyl methacrylamide)-b-DMC block copolymer (NMA-b-APMA-b-DMA, NAD) as an oncolytic virus carrier, which not only improves the long-term circulation of oncolytic viruses in the body but also shows excellent stability for loading an oncolytic virus. The data shows that there was no obvious difference in the transfection effect of the NAD/Ad complex with or without neutralizing antibodies in the medium, which meant that the cationic carrier mediated by NAD/Ad had good serum stability. Only 10 micrograms of NAD carrier are needed to load the oncolytic virus, which can increase the transfection efficiency by 50 times. Cell experiments and mouse animal experiments show that NAD vectors can significantly enhance the anti-tumor effect of oncolytic viruses. We hope that this work will promote the application of acrylamide as an oncolytic virus vector and provide new ideas for methods to modify acrylamide for biomedical applications.

Promoting the healing of diabetic wounds with an antimicrobial gel containing AgNPs with anti-infective and anti-inflammatory properties.

Diabetic wounds are prone to develop chronic wounds due to bacterial infection and persistent inflammatory response. However, traditional dressings are monofunctional, lack bioactive substances, have limited bacterial inhibition as well as difficulties in adhesion and retention. These limit the therapeutic efficacy of traditional dressings on diabetic wounds. Therefore, finding and developing efficient and safe wound dressings is currently an urgent clinical need. In this study, an antimicrobial gel loaded with silver nanoparticles (AgNPs) (referred to as AgNPs@QAC-CBM) was prepared by crosslinking quaternary ammonium chitosan (QAC) with carbomer (CBM) as a gel matrix. AgNPs@QAC-CBM exhibited a reticulated structure, strong adhesion, good stability, and remarkable bactericidal properties, killing 99.9% of Escherichia coli, Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa within 1 min. Furthermore, AgNPs@QAC-CBM improved the wound microenvironment and accelerated wound healing in diabetic mice by promoting tissue production and collagen deposition, inducing M2 macrophages, reducing pro-inflammatory factor secretion and increasing anti-inflammatory factor levels. Moreover, AgNPs@QAC-CBM was proven to be safe for use through skin irritation and cytotoxicity tests, as they did not cause any irritation or toxicity. To summarize, AgNPs@QAC-CBM showed promising potential in enhancing the diabetic wound healing process.

Clinical application of endoscopic diaphragmotomy and dilation in a congenital duodenal diaphragm.

Background: A congenital duodenal diaphragm (CDD) is a rare cause of duodenal obstruction in infants and children. The traditional approach to treatment has been surgical intervention either with excision and duodenoplasty or with bypass through a duodenoduodenostomy, which is invasive and carries the risk of anastomotic leakage. Aims: To summarize the key points of differential diagnosis and treatment of a CDD under gastroscopy and to evaluate its efficacy and safety. Methods: The clinical data of patients with a duodenal obstruction diagnosed and treated by gastroscopy in our hospital between January 2019 and December 2022 were retrospectively analyzed. The gastroscopic features of the CDD were summarized. The clinical outcomes of patients with CDD treated by gastroscopy were collected and investigated. Results: A total of 13 children with a duodenal obstruction underwent a gastroscopic examination and/or treatment, and of these, 10 were diagnosed as having a CDD and 3 were finally diagnosed as having an annular pancreas. A dome-shaped structure during inspiration (9/10) and a guidewire that could be inserted through the opening into the distal lumen (6/10) were the gastroscopic features of the CDD, while the annular pancreas had none of these features. The 10 patients, 4 men and 6 women with the CDD, were treated through endoscopic diaphragmotomy and dilation. The age and weight at operation was 15 days to 7 years (M: 2.25 years) and 2.85-22 kg (M: 13.6 kg), respectively. A total of 11 endoscopic operations were performed in the 10 patients. The time of single operation was 15-55 min (M: 38 min). The patients did not experience complications such as bleeding, pneumoperitoneum, and duodenal papilla injury during the operation. Feeding was started 12-24 h after surgery, and the patients were discharged 2-10 days (M: 7 days) postoperatively. The patients were followed up for 3-36 months (M: 17 months), and none of them had a recurrence of vomiting. However, three showed a recurrence of stenosis in upper gastrointestinal imaging, one of whom underwent a partial diaphragm resection again 2 months after the primary treatment. Conclusions: A CDD can be confirmed by endoscopy based on its characteristic features. Endoscopic diaphragmotomy and balloon dilation are safe and effective, which can be a new option for minimally invasive treatment of a CDD.

The impact of physical activity on household out-of-pocket medical expenditure among adults aged 45 and over in urban China: The mediating role of spousal health behaviour.

Background: Increasing medical expenditure is viewed as one of the critical challenges in the context of population ageing. Physical activity (PA), as a primary prevention strategy for promoting health, is considered as an effective way to curb the excessive growth in medical expenditure. This study aimed to analyze the association between PA and the household out-of-pocket medical expenditure (HOPME) among Chinese urban adults aged 45 and over, and to explore the mediating role of spousal health behaviour. Methods: This study analyzed a nationally longitudinal survey: 2014-2018 China Family Panel Studies (CFPS). Fixed effects regression model was applied to estimate the association between PA and annual HOPME. Sobel model was utilized to test the mediating effect. Results: (1) PA was negatively associated with the annual HOPME among urban resident aged 45 and over in China. Exercising 1-5 times per week and maintaining the duration of each exercise session at 31-60 min were effective in reducing annual HOPME. (2) Spousal PA played a significant mediating role in the relationship between respondent's PA and annual HOPME. (3) The negative association between the respondent's PA and HOPME were found among women and those aged between 45 and 65, so was the mediating effect of spouse's PA. Conclusion: Individual PA not only directly reduces HOPME but also indirectly contributes to this reduction by enhancing the PA levels of their spouses. To capitalize on these benefits, more actions should be taken to increase the availability of PA facilities, enhance the public awareness of PA's benefits, and encourage residents to consistently engage in regular PA.

Progress in Biomarkers Related to Biliary Atresia.

Biliary atresia (BA) is a congenital cholestatic disease that can seriously damage children's liver function. It is one of the main reasons for liver transplantation in children. Early diagnosis of BA is crucial to the prognosis of patients, but there is still a lack of reliable non-invasive diagnostic methods. Additionally, as some children are in urgent need of liver transplantation, evaluating the stage of liver fibrosis and postoperative native liver survival in children with BA using a straightforward, efficient, and less traumatic method is a major focus of doctors. In recent years, an increasing number of BA-related biomarkers have been identified and have shown great potential in the following three aspects of clinical practice: diagnosis, evaluation of the stage of liver fibrosis, and prediction of native liver survival. This review focuses on the pathophysiological function and clinical application of three novel BA-related biomarkers, namely MMP-7, FGF-19, and M2BPGi. Furthermore, progress in well-known biomarkers of BA such as gamma-glutamyltransferase, circulating cytokines, and other potential biomarkers is discussed, aiming to provide a reference for clinical practice.

Pediatric perforated appendicitis diagnosis based on the C-reactive protein/prealbumin ratio.

Pediatric perforated appendicitis, prone to multiple complications, necessitates identifying potential serum biomarkers for early diagnosis and intervention. A cross-sectional study was conducted on patients under 16 with acute appendicitis, admitted to Hainan Women and Children's Medical Center from January 2019 to July 2023. The patients were categorized into perforated and non-perforated groups. Among the 313 included patients, 106 (33.87%, 95% CI 28.59-39.14%) developed perforation. The C-reactive protein to prealbumin ratio (CPA) showed a significant difference between the perforated and non-perforated groups [6.63 (2.9-13.02) vs. 0.7 (0.11-2.18), p < 0.001]. The AUC of CPA on the ROC curve was 0.691 (95% CI 0.513-0.869, p = 0.084) in patients under 4. In patients aged 4-9, the sensitivity of CPA > 3 predicting perforation was 76.2%, with a specificity of 81.6%, and an AUC of 0.816 (95% CI 0.747-0.886, p < 0.001). For patients aged 9-16, the sensitivity of CPA > 2.2 predicting perforation was 85%, with a specificity of 85.7%, and an AUC of 0.919 (95% CI 0.859-0.979, p < 0.001). CPA > 3 and CPA > 2.2 can predict perforated appendicitis in patients aged 4-9 and 9-16, respectively.