Longitudinal ultrasound-based AI model predicts axillary lymph node response to neoadjuvant chemotherapy in breast cancer: a multicenter study.

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

SARS-CoV-2 Antibodies in Human Milk After mRNA and Adenovector-Based Vaccination: A Systematic Review and Meta-Analysis.

BACKGROUND: SARS-CoV-2 specific antibodies exist in human milk expressed by lactating parents after vaccination. In the existing research, the effects of vaccine types on human milk are inconsistent. RESEARCH AIM: This study aims to perform a systematic review and meta-analysis of the existing observational studies to compare the positive rates of SARS-CoV-2 specific antibodies in human milk according to mRNA and adenovector-based vaccination. METHODS: PubMed, Web of Science, Elsevier Science Direct and Cochrane Library databases were systematically searched for relevant articles published from December 30, 2019 to February 15, 2023. Observational studies were considered eligible provided they reported data on SARS-CoV-2 specific antibodies in human milk. The risk of bias in non-randomized studies of interventions (ROBINS-I) tool, the Newcastle-Ottawa Scale (NOS), and the Agency for Healthcare Research and Quality (AHRQ) were used to assess risk of bias. Seven studies, including 511 lactating participants, were included in this review and meta-analysis. RESULTS: The positive rate of SARS-CoV-2 IgA is higher in mRNA vaccine groups than in adenovector-based vaccine groups (OR = 4.80, 95% CI [3.04, 7.58], p < 0.001). The positive rate of SARS-CoV-2 IgG was higher in mRNA vaccines than in adenovector-based vaccines. CONCLUSIONS: Compared to adenovector-based vaccines, mRNA vaccines present a higher positivity rate of IgA and IgG in human milk after vaccination. In other words, mRNA vaccinations may offer breastfed children a higher level of protection than adenovector-based vaccinations. Further high-quality data is still required to substantiate these findings.

Slow-Release Effect Assisted Crystallization for Sequential Deposition Realizes Efficient Inverted Perovskite Solar Cells.

The two-step sequential deposition strategy has been widely recognized in promoting the research and application of perovskite solar cells, but the rapid reaction of organic salts with lead iodide inevitably affects the growth of perovskite crystals, accompanied by the generation of more defects. In this study, the regulation of crystal growth was achieved in a two-step deposition method by mixing 1-naphthylmethylammonium bromide (NMABr) with organic salts. The results show that the addition of NMABr effectively delays the aggregation and crystallization behavior of organic salts; thereby, the growth of the optimal crystal (001) orientation of perovskite is promoted. Based on this phenomenon of delaying the crystallization process of perovskite, the "slow-release effect assisted crystallization" is defined. Moreover, the incorporation of the Br element expands the band gap of perovskite and mitigates material defects as nonradiative recombination centers. Consequently, the power conversion efficiency (PCE) of the enhanced perovskite solar cells (PSCs) reaches 20.20%. It is noteworthy that the hydrophobic nature of the naphthalene moiety in NMABr can enhance the humidity resistance of PSCs, and the perovskite phase does not decompose for more than 3000 h (30-40% RH), enabling it to retain 90% of its initial efficiency even after exposure to a nitrogen environment for 1200 h.

Association between mechanical power during one-lung ventilation and pulmonary complications after thoracoscopic lung resection surgery: a prospective observational study.

BACKGROUND: The role of mechanical power on pulmonary outcomes after thoracic surgery with one-lung ventilation was unclear. We investigated the association between mechanical power and postoperative pulmonary complications in patients undergoing thoracoscopic lung resection surgery. METHODS: In this single-center, prospective observational study, 622 patients scheduled for thoracoscopic lung resection surgery were included. Volume control mode with lung protective ventilation strategies were implemented in all participants. The primary endpoint was a composite of postoperative pulmonary complications during hospital stay. Multivariable logistic regression models were used to evaluate the association between mechanical power and outcomes. RESULTS: The incidence of pulmonary complications after surgery during hospital stay was 24.6% (150 of 609 patients). The multivariable analysis showed that there was no link between mechanical power and postoperative pulmonary complications. CONCLUSIONS: In patients undergoing thoracoscopic lung resection with standardized lung-protective ventilation, no association was found between mechanical power and postoperative pulmonary complications. TRIAL REGISTRATION: Trial registration number: ChiCTR2200058528, date of registration: April 10, 2022.

Puerarin alleviates atherosclerosis via the inhibition of Prevotella copri and its trimethylamine production.

OBJECTIVE: Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans. DESIGN: The impact of PU on AS was examined in ApoE -/- mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with Prevotella copri (P. copri) were employed. RESULTS: PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into ApoE-/- mice fed HFD. Specifically, PU reduced the abundance of P. copri, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of P. copri undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of P. copri and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased P. copri levels and reduced TMAO concentrations in patients with carotid artery plaque. CONCLUSION: PU may provide therapeutic benefits in combating AS by targeting P. copri and its production of TMA. TRIAL REGISTRATION NUMBER: ChiCTR1900022488.

Unveiling the Mechanism of Plasma-Catalyzed Oxidation of Methane to C2+ Oxygenates over Cu/UiO-66-NH2.

Nonthermal plasma (NTP) offers the potential for converting CH4 with CO2 into liquid products under mild conditions, but controlling liquid selectivity and manipulating intermediate species remain significant challenges. Here, we demonstrate the effectiveness of the Cu/UiO-66-NH2 catalyst in promising the conversion of CH4 and CO2 into oxygenates within a dielectric barrier discharge NTP reactor under ambient conditions. The 10% Cu/UiO-66-NH2 catalyst achieved an impressive 53.4% overall liquid selectivity, with C2+ oxygenates accounting for ∼60.8% of the total liquid products. In situ plasma-coupled Fourier-transform infrared spectroscopy (FTIR) suggests that Cu facilitates the cleavage of surface adsorbed COOH species (*COOH), generating *CO and enabling its migration to the surface of Cu particles. This surface-bound *CO then undergoes C-C coupling and hydrogenation, leading to ethanol production. Further analysis using CO diffuse reflection FTIR and 1H nuclear magnetic resonance spectroscopy indicates that in situ generated surface *CO is more effective than gas-phase CO (g) in promoting C-C coupling and C2+ liquid formation. This work provides valuable mechanistic insights into C-C coupling and C2+ liquid production during plasma-catalytic CO2 oxidation of CH4 under ambient conditions. These findings hold broader implications for the rational design of more efficient catalysts for this reaction, paving the way for advancements in sustainable fuel and chemical production.

Proteomic and phosphoproteomic reveal immune-related function of milk fat globule membrane in bovine milk of different lactation periods.

Information regarding protein expression and phosphorylation modifications in the bovine milk fat globule membrane is scarce, particularly throughout various lactation periods. This study employed a complete proteome and phosphoproteome between bovine colostrum and mature milk. A total of 11 proteins were seen in both protein expression and phosphorylation levels. There were 400 proteins identified in only protein expression, and 104 phosphoproteins identified in only phosphorylation levels. A total of 232 significant protein characteristics were identified within the proteome and significant phosphorylation sites within 86 phosphoproteins of the phosphoproteome. Biological activities and pathways primarily exhibited associations with the immune system. Simultaneously, a comprehensive analysis of proteins and phosphorylation sites using a multi-omics approach. Hence, the data we have obtained has the potential to expand our understanding of how the bovine milk fat globule membrane might be utilized as a beneficial component in dairy products.

Fecal microbiota transplantation for irritable bowel syndrome: Current evidence and perspectives.

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology. We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes. The current frontier in this field seeks to elucidate these variations, underscore the existing knowledge gaps that necessitate exploration, and provide a guideline for successful FMT imple-mentation in IBS patients. At the same time, the application of FMT as a treatment for IBS confronts several challenges.

Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

BENEFIT AND HARM OF ASPIRIN ON MORTALITY FROM GASTROINTESTINAL CANCERS VERSUS BLEEDING IN HELICOBACTER PYLORI-ERADICATED PATIENTS.

BACKGROUND: We investigated benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer versus excess mortality from bleeding among Helicobacter pylori (HP)-eradicated patients, and its interaction with proton pump inhibitors (PPIs). METHODS: HP-eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from date of HP therapy till death or end of study (July 2020). Primary exposure was aspirin use as time-varying variable. Primary outcome was GI cancer-related (gastrointestinal, hepatobiliary or pancreatic cancer) death and secondary outcome was bleeding-related (GIB or intracranial bleeding) death. Adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities and concomitant medications. Benefit-risk profile was expressed as adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and non-users. RESULTS: 87,967 subjects were followed for a median of 10.1years, with 1,294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer-related mortality (aHR:0.51;95%CI:0.42-0.61), but higher bleeding-related mortality (aHR:1.52;95%CI:1.11-2.08). Among PPI users, aHR of bleeding-related mortality with aspirin was 1.06 (95%CI:0.70-1.63). For whole cohort, adjusted absolute risk difference between aspirin users and non-users was 7 (95%CI: 5-8) fewer cancer-related and 1 (95%CI: 0.3-3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95%CI:8-10) fewer cancer-related deaths per 10,000 person-years without increase in bleeding-related deaths. CONCLUSIONS: GI-cancer mortality benefit from aspirin outweighs bleeding-related mortality in HP-eradicated subjects, which is further enhanced by PPI use.

Enantio- and Diastereoselective Total Synthesis of Belzutifan Enabled by Rh-Catalyzed Hydrogenation.

Herein, we report a nine-step synthesis of belzutifan enabled by a novel Rh-catalyzed asymmetric hydrogenation to install the contiguous fluorinated stereocenters with high enantioselectivity. Moreover, the final ketone reduction in the synthesis proceeds with high diastereoselectivity, leading to the expedient assembly of the stereotriad. In contrast to the original 16-step synthesis, this route avoids a lengthy bromination-oxidation sequence and introduces the sulfone functionality via nucleophilic aromatic substitution, obviating the need for transition metal catalysis.

Mitigating microplastic stress on peanuts: The role of biochar-based synthetic community in the preservation of soil physicochemical properties and microbial diversity.

Tire-derived rubber crumbs (RC), as a new type of microplastics (MPs), harms both the environment and human health. Excessive use of plastic, the decomposition of which generates microplastic particles, in current agricultural practices poses a significant threat to the sustainability of agricultural ecosystems, worldwide food security and human health. In this study, the application of biochar, a carbon-rich material, to soil was explored, especially in the evaluation of synthetic biochar-based community (SynCom) to alleviate RC-MP-induced stress on plant growth and soil physicochemical properties and soil microbial communities in peanuts. The results revealed that RC-MPs significantly reduced peanut shoot dry weight, root vigor, nodule quantity, plant enzyme activity, soil urease and dehydrogenase activity, as well as soil available potassium, and bacterial abundance. Moreover, the study led to the identification highly effective plant growth-promoting rhizobacteria (PGPR) from the peanut rhizosphere, which were then integrated into a SynCom and immobilized within biochar. Application of biochar-based SynCom in RC-MPs contaminated soil significantly increased peanut biomass, root vigor, nodule number, and antioxidant enzyme activity, alongside enhancing soil enzyme activity and rhizosphere bacterial abundance. Interestingly, under high-dose RC-MPs treatment, the relative abundance of rhizosphere bacteria decreased significantly, but their diversity increased significantly and exhibited distinct clustering phenomenon. In summary, the investigated biochar-based SynCom proved to be a potential soil amendment to mitigate the deleterious effects of RC-MPs on peanuts and preserve soil microbial functionality. This presents a promising solution to the challenges posed by contaminated soil, offering new avenues for remediation.

[Early effectiveness of local injection of multimodal drug cocktail during anterior cruciate ligament reconstruction and its influence on cartilage].

Objective: To explore the early effectiveness and influence on cartilage of local injection of multimodal drug cocktail (MDC) during anterior cruciate ligament reconstruction (ACLR). Methods: Between February 2022 and August 2023, patients undergone arthroscopic ACLR using autologous hamstring tendons were selected as the study subjects. Among them, 90 patients met the selection criteria and were randomly divided into 3 groups ( n=30) according to the different injection drugs after ligament reconstruction. There was no significant difference in baseline data such as gender, age, body mass index, surgical side, disease duration, preoperative thigh circumference, and preoperative levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1, matrix metalloproteinase 3 (MMP-3), MMP-13, and aggrecan (ACAN) in synovial fluid between groups ( P>0.05). After the ligament reconstruction during operation, corresponding MDC (consisting of ropivacaine, tranexamic acid, and betamethasone in group A, and ropivacaine, betamethasone, and saline in group B) or saline (group C) were injected into the joint and tendon site, respectively. The length of hospital stay, postoperative tramadol injection volume, incidence of complications, degree of knee joint swelling and range of motion, visual analogue scale (VAS) score, International Knee Documentation Committee (IKDC) score, Lyshlom score, and Hospital for Special Surgery (HSS) score were recorded and compared between groups. The T2 * values in different cartilage regions were detected by MRI examination and the levels of TNF-α, IL-6, IL-1, MMP-3, MMP-13, and ACAN in synovial fluid were detected by ELISA method. Results: The patients in group A, B, and C were followed up (12.53±3.24), (13.14±2.87), and (12.82±3.32) months, respectively. All incisions healed by first intention. Compared with group C, group A and group B had shorter length of hospital stay, less tramadol injection volume, and lower incidence of complications, showing significant differences ( P<0.05); there was no significant difference between group A and group B ( P>0.05). The degree of knee swelling in group A was significantly less than that in group B and group C ( P<0.05), but there was no significant difference between group B and group C ( P>0.05). At 3, 6, 12, 24, and 48 hours after operation, VAS scores of group A and group B were significantly lower than those of group C ( P<0.05); at 72 hours after operation, there was no significant difference among the three groups ( P>0.05). At 3 days, 14 days, and 1 month after operation, the range of motion of knee joint in group A were significantly better than those in group C ( P<0.05), and there was no significant difference between the other groups ( P>0.05). At 1 month after operation, the IKDC score of group A and group B was significantly higher than that of group C ( P<0.05); there was no significant difference among the three groups at other time points ( P>0.05). There was no significant difference in Lyshlom score and HSS score among the three groups at each time point ( P>0.05). At 14 days after operation, the levels of IL-1 and IL-6 in the synovial fluid in groups A and B were significantly lower than those in group C ( P<0.05). There was no significant difference in the levels of TNF-α, MMP-3, MMP-13, and ACAN between groups A and B ( P>0.05). At 1 month after operation, there was no significant difference in the above indicators among the three groups ( P>0.05). At 3, 6, and 12 months after operation, there was no significant difference in the T2 * values of different cartilage regions among the three groups ( P>0.05). Conclusion: Injecting MDC (ropivacaine, tranexamic acid, betamethasone) into the joint and tendon site during ACLR can achieve good early effectiveness without significant impact on cartilage.

Effect of a 3D-printed reconstruction automated matching system for selecting the size of a left double-lumen tube: a study protocol for a prospective randomised controlled trial.

INTRODUCTION: Lung isolation is primarily accomplished using a double-lumen tube (DLT) or bronchial blocker. A precise and accurate size of the DLT is a prerequisite for ensuring its accurate placement. Three-dimensional (3D) reconstruction technology can be used to accurately reproduce tracheobronchial structures to improve the accuracy of DLT size selection. Therefore, we have developed automatic comparison software for 3D reconstruction based on CT data (3DRACS). In this study, we aimed to evaluate the efficiency of using 3DRACS to select the DLT size for endobronchial intubation in comparison with using the 'blind' DLT intubation method to determine the DLT size, which is based on height and sex. METHODS AND ANALYSIS: This is a prospective, single-centre, double-blind randomised controlled trial. In total, 200 patients scheduled for lung resection using a left DLT will be randomly allocated to the 3D group or the control group at a 1:1 ratio. A 3DRACS will be used for the 3D group to determine the size of the DLT, while in the case of the control group, the size of the DLT will be determined according to patient height and sex. The primary outcome is the success rate of placement of the left DLT without fibreoptic bronchoscopy (FOB). The secondary outcomes include the following: successful intubation time, degree of pulmonary atrophy, grade of airway injury, oxygenation during one-lung ventilation, postoperative sore throat and hoarseness, and number of times FOB is used. ETHICS AND DISSEMINATION: Ethical approval has been obtained from our local ethics committee (approval number: SCCHEC-02-2022-155). Written informed consent will be obtained from all participants before randomisation, providing them with clear instructions about the purpose of the study. The results will be disseminated through peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT06258954.

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.

The impact of vedolizumab therapy on extraintestinal manifestations in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Extraintestinal manifestations (EIMs) pose a significant threat in inflammatory bowel disease (IBD) patients. Vedolizumab (VDZ) primarily affects the gastrointestinal tract. However, its impact on EIMs remains uncertain. Therefore, we conducted this meta-analysis to examine the effects of VDZ on EIMs during treatment. METHODS: Relevant studies were identified by conducting thorough searches across electronic databases, including PubMed, Ovid Embase, Medline, and Cochrane CENTRAL. Primary outcomes focused on the proportion of patients with resolution for pre-existing EIMs in IBD patients receiving VDZ. Secondary outcomes included the proportion of patients with EIM exacerbations and new onset EIMs during VDZ treatment. RESULTS: Our meta-analysis encompassed 21 studies. The proportion of patients with resolution of pre-existing EIMs in VDZ-treated IBD patients was 39% (150/386; 95% confidence interval [CI] 0.31-0.48). The proportion of patients with EIM exacerbations occurred at a rate of 28% (113/376; 95% CI 0.05-0.50), while new onset EIMs had a rate of 15% (397/2541; 95% CI 0.10-0.20). Subgroup analysis revealed a 40% (136/337) proportion of patients with resolution for articular-related EIMs and a 50% (9/18) rate for erythema nodosum. Exacerbation rates for arthritis/arthralgia, erythema nodosum/pyoderma gangrenosum, and aphthous stomatitis during VDZ use were 28% (102/328), 18% (7/38), and 11% (3/28), respectively. The incidence rate of newly developed EIMs during treatment was 11% (564/4839) for articular-related EIMs, with other EIMs below 2%. CONCLUSION: VDZ demonstrates efficacy in skin-related EIMs like erythema nodosum and joint-related EIMs including arthritis, arthralgia, spondyloarthritis, and peripheral joint diseases. Some joint and skin-related EIMs may experience exacerbation during VDZ therapy.

Exosomes Secreted by Wharton's Jelly-Derived Mesenchymal Stem Cells Promote the Ability of Cell Proliferation and Migration for Keratinocyte.

Mesenchymal stem cells (MSCs) isolated from Wharton's jelly (WJ-MSCs) and adipose tissue (AD-MSCs) are alternative sources for bone marrow-derived MSCs. Owing to their multiple functions in angiogenesis, immune modulation, proliferation, migration, and nerve regeneration, MSC-derived exosomes can be applied in "cell-free cell therapy". Here, we investigated the functional protein components between the exosomes from WJ-MSCs and AD-MSCs to explain their distinct functions. Proteins of WJ-MSC and AD-MSC exosomes were collected and compared based on iTRAQ gel-free proteomics data. Results: In total, 1695 proteins were detected in exosomes. Of these, 315 were more abundant (>1.25-fold) in AD-MSC exosomes and 362 kept higher levels in WJ-MSC exosomes, including fibrinogen proteins. Pathway enrichment analysis suggested that WJ-MSC exosomes had higher potential for wound healing than AD-MSC exosomes. Therefore, we treated keratinocyte cells with exosomes and the recombinant protein of fibrinogen beta chain (FGB). It turned out that WJ-MSC exosomes better promoted keratinocyte growth and migration than AD-MSC exosomes. In addition, FGB treatment had similar results to WJ-MSC exosomes. The fact that WJ-MSC exosomes promoted keratinocyte growth and migration better than AD-MSC exosomes can be explained by their higher FGB abundance. Exploring the various components of AD-MSC and WJ-MSC exosomes can aid in their different clinical applications.

Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight.

The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing. Carbohydrates were the major source of total energy (56.61%), followed by fat (27.92%) and protein (15.46%). The rate of infant LBW was 7.8%, which was positively correlated with maternal carbohydrate intake. In the pregnancy gut microbiota, Bacteroides ovatus and Dorea spp. were indirectly and directly negatively associated with fetal growth, respectively; Rosenburia faecis was directly positively associated with neonatal birth weight. Maternal hypertension during pregnancy altered the microbiota features and was associated with poor fetal growth. Microbiota-accessible carbohydrates can modify the composition and function of the pregnancy gut microbiota, thus providing a potential marker to modulate deviations from dietary patterns, particularly in women at risk of hypertension during pregnancy, to prevent neonatal LBW.