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Background: Impaired mitochondrial protein import machinery leads to phenotypically heterogeneous diseases. Here, we report a recurrent homozygous missense variant in the gene that encodes the translocase of outer mitochondrial membrane 7 (TOMM7) in nine patients with microcephaly, short stature, facial dysmorphia, atrophic macular scarring, and moyamoya disease from seven unrelated families., Methods: To prove the causality of the TOMM7 variant, mitochondrial morphology, proteomics, and respiration were investigated in CRISPR/Cas9-edited iPSCs-derived endothelial cells. Cerebrovascular defects and mitochondrial respiration were also examined in CRISPR/Cas9-edited zebrafish., Findings: iPSC-derived endothelial cells with homozygous TOMM7 p.P29L showed increased TOM7 stability, enlarged mitochondria, increased senescence, and defective tube formation. In addition, proteomic analysis revealed a reduced abundance of mitochondrial proteins involved in ATP synthesis or coordinating TCA cycle and gluconeogenesis. Moreover, mitochondrial respiration was slightly decreased while ATP production from glycolysis was significantly increased. Furthermore, deletion of tomm7 in zebrafish caused craniofacial and cerebrovascular defects that recapitulated human phenotypes. Notably, homozygous iPSCs differentially expressed genes involved in glycolysis and response to hypoxia. Finally, the metabolic imbalance was evidenced by decreased oxygen consumption, increased level of hexokinase 2, and enhanced glycolysis in endothelial cells derived from the patient's iPSCs., Interpretation: These results revealed the essential role of TOMM7 in balancing cellular sources of energy production at both proteomic and transcriptomic levels and provided the molecular mechanisms through which TOMM7 p.P29L variant leads to an autosomal recessive microcephalic osteodysplastic dwarfism with moyamoya disease., Funding: This work is supported by National Science and Technology Council grants and National Cheng Kung University Hospital., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Coffee and tea consumption account for most caffeine intake and 2-3 billion cups are taken daily around the world. Caffeine dependence is a widespread but under recognized problem., Objectives: To conduct a systematic review on the genetic susceptibility factors affecting caffeine metabolism and caffeine reward and their association with caffeine intake., Methodology: We conducted PubMed and Embase searches using the terms "caffeine", "reward", "gene", "polymorphism", "addiction", "dependence" and "habit" from inception till 2024. The demographics, genetic and clinical data from included studies were extracted and analyzed. Only case-control studies on habitual caffeine drinkers with at least 100 in each arm were included., Results: A total of 2552 studies were screened and 26 studies involving 1,851,428 individuals were included. Several genes that were involved with caffeine metabolism such as CYP1A2, ADORA2A, AHR, POR, ABCG2, CYP2A6, PDSS2 and HECTD4 rs2074356 (A allele specific to East Asians and monomorphic in Europeans, Africans and Americans) were associated with habitual caffeine consumption with effect size difference of 3% to 32% in number of cups of caffeinated drink per day per effect allele. In addition, ALDH2 was linked to the Japanese population. Genes associated with caffeine reward included BDNF, SLC6A4, GCKR, MLXIPL and dopaminergic genes such as DRD2 and DAT1 which had around 2-5% effect size difference in number of cups of caffeinated drink for each allele per day., Conclusion: Several genes that were involved in caffeine metabolism and reward were associated with up to 30% effect size difference in number of cups of caffeinated drink per day, and some associations were specific to certain ethnicities. Identification of at-risk caffeine dependence individuals can lead to early diagnosis and stratification of at-risk vulnerable individuals such as pregnant women and children, and can potentially lead to development of drug targets for dependence to caffeine., (© 2024. The Author(s).)

Kabuki syndrome (KS) is a rare genetic disorder characterized by distinct facial features, intellectual disability, and multiple congenital anomalies. We conducted a comprehensive analysis of the genetic and phenotypic spectrum of KS in a Taiwanese patient group of 23 patients. KMT2D variants were found in 22 individuals, with missense (26.1%), nonsense (21.7%), and frameshift (17.4%) variants being the most prevalent. One patient had a KMT2D variant of uncertain significance. The most common clinical characteristics included distinct facial features (100%), intellectual disability (100%), developmental delay (95.7%), speech delay (78.3%), hypotonia (69.6%), congenital heart abnormalities (69.6%), and recurrent infections (65.2%). Other abnormalities included hearing loss (39.1%), seizures (26.1%), cleft palate (26.1%), and renal anomalies (21.7%). This study broadens the mutational and phenotypic spectrum of KS in the Taiwanese population, highlighting the importance of comprehensive genetic testing and multidisciplinary clinical evaluations for diagnosis and treatment.

This paper aims to increase the Unmanned Aerial Vehicle's (UAV) capacity for target tracking. First, a control model based on fuzzy logic is created, which modifies the UAV's flight attitude in response to the target's motion status and changes in the surrounding environment. Then, an edge computing-based target tracking framework is created. By deploying edge devices around the UAV, the calculation of target recognition and position prediction is transferred from the central processing unit to the edge nodes. Finally, the latest Vision Transformer model is adopted for target recognition, the image is divided into uniform blocks, and then the attention mechanism is used to capture the relationship between different blocks to realize real-time image analysis. To anticipate the position, the particle filter algorithm is used with historical data and sensor inputs to produce a high-precision estimate of the target position. The experimental results in different scenes show that the average target capture time of the algorithm based on fuzzy logic control is shortened by 20% compared with the traditional proportional-integral-derivative (PID) method, from 5.2 s of the traditional PID to 4.2 s. The average tracking error is reduced by 15%, from 0.8 m of traditional PID to 0.68 m. Meanwhile, in the case of environmental change and target motion change, this algorithm shows better robustness, and the fluctuation range of tracking error is only half of that of traditional PID. This shows that the fuzzy logic control theory is successfully applied to the UAV target tracking field, which proves the effectiveness of this method in improving the target tracking performance., (© 2024. The Author(s).)

Objective: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035., Methods: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex., Results: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035., Conclusion: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth., (© 2024. The Author(s).)

Objective: To explore the mechanism of acupuncture to relieve diabetic proteinuria in Diabetic Kidney Disease (DKD)., Methods: A total of 10 male Sprague-Dawley rats were randomly selected as the negative control group (NC), and a further 30 rats were fed a high-fat diet (HFD) and intraperitoneal streptozotocin (STZ). The DKD model rats in the model group (DKD) and the acupuncture group (DKD + Acu) were randomly assigned. After 4 weeks of intervention, collected urine, peripheral blood, and renal tissues from all rats, and assessed blood urea nitrogen, serum creatinine, triglyceride, 24-h urine protein quantification, and blood glucose, left kidney weight, kidney body ratio index, then observe changes in renal histology in the rats. The renal cortex tissues of three rats from each group were sent for transcriptomic analysis. According to the results of transcriptomic analysis, various kits were used to detect SOD, MDA, GSH, GSH-px, and iron concentration. The expression levels of GPX4 and System Xc-, members of the antioxidative stress pathway, and TfR 1, SLC39A14, FTH 1, and SLC40A1, involved in iron metabolism, in the kidney tissues were measured by western blotting and reverse transcription-quantitative PCR. The expression of mesenchymal phenotype markers and podocyte-specific markers were evaluated by immunofluorescence., Results: Acupuncture promoted the levels of GSH, GSH-px, and SOD, decreased the level of MDA (P < 0.05), promoted the expression of GPX4 and System Xc- ( P  < 0.05), decreased the expression of TfR1 and SLC39A14 ( P  < 0.01), and increased the expression of FTH 1 and SLC40A1 ( P  < 0.05), inhibited the expression of TGF-β1, desmin, FSP-1, and α-SMA ( P  < 0.05), promoted the expression of Nephrin, Podocin, and CD2AP (P < 0.05)., Conclusion: Improving the ability of podocytes to prevent oxidative stress and restoring iron ion homeostasis, can improve Ferroptosis and block epithelial-mesenchymal transition, improve podocyte injury, restore filtration function, and reduce proteinuria in DKD rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Importance: Splenic hilar lymphadenectomy has been recommended for locally advanced proximal gastric cancer (APGC) involving the greater curvature. However, it is unclear whether laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) is associated with a long-term survival benefit for APGC without greater curvature invasion., Objective: To present the 5-year follow-up data from a randomized clinical trial that compared laparoscopic total gastrectomy (D2 group) with D2 plus LSPSHL (D2 + No. 10 group) among patients with resectable APGC., Design, Setting, and Participants: This is a post hoc secondary analysis of a randomized clinical trial that enrolled 536 patients with potentially resectable APGC (cT2-4a, N0 or N+, and M0) without greater curvature invasion from January 5, 2015, to October 10, 2018. All patients were tracked for at least 5 years. The final follow-up was on October 30, 2023., Interventions: Patients were randomly assigned in a 1:1 ratio to the D2 + No. 10 or D2 groups., Main Outcomes and Measures: The 5-year disease-free survival (DFS) and overall survival (OS) rates were measured. Recurrence patterns and causes of death were compared., Results: A total of 526 patients (392 men [74.5%]; mean [SD] age, 60.6 [9.6] years) were included in the modified intent-to-treat analysis, with 263 patients in each group. The 5-year DFS rate was 63.9% (95% CI, 58.1%-69.7%) for the D2 + No. 10 group and 55.1% (95% CI, 49.1%-61.1%) for the D2 group (log-rank P = .04). A statistically significant difference was observed in the 5-year OS between the D2 + No. 10 group and the D2 group (66.2% [95% CI, 60.4%-71.9%] vs 57.4% [95% CI, 51.4%-63.4%]; log-rank P = .03). The No. 10 lymph node exhibited a therapeutic value index (TVI) of 6.5, surpassing that of Nos. 8a (TVI, 3.0), 11 (TVI, 5.8), and 12a (TVI, 0.8). A total of 86 patients in the D2 + No. 10 group (cumulative incidence, 32.7%) and 111 patients in the D2 group (cumulative incidence, 42.2%) experienced recurrence (hazard ratio, 0.72; 95% CI, 0.54-0.95; P = .02). The multivariable competing risk regression model demonstrated that D2 + No. 10 remained an independent protective factor for a lower 5-year cumulative recurrence rate after surgery (hazard ratio, 0.75; 95% CI, 0.56-1.00; P = .05). There was a significant difference in the 5-year cumulative recurrence rate at the No. 10 lymph node area between the 2 groups (D2 + No. 10 group vs D2 group: 0% vs 2.3% [n = 6]; P = .01)., Conclusions: This post hoc secondary analysis of a randomized clinical trial found that laparoscopic total gastrectomy with LSPSHL can improve the prognosis and reduce recurrence for APGC without greater curvature invasion. Future multicenter studies are warranted to validate these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.

Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate., (© 2024. The Author(s).)

Cinnamomum kanehirae Hayata, belonging to Lauraceae family, is an indigenous and endangered species of considerable economic importance in Taiwan. It plays a crucial role as the host for the economically valuable saprotrophic fungus, Taiwanofungus camphorates . However, accurate species identification poses a challenge due to the similarity in morphological features and frequent natural hybridization with closely related species. Acquiring high-quality and pure leaf oils becomes imperative for precise species identification and producing superior goods. In this study, our objective was to establish methodologies for analyzing the chemical composition of leaf essential oils and subsequently apply this knowledge to differentiate among three Cinnamomum species. Gas chromatography-mass spectrometry (GC/MS) was employed to scrutinize the chemical makeup of leaf essential oils from three closely related species: C. kanehirae , C. micranthum , and C. camphora . We utilized Steam Distillation (SD) and steam distillation-solvent extraction (SDSE) methods, with the SDSE-Hexane approach chosen for optimization, enhancing extraction efficiency and ensuring essential oil purity. Through the SDSE-Hexane method, we identified seventy-four compounds distributed across three major classes: monoterpenes hydrocarbons (0.0-7.0 %), oxygenated monoterpenes (3.8-90.9 %), sesquiterpenes hydrocarbons (0.0-28.3 %), and oxygenated sesquiterpenes (1.6-88.1 %). Our findings indicated the presence of more than one chemotype in both C. kanehirae and C. camphora , whereas no specific chemotype could be discerned in C. micranthum . Furthermore, clustering based on chemotypes allowed for the differentiation of samples from the three species. Notably, we demonstrated that the chemical compositions of grafted C. kanehirae remained largely unaffected by the rootstock. Conversely, natural hybrids between C. kanehirae and C. camphora exhibited profiles more closely aligned with C. kanehirae . The optimized extraction method and the chemotype-based classification system established in this study present valuable tools for essential oil preparation, species identification, and further exploration into the genetic variation of Cinnamomum ., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu-Chugn Chiang is the Section Editor of Plant Biology., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC., Methods: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis., Results: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group., Conclusions: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

General anesthetic drugs cause cognitive deficits that persist after the drugs have been eliminated. Astrocytes may contribute to such cognition-impairing effects through the release of one or more paracrine factors that increase a tonic inhibitory conductance generated by extrasynaptic γ-aminobutyric acid type A (GABA A ) receptors in hippocampal neurons. The mechanisms underlying this astrocyte-to-neuron crosstalk remain unknown. Interestingly, astrocytes express anesthetic-sensitive GABA A receptors. Here, we tested the hypothesis that anesthetic drugs activate astrocytic GABA A receptors to initiate crosstalk leading to a persistent increase in extrasynaptic GABA A receptor function in neurons. We also investigated the signaling pathways in neurons and aimed to identify the paracrine factors released from astrocytes. Astrocytes and neurons from mice were grown in primary cell cultures and studied using in vitro electrophysiological and biochemical assays. We discovered that the commonly used anesthetics etomidate (injectable) and sevoflurane (inhaled) stimulated astrocytic GABA A receptors, which in turn promoted the release paracrine factors, that increased the tonic current in neurons via a p38 MAPK-dependent signaling pathway. The increase in tonic current was mimicked by exogenous IL-1β and abolished by blocking IL-1 receptors; however, unexpectedly, IL-1β and other cytokines were not detected in astrocyte-conditioned media. In summary, we have identified a novel form of crosstalk between GABA A receptors in astrocytes and neurons that engages a p38 MAPK-dependent pathway. Brief commentary BACKGROUND: Many older patients experience cognitive deficits after surgery. Anesthetic drugs may be a contributing factor as they cause a sustained increase in the function of "memory blocking" extrasynaptic GABA A receptors in neurons. Interestingly, astrocytes are required for this increase; however, the mechanisms underlying the astrocyte-to-neuron crosstalk remain unknown. TRANSLATIONAL SIGNIFICANCE: We discovered that commonly used general anesthetic drugs stimulate GABA A receptors in astrocytes, which in turn release paracrine factors that trigger a persistent increase in extrasynaptic GABA A receptor function in neurons via p38 MAPK. This novel form of crosstalk may contribute to persistent cognitive deficits after general anesthesia and surgery., Competing Interests: Declaration of Competing Interest All authors have read the journal's policy on disclosure of potential conflicts of interest. Dr. Beverley A. Orser serves as Chair of the Board of Trustees of the International Anesthesia Research Society (San Francisco, CA, USA) and is co-director of the Perioperative Brain Health Centre (Toronto, ON, Canada; http://www.perioperativebrainhealth.com). She is a named inventor on a Canadian patent (2,852,978) and two U.S. patents (9,517,265 and 10,981,954). The patents, which are held by the University of Toronto, are for new methods to prevent and treat delirium and persistent neurocognitive deficits after anesthesia and surgery, as well as to treat mood disorders. Dr. Beverley A. Orser also collaborates on clinical studies that are supported by in-kind software. All of the other authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial., Methods: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern., Results: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05)., Conclusions: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG., Registration Number: NCT02327481 ( http://clinicaltrials.gov )., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes., Methods: The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment., Results: A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264&#95;267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation., Conclusions: Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations., (© 2024. The Author(s).)

Congenital heart defects (CHDs) affect a substantial proportion of patients with Kabuki syndrome. However, the prevalence and type of CHD and the genotype-phenotype correlations in Asian populations are not fully elucidated. This study performed a retrospective analysis of 23 Taiwanese patients with molecularly confirmed Kabuki syndrome. Twenty-two patients presented with pathogenic variants in the KMT2D gene. Comprehensive clinical assessments were performed. A literature review was conducted to summarize the spectrum of CHDs in patients with Kabuki syndrome. In total, 16 (73.9%) of 22 patients with pathogenic KMT2D variants had CHDs. The most common types of CHD were atrial septal defects (37.5%), ventricular septal defects (18.8%), coarctation of the aorta (18.8%), bicuspid aortic valve (12.5%), persistent left superior vena cava (12.5%), mitral valve prolapse (12.5%), mitral regurgitation (12.5%), and patent ductus arteriosus (12.5%). Other cardiac abnormalities were less common. Further, there were no clear genotype-phenotype correlations found. A literature review revealed similar patterns of CHDs, with a predominance of left-sided obstructive lesions and septal defects. In conclusion, the most common types of CHDs in Taiwanese patients with Kabuki syndrome who presented with KMT2D mutations are left-sided obstructive lesions and septal defects.

Objective: This study aimed to evaluate the clinical application and efficacy of a super-low-positioned intestinal decompression tube in the treatment of intestinal obstruction., Methods: A total of 130 patients with postoperative small bowel obstruction were included in this study. The patients were divided into a super-low-positioned intestinal decompression group and a conventional intestinal decompression group. The clinical data, treatment outcomes, and complications were compared between the two groups., Results: The technical success rate of placing the super-low-positioned intestinal decompression tube was 100%, with no intraoperative complications. The patients in the super-low-positioned intestinal decompression group had a significantly shorter hospital stay (8.3 ± 5.2 vs 17.7 ± 13.3, P < 0.001) and a higher non-operative treatment success rate (83.6% vs 57.9%, P = 0.001) compared to the conventional intestinal decompression group. Multivariate logistic regression analysis showed that the placement of a super-low-positioned intestinal decompression tube was an independent protective factor for treatment outcomes (P = 0.001). The hospital stay was significantly shorter in the super-low-positioned intestinal decompression group compared to the conventional group in both successful non-operative treatment patients (6.9 ± 3.0 vs 11.2 ± 7.5, P < 0.001) and failed non-operative treatment patients (16.2 ± 7.4 vs 26.6 ± 14.4, P < 0.001). The super-low-positioned intestinal decompression tube effectively relieved the "Self-strangulation" phenomenon in patients with intestinal obstruction., Conclusion: The super-low-positioned intestinal decompression tube is a safe and effective method for the treatment of intestinal obstruction, with better treatment outcomes and shorter hospital stays compared to conventional intestinal decompression. Further prospective studies are needed to validate these findings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To explore the oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion., Methods: This study is a retrospective cohort study and retrospectively analyzed the clinicopathological data of 128 patients with serosal invasion gastric cancer (cT4NxM0) who received nab-paclitaxel + S-1(SAP) or camrelizumab + nab-paclitaxel + S-1 (C-SAP) regimen and underwent laparoscopy assisted gastrectomy in Fujian Union Hospital from March 2019 to December 2020. The patients were divided into SAP group and C-SAP group. The 2-years overall survival rate, 2-year recurrence free survival rate recurrence rate and initial recurrence time were compared between the two groups., Results: A total of 128 patients were included, including 90 cases in SAP group and 38 cases in C-SAP group. There were no significant differences in age, gender, gastrectomy method, surgical approach, R0 resection, nerve invasion, vascular invasion, total number of harvested lymph nodes, number of positive lymph nodes and major pathologic response (MPR) rate between the two groups (P>0.05). However, the proportion of ypT0, ypN0 and pCR rate in C-SAP group were significantly higher than those in SAP group (P<0.05). The 2-year OS of C-SAP group (80.7%) was higher than that of SAP group (67.8%), and the difference was not statistically significant (P = 0.112); At 2 years after operation, the recurrence rate of C-SAP group (44.3%) was lower than that of SAP group (55.8%) (P = 0.097); Further analysis showed that the average time to recurrence in the C-SAP group was 18.9 months, which was longer than that in SAP group 13.1 months (P = 0.004); The 2-year recurrence free survival rate in C-SAP group was higher than that in SAP group (P=0.076); There was no significant difference in the overall survival time after recurrence between the two groups (P= 0.097)., Conclusion: Camrelizumab combined with neoadjuvant chemotherapy can improve the proportion of ypT0, ypN0 and pCR in patients, while prolonging the initial recurrence time of patients in the C-SAP group, but did not increase the immunotherapy/chemotherapy related side effects and postoperative complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Lin, Lin, Zhong, Lu, Zheng, Xie, Wang, Huang and Li.)

Background This research aims to study the diagnostic patterns, anatomical locations, and age-related trends in pediatric clavicular lesions, filling a gap in pediatric-specific data for these conditions. Methodology A retrospective study of 20 pediatric patients (aged ≤14 years) with clavicular lesions was conducted based on inclusion and exclusion criteria emphasizing confirmed diagnosis and treatment specifics. The diagnostic process relied on open biopsy, followed by excision or curettage and histopathological examination. Results The study primarily involved patients with an average age of 7.1 ± 3.8 years. Eosinophilic granuloma was the most common diagnosis (30% of cases), particularly in the age group of 0-3 years. Clavicular lesions predominantly manifested as either a palpable lump or localized swelling with pain. The medial of the clavicle was the most frequent lesion location. No malignant tumors were found, and the functional outcomes post-treatment were satisfactory. Conclusions Pediatric clavicular lesions exhibit distinct diagnostic and anatomical characteristics compared to adults. Eosinophilic granuloma is significantly prevalent in early childhood, necessitating age-specific diagnostic and therapeutic approaches. The study advocates for multidisciplinary collaboration in the treatment and improved understanding of these lesions, which are vital for pediatric orthopedic oncology., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Jiang et al.)

Background/aim: X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH., Patients and Methods: We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing., Results: The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis., Conclusion: Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Buckwheat green leaves are commonly consumed as functional tea materials due to their various beneficial effects. Although buckwheat green leaves have abundant soluble dietary fibers (SDFs), the information about their structural properties and functional properties remains unknown, largely hindering their applications as functional/health products. Hence, to enhance the usage and application of SDFs from buckwheat green leaves as value-added health products, the structures and biological activities of SDFs derived from different buckwheat green leaves were investigated and compared. Results revealed that SDFs derived from Tartary buckwheat green leaves (TBSDF) and common buckwheat green leaves (CBSDF) were rich in complex pectic-polysaccharides, mainly composing of homogalacturonan (HG) and rhamnogalacturonan I (RG I) pectic domains. Besides, TBSDF had higher proportion of RG I pectic domains than that of CBSDF. Furthermore, the existence of a high content of complex pectic-polysaccharides in TBSDF and CBSDF could contribute to their various biological activities, such as antioxidant, antiglycation, fat/bile acid binding, anticancer, and prebiotic effects. These results can provide some new insights into further development of buckwheat green leaves and related SDFs as value-added health products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear., Methods: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan-Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors., Results: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors., Conclusion: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer., (© 2023. The Author(s).)

Background: Our previous strain-specific systematic review (SR) showed that Lactobacillus reuteri (LR) DSM 17938 reduces necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and time to full feeds (TFF) in preterm infants. Considering progress in the field over the past 6 years, we aimed to update our SR., Methods: SR of randomized controlled trials (RCTs) and non-RCTs was conducted. MEDLINE, Embase, Emcare, Cochrane CENTRAL, and gray literature were searched in June 2023. Primary outcomes were TFF, NEC stage ≥II, LOS, and all-cause mortality. Meta-analysis was performed using random-effects model. Certainty of evidence (CoE) was summarized using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. Trial sequential analysis (TSA) was applied for outcome of NEC in RCTs., Results: Twelve RCTs (n = 2284) and four non-RCTs (n = 1616) were included. Six RCTs and three non-RCTs were new. Meta-analysis of RCTs showed LR significantly reduced TFF (mean difference, -2.70 [95% CI, -4.90 to -1.31] days; P = 0.0001), NEC stage ≥II (risk ratio [RR], 0.57 [95% CI, 0.37-0.87]; P = 0.009; eight RCTs), and LOS (RR, 0.72 [95% CI, 0.54-0.97]; P = 0.03); but not mortality (RR, 0.76 [95% CI, 0.54-1.06]; P = 0.10). TSA showed diversity-adjusted required information size (DARIS) as 3624 for NEC. Overall CoE was "very low." Meta-analysis of non-RCTs showed LR reduced NEC (odds ratio, 0.34 [95% CI, 0.15-0.77]; P = 0.01) but not LOS. LR had no adverse effects., Conclusions: Very low CoE suggests that LR DSM 17938 may reduce NEC and LOS and shorten TFF in preterm infants. Additional RCTs are required to confirm our findings., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Precise optical mode matching is of critical importance in experiments using squeezed-vacuum states. Automatic spatial-mode matching schemes have the potential to reduce losses and improve loss stability. However, in quantum-enhanced coupled-cavity experiments, such as gravitational-wave detectors, one must also ensure that the sub-cavities are also mode matched. We propose what we believe to be a new mode sensing scheme, which works for simple and coupled cavities. The scheme requires no moving parts, nor tuning of Gouy phases. Instead a diagnostic field tuned to the HG20/LG10 mode frequency is used. The error signals are derived to be proportional to the difference in waist position, and difference in Rayleigh ranges, between the sub-cavity eigenmodes. The two error signals are separable by 90 degrees of demodulation phase. We demonstrate reasonable error signals for a simplified Einstein Telescope optical design. This work will facilitate routine use of extremely high levels of squeezing in current and future gravitational-wave detectors.

Background: Patients with glycogen storage disease type Ia (GSDIa) are prone to hypoglycemia. Uncooked cornstarch (CS) is the treatment, but maintaining nighttime blood glucose levels is still difficult., Methods: The study enrolled patients with GSDIa to investigate the benefits of bedtime extended release CS (ER-CS, Glycosade®) versus regular CS. The daytime CS schedule was not altered. A 7-day continuous glucose monitoring (CGM) was performed at the baseline and 12 weeks after using ER-CS. Biochemical profile, sleep quality (Pittsburgh Sleep Quality Index, PSQI), and quality of life (SF-36 questionnaire) were measured at the baseline and 24 weeks after using ER-CS., Results: Nine patients (9 to 33 years of age) were enrolled. Compared with the baseline (80.0 ± 6.33 mg/dL), the 12-week evaluations revealed higher mean morning glucose levels (86.5 ± 8.26 mg/dL, p = 0.015). Twenty-four weeks after the use of bedtime ER-CS, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both decreased (from 69.3 ± 77.8 to 41.1 ± 40.4 U/L and from 78.8 ± 99.6 to 37.8 ± 28.81 U/L, respectively, p = 0.013 for both analyses), and sleep and fasting time both elongated (from 7.8 ± 0.87 to 8.6 ± 1.02 h and from 6.5 ± 1.22 to 7.6 ± 1.02 h, respectively, p = 0.011 for both analyses). The mean PSQI score in the five adult patients decreased significantly (from 5.8 ± 1.29 to 3.0 ± 1.71, p = 0.042)., Conclusion: This study provides evidence of clinically meaningful improvements by shifting only bedtime regular CS to ER-CS in patients with GSDIa. As ER-CS is considerably more expensive than regular CS, this approach presents a cost-effective alternative., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objective: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism., Methods: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D 3 (VD 3 )., Results: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD 3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316)., Significance: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy., (© 2023 International League Against Epilepsy.)

Background: The accuracy of the eighth AJCC ypTNM staging system on the prognosis of gastric cancer (GC) patients after neoadjuvant therapy (NAT) is controversial. This study aimed to develop and validate a novel staging system using the log odds of positive lymph nodes scheme (LODDS)., Methods: A retrospective analysis of 606 GC patients who underwent radical gastrectomy after neoadjuvant therapy was conducted as the development cohort. (Fujian Medical University Affiliated Union Hospital (n = 183), Qinghai University Affiliated Hospital (n = 169), Mayo Clinic (n = 236), Lanzhou University First Hospital (n = 18)). The validation cohort came from the SEER database (n = 1701). A novel ypTLoddsS (ypTLM) staging system was established using the 3-year overall survival. The predictive performance of two systems was compared., Results: Two-step multivariate Cox regression analysis in both cohorts showed that ypTLM was an independent predictor of overall survival of GC patients after neoadjuvant therapy (HR: 1.57, 95% CI: 1.30-1.88, p < 0.001). In the development cohort, ypTLM had better discrimination ability than ypTNM (C-index: 0.663 vs 0.633, p < 0.001), better prediction homogeneity (LR: 97.7 vs. 70.9), and better prediction accuracy (BIC: 3067.01 vs 3093.82; NRI: 0.36). In the validation cohort, ypTLM had a better prognostic predictive ability (C-index: 0.614 vs 0.588, p < 0.001; LR: 11,909.05 vs. 11,975.75; BIC: 13,263.71 vs 13,328.24; NRI: 0.22). The time-dependent ROC curve shows that the predictive performance of ypTLM is better than ypTNM, and the analysis of the decision curve shows that ypTLM achieved better net benefits., Conclusion: A LODDS-based ypTLM staging system based on multicenter data was established and validated. The predictive performance was superior to the eighth AJCC ypTNM staging system., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background: There is limited information about the mortality and neurodevelopmental outcomes of very preterm infants (<32 weeks) with spontaneous intestinal perforation (SIP)., Objective: To explore the association between SIP and neurodevelopmental outcomes and mortality in very preterm infants., Data Sources: Medline, EMBASE, Cochrane Library, EMCARE and MedNar., Study Selection: Databases were searched until September 2021. Studies comparing outcomes of 'SIP' versus 'no SIP or necrotising enterocolitis (NEC)' were included., Data Extraction: Neurodevelopmental outcomes at ≥1 year corrected age were extracted as the main outcome measure. Data were pooled separately for adjusted and unadjusted ORs using the random-effects model. The evidence level was assessed using the GRADE (Grading of Recommendations, Assessments, Development and Evaluations) framework., Results: Eighteen cohort studies (13 606 infants) were included. Meta-analysis of unadjusted ORs showed that SIP was significantly associated with increased odds of mortality, cerebral palsy, composite outcome of death or disability, visual impairment and hearing impairment. However, pooling of adjusted ORs (aOR) found significant associations only for mortality (aOR (95% CI) 2.27 (2.07 to 2.49); I 2 : 0%; four studies (n=10 695)), severe disability (aOR (95% CI) 2.06 (1.38 to 3.08); I 2 : 0%; two studies (n=321)) and composite outcome of 'death or disability' (aOR (95% CI) 2.18 (1.55 to 3.06); I 2 : 0%; two studies (n=321)). The level of evidence was 'low' or 'very low'., Limitations: Lack of information on aORs from many studies., Conclusions: SIP in very preterm infants is associated with higher odds of mortality, severe disability, and death or disability ., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

To compare the short-term outcomes of a new gastrointestinal decompression tube combined with conservative treatment in patients with esophagojejunal anastomotic leakage (EJAL) after total gastrectomy. We retrospectively analyzed the data of 81 patients with EJAL who had undergone total gastrectomy and Roux-en-Y reconstruction at Fujian Medical University Union Hospital between January 2014 and December 2021. The patients were divided into experimental (12 patients with new gastrointestinal decompression tube plus conservative treatment) and control (69 patients with conservative treatment) groups, according to the different treatment methods they received. Anatomic defect size linearly correlated with time to clinical success, hospital stay, and hospital cost in the control group. The two groups showed no significant differences in anastomotic defect size, time of defect after surgery, hospitalization cost, and time of antibiotic use. However, the time to clinical success was significantly shorter in the experimental group than in the control group (16.0 ± 8.3 vs. 23.6 ± 17.8, P = 0.04), as was the length of hospital stay (30.1 ± 6.3 vs. 36.8 ± 16.7, P = 0.017). Furthermore, when the defect size was ≥ 4 mm, the time to clinical success, hospital stay, and hospital cost in the experimental group were lower than those in the control group (P < 0.05). Placement of a new gastrointestinal decompression tube is a safe treatment. When the defect size is ≥ 4 mm, the time to clinical success, length of hospital stay, and hospital cost can be reduced., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Chronic pain is a public health concern throughout the world. Ascertaining and managing its risk factors helps develop well-directed treatment plans and prevention strategies. Phthalates (PAEs) exposure leads to various health problems. The present study aims to explore the potential correlation between urinary PAEs metabolites and chronic pain in adults., Methods: The study population data were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2004 in the United States. Seven urinary PAEs metabolites were used to assess long-term PAEs exposure. The assessment of chronic pain was determined by a self-report questionnaire. Weighted analyses were conducted to consider the complex sampling design. Models were adjusted by demographic data and lifestyle factors. Urinary PAEs metabolites were assessed as both continuous and categorical variables. Tertile 1 was considered as the reference. Stratified analyses were performed by gender and pain site. All data analyses were conducted with STATA, version 15.1. P < 0.05 was considered with statistical significance., Results: A total of 4,196 participants were considered in our final analysis. Chronic pain prevalence reached 52.19% ( n = 2,138) among the participants, with women accounting for a large proportion (57.75% vs. 42.25%). After multivariable logistic regression analysis, a higher prevalence of chronic pain was observed among participants in the third tertile of mono-(2-ethyl)-hexyl phthalate (MEHP) (OR = 1.23, 95% CI = 1.02-1.48, P = 0.034) and mono-benzyl phthalate (MBzP) (OR = 1.28, 95% CI = 1.04-1.58, P = 0.022) in our adjusted model. The logtransformed concentration of MBzP also showed a significant association with chronic pain prevalence (OR = 1.09, 95% CI = 1.01-1.18, P = 0.036) in the adjusted model. In further analysis, the positive correlations of urinary phthalate metabolites with chronic pain remained robust when stratified by gender and chronic pain site., Conclusions: Our findings presented a positive correlation between urinary PAEs metabolites and chronic pain among adult participants, and more causal research should be conducted to ascertain the interactions between the two and to expound their underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jin, Nie, Fan, Yang, Chen, Li and Ju.)

Quinoa leaf is consumed as a promising value-added vegetable in the diet. Although quinoa leaf is rich in soluble dietary fibers, the knowledge regarding their chemical structures and biological activities is still limited, which astricts their application in the functional food industry. Thus, to improve the precise use and application of soluble dietary fibers (SDFs) isolated from quinoa leaves in the food industry, the physicochemical structures and bioactivities of SDFs isolated from different quinoa leaves were systematically investigated. Results indicated that quinoa leaves were rich in SDFs, ranging from 3.30 % to 4.55 % (w/w). Quinoa SDFs were mainly composed of acidic polysaccharides, such as homogalacturonan and rhamnogalacturonan I, which had the molecular weights in the range of 4.228 × 10 4 -7.059 × 10 4 Da. Besides, quinoa SDFs exerted potential in vitro antioxidant activities, lipid and bile acid-adsorption capacities, immunoregulatory activities, and prebiotic effects, which might be partially associated with their molecular mass, content of uronic acid, and content of bound polyphenol. Collectively, these findings are beneficial to better understanding the chemical structures and bioactivities of SDFs extracted from different quinoa leaves, which can also provide a scientific basis for developing quinoa SDFs into functional foods in the food industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: The survival benefit of laparoscopic total gastrectomy combined with spleen-preserving splenic hilar lymphadenectomy (LSTG) for locally advanced proximal gastric cancer (APGC) without invasion into the greater curvature remains uncertain., Objective: To compare the long-term and short-term efficacy of LSTG (D2 + No. 10 group) and conventional laparoscopic total gastrectomy (D2 group) for patients with APGC that has not invaded the greater curvature., Design, Setting, and Participants: In this open-label, prospective randomized clinical trial, a total of 536 patients with clinical stage cT2 to 4a/N0 to 3/M0 APGC without invasion into the greater curvature were enrolled from January 2015 to October 2018. The final follow-up was on October 31, 2021. Data were analyzed from December 2021 to February 2022., Interventions: Eligible patients were randomized to the D2 + No. 10 group or the D2 group., Main Outcomes and Measures: The primary outcome was 3-year disease-free survival (DFS). The secondary outcomes were 3-year overall survival (OS) and morbidity and mortality within 30 days after surgery., Results: Of 526 included patients, 392 (74.5%) were men, and the mean (SD) age was 60.6 (9.6) years. A total of 263 patients were included in the D2 + No. 10 group, and 263 were included in the D2 group. The 3-year DFS was 70.3% (95% CI, 64.8-75.8) for the D2 + No. 10 group and 64.3% (95% CI, 58.4-70.2; P = .11) for the D2 group, and the 3-year OS in the D2 + No. 10 group was better than that in the D2 group (75.7% [95% CI, 70.6-80.8] vs 66.5% [95% CI, 60.8-72.2]; P = .02). Multivariate analysis revealed that splenic hilar lymphadenectomy was not an independent protective factor for DFS (hazard ratio [HR], 0.86; 95% CI, 0.63-1.16) or OS (HR, 0.81; 95% CI, 0.59-1.12). Stratification analysis showed that patients with advanced posterior gastric cancer in the D2 + No. 10 group had better 3-year DFS (92.9% vs 39.3%; P < .001) and OS (92.9% vs 42.9%; P < .001) than those in the D2 group. Multivariate analysis confirmed that patients with advanced posterior gastric cancer could have the survival benefit from No. 10 lymph node dissection (DFS: HR, 0.10; 95% CI, 0.02-0.46; OS: HR, 0.12; 95% CI, 0.03-0.52)., Conclusions and Relevance: Although LSTG could not significantly improve the 3-year DFS of patients with APGC without invasion into the greater curvature, patients with APGC located posterior gastric wall may benefit from LSTG., Trial Registration: ClinicalTrials.gov Identifier: NCT02333721.

We have demonstrated that CDK5RAP3 exerts a tumour suppressor effect in gastric cancer, but its role in regulating tumour-associated macrophages (TAMs) has not yet been reported. Here, we show that CDK5RAP3 is related to the infiltration and polarization of macrophages. It inhibits the polarization of TAMs to M2 macrophages and promotes the polarization of the M1 phenotype. CDK5RAP3 reduces the recruitment of circulating monocytes to infiltrate tumour tissue by inhibiting the CCL2/CCR2 axis in gastric cancer. Blocking CCR2 reduces the growth of xenograft tumours and the infiltration of monocytes. CDK5RAP3 inhibits the nuclear transcription of NF-κB, thereby reducing the secretion of the cytokines IL4 and IL10 and blocking the polarization of M2 macrophages. In addition, the absence of CDK5RAP3 in gastric cancer cells allows macrophages to secrete more MMP2 to promote the epithelial-mesenchymal transition (EMT) process of gastric cancer cells, thereby enhancing the invasion and migration ability. Our results imply that CDK5RAP3 may be involved in the regulation of immune activity in the tumour microenvironment and is expected to become a potential immunotherapy target for gastric cancer., (© 2022. The Author(s).)

Background: Immune checkpoint inhibitors are increasingly used in neoadjuvant therapy for locally advanced gastric cancer. However, the effect of body composition on the efficacy of neoadjuvant therapy has not been reported., Methods: The computed tomography (CT) images and clinicopathological data of 101 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy combined with immunotherapy (NCI) from 2019 to 2021 were collected. The CT image of L3 vertebral body section was selected, and the body composition before and after the neoadjuvant treatment was calculated using the SliceOmatic software, mainly including skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). The relationship between body composition and the efficacy and adverse events of NCI was analyzed., Results: Of the 101 patients, 81 with evaluable data were included in the analysis. Of the included patients, 77.8% were male; the median age of all the patients was 62 years, and the median neoadjuvant therapy cycle was three. After the neoadjuvant therapy, 62.9% of the tumors were in remission (residual tumor cells ≤ 50%), and 37.1% of the tumors had no remission (residual tumor cells>50%). Moreover, 61.7% of the patients had treatment-related adverse events (TRAEs), and 18.5% had immune-related adverse events (irAEs). After neoadjuvant therapy, the body mass index (from 23 to 22.6 cm 2 /m 2 , p=0.042), SAI (from 34.7 to 32.9 cm 2 /m 2 , p=0.01) and VAI (from 32.4 to 26.8 cm 2 /m 2 , p=0.005) were significantly lower than those before treatment, while the SMI had no significant change (44.7 vs 42.5 cm 2 /m 2 , p=0.278). The multivariate logistics regression analysis revealed that low SMI (odds ratio [OR]: 3.23,95% confidence interval [CI]: 1.06-9.81, p=0.047), SMI attenuation (△SMI) ≥ 1.8(OR: 1.45,95%CI: 1.20-3.48, p=0.048), and clinical node positivity (OR: 6.99,95%CI: 2.35-20.82, p=0.001) were independent risk factors for non-remission. Additionally, high SAI is an independent risk factor for irAEs (OR: 14, 95%CI: 1.73-112.7, p=0.013)., Conclusion: Low SMI and △SMI≥1.8 are independent risk factors for poor tumor regression in patients with advanced gastric cancer receiving NCI. Patients with a high SAI are more likely to develop irAEs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Huang, Lin, Lin, Xie, Wang, Lu, Zheng, Huang and Li.)

Background: Millions of people suffer from Alzheimer's disease (AD) and Parkinson's disease (PD) worldwide. Due to their complex pathology, no effective pharmacological treatment has been found to date, despite extensive research. Developing new, effective therapeutic agents to cure these disease remains a major challenge. Although the cause of AD and PD remains illusive, numerous studies indicates that oxidative stress and neuro-inflammation lead to neurodegeneration in the central nervous system and play vital role in AD and PD morbidity and progression. Flavonoids, which are found widely in nature, exhibit anti-oxidative, anti-inflammatory, anti-mutative, anti-microbial, and neuroprotective properties, so have potential to treat these two kinds of diseases., Methods: In this review, we focus on the anti-oxidative and neuroprotective action of flavonoids in attenuating Alzheimer's and Parkinson's disease, and how they might be harnessed in the development of new pharmacological agents to treat these two diseases., Result: Some flavonoid compounds, like hesperidin, naringin, naringenin, tangeretin, nobiletin, silibinin, Epigallocatechin-3-gallate, displayed to be effective in both AD and PD., Conclusion: Considerable studies have demonstrated the anti-AD and anti-PD effects of flavonoids through various in vitro and in vivo models. However, more rigorous studies are needed to be done for flavonoids to develop into effective drugs and apply them to clinical practice., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Objective: To compare the short-term outcomes, surgery burden, and technical performance of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) for gastric cancer (GC)., Summary of Background Data: The impact of robotic systems on total gastrectomy remains obscure., Methods: This prospective study included 50 patients with advanced proximal GC underwent RTG combined with spleen-preserving splenic hilar lymphadenectomy between March 2018 and February 2020. Patients who underwent LTG in the FUGES-002, http://links.lww.com/SLA/C929 study were enrolled to compare the outcomes between RTG and LTG., Results: After propensity score matching, 48 patients in the RTG group and 96 patients in the LTG group were included in the analysis. The RTG group had a lower volume of intraoperative blood loss than the LTG group (38.7 vs 66.4 mL, P = 0.042). Significantly more extraperigastric lymph nodes were retrieved in the RTG group than in the LTG group (20.2 vs 17.5, P = 0.039). The average number of errors was lower in the RTG group than in the LTG group (43.2 vs 53.8 times/case, P < 0.001). The RTG group had a higher technical skill score (30.2 vs 28.4, P < 0.001) and a lower surgery task load index (33.2 vs 39.8, P < 0.001) than the LTG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.6% vs 16.7%, P = 0.748)., Conclusions: In complex total gastrectomy for GC, compared with traditional laparoscopic surgery, robotic surgery provides a technically superior operative environment and reduces surgeon workload at high-volume specialized institutions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Robotic surgery may be advantageous for complex surgery. We aimed to compare the intraoperative and postoperative short-term outcomes of spleen-preserving splenic hilar lymphadenectomy (SPSHL) during robotic and laparoscopic total gastrectomy., Methods: From July 2016 to December 2020, the clinicopathological data of 115 patients who underwent robotic total gastrectomy combined with robotic SPSHL (RSPSHL) and 697 patients who underwent laparoscopic total gastrectomy combined with laparoscopic SPSHL (LSPSHL) were retrospectively analyzed. A 1:2 ratio propensity score matching (PSM) was used to balance the differences between the two groups to compare their outcomes. The Generic Error Rating Tool was used to evaluate the technical performance., Results: After PSM, the baseline preoperative characteristics of the 115 patients in the RSPSHL and 230 patients in the LSPSHL groups were balanced. The dissection time of the region of the splenic artery trunk (5.4 ± 1.9 min vs. 7.8 ± 3.6 min, P < 0.001), the estimated blood loss during SPSHL (9.6 ± 4.8 ml vs. 14.9 ± 7.8 ml, P < 0.001), and the average number of intraoperative technical errors during SPSHL (15.1 ± 3.4 times/case vs. 20.7 ± 4.3 times/case, P < 0.001) were significantly lower in the RSPSHL group than in the LSPSHL group. The RSPSHL group showed higher dissection rates of No. 10 (78.3% vs. 70.0%, P = 0.104) and No. 11d (54.8% vs. 40.4%, P = 0.012) lymph nodes and significantly improved postoperative recovery results in terms of times to ambulation, first flatus, and first intake (P < 0.05). The splenectomy rates of the two groups were similar (1.7% vs. 0.4%, P = 0.539), and there was no significant difference in morbidity and mortality within postoperative 30 days (13.0% vs. 15.2%, P = 0.589)., Conclusion: Compared to LSPSHL, RSPSHL has more advantages in terms of surgical qualities and postoperative recovery process with similar morbidity and mortality. For complex SPSHL, robotic surgery may be a better choice., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: There is insufficient evidence to evaluate the long-term outcomes of robotic radical gastrectomy. The aim of this study was to compare the radical results and long-term outcomes of robotic and laparoscopic radical gastrectomy., Methods: We prospectively collected and retrospectively analyzed the general clinicopathological data of gastric cancer patients treated with robotic radical gastrectomy (RG) and laparoscopic radical gastrectomy (LG) from July 2016 to July 2018 at Fujian Medical University Union Hospital. The RG cohort was matched 1:3 with the LG cohort by using propensity score matching (PSM). The primary endpoints of the study were 3-year overall survival (OS) and 3-year relapse-free survival (RFS)., Results: The study included 221 patients treated with RG and 1106 patients treated with LG for gastric cancer. After PSM, 211 patients were included in the RG cohort, and 663 patients were included in the LG cohort. The 3-year OS rate was 81.0% in the robotic cohort and 79.3% in the laparoscopic cohort (log-rank test, P = 0.516). The 3-year RFS rate was 78.7% in the robotic cohort and 75.6% in the laparoscopic cohort (log-rank test, P = 0.600). In the subgroup analyses, no significant differences were noted between the RG and LG cohorts in terms of 3-year OS and 3-year RFS (all P > 0.05). The therapeutic value index of each lymph node station dissection in the robotic cohort was comparable to that in the laparoscopic cohort., Conclusion: Robotic radical gastrectomy can achieve radical results and long-term outcomes comparable to laparoscopic surgery, and further multicenter prospective studies can be conducted to assess the clinical efficacy of robotic radical gastrectomy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To develop and validate a simple metabolic score (Metabolic score, MS) for use in evaluating the prognosis of gastric cancer (GC) patients and dynamically monitor for early recurrence., Methods: We retrospectively collected general clinicopathological data of patients who underwent radical gastrectomy for GC between September 2012 and December 2017 in the Department of Gastric Surgery of the Fujian Medical University Union Hospital. Using a random forest algorithm to screen preoperative blood indicators into the Least absolute shrinkage and selection operator (LASSO) model, we developed a novel MS to predict prognosis., Results: Data of 1974 patients were used to develop and validate the model. Total cholesterol (TCHO), bilirubin (TBIL), direct bilirubin (DBIL), and 15 other metabolic indicators had significant predictive value for the prognosis using the random forest algorithm. In the overall population, 533 patients (27.0%) had high and 1441 (73%) had low MS status. High MS status was related to tumor progression. The KM curves of 3-year OS and RFS for training set patients showed low MS had a better prognosis than high MS (OS: 79.4% vs 59.7%, P < 0.001; RFS: 76.0% vs 56.2%, P < 0.001)., Conclusions: We have developed and validated MS to predict the long-term survival of GC patients and allow early monitoring of recurrence. This will provide physicians with simple, economical, and dynamic tumor monitoring information., (Copyright © 2022. Published by Elsevier Ltd.)

Background: This study aims to analyze the effect of textbook outcome (TO) on the long-term prognosis and adjuvant chemotherapy (AC) compliance of patients with gastric cancer (GC) in a single institute., Materials and Methods: Consecutive patients who underwent radical gastrectomy with pathological stage I-III at Union Hospital of Fujian Medical University from January 2010 to June 2017 were included. TO was defined as receiving a complete-potentially curative status, ≥15 lymph nodes examined, hospital stay ≤21 days, and freedom from intraoperative and postoperative complications, re-intervention in 30 days, 30-day readmission to the hospital or intensive care unit, and 30-day postoperative mortality., Results: Totally 3993 patients were included, of which 3361 (84.2%) patients achieved TO. The overall, disease-specific, and recurrence-free survival of patients achieving TO were significantly better than those of patients without achieving TO (all P < 0.05). The total number of AC cycles was greater and the interval from surgery to first AC was shorter in the TO group compared with the Non-TO group. Age >65 years old, open surgery, pT3-4 stage, and total radical gastrectomy (TG) were identified as related high-risk factors for failure to achieve TO. Laparoscopic surgery facilitated TO achievement in high-risk groups., Conclusion: TO is a reliable indicator of favorable prognosis of patients with GC and contributes to postoperative chemotherapy compliance. Age ≤65 years old, non-TG, pT1-2 stage, and laparoscopic surgery may promote the achievement of TO., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Yellow water lily ( Nuphar shimadai Hayata) is a critically endangered species in Taiwan. Here, we examined genetic structures of four extant populations, WP, GPa, GPb and GPn, using 39 simple sequence repeat (SSR) markers. Positive genetic correlation was observed within 50 m, beyond which no correlation was detected due to isolation by distance according to Mantel correlogram. This suggests a significant genetic structuring of the species. Besides, multilocus genotype (MLG) analysis revealed that GPa was a panmictic population and the species' putative center of origin. Genetic exchange was observed between GPa and GPb populations, which likely resulted from their geographic proximity. Nevertheless, there was a strong asymmetric migration detected from GPa to WP, but a recent genetic barrier prevented dispersal further northward (WP). Geneland estimated the best number of clusters as K = 2, where WP distinctly separated from the rest of the populations. In STRUCTURE output of K = 3, a third cluster was abundant only in WP. We suggest to consider GPn and WP as separate conservation units, being far from GPa. There is indeed a need to investigate these populations; as predicted, Ne = 1.6 to 3.0 is considered low and that may put the species at risk of extinction.

Electric vehicles (EVs) have been promoted acceleratively to reduce greenhouse gas (GHG) emissions, however, the GHG emission reduction potential of different powertrain EVs has not been investigated thoroughly. In this study, we firstly quantified and compared the GHG emissions of different powertrain vehicles in a life cycle perspective with particular focus on energy and climate consequences, for current and future integrated scenarios, to facilitate carbon reduction assessment for Shanghai. Four major types of EVs were considered. The results show that life cycle total energy consumption and GHG emissions of all EVs are lower than that of gasoline internal combustion engine vehicles (GICEVs), among which battery-powered electric vehicles (BEVs) is the lowest. Compared with GICEVs, the total energy use and GHG emissions of BEVs decrease by 34.2% and 41.7% respectively. As the electrification of vehicle powertrain system innovates, the life cycle emissions of GHG are gradually concentrated to the upstream stage. The sensitivity analysis demonstrates that life cycle GHG emissions of vehicles are most sensitive to the proportion of thermal power than other three parameters (utilization rate of recycled steel, vehicle lifetime and curb weight). The scenario analysis indicates that BEVs present the more favorable carbon emission decline performance over other EVs from a long-term perspective. It is estimated that up to 12.5 million tons of GHG emissions could be reduced under the optimistic scenario in 2050 in Shanghai. In the process of energy conversion from oil to electricity in transport in Shanghai, BEVs should be constantly promoted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Few studies have reported the association between the pattern and time point of recurrence in different groups stratified by age in postoperative survival of patients with gastric cancer., Methods: The clinicopathological data and recurrence data of 2028 patients with GC who underwent curative surgery from January 2010 to March 2015 were enrolled in this study. Patients were grouped according to age: young group (YG) (≤45 years old) (n = 180) and non-young group (OG) (&gt;45 years old) (n = 1848)., Results: A total of 2028 patients were enrolled. The young group had better 5-year OS and DFS than the non-young group. In peritoneal recurrence, the cumulative incidence of recurrence in YG was higher than that in OG (P &lt; 0.001). In distant recurrence, the cumulative incidence of recurrence YG was always lower than that of OG (P = 0.004). Recurrence hazard function varied over time between the two groups:in the peritoneal metastasis, the recurrence hazard for YG was higher and earlier than that of OG and the YG was observed during five years after surgery with two recurrence peaks in 8.5 months and in 41.5 months. In distant recurrence, the recurrence hazard for OG had an earlier and higher single peak than that of YG (6.0 months)., Conclusion: The recurrence characteristics of patients with gastric cancer after curative resection between young group and older group are different. Personalized follow-up strategies should be developed according to the age and time point after operation for the early detection of recurrence and making decision for further treatment., Competing Interests: Declaration of competing interest All authors such as Wen-Wu Qiu,Qi-Yue Chen, Wen-Ze Zheng,Qi-Chen He,Ze-Ning Huang, Jian Wei Xie, Jia-Bin Wang, Jian-Xian Lin, Jun Lu, Long-Long Cao, Mi Lin, Ru-Hong Tu, Ju-Li Lin, Hua-Long Zheng, Guang-Tan Lin,Guo-Sheng Lin,Chao-Hui Zheng,Chang-Ming Huang, Ping Li have no conflict of interest and no potential benefits. The institutional review boards of all the participating institutions approved the study.The authors have no other disclosures to report., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Due to the high technical requirements of laparoscopic radical gastrectomy (LRG), establishing an effective training system to promote clinical technology and operation specifications is necessary. We aimed to evaluate the effect of a national advanced training program for LRG (ATP-LRG)., Materials and Methods: The contents of the training include the following: 1) detailed technique descriptions; 2) prevention and solving of intraoperative complications; 3) live surgery performance; 4) theory and practice of clinical research; 5) comments on trainees' videos; and 6) questions, answers, and discussions. This retrospective before and after study surveyed 875 trainees from January 2015 to October 2020. Endpoints were general surgical skills (GSS), laparoscopic gastrectomy acceptance (LGA), and clinical research possibilities (CRP). The analysis took place in December 2021., Results: The response rate was 70.5% (617/875). ATP-LRG reportedly had a positive impact on the LRG practice of 99.5% (614/617) of trainees. Their GSS (before vs. after: 16.5 ± 3.7 vs. 20.3 ± 3.1, P < 0.001), LGA (4.2 ± 0.9 vs. 4.6 ± 0.7, P < 0.001), and CRP (2.6 ± 1.2 vs. 3.2 ± 1.1, P < 0.001) significantly improved. The improvement in GSS for those with professional titles of associate chief surgeons and below was significantly higher than that for chief surgeons (4.0 ± 3.0 vs 3.3 ± 2.4, P = 0.017), while those of LGA and CRP were not. The annual number of operations before training was negatively correlated with improvement in GSS (P < 0.001, Pearson's correlation coefficient: 0.14). Multivariate logistic regression showed that those with professional titles of associate chief surgeons and below (odds ratio [OR]: 1.719, 95% confidence interval [CI]: 1.038-2.846, P = 0.035), and with annual number of operations before training being <60, (OR: 5.257, 95% CI: 2.573-10.742, P < 0.001) were most prone to high-GSS improvement., Conclusion: The nationwide ATP-LRG facilitates the improvement of trainees' GSS, LGA, and CRP levels. Surgeons with lower professional titles and fewer performed operations are most likely to improve their GSS through training., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup ( P trend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Chen, Chen, Feng, Jin, Zhong, Ju, Zhu, Xiao, Jia, Xu, Yu, Zhang and Lou.)

Fullerene-derived carbons have been demonstrated as effective electrode materials for electrocatalytic reactions. The heteroatoms in the carbon matrix are essential to enhance their electrocatalytic performance but are still challenging for effective doping strategies and understanding their synergistic effect. Herein, we regulate the phosphorus/nitrogen (P/N) doping in the carbon structure based on the control mixing of pyritic acid (PA) with the assembled diamine-C 60  hollow spheres (N@FHS). After pyrolysis, the carbon spheres are shown to have a homogenous distribution of N and P (NP@CHS). The structural and molecular analysis reveals that the doping of P may facilitate the formation of graphitic N in the carbon framework. When used as electrocatalysts for the oxygen reduction reaction (ORR), NP@CHSs exhibit superior oxygen reduction reaction (ORR) performance in contrast to those of fullerene-derived carbon with single N doping and the commercial Pt/C (20 wt%) catalyst. Density functional theory (DFT) studies indicate that P/N-doping promotes the charge transfer in the carbon structure owing to its strong electronegativity. The enhanced ORR activity should be mainly due to the P- and N-coordinated neighboring C sites with the defective fullerene pentagon ring.

Background: Laparoscopic surgical approaches for gastric cancer after neoadjuvant chemotherapy are increasing, yet there is limited evidence of their safety and effectiveness., Methods: This prospective single-armed clinical trial enrolled 80 neoadjuvant chemotherapy patients who underwent laparoscopic gastrectomy. In addition, to better analyze the outcomes of this study, 1:2 propensity score matching was performed, and a contemporaneous historic control group containing 160 laparoscopic gastrectomy patients without neoadjuvant chemotherapy was established., Results: Analyses were performed to compare the neoadjuvant chemotherapy group (n = 80) and the control group (n = 160). The general clinical data of both groups were comparable. The neoadjuvant chemotherapy group showed less intraoperative bleeding (P = .029) and recovered more quickly than the control group (all P < .05). The 2 groups did not exhibit major differences in terms of postoperative complications (P = .679) or severe complications (P = .055). The proportion of patients with ypT4 stage and ypN3 stage disease in the neoadjuvant chemotherapy group totaled 20.7% and 23.8%, respectively, which was significantly lower than that observed in the control group (P < .05). The number of metastatic lymph nodes was 4.8 ± 7.0 in the neoadjuvant chemotherapy group, which was lower than that in the control group (P < .001). In the neoadjuvant chemotherapy group, the major pathological regression rate was 27.5%, while the objective radiologic response rate (complete response + partial response) was 64.0%. In contrast to nonresponding patients, the patients who experienced an objective response had a shorter operation time (P < .001), less intraoperative bleeding (P < .001), and fewer metastatic lymph nodes (P = .005). The short-term effects observed in the nonresponding patients were similar to those observed in the control group., Conclusion: Laparoscopic gastrectomy could achieve improved short-term outcomes through NACT tumor downstaging without increasing the incidence of postoperative complications. Further multicenter and prospective clinical trials are warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: It remains inconclusive whether laparoscopic gastrectomy (LG) has better long-term outcomes when compared with open gastrectomy (OG) for elderly gastric cancer (EGC). We attempted to explore the influence of the immune prognostic index (IPI) on the prognosis of EGCs treated by LG or OG to identify a population among EGC who may benefit from LG., Methods: We included 1539 EGCs treated with radical gastrectomy from January 2007 to December 2016. Propensity score matching was applied at a ratio of 1:1 to compare the LG and OG groups. The IPI based on dNLR ≥ cut-off value (dNLR) and sLDH ≥ cut-off value (sLDH) was developed, characterizing two groups (IPI = 0, good, 0 factors; IPI = 1, poor, 1 or 2 factors)., Results: Of the 528 EGCs (LG: 264 and OG: 264), 271 were in the IPI = 0 group, and 257 were in the IPI = 1 group. In the entire cohort, the IPI = 0 group was associated with good 5-year overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.003) compared to the IPI = 1 group; no significant differences in 5-year OS and PFS between the LG and OG groups were observed. In the IPI = 1 cohort, there was no significant difference in OS or PFS between the LG and OG groups across all tumor stages. However, in the IPI = 0 cohort, LG was associated with longer OS (p = 0.015) and PFS (p = 0.018) than OG in stage II EGC, but not in stage I or III EGC. Multivariate analysis showed that IPI = 0 was an independent protective factor for stage II EGC receiving LG, but not for those receiving OG., Conclusion: The IPI is related to the long-term prognosis of EGC. Compared with OG, LG may improve the 5-year survival rate of stage II EGC with a good IPI score. This hypothesis needs to be further confirmed by prospective studies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The oncologic efficacy of laparoscopic versus open surgery for advanced distal gastric cancer (ADGC) beyond 3 years after surgery remain obscure., Methods: A total of 1256 patients with ADGC at two teaching institutions in China from April 2007 to December 2014 were enrolled. The general data of the two groups were identified to enable rigorous estimation of propensity scores. Restricted mean survival time (RMST) and Landmark analysis was used to compare survival., Results: After matching 461 patients each in the open distal gastrectomy (ODG) and laparoscopic distal gastrectomy (LDG) groups, they were included into analysis. The 3- and 5-year overall survival (OS) and disease-free survival were comparable in two groups. RMST-stratified analysis showed that the 3-year RMST of ODG group was similar to that of LDG group in patients with cT4a (- 1.38 years, p = 0.163) or with cT4a and tumor size > 5 cm, whereas the 5-year RMST had significant differences between groups in cT4a patients(- 8.36 years, P = 0.005) or cT4a and tumor size > 5 cm patients(4.67 years, P = 0.042). In patients with cT4a and tumors > 5 cm, the number of peritoneal recurrences was significantly fewer in the ODG group than in the LDG group (4 vs. 17, P = 0.033), and the peritoneal recurrence time and multiple-site recurrence time were both later in the ODG group., Conclusion: By reducing recurrence, ODG achieves a better survival for GC patients with serous infiltration and tumors larger than 5 cm beyond 3 years after surgery. The present findings can serve as a reference for surgical options and the setting of follow-up time point for clinical studies., (© 2021. The Author(s).)

Objective: To investigate the safety and efficacy of camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion., Method: Two hundred patients with gastric cancer with serosal invasion who received neoadjuvant therapy from January 2012 to December 2020 were retrospectively analyzed. According to the different neoadjuvant therapy regimens, the patients were divided into the following three groups: the SOX group (S-1 + oxaliplatin) (72 patients), SAP group (S-1 + nab-paclitaxel) (95 patients) and C-SAP group (camrelizumab + S-1 + nab-paclitaxel) (33 patients)., Result: The pathological response (TRG 1a/1b) in the C-SAP group (39.4%) was not significantly different from that in the SAP group (26.3%) and was significantly higher than that in the SOX group (18.1%). The rate of ypT0 in the C-SAP group (24.2%) was higher than that in the SAP group (6.3%) and the SOX group (5.6%). The rate of ypN0 in the C-SAP group (66.7%) was also higher than that in the SAP group (38.9%) and the SOX group (36.1%). The rate of pCR in the C-SAP group (21.2%) was higher than that in the SAP group (5.3%) and the SOX group (2.8%). The use of an anti-PD-1 monoclonal antibody was an independent protective factor for TRG grade (1a/1b). The use of camrelizumab did not increase postoperative complications or the adverse effects of neoadjuvant therapy., Conclusion: Camrelizumab combined with nab-paclitaxel plus S-1 could significantly improve the rate of tumor regression grade (TRG 1a/1b) and the rate of pCR in gastric cancer with serosal invasion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Lin, Lin, Zheng, Li, Xie, Wang, Lu, Chen and Huang.)