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Fang Wang,1,&ast; Feng-Hua Wang,2,3,&ast; Kaiyu Sun,4,&ast; Chang Jiang,2,5 Sui Peng,6 Li-Xia Xu,1 Ming Kuang,7 Gui-Fang Guo,2,5,8 Shu-Ling Chen9 1Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Oncology, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 4Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Collaborative Innovation Center for Cancer Medicine, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 6Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 7Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 8VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 9Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Ling Chen; Gui-Fang Guo, Email chenshling@mail.sysu.edu.cn; guogf@sysucc.org.cnIntroduction: Advanced biliary tract carcinoma (BTC) has a poor prognosis and few treatment options. We compared the efficacy of the PD-1 monoclonal antibody (PD-1-mAb) combined regimens with the standard chemotherapy in the first-line and second-line treatment of advanced BTC.Methods: We retrospectively assessed the patients with advanced BTC, who received treatment at the First Affiliated Hospital of Sun Yat-Sen University and the Sun Yat-Sen University Cancer Center. The patients were treated with PD-1-mAb combined regimens or standard chemotherapy at the first line or treated with PD-1-mAb combined regimens or systematic therapy at the second line. Further subgroup analyses were assessed to identify superior regimens.Results: This study included 210 patients. The first-line PD-1-mAb combination group (n = 83) achieved longer median PFS (mPFS) (7.3 vs 5.3 months, p=0.001) and median OS (mOS) (15.6 vs 11.4 months, p=0.002) than the first-line standard chemotherapy group (n=76). Similarly, the second-line PD-1-mAb combination group (n=50) yielded longer mPFS (6.1 vs 2.6 months, p< 0.001) and mOS (11.7 vs 7.2 months, p=0.008) than the second-line systematic therapy group (n=51). Subgroup analyses showed that the PD-1-mAb combined with TKI group achieved better mPFS than the chemotherapy group whether in the first-line (HR = 0.468, p=0.005) or the second-line setting (HR = 0.45, p=0.009), but did not achieve superiority in mOS (both p> 0.05). Compared with the chemotherapy group, the PD-1-mAb combined with chemotherapy group achieved longer mOS (HR = 0.53, p=0.023) in the first-line setting and longer mPFS in the second-line setting (HR = 0.54, p=0.044).Conclusion: The PD-1-mAb combination therapy is superior to the standard chemotherapy in advanced or unresectable BTC, whether as a first-line or second-line treatment. Among the combination therapy, both the PD-1-mAb combined with TKI and combined with standard chemotherapy were promising options for advanced BTC patients.Keywords: biliary tract carcinoma, PD-1-mAb, PD-1 plus anti-angiogenesis TKI, PD-1 plus chemotherapy, the first-line chemotherapy, the second-line chemotherapy

Lu-Ping Yang,1 Zi-Xian Wang,1 Ming-Ming He,1 Hao-Xiang Wu,1 Shu-Qiang Yuan,2 Wei Wang,2 Ying Jin,1 Chao Ren,1 Zhi-Qiang Wang,1 Feng-Hua Wang,1 Yu-Hong Li,1 Feng Wang,1 Rui-Hua Xu11Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China; 2Department of Gastric and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of ChinaBackground: The benefit of palliative gastrectomy for patients with metastatic gastric cancer (mGC) is controversial, and suitable candidates for surgery and treatment strategies remain unclear. The present study aimed to investigate the efficacy of palliative gastrectomy plus chemotherapy among patients with mGC and to identify the potential patients for such treatment using real-world data.Methods: A dataset of 236 patients with mGC diagnosed at the Sun Yat-Sen University Cancer Center from January 1, 2006 to December 31, 2012 were analyzed retrospectively. The cohort comprised 80 patients who had palliative gastrectomy plus chemotherapy (SC) and 156 patients who had chemotherapy only (CO). Propensity score matching (PSM) was employed to minimize the influence of confounders.Results: The median overall survival of the SC group was significantly better than that of the CO group (Before PSM: 17.0 months vs 12.0 months, P=0.038; after PSM: 17.0 months vs 13.0 months, P=0.017). In the multivariate analysis, SC (Before PSM: hazard ratio (HR) =0.68, P=0.023; after PSM: HR =0.64, P=0.021) was favored for better survival after adjustment for sex, age, year of diagnosis, primary tumor location, and tumor grade. Total gastrectomy (P=0.026) was associated with worse survival for the SC group. The significant survival advantage of SC over CO was retained in patients with single organ metastasis (P=0.016), peritoneal seedings (P=0.039), and those receiving taxane-based chemotherapy (P=0.011).Conclusion: SC could improve the overall survival of patients with mGC as compared with CO. The chemotherapy regimen and type of resection were proven to influence efficacy. Patients who received taxane-based regimens might be suitable for palliative gastrectomy.Keywords: first-line chemotherapy, metastatic gastric cancer, palliative gastrectomy, propensity score matching, survival

OBJECTIVES: Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However there is no standard second-line treatment. This study was designed to evaluate the efficacy and safety of a gemcitabine and vinorelbine combination (GV) in patients with metastatic NPC previously treated with platinum-based chemotherapy. METHODS: A total of 61 patients with metastatic NPC after prior platinum-based chemotherapy were enrolled. Gemcitabine (1000mg/m(2)) and vinorelbine (25mg/m(2)) were administered intravenously on Day 1 and Day 8 every 3weeks. RESULTS: In this study, the overall response rate was 37.7% (95% CI, 25.5-49.9%) one complete response (1.6%) and 22 partial responses (36.1%). The median progression-free survival was 5.2months (95% CI, 3.4-7.0months) and the median overall survival was 14.1months (95% CI, 11.1-17.1months). Grade 3/4 toxicity including leucopenia (19.7%), neutropenia (18%), anemia (4.9%) and thrombocytopenia (6.5%) were tolerable. Univariate and multivariate analyses indicated age and salvage treatment after failure of GV treatment were independently significant prognostic factors. CONCLUSION: Our preliminary result shows gemcitabine and vinorelbine combination is effective and safe for the patients with advanced NPC pretreated with platinum-based chemotherapy. Further clinical study is warranted. [ABSTRACT FROM AUTHOR]

Background: Adenovirus are the important pathogen of pediatric severe pneumonia. The aim of this study is to analyze the infection, subtype and distribution of adenovirus in autopsied pulmonary tissue of fatal pneumonia in infants and children, and the relationships between adenovirus infection and respiratory illness in South China. Methods: Nested PCR was performed on DNA extracted from autopsied lung tissue from patients who died of severe pneumonia, and the positive nested PCR products were cloned and sequenced. The adenovirus in autopsied pulmonary tissue was also analyzed by immunohistochemistry assay in a blind way. Results: In the 175 autopsied pulmonary tissues, the positive percentage of adenovirus was 9.14% (16/175) and 2.29% (4/175) detected with nested PCR and immunohistochemistry, respectively. There are three cases of adenovirus serotype 3, twelve cases of adenovirus serotype 4 and one case of serotype 41 determined by sequencing of the cloned positive nested PCR products. Conclusion: Adenovirus is an important cause of severe pneumonia, and these data suggest that adenovirus serotype 4 might be an important pathogen responsible for the fatal pneumonia in Guangzhou, South China. [ABSTRACT FROM AUTHOR]

Background and Purpose: To investigate the impact of radiotherapy (RT) on the risk of secondary pelvic neoplasms (SPN) and the survival outcomes of patients following a diagnosis of female patients with genital neoplasm(FGN)., Materials and Methods: Utilizing SEER databases, this study involved 102,895 patients from nine oncology centers, spanning 1990 to 2015. We employed the Fine-Gray competing risks regression methodology to chart the trajectory of SPN development and used the Kaplan-Meier method to calculate the 10-year overall survival rates., Results: This study included 25,774 patients in the RT group and 77,121 in the non-radiotherapy (NRT) group. The cumulative incidence rate of SPN was 5.10 % in the RT group and 3.42 % in the NRT group. The RT group showed a significantly higher incidence of bladder cancer (adjusted hazard ratio [HR]: 1.75; 95 % confidence interval [CI]: 1.43-2.14; P < 0.05), colon cancer (adjusted HR: 1.32; 95 % CI: 1.16-1.49; P < 0.05), and rectal cancer (adjusted HR: 1.34; 95 % CI: 1.10-1.65; P < 0.05) compared to the NRT group. After propensity score matching, patients in the RT group who developed bladder cancer had significantly reduced 10-year survival rates compared to patients with primary pelvic tumors (P = 0.01)., Conclusion: RT is identified as an independent risk factor for the development of SPN in patients with FGN. Patients with FGN who undergo RT demonstrate a significant increase in the risk of developing secondary neoplasms, specifically bladder cancers, and experience a reduction in 10-year survival rates., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hepatic ischemia/reperfusion (HI/R) presents significant challenges in surgical liver transplantation and hepatic ischemic shock, with few effective clinical preventive measures available. This study explores the potential protective effects and underlying mechanisms of phosphocreatine (PCr) in the context of HI/R. We established an in vitro ischemia/reperfusion model using hepatocellular carcinoma HepG2 cells and normal liver L02 cells. For in vivo assessments, C57BL/6 mice were subjected to the HI/R model to evaluate the impact of PCr on liver protection. PCr pretreatment significantly improved liver cell survival rates, maintained mitochondrial membrane potential (MMP), reduced apoptosis, and alleviated oxidative damage and inflammatory responses. Importantly, PCr exerted its protective effects by downregulating TLR4 and activating the Akt signaling pathway, which suppressed inflammation, mitigated oxidative stress, inhibited apoptosis, and modulated key biomarkers, including ALT, AST, IL-6, IL-1β, TNF-α, SOD, MDA, and reactive oxygen species (ROS). Western blot analyses demonstrated PCr's anti-inflammatory effects through the regulation of UCP2, Cyp-D, Cyt-C, and PGC-1α, thereby preserving mitochondrial structure and function, maintaining MMP, and regulating membrane pores. Transmission electron microscopy further highlighted PCr's role in sustaining mitochondrial integrity. In conclusion, our findings suggest that PCr helps maintain mitochondrial homeostasis by intervening in the TLR4 inflammatory pathway and activating the Akt signaling pathway, ultimately reducing liver injury. This study offers new insights and potential treatment strategies for HI/R, providing valuable guidance for future clinical applications., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

TaMTPs belong to metal tolerance proteins (MTPs) family in common wheat and have significant potential to address the "hidden hunger" caused by inadequate dietary intake of a key micronutrient (Zn). In this study, a total of 33 MTP members in Triticum aestivum were identified, among which six TaMTP1-likes were closely related to Arabidopsis thaliana MTP1 and were designated as TaMTP1-A/B/D and TaMTP1.1-A/B/D. When heterologously expressed in yeast mutants, TaMTP1-likes complemented their hypersensitivity to Zn and Co, and three of the most metal-resistant members, TaMTP1-A, TaMTP1-D and TaMTP1.1-B, were selected for further subcellular localization and functional experiment in Arabidopsis and rice. The results showed that all three proteins were localized in the vacuole membrane, that TaMTP1-D was more resistant to Zn and less resistant to Co than other TaMTP1-like members, and that TaMTP1-D was expressed at a higher level in the endosperm than other members. All results reveal that the use of TaMTP1-D for biofortification can substantially increase the content of Zn in the edible part of wheat and avoid the overaccumulation of Co, suggesting that TaMTP1-D is a potential Zn biofortifier / bioreinforcement., 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 © 2024. Published by Elsevier B.V.)

Objective: To investigate the current comorbidity status among hypertension, diabetes, and dyslipidemia in residents aged 35-75 years in Tianjin and to explore the main influencing factors to provide a scientific basis for the prevention and treatment of chronic disease comorbidity. Methods: From June 2019 to November 2023, 10 districts (Hedong, Hexi, Dongli, Beichen, Nankai, Xiqing, Wuqing, Baodi, Jizhou, and Binhai New District) in Tianjin were selected as the project sites. The community and natural village was used as the primary sampling unit, and each project site selected the screening sites by cluster random sampling method. Residents aged 35-75 who lived in the screening sites for 6 months and above were surveyed by questionnaire, physical examination, and biochemical tests. The chi-square test, analysis of variance, and multivariate unconditional logistic regression analysis were used for statistical analysis. Age-standardized prevalence was based on the data of the sixth national census. Results: A total of 146 832 participants were included in this study, including 61 994 males (42.22%) and 84 838 females (57.78%), with an age of (56.83±8.84) years. The number of people with only one disease was 55 485 (37.79%), the number of people with two diseases was 36 942 (25.16%), and the number of people with three diseases was 9 683 (6.59%). The prevalence of hypertension combined with dyslipidemia was the highest (17.23%), and the standardized prevalence were 14.44%. The prevalence rates of three diseases and hypertension combined with diabetes was 6.59% and 4.98%, respectively, and the standardized prevalence was 5.42% and 4.11%, respectively. The prevalence of diabetes combined with dyslipidemia was 2.95%, and the standardized prevalence was 2.45%. Multivariate unconditional logistic regression analysis showed that advanced age (65- 75 years old: OR =2.69, 95% CI : 2.28-3.18), overweight/obesity (overweight: OR =2.21, 95% CI : 2.02-2.41; obesity: OR =4.50, 95% CI : 4.03-5.02), daily smoking ( OR =1.96, 95% CI : 1.72-2.24), regular and heavy drinking ( OR =1.63, 95% CI : 1.18-2.27), family history of hypertension/diabetes/hyperlipidemia (family history of hypertension: OR =81.17, 95% CI : 74.68-88.22; family history of diabetes: OR =15.26, 95% CI : 13.71-16.99; family history of hyperlipidemia: OR =7.13, 95% CI : 5.92-8.59), tea drinking (occasional tea drinking group: OR =1.74, 95% CI : 1.52-2.00; frequent tea drinking group: OR =2.23, 95% CI : 1.92-2.59) were risk factors for the comorbidity of hypertension, diabetes and dyslipidemia (all P <0.05), while higher education level was a protective factor (senior high school/technical secondary school: OR =0.79, 95% CI : 0.72-0.86; college/bachelor's degree and above: OR =0.60, 95% CI : 0.53-0.68, all P <0.001). Conclusions: The comorbidity rate of hypertension, diabetes, and dyslipidemia is high in residents aged 35-75 years in Tianjin. It is necessary to strengthen the co-management of blood pressure, blood glucose, and blood lipid in key populations with old age, overweight/obesity, junior high school education or below, daily smoking, daily drinking, occasional or frequent tea drinking, and family history of hypertension/diabetes/dyslipidemia, and promote a healthy lifestyle.

Photodetectors and gas sensors are vital in modern technology, spanning from environmental monitoring to biomedical diagnostics. This paper explores the UV detection and gas sensing properties of a zinc oxide (ZnO) nanorod array (ZNA) grown on silver nanowire mesh (AgNM) using a hydrothermal method. We examined the impact of different zinc acetate precursor concentrations on their properties. Results show the AgNM forms a network with high transparency (79%) and low sheet resistance (7.23 Ω/□). A sol-gel ZnO thin film was coated on this mesh, providing a seed layer with a hexagonal wurtzite structure. Increasing the precursor concentration alters the diameter, length, and area density of ZNAs, affecting their performance. The ZNA-AgNM-based photodetector shows enhanced dark current and photocurrent with increasing precursor concentration, achieving a maximum photoresponsivity of 114 A/W at 374 nm and a detectivity of 6.37 × 10 14 Jones at 0.05 M zinc acetate. For gas sensing, the resistance of ZNA-AgNM-based sensors decreases with temperature, with the best hydrogen response (2.71) at 300 °C and 0.04 M precursor concentration. These findings highlight the potential of ZNA-AgNM for high-performance UV photodetectors and hydrogen gas sensors, offering an alternative way for the development of future sensing devices with enhanced performance and functionality.

Objective: To summarize the clinical, pathological and molecular characteristics of various types of pediatric glioma, and to explore the differences in the morphology and clinical significance among various types of pediatric glioma. Methods: Based on the fifth edition of the World Health Organization classification of central nervous system tumors, this study classified or reclassified 111 pediatric gliomas that were diagnosed at Guangzhou Medical University Affiliated Women and Children's Medical Center from January 2020 to June 2023. The clinical manifestations, imaging findings, histopathology, and molecular characteristics of these tumors were analyzed. Relevant literature was also reviewed. Results: The 111 patients with pediatric glioma included 56 males and 55 females, with the age ranging from 10 days to 13 years (average age, 5.5 years). Clinically, manifestations presented from 5 days to 8 years before the diagnosis, including epilepsy in 16 cases, increased intracranial pressure in 48 cases and neurological impairment in 66 cases. MRI examinations revealed tumor locations as supratentorial in 43 cases, infratentorial in 65 cases, and spinal cord in 3 cases. There were 73 cases presented with a solid mass and 38 cases with cystic-solid lesions. The largest tumor diameter ranged from 1.4 to 10.6 cm. Among the 111 pediatric gliomas, there were 6 cases of pediatric diffuse low-grade glioma (pDLGG), 63 cases of circumscribed astrocytoma glioma (CAG), and 42 cases of pediatric diffuse high-grade glioma (pDHGG). Patients with pDLGG and CAG were younger than those with pDHGG. The incidence of pDLGG and CAG was significantly lower in the midline of the infratentorial region compared to that of pDHGG. They were more likely to be completely resected surgically. The pDLGG and CAG group included 4 cases of pleomorphic xanthoastrocytoma, showing histological features of high-grade gliomas. Among the high-grade gliomas, 13 cases were diffuse midline gliomas and also showed histological features of low-grade glioma. Immunohistochemical studies of H3K27M, H3K27ME3, p53, ATRX, BRAF V600E, and Ki-67 showed significant differences between the pDLGG and CAG group versus the pDHGG group ( P <0.01). Molecular testing revealed that common molecular variations in the pDLGG and CAG group were KIAA1549-BRAF fusion and BRAF V600E mutation, while the pDHGG group frequently exhibited mutations in HIST1H3B and H3F3A genes, 1q amplification, and TP53 gene mutations. With integrated molecular testing, 2 pathological diagnoses were revised, and the pathological subtypes of 35.3% (12/34) of the pediatric gliomas that could not be reliably classified by histology were successfully classified. Conclusions: There are significant differences in clinical manifestations, pathological characteristics, molecular variations, and prognosis between the pDLGG, CAG and pDHGG groups. The integrated diagnosis combining histology and molecular features is of great importance for the accurate diagnosis and treatment of pediatric gliomas.

Background: The transcription product of tramtrack (ttk) is an important transcription factor which plays many roles in the regulation of the development, differentiation and chromosome recombination of organisms. Few studies have been reported on the specific functions of ttk in other insects except Drosophila melanogaster. Our aims are to reveal the ttk effects on development and courtship of male rice pest brown planthopper (BPH), Nilaparvata lugens., Results: In this study, we first assayed spatiotemporal expression of ttk in BPH, then treated the fourth nymphs of BPH with dsttk. We found most individuals died before emerging to adults, the adult eclosion rate was only 18.89%. No courtship behavior was found in individuals injected with dsttk. Further research showed that the main frequency of courtship vibration signal (CVS) 431.3 Hz in the individuals injected with dsttk was significantly higher than 223 Hz in the individuals injected with dsGFP, and female adults nearly had no response to the 431.3 Hz CVS., Conclusion: We found that about 81% of the 4-instar nymphs of BPH treated with dsttk died before they emerged as adults, the successfully emerged adults emitted the 431.3 Hz CVS to which female adults did not respond and lost the ability of courtship. This was first finding about the functions of ttk in rice planthopper and illustrated the potential of ttk as target for RNAi to control rice planthopper. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Li-rich layered oxides are promising candidates for high-capacity Li-ion battery cathode materials. In this study, we employ first-principles calculations to investigate the effect of F doping on Li-rich Li 2 MnO 3 layered cathode materials. Our findings reveal that both Li 2 MnO 3 and Li 2 MnO 2.75 F 0.25 exhibit significant volume changes (greater than 10%) during deep delithiation, which could hinder the cycling of more Li ions from these two materials. For Li 2 MnO 3 , it is observed that oxygen ions lose electrons to compensate for charge during the delithiation process, leading to a relatively high voltage plateau. After F doping, oxidation occurs in both the cationic (Mn) and anionic (O) components, resulting in a lower voltage plateau at the beginning of the charge, which can be attributed to the oxidation of Mn 3+ to Mn 4+ . Additionally, F doping can somewhat suppress the release of oxygen in Li 2 MnO 3 , improving the stability of anionic oxidation. However, the increase of the activation barriers for Li diffusion can be observed after F doping, due to stronger electrostatic interactions between F - and Li + , which adversely affects the cycling kinetics of Li 2 MnO 2.75 F 0.25 . This study enhances our understanding of the impact of F doping in Li 2 MnO 3 based on theoretical calculations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Phyllachora ( Phyllachoraceae , Phyllachorales ) species are parasitic fungi with a wide global distribution, causing tar spots on plants. In this study, we describe three newly discovered species: Phyllachora chongzhouensis , Phyllachora neidongensis , and Phyllachora huiliensis from Poaceae in China. These species were characterized using morphological traits and multi-locus phylogeny based on the internal transcribed spacer region (ITS) with the intervening 5.8S rRNA gene, the large subunit of the rRNA gene (LSU), and the 18S ribosomal RNA gene (SSU). Three known species of P. chloridis , P. graminis , and P. miscanthi have also been redescribed, because, in reviewing the original references of P. chloridis , P. graminis , and P. miscanthi , these were found to be relatively old and in Chinese or abbreviated. In addition, the illustrations were simple. In molecular identification, the ITS sequence is short, while the ITS, LSU, and SSU are incomplete. Therefore, this study provides new important references for the redescription of three known species and provides further evidence for the identification of new taxa.

Background: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors., Patients and Methods: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials., Results: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%., Conclusions: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cholangiocarcinoma is the most common malignancy of the biliary tree and has a poor prognosis. Adenocarcinoma is the most common pathological type of cholangiocarcinomas, but rare squamous, adenosquamous, and mucinous variants have been reported without adequate clinical data., Case Summary: This report describes a rare case of primary squamous cell carcinoma (SCC) of the intrahepatic bile duct. The patient was admitted with a tumor in the hepatic caudate lobe with no obvious clinical symptoms. Examination revealed hepatitis B surface antigen positivity, a slight increase in alfa-fetoprotein to 16.34 ng/mL, and an irregular slightly heterogeneous enhancing lesion in the hepatic caudate lobe, which was initially thought to be hepatocellular carcinoma. Laparoscopic resection was performed, and the final pathology suggested a rare primary SCC of the intrahepatic bile duct. Immunohistochemistry indicated positivity for villin, partial positivity for p63, and negativity for hepatocyte, CK7, CK8, CK19, and CK20. The Ki-67 index was approximately 60%. The patient received six cycles of Tegio chemotherapy. A new lesion was detected in the liver after 15 months. The surgery was performed, and the patient was followed-up at a local hospital. To date, no new lesions have been observed., Conclusion: Surgery is the first choice for resectable lesions, and combined chemotherapy based on pathology is essential for increasing overall survival., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Arthrobotrys flagrans, a nematode-eating fungus, is an effective component of animal parasitic nematode biocontrol agents. In the dried formulation, the majority of spores are in an endogenous dormant state. This study focuses on dormant chlamydospore and nondormant chlamydospore of A. flagrans to investigate the differences in cyclic adenosine monophosphate (cAMP) and protein content between the two types of spores. cAMP and soluble proteins were extracted from the nondormant chlamydospore and dormant chlamydospore of two isolates of A. flagrans. The cAMP Direct Immunoassay Kit and Bradford protein concentration assay kit (Coomassie brilliant blue method) were used to detect the cAMP and protein content in two types of spores. Results showed that the content of cAMP in dormant spores of both isolates was significantly higher than that in nondormant spores (p < 0.05). The protein content of dormant spores in DH055 bacteria was significantly higher than that of nondormant spores (p < 0.05). In addition, the protein content of dormant spores of the SDH035 strain was slightly higher than that of nondormant spores, but the difference was not significant (p > 0.05). The results obtained in this study provide evidence for the biochemical mechanism of chlamydospore dormancy or the germination of the nematophagous fungus A. flagrans., (© 2024 Wiley‐VCH GmbH.)

Background: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial., Methods: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis., Results: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029)., Conclusions: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy., (© 2024. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P  <  0.001 ; EFS: P  <  0.001 ) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P  <  0.001 ; EFS: P  <  0.001 ) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20 high CD138 low expression had a consistently favorable OS and EFS compared with those with CD20 low CD138 high expression in both the training and validation cohorts ( P  <  0.0001 and P  <  0.01 , respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokine‒cytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma., 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.)

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8 + T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported., Methods: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM)., Results: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02)., Conclusions: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy., (© 2023. Society of Surgical Oncology.)

Background: Disorders of the gut microbiome could be responsible for the progression of multiple organ dysfunction syndrome. In this study, we examined the effect of esmolol on the gut microbiome in a rat model of sepsis induced by cecal ligation and puncture (CLP)., Methods: The animals (n = 32) were randomly divided into 3 groups: Sham group (sham operation + normal saline treatment, n = 8), CLP group (cecal ligation and puncture + normal saline treatment, n = 12), and CLP + ESM group (cecal ligation and puncture + esmolol treatment, n = 12). After 24 h, feces in the colon were collected for 16S rRNA gene sequencing and nitric oxide analysis. In addition, colon was removed for immunohistochemical staining of inducible nitric oxide synthase (iNOS)., Results: Four rats in the CLP group and two rats in the CLP + ESM group died. The abundance of Lactobacillus in the CLP + ESM group was higher than CLP group (P = 0.048). In the linear discriminant analysis effect size analysis, Norank f Muribaculaceae, Escherichia-Shigella and Lactobacillus were the predominant bacteria in the Sham group, CLP group and CLP + ESM group, respectively. The iNOS expression in colonocytes stained by brown in the CLP group were much more than Sham group (P = 0.001). Compared to CLP group, the iNOS expression in colonocytes reduced after esmolol treatment (P = 0.013). The concentration of nitric oxide in colon feces was different in Sham group, CLP group and CLP + ESM group (1.31 ± 0.15μmmol/l vs. 1.98 ± 0.27μmmol/l vs. 1.51 ± 0.14μmmol/l, P = 0.001). In addition, the concentration of nitric oxide in CLP group was higher than Sham group (P = 0.001) or CLP + ESM group (P = 0.001)., Conclusions: Esmolol increased the fecal abundance of Lactobacillus in a rat model of sepsis. Moreover, esmolol reduced the iNOS expression of colonocytes and the nitric oxide concentration of colon feces., (© 2024. The Author(s).)

The organic anion transporter 3 (OAT3), an important renal uptake transporter, is associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OAT3 inhibitors with little toxicity in natural products, especially flavonoids, in reducing OAT3-mediated AKI is of great value. The five strongest OAT3 inhibitors from the 97 flavonoids markedly decreased aristolochic acid I-induced cytotoxicity and alleviated methotrexate-induced nephrotoxicity. The pharmacophore model clarified hydrogen bond acceptors and hydrophobic groups are the critical pharmacophores. These findings would provide valuable information in predicting the potential risks of flavonoid-containing food/herb-drug interactions and optimizing flavonoid structure to alleviate OAT3-related AKI.

The chlamydospores of Duddingtonia flagrans are an essential survival and reproductive structure and also an effective ingredient for the biocontrol of parasitic nematodes in livestock. In this study, entering and exiting dormancy conditions and predatory activity of the fungal chlamydospores were conducted. During this fungal growth process, the cultivation time is negatively correlated with spore germination rates. After the spores were processed by vacuum drying for 168 h, their germination rate dropped to 0.94%. In contrast, the percentage of living spores remained 54.82%, suggesting that the spores entered structural dormancy in the arid environment. Meanwhile, the efficacies of the spore against Haemonchus contortus larvae were 93.05% (0 h), 92.19% (16 h), 92.77% (96 h), and 86.45% (168 h), respectively. After dormant spores were stored at 4°C, -20°C, and 28°C (RH90 ~ 95%) for 7 days, their germination rate began to increase significantly (p < 0.05). For in vitro predation assay under the condition of 28°C (RH90 ~ 95%), the predation rate was significantly higher on the 7th day after incubation than that on the 3rd day (p < 0.05). During the period when spores were stored at room temperature for 8 months, their germination rate decreased in the first 5 months and then increased slowly to reach a peak in the 7th month. However, the reduction rate of H. contortus L3 in feces captured by spores remained above 71% for the first 7 months. These results will help us increase the end products yield and the quality of biological control of parasitic nematodes in livestock., (© 2023 Wiley-VCH GmbH.)

In word learning, learners need to identify the referent of words by leveraging the fact that the same word may co-occur with different sets of objects. This raises the question, what do children remember from "in the moment" that they can use for cross-situational learning? Furthermore, do children represent pictures of familiar animals versus drawings of non-existent novel objects as potential referents differently? This study examined these questions by creating learning scenarios with only two potential referents, requiring the least amount of memory to represent all co-present objects. Across three experiments (n > 250) with 4- and 6-year-old children, children reliably selected the intended referent from learning at test, though the learning of novel objects was better than familiar objects. When asked for a co-present object, children of all ages in the study performed at chance in all of the conditions. We discuss the developmental differences in cross-situational word learning capabilities with regard to representing different stimuli as potential referents. Importantly, all children used a propose-but-verify procedure for learning novel words even in the simplest of the learning scenarios given repeated exposure., (© 2023 John Wiley & Sons Ltd.)

Background: Systemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory factors are associated with short - and long-term outcomes has not been reported., Methods: This study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups., Results: Ultimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005)., Conclusion: There were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC., (© 2024. The Author(s).)

Objective: To investigate the clinical efficacy of the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia. Methods: A retrospective case series study was conducted. Clinical data were collected from patients who underwent the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia at Eye Hospital of Shandong First Medical University from February 2017 to February 2022. During the procedure, the superior rectus and lateral rectus muscles were fully separated. A longitudinal blunt incision was made in the central muscle belly extending posteriorly to 12-14 mm from the muscle insertion. The temporal half of the superior rectus muscle and the upper half of the lateral rectus muscle belly were transposed and secured to the contralateral muscle insertion. Simultaneously, medial rectus muscle recession was performed. Follow-up visits were conducted at 1 week, 1 month, 3 months, and 6 months postoperatively. Patients' ocular alignment, eye movements, improvement in compensatory head posture, objective degrees of strabismus using synoptophore, changes in extraocular muscles and globe position on orbital CT scan were recorded. Surgical complications were also documented. Results: Five patients (8 eyes) were included in this study, including 4 females (7 eyes) and 1 male (1 eye), with an average age of (63±11) years and an average axial length of (34.58±2.25) mm. The medial rectus muscle recession during surgery was (7.6±2.3) mm. Preoperatively, all patients had esotropia with a horizontal range of+15°to+45° and a vertical range of+15°to+45°. Significant limitations in lateral and upward gaze were observed, with a degree of restriction ranging from-3 (-4 to-1). Three patients with bilateral involvement and one patient with unilateral involvement exhibited significant compensatory head postures. One patient with unilateral involvement had no compensatory head posture. Preoperative orbital CT scans indicated nasal displacement of the superior rectus muscle and inferior displacement of the lateral rectus muscle, with the eyeball herniating from the muscle cone. At the 6-month follow-up, all patients achieved nearly orthophoric alignment. Objective degrees of horizontal strabismus ranged from-4°to+7°, and vertical strabismus ranged from 0°to +6°, as determined by synoptophore examination. Eye movements significantly improved, with a degree of restriction of-1 (-2 to-1) for lateral gaze and-2 (-3 to-1) for upward gaze. Compensatory head postures disappeared, and orbital CT scans indicated the eyeball was located within the muscle cone. There were no severe complications such as anterior segment ischemia, muscle adhesions, disease recurrence, secondary glaucoma, or globe penetration. Conclusion: The preliminary clinical outcomes of the modified Yokoyama procedure with extraocular muscle transposition for high myopic eyes with restrictive esotropia are promising.

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro . Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors have the following competing interests. The technology transfer office of National Chung Hsing University has received consultancy, speaker fees, and research grants on behalf of H-LS from Duogenic StemCells Corporation and Hualien Tzu Chi Medical Center. F-HW, C-YH, and C-IS are employees of Duogenic StemCells Corporation. F-HW, C-YH, C-IS, H-LS, and C-LL are shareholders of Duogenic StemCells Corporation. Y-HC, M-HH, S-CK, Y-HK, C-HC, and D-WCC have no conflict of interest with respect to the research, authorship, and publication of this article. Patents, products in development, and marketing products are associated with this research.

The morphological and structural differences of different types of chlamydospore of Arthrobotrys flagrans, a nematophagous fungus, were studied under light microscope and electron microscope to provide a reference for the biological control of parasitic nematodiasis. In this study, A. flagrans isolate F088 dormant chlamydospore and nondormant chlamydospore were selected as the research objects. The structural differences of these spores were observed by optical microscopy through lactol cotton blue, Trypan blue, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. FunXite -1, 4',6-diamidino-2-phenylindole, and calcofluor white staining were used to observe the metabolic activity, cell wall, and nucleus differences of the two types of spores under fluorescence microscope. Ultrastructure of the two kinds of spores was observed using scanning electron microscope (SEM) and transmission electron microscope (TEM). Since lacto phenol cotton blue, trypan blue staining cannot distinguish dormant spores from dead spores, MTT assay was performed. Fluorescence microscopy observation showed that the cytoplasmic metabolic activity of nondormant spores was stronger than that of dormant spores. The nucleus of dormant spores was bright blue, and their fluorescence was stronger than that of nondormant spores. The cell wall of nondormant spores produced stronger yellow-green fluorescence than that of dormant spores. Ultrastructural observation showed that there were globular protuberances on the surface of the two types of spores but with no significant difference between them. The inner wall of dormant spore possesses a thick zona pellucida with high electron density which was significantly thicker than that of nondormant spores, and their cytoplasm is also changed. In this study, the microstructure characteristics of dormant and nondormant chlamydospores of A. flagrans fungi were preliminarily clarified, suggesting that the state of cell wall and intracellular materials were changed after spores entered to dormancy., (© 2023 Wiley-VCH GmbH.)

One of the first problems in language learning is to segment words from continuous speech. Both prosodic and distributional information can be useful, and it is an important question how the two types of information are integrated. In this paper, we propose that the distinction between input (the statistical properties of the syllable sequence), and intake (how learners perceptually represent the syllable sequence) is a useful framework to integrate different sources of information. We took a novel approach, observing how a large number of syllable sequences were segmented. These sequences had the same transitional probability information for finding word boundaries but different syllables in them. We found large variability in the performance of the segmentation task, suggesting that factors other than the statistical properties of sequences were at play. This variability was explored using the input/intake asymmetry framework, which predicted that factors that shaped the representation of different syllable sequences could explain the variability of learning. We examined two factors, the saliency of the rhythm in these syllable sequences and how familiar the novel word forms in the sequence were to the existing lexicon. Both factors explained the variance in the learnability of different sequences, suggesting that processing of the sequences shaped learning. The implications of these results to computational models of statistical learning and broader implications to language learning were discussed., (Copyright © 2023. Published by Elsevier B.V.)

Maize is an important food crop in the world, but the yield and quality of maize have been significantly reduced due to the impact of insect pests. In order to address this issue, the cry1Ah gene was subjected to error-prone PCR for mutagenesis, and subsequently, the mutant cry1Ah-1 gene was introduced into maize inbred line GSH9901 callus using the Agrobacterium-mediated method. The T2 generation transformed plants were obtained by subculture, and 9 transgenic positive plants were obtained by molecular detection which was carried out by PCR, qRT-PCR, Bt gold-labeled immunoassay test strips, Western blot and ELISA. It was found that the Cry1Ah-1 gene could be transcribed normally in maize leaves, of which OE1 and OE3 had higher relative expression levels and could successfully express proteins of 71.94 KD size. They were expressed in different tissues at the 6-leaf stage, heading stage and grain-filling stage, and could ensure the protection of maize from corn borer throughout the growth period. The biological activities of OE1 and OE3 were tested indoors and in the field, and the results showed that in indoors, the corn borer that fed on OE1 and OE3 corn leaves had a mortality rate of 100 % after 3 days; in the field, OE1 and OE3 had strong insecticidal activity against corn borer, reaching a high resistance level. In conclusion, the transgenic cry1Ah-1 maize has a strong insecticidal effect on corn borer, and has a good prospect of commercialization., 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. Published by Elsevier Ltd.)

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors with unpredictable evolution and with a recurrence or metastasis rate of 10-40%. Current medical treatments for relapsed SFTs remain ineffective. Here, we identify potential therapeutic targets and risk factors, including IDH1 p.R132S, high PD-L1 expression, and predominant macrophage infiltration, suggesting the potential benefits of combinational immune therapy and targeted therapy for SFTs. An integrated risk model incorporating mitotic count, density of Ki-67+ cells and CD163+ cells, MTOR mutation is developed, applying a discovery cohort of 101 primary non-CNS patients with negative tumor margins (NTM) and validated in three independent cohorts of 210 SFTs with the same criteria, and in 36 primary CNS SFTs with NTM. Compared with the existing models, our model shows significantly improved efficacy in identifying high-risk primary non-CNS and CNS SFTs with NTM for tumor progression.Our findings hold promise for advancing therapeutic strategies and refining risk prediction in SFTs., (© 2023. The Author(s).)

Parapharyngeal infection is a well-known disease of otorhinolaryngologists. Rapid onset, short duration, severe symptoms, and manifestations such as sore throat and dysphagia are common characteristics treated primarily by surgical incision and drainage. Traditional surgical approaches encompass endoscopic transoral/nasal, transparotid, transcervical, or a combination thereof. We report a novel technique of nasal endoscopic incision and drainage transnasal retropterygoid approach to an upper parapharyngeal abscess. This report presents a case of a 14-year-old man presented with severe right neck and head pain, who was found to have an upper parapharyngeal abscess during a nasal endoscopic parapharyngeal exploration via a retropterygoid approach. The intraoperative frozen section revealed chronic mucosal inflammation and mild to moderate dysplasia of the squamous epithelium, but no carcinoma., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Whether and when to monitor the amount of anti-factor Xa (aFXa) activity in critically ill patients with complex diseases to prevent venous thromboembolism (VTE) remain unclear. This study is a randomised controlled trial to investigate the effect of aFXa level monitoring on reducing VTE and to establish a new method for accurately preventing VTE in critically ill patients with low-molecular-weight heparin (LMWH)., Methods and Analysis: A randomised controlled trial is planned in two centres with a planned sample size of 858 participants. Participants will be randomly assigned to three groups receiving LMWH prophylaxis at a 1:1:1 ratio: in group A, peak aFXa levels will serve as the guide for the LMWH dose; in group B, the trough aFXa levels will serve as the guide for the LMWH dose; and in group C, participants serving as the control group will receive a fixed dose of LMWH. The peak and trough aFXa levels will be monitored after LMWH (enoxaparin, 40 mg, once daily) reaches a steady state for at least 3 days. The monitoring range for group A's aFXa peak value will be 0.3-0.5 IU/mL, between 0.1 and 0.2 IU/mL is the target range for group B's aFXa trough value. In order to reach the peak or trough aFXa levels, groups A and B will be modified in accordance with the monitoring peak and trough aFXa level. The incidence of VTE will serve as the study's primary outcome indicator. An analysis using the intention-to-treat and per-protocol criterion will serve as the main outcome measurement., Ethics and Dissemination: The Xuanwu Hospital Ethics Committee of Capital Medical University and Peking University First Hospital Ethics Committee have approved this investigation. It will be released in all available worldwide, open-access, peer-reviewed publications., Trial Registration Number: NCT05382481., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A flexible, non-enzymatic glucose sensor was developed and tested on a polyethylene terephthalate (PET) substrate. The sensor's design involved printing Ag (silver) as the electrode and utilizing mixtures of either gold-copper oxide-modified reduced graphene oxide (Au-CuO-rGO) or gold-copper oxide-modified reduced graphene oxide-multi-walled carbon nanotubes (Au-CuO-rGO-MWCNTs) as the carrier materials. A one-pot synthesis method was employed to create a nanocomposite material, consisting of Au-CuO-rGO mixtures, which was then printed onto pre-prepared flexible electrodes. The impact of different weight ratios of MWCNTs (0~75 wt%) as a substitute for rGO was also investigated on the sensing characteristics of Au-CuO-rGO-MWCNTs glucose sensors. The fabricated electrodes underwent various material analyses, and their sensing properties for glucose in a glucose solution were measured using linear sweep voltammetry (LSV). The LSV measurement results showed that increasing the proportion of MWCNTs improved the sensor's sensitivity for detecting low concentrations of glucose. However, it also led to a significant decrease in the upper detection limit for high-glucose concentrations. Remarkably, the research findings revealed that the electrode containing 60 wt% MWCNTs demonstrated excellent sensitivity and stability in detecting low concentrations of glucose. At the lowest concentration of 0.1 μM glucose, the nanocomposites with 75 wt% MWCNTs showed the highest oxidation peak current, approximately 5.9 μA. On the other hand, the electrode without addition of MWCNTs displayed the highest detection limit (approximately 1 mM) and an oxidation peak current of about 8.1 μA at 1 mM of glucose concentration.

Epstein‒Barr virus (EBV)-associated gastric cancer (GC) manifests an intriguing immunotherapy response. However, the cellular basis for EBV-imprinted tumour immunity and on-treatment response remains undefined. This study aimed to finely characterize the dynamic tumour immune contexture of human EBV (+) GC treated with immunochemotherapy by longitudinal scRNA-seq and paired scTCR/BCR-seq. EBV (+) GC exhibits an inflamed-immune phenotype with increased T-cell and B-cell infiltration. Immunochemotherapy triggers clonal revival and reinvigoration of effector T cells which step to determine treatment response. Typically, an antigen-specific ISG-15 + CD8 + T-cell population is highly enriched in EBV (+) GC patients, which represents a transitory exhaustion state. Importantly, baseline intratumoural ISG-15 + CD8 + T cells predict immunotherapy responsiveness among GC patients. Re-emerged clonotypes of pre-existing ISG-15 + CD8 + T cells could be found after treatment, which gives rise to a CXCL13-expressing effector population in responsive EBV (+) tumours. However, LAG-3 retention may render the ISG-15 + CD8 + T cells into a terminal exhaustion state in non-responsive EBV (+) tumours. In accordance, anti-LAG-3 therapy could effectively reduce tumour burden in refractory EBV (+) GC patients. Our results delineate a distinct implication of EBV-imprinted on-treatment T-cell immunity in GC, which could be leveraged to optimize the rational design of precision immunotherapy., (© 2023. West China Hospital, Sichuan University.)