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Chong-Rui Xu,1* Huan Lin,1,2* Jian Su,1 Xu-Chao Zhang,1 Yi-Sheng Huang,3 Xue-Ning Yang,1 Qing Zhou,1 Jin-Ji Yang,1 Wen-Zhao Zhong,1 Yi-Long Wu11Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China; 2The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Affiliated Zhongshan Hospital of Guangdong Medical University, Zhongshan, Guangdong, People’s Republic of China*These authors contributed equally to this work Purpose: Besides the smoking and occupational exposures, heritable factors have been proven to be a risk factor for lung cancer by several population-based studies, which would misestimate the risk of lung cancer.Patients and methods: To quantify the magnitude of the high risk of lung cancer with family history, we performed a case-based study with 1373 enrolled individuals, which may be more accurate than a population-based study.Results: Risk of lung cancer was higher in people with lung cancer family history than in the control group (OR 2.50, p

Coronary microembolization (CME) is defined as atherosclerotic plaque erosion, spontaneous rupture, or rupture of the plaque while undergoing interventional therapy resulting in the formation of tiny emboli that obstruct the coronary microcirculatory system. For percutaneous coronary intervention, CME is a major complication, with a periprocedural incidence of up to 25%. Recent studies have demonstrated that regulatory cell death (RCD) exerts a profound influence on CME through its modulation of inflammatory responses, oxidative stress, cell death, and angiogenesis. RCD, including apoptosis, autophagy, and pyroptosis, is a unique class of genetically highly regulated death patterns pervasive in instances of coronary microembolization. The aim of this review is to summarize the currently known molecular mechanisms underlying CME. Further investigations of the RCD mechanisms may unravel new avenues for the prevention and treatment of CME., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objectives: In recent years, with the advancement of sublobar resection, A safe, painless method for locating peripheral pulmonary nodules is required. Previously, an alternative method of arterial watershed localization was been introduced to remedy the shortcomings of preoperative CT-guided localization or other methods for locating pulmonary nodules, but its technical limitations were discovered during clinical application. Therefore, we innovated a technique to localize non-subpleural nodules using basin analysis of the target vein and validated its feasibility and safety., Methods: Retrospective analysis of surgical cases of pulmonary nodules smaller than 2 cm in our center. Comparison of vein watershed locational method (V-WALM) and CT-guided percutaneous puncture localization wedge dissection based on locating success rate, mean operation duration, mean intraoperative bleeding and median postoperative stay, mean postoperative drainage and mean drainage tube indwelling time., Results: V-WALM and CT-guided localization were used for localized resection of pulmonary nodules in 50 patients each. The localization success rates were 94.0% for V-WALM and 90.0% for CT-guided localization, respectively, with no statistical difference. There was also no statistical difference in patient population distribution between the two groups. The operation time was 95.5 ± 26.4 min for V-WALM and 94.3 ± 37.5 min for CT-guided with no statistical difference, and there was no statistical difference in intraoperative bleeding, postoperative drainage and drainage tube indwelling time. And the lymph node simpling rate of V-WALM was 48.0% much higher than 24% in the localization group., Conclusions: This study demonstrates that the V-WALM is a safe and feasible intraoperative localization method for peripheral lung nodules. It provides a high-precision, fast and minimally invasive approch of intraoperative localization., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Helicobacter pylori is increasingly resistant to antibiotics, significantly lowering eradication rates and posing a major public health challenge. This study investigated the distribution of antibiotic-resistant phenotypes and genotypes of H. pylori in Hainan Province. It determined the minimum inhibitory concentrations (MICs) of six antibiotics using the E-test method and detected resistance genes via Sanger sequencing. Furthermore, we compared resistance detection based on phenotypic analysis and whole genome sequencing (WGS) across 19 clinical isolates of H. pylori . A total of 140 H. pylori strains were isolated. The resistance rates to levofloxacin (LEV), clarithromycin (CLA), and metronidazole (MTZ) were 37.9%, 40.0%, and 93.6%, respectively. Notably, only 3.3% of the strains were susceptible to all six antibiotics. Multidrug-resistant strains accounted for 25.0% of the total, with no resistance detected to amoxicillin (AMX), tetracycline (TET), or furazolidone (FR) during the study period. Genotypic resistance to CLA and LEV showed near-perfect concordance with phenotypic resistance, with Kappa values of 0.910 and 0.938, respectively. Although all isolates were phenotypically sensitive to TET, 16 exhibited a mutation in the 16S rRNA gene (A926G). All strains harboring the R16H/C mutation and truncated rdxA were resistant to metronidazole, demonstrating a specificity of 100%. Therefore, FR, AMX, and TET are recommended as suitable empirical treatment options for H. pylori infections in this region. Genotypic analysis provides a reliable method for predicting resistance to CLA and LEV. WGS proves to be a valuable tool for identifying novel resistance loci in H. pylori and contributes to the phylogenetic classification of strains., 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 Lv, Li, Zhang, Chen, Chen, Wang, Yang, Gao, Zeng, Xiong, Huang, Huang, Zhang, Chen and Bai.)

Cancer stands as a predominant cause of mortality across the globe. Traditional cancer treatments, including surgery, radiotherapy, and chemotherapy, are effective yet face challenges like normal tissue damage, complications, and drug resistance. Biomaterials, with their advantages of high efficacy, targeting, and spatiotemporal controllability, have been widely used in cancer treatment. However, the biocompatibility limitations of traditional synthetic materials have restricted their clinical translation and application. Natural cell-inspired biomaterials inherently possess the targeting abilities of cells, biocompatibility, and immune evasion capabilities. Therefore, cell-inspired biomaterials can be used alone or in combination with other drugs or treatment strategies for cancer therapy. In this review, we first introduce the timeline of key milestones in cell-inspired biomaterials for cancer therapy. Then, we describe the abnormalities in cancer including biophysics, cellular biology, and molecular biology aspects. Afterwards, we summarize the design strategies of cell-inspired antitumor biomaterials. Subsequently, we elaborate on the application of antitumor biomaterials inspired by various cell types. Finally, we explore the current challenges and prospects of cell-inspired antitumor materials. This review aims to provide new opportunities and references for the development of antitumor cell-inspired biomaterials., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Wenzhi Song reports financial support was provided by International Cooperation Project of the Jilin Department of Science and Technology. If there are other authors, they 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 Published by Elsevier Ltd.)

Temperature-responsive metamaterials have remarkable shape-morphing ability during thermal energy conversion. However, integrating the thermal shape programmability, wide-working temperature range, fast temperature response, and actuation into metamaterials remains challenging. Here, we introduce using thermostat metal strips to assemble metamaterials with desirable and balanced temperature-responsive properties, and we systematically investigate the thermal deformation performance. Achieving 70 to 80% of the designed strain requires only 5 seconds of heating. A thermal strain of around 30% is achieved for the assembled metamaterials, surpassing other bimetallic metamaterials by a magnitude of 100 to 200. The actuation capacity of thermostat metal strips exceeds 26 times their weight. Further, by leveraging the highly programmable thermal deformation, the tuneable bandgap range is 3847 to 40,000 hertz. These fully integrated mechanical performances in the multiphysics have great application potential, for example, as soft actuators and soft robots in intelligent structure systems, vibration isolation and noise reduction in hypersonic vehicles, and unique thermal deformation in precision instruments.

This study investigates the enhancement of diesel degradation in contaminated soil through the synergistic effects of functional microbiomes and phytoremediation, emphasizing increased enzyme activity. The approach integrates a hydrogen-producing microbiome (HMb) with phytoremediation techniques. Observations revealed changes in soil conditions, including increases in moisture levels from 12.5% to 20% and a shift in pH from 6.9 to an alkaline range of 8.0-8.5 due to the treatment. Organic matter content also improved, supporting microbial activity. These modifications were closely monitored to evaluate their impact on microbial growth and enzyme activity. The findings showed that total petroleum hydrocarbons (TPH) in diesel-contaminated soil decreased by 78.1% using the combined HMb and phytoremediation method. This decrease was markedly higher than the 30.4% achieved through water drenching and the 30.9% with HMb alone. Central to this success were Clostridium sp. and Sporolactobacillus sp., which played essential roles in hydrocarbon degradation. Improved soil conditions supported an increase in microbial populations, with bacterial counts peaking at 6.0 x 10 11 by day 4, enhancing degradation. Additionally, Bermuda grass survival rates increased to 35% by day 35. In the HMb and planting combination, amylase activity peaked at 100% by day 10, significantly aiding degradation, although it later decreased to 1% by day 35. This research presents a robust strategy for diesel-contaminated soil remediation, highlighting significant advancements in microbial growth and degradation efficiency., 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 Elsevier Ltd. All rights reserved.)

Background: Numerous systematic reviews and meta-analyses have been published that evaluate the association between periodontal disease and systemic diseases, many of which address similar topics. Moreover, their quality requires assessment. Therefore, we performed a cross-sectional analysis to examine the evidence on the relationship between periodontal disease and systemic diseases., Methods: The PubMed, Embase, Web of Science, and the Cochrane Library databases were systematically searched to identify relevant systematic reviews and meta-analyses. Only studies that considered periodontal disease as the exposure factor and various systemic diseases as the outcome were included. The basic characteristics and pertinent data from the selected studies were extracted. The modified version of A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) was employed for quality assessment, while R software was used for statistical analysis., Results: Among the 212 relevant systematic reviews and meta-analyses, 57 were finally included in our analysis. These studies involved 75 diseases and 81 disease-related outcomes, with cancer (19/81) being the most frequently addressed topic. Of the 81 outcomes, 67 demonstrated a significant association. Notably, the highest risk estimate was found for head and neck cancer [odds ratio (OR) = 3.17, 95% confidence interval (CI) 1.78 - 5.64], while the lowest was observed for premature rupture of the amniotic sac [relative risk (RR) = 1.10, 95% CI 1.08 - 1.12]. The methodological quality ratings indicated that approximately 71.93% of included studies were classified as "Critically low", with another 17.54% rated as "Low", and only about 10.53% categorized as "Moderate"., Conclusions: Periodontal disease significantly elevates the risks associated with 15 cancer-related, 8 cardiovascular-related, 8 metabolic-related, and 5 neurological-related outcomes. However, the overall methodological quality of existing systematic reviews and meta-analyses is generally suboptimal and requires enhancement to generate higher-quality evidence in the future., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Streptococcus pyogenes is a common gram-positive bacterium, belonging to group A Streptococcus (GAS), and is responsible for causing a range of clinical conditions. Brain abscess caused by GAS is uncommon in pediatric infectious diseases, and GAS brain abscess without acute infectious symptoms has been rarely reported., Case Presentation: We present a case of one GAS brain abscess in a previously healthy child with unusual clinical manifestations of decreased muscle strength in the left limbs. The right frontal lobe mass lesion was resected using a microscope-based neuronavigation system. A sole defectively beta-hemolytic Streptococcus pyogenes was isolated from the lesion. The patient's peripheral blood whole-exome and the pathogen's whole-genome sequencing were performed respectively, revealing a heterozygous mutation in the interferon regulatory factor-8 (IRF8) gene in the patient and lack of hyaluronic acid capsules in Streptococcus pyogenes (genotype emm22). The patient eventually recovered after prompt surgical drainage of the abscess and appropriate antibiotic treatment., Conclusions: It is important to pay attention to Streptococcus pyogenes brain abscesses with mild clinical manifestations. Upon reviewing all the cases of pediatric GAS brain abscess reported in the published literature, we discovered that early diagnosis and treatment are crucial factors that impact the prognosis of GAS brain abscess., Competing Interests: Declarations Ethics approval and consent to participate Study approval and ethical clearance were obtained from the Children’s Hospital, Zhejiang University School of Medicine. Written informed consent was obtained from the guardian of the child and all the participants for participation before data collection. All methods were performed following the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication Written informed consent was obtained from the guardian of the child and all the participants for publication of medical images were taken from the patient. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: EGFR tyrosine kinase inhibitor (TKI) is the standard adjuvant treatment for patients with stages IB to IIIA EGFR -mutated NSCLC. Nevertheless, adapting this approach to include a molecular residual disease (MRD)-guided de-escalation strategy warrants further investigation., Methods: From January 2019 to December 2022, 71 patients with stages I to III NSCLC and EGFR (exon 19 deletion or L858R) mutations were enrolled in this observational study. A total of 375 blood samples were analyzed using the MRD_Navigator assay. Among them, 27 patients suspended EGFR TKI treatment based on undetectable MRD and were thus included in the adaptive, de-escalation group., Results: Overall, the sensitivity of longitudinal MRD was 86.2%. Only four patients (11.8%) recurred with longitudinal undetectable MRD, indicating a negative predictive value of 88.2%. Of the patients who had detectable MRD after surgery, nine subsequently received EGFR TKI treatment, with only one (11.1%) achieving persistent circulating tumor DNA clearance post-EGFR TKI. Furthermore, 22 patients with stages IB to III disease who had previously suspended their TKI treatment based on undetectable MRD were included in the adaptive group, with an average duration of TKI 3.9 (range: 0-35.0) months. The 2-year disease-free survival rate of these 22 patients was 80.2%, and the median was not reached. Five patients (n = 5 of 22, 22.7%) had disease recurrence during the period of drug cessation but were stable under EGFR TKI treatment until the latest follow-up. Two patients remained in complete remission., Conclusions: Our initial findings underscore the potential of an adaptive, de-escalation approach to adjuvant EGFR TKIs based on circulating tumor DNA-MRD monitoring., Competing Interests: Dr. Zhou declares receiving speaker fees from 10.13039/100004325AstraZeneca and 10.13039/100004337Roche. Dr. Zhong declares receiving speaker fees from AstraZeneca and Roche. Dr. Wu declares receiving speaker fees from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Taenia multiceps is a neglected parasite having veterinary and public health importance. The predilection sites of the parasite larva (Coenurus cerebralis) are brain (cerebral coenurosis) and subcutaneous (non-cerebral coenurosis). There is a dearth of data regarding molecular characterization of T. multiceps and even fewer population structure-based studies on T. multiceps. The current study was conducted to provide epidemiological information regarding the global population structure of the parasite. The NCBI GenBank database was accessed to download the sequences of cox1 gene, which were further subjected to PopArt software to construct median-joining networks. The DnaSp software was used to compute neutrality and diversity indices. Host and region-wise indices of neutrality and diversity were also computed. There were 166 gene sequences found in the NCBI database. Followed by removal of short gene sequences, 143 were considered to perform bioinformatic analyses. A total of 30 haplotypes with 46 mutations and 23 parsimony informative sites were found. High diversity (Hd = 0.889, π = 0.01186) and negative but statistically insignificant neutrality indices (Tajima's D = -1.57659, Fu's Fs = -10.552) were found. Region-wise results revealed highest haplotype diversities in isolates from KSA (Hd = 1.00) followed by Greece and Italy (Hd = 0.962), and China (Hd = 0.931). Host-wise data analysis showed an overall negative Tajima's D value and there exists highest haplotype diversity in cattle (Hd = 1.00) followed by dogs (Hd = 0.833), sheep (Hd = 0.795) and goats (Hd = 0.788). The findings of the study indicate that the population diversity of T. multiceps will increase worldwide as shown by high diversity and negative neutrality indices. The findings of the study significantly add-in to the existing bank of knowledge about population structure of T. multiceps. We recommend conducting more studies employing different genetic markers to better comprehend the epidemiology of the parasite., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the work, the 1/2 order subharmonic wave of two coupling cavitation bubbles is investigated numerically via Fourier spectrum analysis. By analyzing the dynamics of bubble, we find that the mutual interaction between bubbles can affect the appearance of 1/2 order subharmonic. The results of parameter dependence show that the intensity of 1/2 order subharmonic would be promoted or inhibited with the increase of mutual interaction. The higher the driving amplitude or the smaller the distance between bubbles, the stronger the mutual interaction is, and also the greater the promotion or suppression of the 1/2 order subharmonic is. Moreover, while the 1/2 order subharmonic occurs, the energy of bubble would alternate between two different peaks, and the temperature inside bubble has a similar fluctuation while the bubble collapses. This qualitative analysis suggests that the bubble's dynamics for multi-bubble case is complex. Understanding the generation of subharmonic of bubble's dynamics is of great significance for helpful applying of cavitation bubble., 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.)

Purpose: Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE)., Patients and Methods: This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification., Results: The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set., Conclusion: For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Lu et al.)

Astrocytes play significant roles in regulating the central stress response. Chronic stress impairs the structure and function of astrocytes in many brain regions such as media prefrontal cortex (mPFC) in multiple neuropsychiatric conditions, but the astrocytic dynamics on the timescale of behavior remains unclear. Here, we recorded mPFC astrocytic activity in freely behaving mice and found that astrocytes are activated immediately by different aversive stimuli. Astrocyte specific GCaMP6s calcium indicator were virally expressed in mPFC astrocytes and fiber photometry experiments revealed that astrocytes are activated by tail-restraint (TRT), foot shock (FS), open arm exploration, stressor of height, predator odor and social defeat (SD) stress. ΔF/F analyses demonstrated that an unpredictable stimulus such as elevated platform stress (EPS) at the initial encounter induced the most intense and rapid changes in astrocytic calcium activity, while a predictable 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) stimulus resulted in the weakest response with a longer peak latency. In TRT, FS or SD test, a somatic stimulus led to higher average calcium activity level and faster average peak latency in repeated trails. Similar to TMT stimulus, astrocytic calcium activity in elevated plus maze (EPM) test exhibited a smaller average change in amplitude and the longest peak latency during open arm exploration. Moreover, astrocytic calcium activity exhibited different changes across behavioral states in SD tests. Our findings show that mPFC astrocytes exhibit distinct patterns of calcium activity in response to various negative stimuli, indicating that the dynamic activity of astrocytes may reflect the stress-related behavioral state under different stimulus conditions., 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., (© 2024 The Authors. Published by Elsevier Inc.)

Background: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression., Methods: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS., Results: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed., Conclusion: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals., (© 2024. The Author(s).)

Background: Currently, there are no optimal biomarkers available for distinguishing patients who will respond to immune checkpoint inhibitors (ICIs) therapies. Consequently, the exploration of novel biomarkers that can predict responsiveness to ICIs is crucial in the field of immunotherapy., Methods: We estimated the proportions of 22 immune cell components in 10 cancer types (6,128 tumors) using the CIBERSORT algorithm, and further classified patients based on their tumor immune cell proportions in a pan-cancer setting using k-means clustering. Differentially expressed immune genes between the patient subgroups were identified, and potential predictive biomarkers for ICIs were explored. Finally, the predictive value of the identified biomarkers was verified in patients with urothelial carcinoma (UC) and esophageal squamous cell carcinoma (ESCC) who received ICIs., Results: Our study identified two subgroups of patients with distinct immune infiltrating phenotypes and differing clinical outcomes. The patient subgroup with improved outcomes displayed tumors enriched with genes related to immune response regulation and pathway activation. Furthermore, CCL5 and CSF2 were identified as immune-related hub-genes and were found to be prognostic in a pan-cancer setting. Importantly, UC and ESCC patients with high expression of CCL5 and low expression of CSF2 responded better to ICIs., Conclusion: We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies., (© 2024. The Author(s).)

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs., Competing Interests: Declaration of interests Y.-L.W. has received honoraria from AstraZeneca, Eli Lilly, Roche, Pierre Fabre, Pfizer, and Sanofi and has consulting or advisory roles with AstraZeneca, Roche, Merck, Boehringer Ingelheim, and Roche outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs)., Aim: To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort., Methods: Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed., Results: A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods., Conclusion: The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage., 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.)

To investigate the efficacy of chiropractic rehabilitation therapy in Crowe IV developmental dysplasia of the hip (DDH) patients after total hip arthroplasty. Seventy-two patients with Crowe IV type DDH hospitalized in the Department of Orthopedics I of Ya'an Hospital of Traditional Chinese Medicine from January 2021 to June 2023 were selected for the study, and they were divided into 36 cases in the chiropractic rehabilitation therapy group (the treatment group) and 36 cases in the traditional rehabilitation therapy group (the control group) according to the method of randomized grouping. All patients were evaluated at preoperative, 1, 3, and 6 months postoperatively for follow-up, and the muscle strength of the affected limb, the patient's walking gait, the shortened length of the affected limb, the visual analog scale score (VAS score), the Oswestry Dysfunction Index Score (ODI score), the Harris Hip Score, and the degree of pelvic tilt were recorded to evaluate the results of the study. A total of 4 subjects withdrew from the study, 2 in the treatment group, and 2 in the control group. The muscle strength of the affected limb, walking gait, shortened length of the affected limb, VAS score, ODI score, Harris score, and pelvic tilt in the treatment and control groups improved significantly compared with the preoperative period. Comparisons between the 2 groups revealed that at the final follow-up visit, the limp gait of the patients in the treatment group was significantly reduced, the shortened length of the affected limb was significantly reduced, the VAS score was significantly reduced, and the ODI score was significantly reduced, in the treatment group relative to that of the control group, Harris Hip Score was significantly improved, and the degree of pelvic tilt was significantly reduced, but the improvement in muscle strength of the affected limb was not statistically significant. In future clinical practice, we recommend that chiropractic rehabilitation be used as a routine adjunctive treatment after TKA in patients with Crowe IV DDH to optimize outcomes and improve patients' quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSV A ) and B (HRSV B ) of HRSV. Next, the Pyrococcus furiosus Argonaute ( PfAgo ) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/μL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSV A and HRSV B infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings., 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 Liao, Feng, Zhang, Yang, Zhan, Zeng, Huang, Lian, Ke, Cai, Zhang, Fang, Cai, Chen, Lin, Lin, Chen, Liu, Huang, Lin and Lin.)

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8 + regulatory T (Treg) hi /CXCL13 + exhausted T (Tex) lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC., Competing Interests: Declaration of interests W.-Z.Z.. received speech honoraria from AstraZeneca, Roche, Eli Lilly, and Pfizer outside the submitted work. Z.-M.Z. is a founder of Analytical BioSciences. Y.-L.W. received research funding from Roche and speech honoraria from AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi, and he was a research consultant for AstraZeneca. Q.Z. reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ganoderma is a large and diverse genus containing fungi that cause white rot to infect a number of plant families. This study describes G.phyllanthicola and G.suae as new species from Southwest China, based on morphological and molecular evidence. Ganodermaphyllanthicola is characterized by dark brown to purplish black pileus surface with dense concentric furrows, pale yellow margin, irregular pileipellis cells, small pores (5-7 per mm) and ellipsoid to sub-globose basidiospores (8.5-10.0 × 6.0-7.5 µm). Ganodermasuae is characterized by reddish brown to oxblood red pileus surface and lead gray to greyish-white pore surface, heterogeneous context, wavy margin and almond-shaped to narrow ellipsoid basidiospores (8.0-10.5 × 5.0-7.0 μm). The phylogeny of Ganoderma is reconstructed with multi-gene sequences: the internal transcribed spacer region (ITS), the large subunit (nrLSU), translation elongation factor 1-α gene (TEF-1α) and the second subunit of RNA polymerase II (RPB2). The results show that G.suae and G.phyllanthicola formed two distinct line-ages within Ganoderma . Descriptions, illustrations and phylogenetic analyses results of the two new species are presented., Competing Interests: The authors have declared that no competing interests exist., (Jun He, Xiao-Jun Li, Wan-Zhong Tan, Xiao-Qu Wu, Dan Wu, Zong-Long Luo, Qi Wu Zhou, E-Xian Li, Shu-Hong Li.)

Background: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family., Methods: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR., Results: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs., Conclusions: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites., (© 2024. The Author(s).)

In China, both vanadium(V) and chromium(VI) are present in wastewater resulting from vanadate precipitation (AVP wastewater) and from leaching vanadium-chromium reduction slag. Addressing environmental preservation and the comprehensive utilization of metal resources necessitates the extraction and separation of V(V) and Cr(VI) from these mixed solutions. However, their separation is complicated by very similar physicochemical properties. This study establishes a method for the dynamic selective adsorption of V(V) from such mixtures. It evaluates the impact of various operating conditions in columns on dynamic adsorption behavior. This study examines the migration patterns of the mass transfer zone (MTZ) and forecasts its effective adsorption capacity through multivariate polynomial regression and a neural network (NN) model. The NN model's outcomes are notably more precise. Its analysis reveals that C 0 is the most critical factor, with Q and H following in importance. Furthermore, the dynamic properties were analyzed using two established models, Thomas and Klinkenberg, revealing that both intraparticle and liquid film diffusion influence the rates of exchange adsorption, with intraparticle diffusion being the more significant factor. Using 3 wt % sodium hydroxide as the eluent to elute V(V)-loaded resin at a flow rate of 4 mL/min resulted in a chromium concentration of less than 3 mg/L in the V(V) eluate, indicating high vanadium-chromium separation efficiency in this method. These findings offer theoretical insights and economic analysis data that are crucial for optimizing column operation processes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH., Methods: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration., Results: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH., Conclusion: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway., (© 2024. The Author(s).)

Introduction: Sleep insufficiency has been linked to an increased risk of high blood pressure and cardiovascular diseases. Emerging studies have demonstrated that impaired baroreflex sensitivity (BRS) is involved in the adverse cardiovascular effects caused by sleep deprivation, however, the underlying mechanisms remain unknown. Therefore, the present study aims to clarify the role of abnormal renin-angiotensin system in the nucleus tractus solitarii (NTS) in impaired BRS induced by sleep deprivation., Methods: Rats were randomly divided into two groups: normal sleep (Ctrl) and chronic sleep deprivation (CSD) group. Rats were sleep deprived by an automated sleep deprivation system. The blood pressure, heart rate, BRS, the number of c-Fos positive cells and the expression of angiotensin (Ang) II subtype 1 receptors (AT1R) in the NTS of rats were assessed., Results: Compared to Ctrl group, CSD group exhibited a higher blood pressure, heart rate, and reduced BRS. Moreover, the number of c-Fos positive cells and local field potential in the NTS in CSD group were increased compared with the Ctrl group. It was shown that the expression of the AT1R and the content of Ang II and the ratio of Ang II to Ang-(1-7) were increased in the NTS of rats in CSD group compared to Ctrl group. In addition, microinjection of losartan into the NTS significantly improved the impaired BRS caused by sleep deprivation., Discussion: In conclusion, these data suggest that the elevated AT1R expression in the NTS mediates the reduced BRS induced by chronic sleep deprivation., 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 Liu, Wang, Sun, Wang, Tan and Wang.)

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redox high LUAD and redox low LUAD. Genetically, redox high LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redox high LUAD (72.5%) compared to redox low LUAD (17.4%), whereas EGFR mutations are more common in redox low LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redox high LUAD. The redox high phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redox high phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p  = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p  = 0.004), and overall survival (12.1 vs. 31.2 months, p  = 0.022) when treated with ICIs. The redox high phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs., Competing Interests: Prof. Yi-Long Wu reports personal financial interests: consulting and advisory services, speaking engagements of Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Sanofi, MSM, and BMS. Prof. Qing Zhou reports lecture and presentations fees from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSM, Pfizer, Roche, and Sanofi outside the submitted work. The remaining authors declare no competing interests that may have influenced the reported work., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Introduction: EGFR C797X (C797S or C797G) mutation is the most frequent on-target mechanism of resistance to osimertinib. The hypothesis that the allelic context of C797X/T790M has implications for treatment is on the basis of sporadic reports and needs validation with larger cohorts., Methods: We identified patients with EGFR C797X-mutant NSCLC from nine centers who progressed on osimertinib, all analyzed in a single laboratory through next-generation sequencing. We analyzed genomic profiles and assessed associations between clinical outcomes and C797X status., Results: A total of 365 EGFR C797X-mutant cases were categorized into four subtypes on the basis of allelic context: in cis (75.3%), in trans (6.4%), cis&trans (10.4%), and C797X-only (7.9%). Genomically, the cis&trans subtype displayed the highest frequency of concurrent alterations at osimertinib resistance sites (21.1%), while the in cis subtype had the lowest (8.4%). Clinically, cis&trans patients exhibited the worst progression-free survival (PFS) on both previous (median 7.7 mo) and subsequent treatment (median 1.0 mo) and overall survival (median 3.9 mo). In subsequent treatments, in cis patients exhibited superior PFS with combined brigatinib and cetuximab (median 11.0 mo) compared with other regimens (p = 0.005), while in trans patients exhibited variable outcomes with combined first or second- and third-generation EGFR inhibitor (PFS range: 0.7-8.1 mo, median 2.6 mo). Notably, subtype switching was observed after subsequent treatments, predominantly toward the in cis subtype., Conclusions: Allelic context could define four EGFR C797X-mutant NSCLC subtypes with heterogeneous genetic landscapes and distinct clinical outcomes. Subsequent treatments further complicate the scenario through subtype switching., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: To elucidate the impact of [ 18 F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC., Methods: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis., Results: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90)., Conclusion: Addition of preoperative [ 18 F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: Myocardial infarction (MI) is a critical cardiovascular event with multifaceted etiology, involving several genetic and environmental factors. It is essential to understand the function of plasma metabolites in the development of MI and unravel its complex pathogenesis., Methods: This study employed a bidirectional Mendelian randomization (MR) approach to investigate the causal relationships between plasma metabolites and MI risk. We used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa. In addition, the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite (1400 metabolites) and MI (20,917 individuals with MI and 440,906 individuals without MI) susceptibility. Inverse variance weighted was the primary method for estimating causal effects. MR estimates are expressed as beta coefficients or odds ratio (OR) with 95% CI., Results: We identified 14 plasma metabolites associated with the occurrence of MI ( P < 0.05), among which 8 plasma metabolites [propionylglycine levels (OR = 0.922, 95% CI: 0.881-0.965, P < 0.001), gamma-glutamylglycine levels (OR = 0.903, 95% CI: 0.861-0.948, P < 0.001), hexadecanedioate (C16-DC) levels (OR = 0.941, 95% CI: 0.911-0.973, P < 0.001), pentose acid levels (OR = 0.923, 95% CI: 0.877-0.972, P = 0.002), X-24546 levels (OR = 0.936, 95% CI: 0.902-0.971, P < 0.001), glycine levels (OR = 0.936, 95% CI: 0.909-0.964, P < 0.001), glycine to serine ratio (OR = 0.930, 95% CI: 0.888-0.974, P = 0.002), and mannose to trans-4-hydroxyproline ratio (OR = 0.912, 95% CI: 0.869-0.958, P < 0.001)] were correlated with a decreased risk of MI, whereas the remaining 6 plasma metabolites [1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) levels (OR = 1.051, 95% CI: 1.018-1.084, P = 0.002), behenoyl dihydrosphingomyelin (d18:0/22:0) levels (OR = 1.076, 95% CI: 1.027-1.128, P = 0.002), 1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6) levels (OR = 1.067, 95% CI: 1.027-1.109, P = 0.001), alpha-ketobutyrate levels (OR = 1.108, 95% CI: 1.041-1.180, P = 0.001), 5-acetylamino-6-formylamino-3-methyluracil levels (OR = 1.047, 95% CI: 1.019-1.076, P < 0.001), and N-acetylputrescine to (N (1) + N (8))-acetylspermidine ratio (OR = 1.045, 95% CI: 1.018-1.073, P < 0.001)] were associated with an increased risk of MI. Furthermore, we also observed that the mentioned relationships were unaffected by horizontal pleiotropy ( P > 0.05). On the contrary, MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites ( P > 0.05 for each comparison)., Conclusions: Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI, among which 13 plasma metabolites have not been reported previously. These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets., (© 2024 JGC All rights reserved; www.jgc301.com.)

Objectives: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images., Methods: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed., Results: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001)., Conclusions: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis., (© 2024. The Author(s).)

Optimum irrigation scheduling is important for ensuring high yield and water productivity in substrate-cultivated vegetables and is determined based on information such as substrate water content, meteorological parameters, and crop growth. The aim of this study was to determine a precise irrigation schedule for coconut coir culture in a solar greenhouse by comparing the irrigation, evapotranspiration (ET), substrate water content (VWC), as well as the crop growth indices and yield of cucumber, and irrigation water productivity (IWP) under three irrigation schedules: the soil moisture sensor-based method (T-VWC), the accumulated radiation combined with soil moisture sensor-based method (Rn-VWC), and the crop evapotranspiration estimated method using the hourly PM-ETo equation with an improved calculation of Kc (T-ETc). The results showed that the daily irrigation and evapotranspiration amount were the highest under T-VWC treatment, while the lowest under T-ETc treatment. In different meteorological environments, the change in irrigation amount was more consistent with the ET,and the VWC was relatively stable in T-ETc treatment compared with that under T-VWC or Rn-VWC treatments. The plant height, leaves number, leaf area, and stem diameter of T-VWC and Rn-VWC treatments were higher than those of the T-ETc treatments, but there was no significant difference in cucumber yield. Compared with the T-VWC treatment, total irrigation amount under Rn-VWC and T-ETc treatments significantly decreased by 25.75% and 34.04%, respectively ([Formula: see text]). The highest IWP values of 25.07 kg m[Formula: see text] was achieved from T-ETc treatment with significantly increasing by 44.33% compared to the T-VWC treatment (17.37 kg m[Formula: see text]). In summary, the T-ETc treatment allowed more reasonable irrigation management and was appropriate for growing cucumber in coconut coir culture., (© 2024. The Author(s).)

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage T any N3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage T any N3M0 nasopharyngeal carcinoma., (© 2024. The Author(s).)

Introduction: To investigate the clinical features, pregnancy care, timing, and approaches of pregnancy termination as well as the perinatal management of pregnant women with ectopic pheochromocytomas (EPCC) (paragangliomas, PGL)., Methods: We report the diagnosis and treatment of a pregnant women with EPCC which was confirmed in the third trimester in our hospital. Literature in relation to EPCC during pregnancy both in and outside China was searched for data analysis such as maternal clinical features and maternal and fetal prognosis., Results: A total of 20 papers including 21 cases (plus ours) were retrieved. The average age of pregnant patients was 28 years old (from 21 to 37). Two patients presented no hypertension. Nineteen had hypertension in various extent with the accompany of headache (11 cases, 57.9%), palpitations (8 cases, 42.1%), sweating (6 cases, 31.6%), nausea (6 cases), abdominal pain (2 cases), etc. The tumor was found in the chest in 3 patients, in the upper abdomen in 1 patient, in the middle abdomen in 10 patients, between the lower abdomen and pelvic cavity in 3 patients and in the pelvic cavity in 3 patients. Five patients had a surgical removal of the tumor before delivery, 3 during cesarean section and 10 after giving birth., Conclusion: EPCC (PGL) during pregnancy is a rare extra-adrenal tumor, whose manifestations are often confused with those of pregnancy-induced hypertension. It is extremely hard to diagnosis the disease before surgery. Patients still have an opportunity of undergoing spontaneous delivery if their tumors have been removed before labor. However, for patients whose pheochromocytomas is localized before labor, it is better to terminate their pregnancy via cesarean section in a proper time according to their obstetric conditions, while under the supervision of multidisciplinary specialists. The preparations of both α and β adrenergic receptor blocker treatment that is normally carried out before PGL removal surgery are unnecessary to be overemphasized before the cesarean section., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: A guidewire-free angiography-derived microcirculatory resistance (AMR) derived from Quantitative flow ratio (QFR) exhibits good diagnostic accuracy for assessing coronary microvascular dysfunction (CMD), but there are no relevant studies supporting the specific application of AMR in patients with ST-elevation myocardial infarction (STEMI). The study aims to evaluate CMD in patients with STEMI using the AMR index., Methods: This study included patients with STEMI who underwent percutaneous coronary intervention (PCI) from June 1, 2020 to September 28, 2021. All patients were divided into two groups: the CMD (n = 215) and non-CMD (n = 291) groups. After matching, there were 382 patients in both groups.1-year follow-up major adverse cardiac events (MACEs) were evaluated., Results: After matching, the primary endpoint was achieved in 41 patients (10.7%), with 27 and 14 patients in the CMD and non-CMD groups, respectively (HR 1.954 [95% CI 1.025-3.726]; 14.1% versus 7.3%, p = .042). Subgroup analysis revealed that 18 patients (4.7%) were readmitted for heart failure, with 15 and 3 in the CMD and non-CMD groups, respectively (HR 5.082 [95% CI 1.471-17.554]; 7.9% versus 1.6%, p = .010). Post-PCI AMR ≥ 250 was significantly associated with a higher risk of the primary endpoint and was its independent predictor (HR 2.265 [95% CI 1.136-4.515], p = .020)., Conclusion: The retrospective use of AMR with a cutoff value of ≥250 after PCI in patients with STEMI can predict a significant difference in the 1-year MACE rates when compared with a propensity score-matched group with normal AMR., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Carcinoembryonic antigen (CEA) has been routinely used as a postoperative monitoring biomarker for non-small cell lung cancer (NSCLC). Emergingly, circulating tumor DNA (ctDNA)-molecular residual disease (MRD) detection is a well-established prognostic marker, with better positive predictive value (PPV) and negative predictive value (NPV). However, the actual clinical efficiency of CEA in MRD context remain unknown. Hence, we conducted this study for direct comparison of CEA and MRD., Methods: Two cohorts were analyzed in this study. To investigate the prognostic and predictive value of CEA, we retrospective enrolled NSCLC patient stage IA2-IIIA (8th tumor-node-metastasis staging system) with longitudinal CEA between 2018 and 2019. We also performed a paired comparison of CEA and MRD in our previous published cohort. Survival data were analyzed using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Sensitivity, specificity, PPV and NPV were calculated using the R package " epiR ". McNemar's test was used to analyze the paired data. Statistical differences were set at a P value <0.05., Results: In the retrospective cohort, the sensitivity of longitudinal CEA was only 0.49 [95% confidence interval (CI): 0.37-0.60]. Even for patients with progressively elevated CEA levels, 32% of them still remained disease-free, with PPV of 0.68 (0.49-0.83) and NPV of 0.81 (0.77-0.85). Furthermore, we then compared CEA and MRD values in a previously described MRD cohort. As expected, CEA levels could not stratify the risk of recurrence in detectable versus undetectable MRD populations., Conclusions: MRD is superior to CEA in postoperative monitoring. there is insufficient evidence to support its use as postoperative monitoring tumor marker., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-507/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Early life stress can cause cognitive impairment in aged offspring. Environmental enrichment (EE) is considered to be an effective non-pharmacological treatment for improving cognitive decline. The aim of this research was to evaluate the effect of EE, on cognitive impairment in aged offspring induced by maternal sleep deprivation (MSD) and the underlying mechanisms involved to investigate its potential value in clinical practice., Methods: CD-1 damns were subjected or not to sleep deprivation during late gestation. Twenty-one days after birth, the offspring were assigned to standard or EE cages. At 18 months-old, the learning and memory function of the offspring mice was evaluated using Morris water maze. The hippocampal and prefrontal cortical levels of protein, gene, proinflammation cytokines, and oxidative stress indicators was examined by Western blot, real-time polymerase chain reaction, enzyme linked immunosorbent assay, and biochemical assays., Results: Offspring in MSD group exhibited declined learning and memory abilities compared with control animals. Moreover, the hippocampal and prefrontal cortical levels of Sirtuin1 (Sirt1), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), postsynaptic density protein-95, and synaptophysin were lower and those of proinflammation cytokines higher in the MSD group; meanwhile, the superoxide dismutase content was higher and the malondialdehyde and reactive oxygen species contents were lower. However, these deleterious changes were ameliorated by exposure to EE., Conclusions: EE attenuates MSD-induced cognitive impairment, oxidative stress, and neuroinflammation and reverses the reduction in synaptic protein levels in aged offspring mice via the Sirt1/PGC-1α pathway.

It has been documented that increased sympathetic activity contributes to the development of cardiovascular diseases, such as hypertension. We previously reported that β-arrestin-1, a multifunctional cytoskeletal protein, was downregulated in the rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rat (SHR), and its overexpression elicited an inhibitory effect on sympathetic activity in hypertension. microRNA (miR)-22-3p has been reported to be associated with the pathological progress of hypertension. The purpose of this study was to determine the role of miR-22-3p in β-arrestin-1-mediated central cardiovascular regulation in hypertension. It was observed that miR-22-3p was upregulated in the RVLM of SHRs compared with normotensive Wistar-Kyoto (WKY) rats, and it was subsequently confirmed to target the β-arrestin-1 gene using a dual-luciferase reporter assay. miR-22-3p was downregulated in the RVLM using adeno-associated virus with 'tough decoys', which caused a significant increase of β-arrestin-1 expression and decrease of noradrenaline and blood pressure (BP) in SHRs. However, upregulation of miR-22-3p using lentivirus in the RVLM of WKY rats significantly increased BP. In in vitro PC12 cells, enhanced oxidative stress activity induced by angiotensin II was counteracted by pretreatment with miR-22-3p inhibitor, and this effect could be abolished by β-arrestin-1 gene knockdown. Furthermore, microglia exhaustion significantly diminished miR-22-3p expression, and enhanced β-arrestin-1 expression in the RVLM of SHRs. Activation of BV2 cells in vitro evoked a significant increase of miR-22-3p expression, and this BV2 cell culture medium was also able to facilitate miR-22-3p expression in PC12 cells. Collectively, our findings support a critical role for microglia-derived miR-22-3p in inhibiting β-arrestin-1 in the RVLM, which is involved in central cardiovascular regulation in hypertension. KEY POINTS: Impairment of β-arrestin-1 function in the rostral ventrolateral medulla (RVLM) has been reported to be associated with the development of sympathetic overactivity in hypertension. However, little is known about the potential mechanisms of β-arrestin-1 dysfunction in hypertension. miR-22-3p is implicated in multiple biological processes, but the role of miR-22-3p in central regulation of cardiovascular activity in hypertension remains unknown. We predicted that miR-22-3p could directly bind to the β-arrestin-1 gene (Arrb1), and this hypothesis was confirmed by using a dual-luciferase reporter assay. Inhibition of β-arrestin-1 by miR-22-3p was further verified in both in vivo and in vitro experiments. Furthermore, our results suggested miR-22-3p as a risk factor for oxidative stress in the RVLM, thus contributing to sympatho-excitation and hypertension. Our present study provides evidence that microglia-derived miR-22-3p may underlie the pathogenesis and progression of neuronal hypertension by inhibiting β-arrestin-1 in the RVLM., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

Objective: To explore the changes of serum-related indexes at different time points, so as to identify the critical time of converting from simple premature thelarche (PT) to idiopathic central precocious puberty (ICPP)., Methods: This is a retrospective study. The subjects of the study were 50 girls with PT who were admitted to the Children's Hospital of Hebei Province from January 2019 to September 2020. The enrolled 50 children were divided into the conversion group(n=12) and the non-conversion group(n=38) according to whether PT was converted into ICPP during follow-up. Furthermore, the levels of serum-related indexes and uterine and ovarian volumes were compared after the diagnosis of PT., Results: The IGF-1 and IGFBP-3 levels of children in the conversion group began to change significantly from six months after the diagnosis, with statistically significant differences when compared with the levels of children at the initial diagnosis, three months and those of the non-conversion group at the same time points ( p< 0.05). The levels of vitamin-D, DHEA and leptin began to change significantly at nine months after the diagnosis ( p< 0.05). Besides, uterine and ovarian volumes in the conversion group began to increase significantly six months after the diagnosis, with statistically significant differences when compared with those in the non-conversion group ( p< 0.05)., Conclusion: Findings in our study suggest that regular monitoring of vitamin-D, IGF-1, IGFBP-3, DHEA and leptin levels, and uterine and ovarian volumes can predict the conversion from PT to ICPP at an early stage., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People's Republic of China from ADAURA., Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety., Results: Of 682 patients enrolled globally, 159 patients in the People's Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13-0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17-0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21-1.20). HRQoL was maintained from baseline, and safety was consistent with the global population., Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population., (© 2024 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.)

Background: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic., Methods: We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators., Results: Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%)., Conclusion: Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening., (© 2023. The Author(s).)

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab-chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA-IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression. The primary endpoint was the major pathological response (MPR). Key secondary endpoints included the pathologic complete response (pCR), objective response rate (ORR), and event-free survival (EFS). Baseline PD-L1 expression and perioperative circulating tumor DNA (ctDNA) status were correlated with pCR and EFS. Fifty-two patients were enrolled, with 46 undergoing surgeries. The MPR was 50.0% (26/52), with 25.0% (13/52) achieving pCR, and 16.7% and 66.7% for patients with PD-L1 ≥ 50% in N and N/C groups, respectively. Thirteen (25.0%) patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment. Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR (39.1%) compared with those remained positive (6.7%, odds ratio = 6.14, 95% CI 0.84-Inf, p = 0.077). With a median follow-up of 25.1 months, the 18-month EFS rate was 64.8% (95% CI 51.9-81.0%). For patients with ctDNA- vs. ctDNA + , the 18m-EFS rate was 93.8% vs 47.3% (HR, 0.15; 95% CI 0.04, 0.94; p = 0.005). Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression ≥ 50%. ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits, which requires further confirmation in a prospective clinical trial (NCT04015778)., (© 2023. The Author(s).)

Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs. In this review, we first introduce TCR structure-based antigen recognition and signaling, then describe recent advances in neoantigens and their specific TCR screening technologies, and finally summarize ongoing clinical trials of TCR-T therapies against neoantigens. More importantly, we also present the current challenges of TCR-T cell-based immunotherapies, e.g., the safety of viral vectors, the mismatch of T cell receptor, the impediment of suppressive tumor microenvironment. Finally, we highlight new insights and directions for personalized TCR-T therapy., (© 2023. The Author(s).)

Background: Chimeric antigen receptor (CAR)-T-cell therapy is a revolutionary treatment that has become a mainstay of advanced cancer treatment. Conventional glypican-3 (GPC3)-CAR-T cells have not produced ideal clinical outcomes in advanced hepatocellular carcinoma (HCC), and the mechanism is unclear. This study aims to investigate the clinical utility of novel GPC3-7-19-CAR-T cells constructed by our team and to explore the mechanisms underlying their antitumor effects., Methods: We engineered a novel GPC3-targeting CAR including an anti-GPC3 scFv, CD3ζ, CD28 and 4-1BB that induces co-expression of IL-7 at a moderate level (500 pg/mL) and CCL19 at a high level (15000 pg /mL) and transduced it into human T cells. In vitro, cell killing efficacy was validated by the xCELLigence RTCA system, LDH nonradioactive cytotoxicity assay and was confirmed in primary HCC organoid models employing a 3D microfluid chip. In vivo, the antitumor capacity was assessed in a humanized NSG mouse xenograft model. Finally, we initiated a phase I clinical trial to evaluate the safety and effect of GPC3-7-19-CAR-T cells in the clinic., Results: GPC3-7-19-CAR-T cells had 1.5-2 times higher killing efficiency than GPC3-CAR-T cells. The tumor formation rates in GPC3-7-19-CAR-T cells treated model were reduced (3/5vs.5/5), and the average tumor volumes were 0.74 cm 3  ± 1.17 vs. 0.34 cm 3  ± 0.25. Of note, increased proportion of CD4 + T EM and CD8 + T CM cells was infiltrated in GPC3-7-19-CAR-T cells group. GPC3-7-19-CAR-T cells obviously reversed the immunosuppressive tumor microenvironment (TME) by reducing polymorphonuclear (PMN)-myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells infiltration and recruiting more dendritic cells (DCs) to HCC xenograft tumor tissues. In one patient with advanced HCC, GPC3-7-19-CAR-T-cell treatment resulted in tumor reduction 56 days after intravenous infusion., Conclusions: In conclusion, GPC3-7-19-CAR-T cells achieved antitumor effects superior to those of conventional GPC3-CAR-T cells by reconstructing the TME induced by the dominant CD4 + T EM and CD8 + T CM cell subsets. Most importantly, GPC3-7-19-CAR-T cells exhibited good safety and antitumor efficacy in HCC patients in the clinic. ► Novel GPC3-7-19-CAR-T cells designed with mediate level of IL-7 secretion and high level of CCL19 secretion, which could recruit more mature DCs to assist killing on GPC3 + HCCs. ►DC cells recruited by CCL19 could interact with CD4 + T cells and promote the differentiation of CD4 + T EFF cells into CD4 + T EM and CD8 + T CM subsets, leading a better anti-tumor effect on GPC3 + HCCs. ►Compared with conventional GPC3-CAR-T, GPC3-7-CCL19-CAR-T cells could reverse tumor immunosuppressive microenvironment by reducing PMN-MDSC and Treg cell infiltration., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Patients with inflammatory bowel diseases (IBDs) generally have poor knowledge, attitude, and practice of their disease, while the data from China are lacking., Aim: To address this knowledge disparity among Chinese patients with IBD., Methods: This web-based, cross-sectional study was conducted on a cohort of IBD patients who visited the Second Affiliated Hospital of Wenzhou Medical University between December 2022 and February 2023. Their socio-demographic information and the knowledge, attitude, and practice scores were collected and estimated using a self-designed questionnaire. Pearson's correlation analysis was used to determine the pairwise correlations among knowledge, attitude, and practice scores. A multivariate logistic regression analysis was further performed to determine the independent factors associated with their knowledge, attitude, and practice scores., Results: A total of 353 patients (224 males) with IBD completed the questionnaires. The mean knowledge, attitude, and practice scores were 10.05 ± 3.46 (possible range: 0-14), 41.58 ± 5.23 (possible range: 0-56), 44.20 ± 7.39 (possible range: 0-56), respectively, indicating good knowledge, positive attitude, and proactive practice toward IBD. Pearson's correlation analysis showed that the knowledge score had significant positive correlations with the attitude score ( r = 0.371, P < 0.001) and practice score ( r = 0.100, P < 0.001). The attitude score had a significant positive correlation with the practice score ( r = 0.452, P < 0.001). Moreover, multivariate logistic regression analysis showed that aged 30-40 years [odds ratio (OR) = 4.06, 95% confidence interval (CI): 1.04-15.82, P = 0.043], middle school education (OR = 3.98, 95%CI: 1.29-12.33, P = 0.017), high school/technical secondary school education (OR = 14.06, 95%CI: 3.92-50.38, P < 0.001), and junior college/bachelor's degree and above education (OR = 15.20, 95%CI: 4.15-55.650, P < 0.001) were independently associated with good knowledge. The higher knowledge score was independently associated with a positive attitude (OR = 1.23, 95%CI: 1.11-1.36, P < 0.001). The higher attitude score was independently associated with proactive practice (OR = 1.20, 95%CI: 1.11-1.30, P < 0.001)., Conclusion: Chinese patients with IBD might have good knowledge, a positive attitude, and proactive practice toward their disease. However, a small number of specific items require education., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

The marked increase in the incidence rate of brucellosis is a serious public health concern in Jiangsu Province. However, its temporal and spatial distribution has not been studied in depth. The main purpose of this study is to depict the demographic, temporal and spatial distribution patterns and clustering characteristics of brucellosis cases in Jiangsu Province, China, from 2006 to 2021 to develop and implement effective scientific prevention and control strategies. Data for human brucellosis cases in Jiangsu Province from 2006 to 2021 were obtained from the Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS). Spatial autocorrelation analysis and temporal-spatial scan statistics were used to identify potential changes in the spatial and temporal distributions of human brucellosis in Jiangsu Province. During the years 2006-2021, 1347 brucellosis cases were reported in Jiangsu Province, with an average annual incidence rate of 0.1036 per 100,000 individuals. Middle-aged and elderly individuals (aged 40-69 years) were the main infected populations, accounting for 69.72% (939/1347) of all reported cases. The incidence of brucellosis in Jiangsu showed a long-term increasing trend and displayed pronounced seasonal variations, with the peak occurring between April and June annually. The incidence gradually expanded from the northern and southern areas to the central areas between 2006 and 2021. Global spatial autocorrelation analysis demonstrated a positive correlation in the incidence of brucellosis between 2008 and 2012-2021. Temporal-spatial clustering analysis showed that the primary cluster was detected in the northern, highly endemic regions of Jiangsu, and the three secondary clusters were in areas where there had been outbreaks of brucellosis. Human brucellosis remains a serious public health issue in Jiangsu Province. Northern and southern Jiangsu regions, with high rates of brucellosis, may require special plans and measures to monitor and control the disease. Additionally, the capacity to respond to outbreaks in high-incidence areas should be improved to prevent further brucellosis outbreaks., (© 2023. The Author(s).)