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Xiu-Li Xiao,1,&ast; Qian-Xue Yang,2,&ast; Hui-Zhong Niu,1 Li-Jing Li,1 Jian-Lei Geng,1 Dan Zhao,1 Hui Ren,1 Pan-Pan Yang1 1Department of General Surgery I, Hebei Children’s Hospital, Shijiazhaung, 050000, People’s Republic of China; 2Department of Operating Room, Hebei Children’s Hospital, Shijiazhaung, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiu-Li Xiao, Department of General Surgery I, Hebei Children’s Hospital, No. 133 Jianhuanan Street, Shijiazhuang, Yuhua District, 050000, People’s Republic of China, Tel +86 0311 8591 1321, Email xxlwwvt7@email.cnPurpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD).Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test.Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23± 6.17 VS 7.89± 2.38). The difference between the two groups had statistical significance (P < 0.05).Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.Keywords: catheter blockage rate, catheter sealing fluid volume, pain, puncture method, totally implantable venous access device

Xiu-Li Xiao,1 Qian-Xue Yang,2 Hui-Zhong Niu,1 Li-Jing Li,1 Zhen-Jing Xie1 1Department of General Surgery I, Children’s Hospital of Hebei Province, Shijiazhaung, 050000, People’s Republic of China; 2Department of Operating Room, Children’s Hospital of Hebei Province, Shijiazhaung, 050000 People’s Republic of ChinaCorrespondence: Xiu-Li Xiao, Department of General Surgery I, Children’s Hospital of Hebei Province, No. 133 Jianhuanan Street, Yuhua District, Shijiazhuang, Hebei, 050000, People’s Republic of China, Tel +86-0311-85911010, Email xxlwwvt7@email.cnObjective: To explore the effective response strategies for infections in infants with short bowel syndrome and solid abdominal tumours, treated with totally implantable venous access ports (TIVAPs).Methods: A total of 210 children who were treated with a TIVAP in our department from 2020 to 2021 were selected for this retrospective study. Eight of these children diagnosed with a catheter-related bloodstream infection were studied in this study; antibiotic lock therapy (ALT) and cluster nursing management were used for treatment, and their effects on the infection outcome were observed.Results: Among the eight children, seven access ports were successfully protected, and one catheter was removed from the right chest wall port due to repeated infection. In this one child, the left side was re-implanted.Conclusion: The use of the ALT combined with cluster-based nursing can better treat infections of TIVAPs, improve the children’s healing time, and has important clinical significance in the prevention of complications from the infection and improving the treatment and nursing of the patients diagnosed with these infections.Keywords: totally implantable venous access port, short bowel syndrome and solid abdominal tumours, catheter-related bloodstream infection, cluster nursing management

Wen-Zhuo He,1,* Qiu-Xia Yang,2,* Jin-Ye Xie,3,* Peng-Fei Kong,1 Wan-Ming Hu,4 Lin Yang,1 Yuan-Zhong Yang,4 Qian-Kun Xie,1 Chang Jiang,1 Chen-Xi Yin,1 Gui-Fang Guo,1 Hui-Juan Qiu,1 Bei Zhang,1 Liang-Ping Xia1 1VIP Region, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 2Department of Medical Imaging, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 3Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510060, People’s Republic of China; 4Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China *These authors contributed equally to this work Background: Skeletal muscle depletion is a prognostic factor in patients with cancer. Here, we evaluated the association between the skeletal muscle index (SMI) and local and systemic responses in patients with colon cancer.Patients and methods: We analyzed the relationships of the SMI with neutrophil, lymphocyte, monocyte, and platelet counts; the neutrophil-to-lymphocyte ratio; albumin levels; and C-reactive protein levels in a cohort of 561 patients, and with the circulating levels of 39 cytokines in a cohort of 125 patients. We also studied the association between the SMI and tumor local inflammatory response and the effect of SMI on survival.Results: The median SMIs for male and female subjects were 44.1 and 34.2 cm2/m2, respectively. We observed positive correlations of the SMI with neutrophil (p=0.022), lymphocyte (p=0.001), and monocyte counts (p=0.003). A low SMI correlated significantly with an increased platelet count (p=0.017), decreased albumin level (p=0.006), neutrophil-to-lymphocyte ratio >3 (p=0.021), and an increased interferon γ-induced protein 10 level (IP-10, r = –0.276, p=0.002). The SMI did not correlate significantly with local inflammatory reactions or the C-reactive protein level. Finally, the SMI was a significant prognosticator in patients with stage III colon cancer (3-year disease-free survival rates: 35.1% for the low SMI arms versus 46.0% in the high SMI arms; HR =2.036; p=0.034).Conclusion: This study highlights the association of a low SMI with a high systematic inflammatory response and IP-10 levels. Furthermore, low SMI is a predictor of poor disease-free survival in patients with stage III colon cancer. Keywords: colon cancer, skeletal muscle, interferon γ-induced protein 10

With the release of large-scale genomic resources from ancient and modern populations, advancements in computational biology tools, and the enhancement of data mining capabilities, the field of genomics is undergoing a revolutionary transformation. These advancements and changes have not only significantly deepened our understanding of the complex evolutionary processes of human origins, migration, and admixture but have also unveiled the impact of these processes on human health and disease. They have accelerated research into the genetic basis of human health and disease and provided new avenues for uncovering the evolutionary trajectories recorded in the human genome related to population history and disease genetics. The ancestral recombination graph (ARG) reconstructs the evolutionary relationships between genomic segments by analyzing recombination events and coalescence patterns across different regions of the genome. An ARG provides a record of all coalescence and recombination events since the divergence of the sequences under study and specifies a complete genealogy at each genomic position, which is the ideal data structure for genomic analysis. Here, we review the theoretical foundations and research advancements of the ARG, and explore its translational applications and future prospects across various disciplines, including forensic genomics, population genetics, evolutionary medicine, and medical genomics. Our goal is to promote the application of this technique in genomic research, thereby deepening our understanding of the human genome.

Cervical cancer accounts for 10-15% of cancer-related mortality among women globally. Infection with high-risk human papillomavirus (HPV) types constitutes a significant etiological factor in the development of cervical carcinoma. The integration of HPV DNA into the host genome is considered a pivotal event in cervical carcinogenesis. Nevertheless, the precise mechanisms underlying HPV integration and its role in promoting cancer progression remain inadequately understood. Therefore, this study aims to identify potential common denominators at HPV DNA integration sites and to analyze the adjacent cellular sequences. We conducted whole-genome sequencing on 13 primary cervical cancer samples, employing the chromosomal coordinates of 537 breakpoints to assess the statistical overrepresentation of integration sites in relation to various chromatin features. Our analysis, which encompassed all chromosomes, identified several integration hotspots within the human genome, notably at 14q32.2, 10p15, and 2q37. Additionally, our findings indicated a preferential integration of HPV DNA into intragenic and gene-dense regions of human chromosomes. A substantial number of host cellular genes impacted by the integration sites were associated with cancer, including IKZF2, IL26, AHRR, and PDCD6. Furthermore, the cellular genes targeted by integration were enriched in tumor-related terms and pathways, as demonstrated by gene ontology and KEGG analysis. In conclusion, these findings enhance our understanding of HPV integration sites and provide deeper insights into the molecular mechanisms underlying the pathogenesis of cervical carcinoma., Competing Interests: None., (AJCR Copyright © 2024.)

Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the neural circuitry mediating olfactory-trigeminal (OT) integration remains poorly understood. Using functional magnetic resonance imaging (fMRI), combined with psychophysics, this study investigated the neural mechanisms underlying OT integration. Fifteen participants with normal olfactory function performed a localization task with air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination thereof while being scanned. The ability to localize PEA to either nostril was at chance. Yet, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, when both stimuli were delivered concurrently to the same nostril, but not when different nostrils received the two stimuli. This enhancement in localization accuracy, exemplifying the principles of spatial coincidence and inverse effectiveness in multisensory integration, was associated with multisensory integrative activity in the primary olfactory (POC), orbitofrontal (OFC), superior temporal (STC), inferior parietal (IPC) and cingulate cortices, and in the cerebellum. Multisensory enhancement in most of these regions correlated with behavioral multisensory enhancement, as did increases in connectivity between some of these regions. We interpret these findings as indicating that the POC is part of a distributed brain network mediating integration between the olfactory and trigeminal systems. PRACTITIONER POINTS: Psychophysical and neuroimaging study of olfactory-trigeminal (OT) integration. Behavior, cortical activity, and network connectivity show OT integration. OT integration obeys principles of inverse effectiveness and spatial coincidence. Behavioral and neural measures of OT integration are correlated., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background and Purpose: Preferences can be developed for, or against, specific brands and services. Using two functional magnetic resonance imaging (fMRI) experiments, this study investigated two dissociable aspects of reward processing, craving and liking, in chocolate lovers. The goal was to further delineate the neural basis supporting branding effects using familiar chocolate (FC) and unfamiliar chocolate (UC) brand images., Methods: In the first experiment, subjects rated their subjective craving and liking on a scale of 1-5 (weak-strong) for each FC and UC image. In the second experiment, they performed a choice task between FC and UC images., Results: Both the craving and liking ratings were significantly greater for FC and were differentially correlated with choice behavior. Craving ratings predicted greater preference for UC, and liking ratings predicted greater preference for FC. A contrast of neural activity for UC versus FC choice trials revealed significantly greater activation for UC choices in the bilateral inferior frontal gyrus and right caudate head. Response times for the FC images were faster than UC images; fMRI activity in the ventromedial prefrontal cortex was significantly correlated with response times during FC trials, but not UC trials. These correlations were significantly different from each other at the group level., Conclusions: The choices for branded chocolate products are driven by higher subjective reward ratings and lower neural processing demands., (© 2024 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Endophytic fungi associated with plants may contain undiscovered bioactive compounds. Under standard laboratory conditions, most undiscovered compounds are inactive, whereas their production could be stimulated under different cultivation conditions. In this study, six endophytic fungi were isolated from the bark of Koelreuteria paniculata in Quancheng Park, Jinan City, Shandong Province, one of which was identified as a new subspecies of Aureobasidium pullulans, named A. pullulans KB3. Additionally, metabolomic tools were used to screen suitable media for A. pullulans KB3 fermentation, and the results showed that peptone dextrose medium (PDM) was more beneficial to culture A. pullulans KB3 for isolation of novel compounds. Sphaerolone, a polyketone compound, was initially isolated from A. pullulans KB3 via scaled up fermentation utilizing PDM. Additionally, the whole-genome DNA of A. pullulans KB3 was sequenced to facilitate compound isolation and identify the biosynthesis gene clusters (BGCs). This study reports the multi-omics (metabolome and genome) analysis of A. pullulans KB3, laying the foundation for discovering novel compounds of silent BGCs and identifying their biosynthesis pathway., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot) , is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar., Case Presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly., Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches., 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 Jian, Yang, Duan, Lai, Che, Teng, Chang, Liu, Luo and Liu.)

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality., 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 Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Alzheimer's disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future., 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, Lu, Wei, Yao, Yang, Lv, Wang, Zhu, Zhu, Zhang, Chen, Yang and Zhang.)

Objective: To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province. Methods: Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ 2 Inspection. Results: A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old ( χ 2 =146.59, P <0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) ( χ 2 =3.91, P =0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath ( χ 2 =259.15, 366.06, 12.48, P <0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old ( χ 2 =9.74, P <0.001), while RSV is more common in children under 1 year old ( χ 2 =178.63, P <0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old ( χ 2 =92.54, 12.90,22.21, P <0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak ( χ 2 =252.68, P <0.001). Conclusion: The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

Inherited retinal degenerations (IRDs) are a group of untreatable and commonly blinding diseases characterized by progressive photoreceptor loss. IRD pathology has been linked to an excessive activation of cyclic nucleotide-gated channels (CNGC) leading to Na + - and Ca 2+ -influx, subsequent activation of voltage-gated Ca 2+ -channels (VGCC), and further Ca 2+ influx. However, a connection between excessive Ca 2+ influx and photoreceptor loss has yet to be proven.Here, we used whole-retina and single-cell RNA-sequencing to compare gene expression between the rd1 mouse model for IRD and wild-type (wt) mice. Differentially expressed genes indicated links to several Ca 2+ -signalling related pathways. To explore these, rd1 and wt organotypic retinal explant cultures were treated with the intracellular Ca 2+ -chelator BAPTA-AM or inhibitors of different Ca 2+ -permeable channels, including CNGC, L-type VGCC, T-type VGCC, Ca 2+ -release-activated channel (CRAC), and Na + /Ca 2+ exchanger (NCX). Moreover, we employed the novel compound NA-184 to selectively inhibit the Ca 2+ -dependent protease calpain-2. Effects on the retinal activity of poly(ADP-ribose) polymerase (PARP), sirtuin-type histone-deacetylase, calpains, as well as on activation of calpain-1, and - 2 were monitored, cell death was assessed via the TUNEL assay.While rd1 photoreceptor cell death was reduced by BAPTA-AM, Ca 2+ -channel blockers had divergent effects: While inhibition of T-type VGCC and NCX promoted survival, blocking CNGCs and CRACs did not. The treatment-related activity patterns of calpains and PARPs corresponded to the extent of cell death. Remarkably, sirtuin activity and calpain-1 activation were linked to photoreceptor protection, while calpain-2 activity was related to degeneration. In support of this finding, the calpain-2 inhibitor NA-184 protected rd1 photoreceptors.These results suggest that Ca 2+ overload in rd1 photoreceptors may be triggered by T-type VGCCs and NCX. High Ca 2+ -levels likely suppress protective activity of calpain-1 and promote retinal degeneration via activation of calpain-2. Overall, our study details the complexity of Ca 2+ -signalling in photoreceptors and emphasizes the importance of targeting degenerative processes specifically to achieve a therapeutic benefit for IRDs. Video Abstract., (© 2024. The Author(s).)

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Pancreatic cancer, referred to as the "monarch of malignancies," is a neoplastic growth mostly arising from the epithelial cells of the pancreatic duct and acinar cells. This particular neoplasm has a highly unfavorable prognosis due to its marked malignancy, inconspicuous initial manifestation, challenging early detection, rapid advancement, and limited survival duration. Cellular immunotherapy is the ex vivo culture and expansion of immune effector cells, granting them the capacity to selectively target malignant cells using specialized techniques. Subsequently, these modified cells are reintroduced into the patient's organism with the purpose of eradicating tumor cells and providing therapeutic intervention for cancer., Present Situation: Presently, the primary cellular therapeutic modalities employed in the treatment of pancreatic cancer encompass CAR T-cell therapy, TCR T-cell therapy, NK-cell therapy, and CAR NK-cell therapy., Aim of Review: This review provides a concise overview of the mechanisms and primary targets associated with various cell therapies. Additionally, we will explore the prospective outlook of cell therapy in the context of treating pancreatic cancer., 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. Production and hosting by Elsevier B.V.)

Rationale: The rare t(3;21)(q26;q22) translocation results in gene fusion and generates multiple fusion transcripts, which are typically associated with therapy-related myelodysplastic syndrome, acute myeloid leukemia, and chronic myelogenous leukemia. Here, we report a rare case of de novo acute myelomonocytic leukemia in a young child with t(3;21)(q26;q22)., Patient Concerns: A 2-and-a-half-year-old female patient presented with abdominal pain, cough, paleness, and fever for 3 weeks, without any history of malignant diseases., Diagnoses: Chest computed tomography revealed pneumonia. Bone marrow smear confirmed acute myelomonocytic leukemia. Cytogenetic analysis and Sanger sequencing identified RUNX1-MECOM and RUNX1-RPL22 fusion genes as a result of t(3;21)(q26;q22)., Interventions: The patient received 3 courses of chemotherapy, but bone marrow smear examination showed no remission. According to the wishes of the patient family, the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was chosen., Outcomes: The patient did not experience any adverse reactions after Allo-HSCT. The red blood cells and platelets increased without transfusion. The pneumonia recovered after antibiotic treatment., Lessons: The patient recovered well after Allo-HSCT. Therefore, for patients with RUNX1-MECOM and RUNX1-RPL22 fusion genes, transplantation may be a good choice when chemotherapy is not effective., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Biotic and abiotic factors influence the formation of fungal-algal pairings in lichen symbiosis. However, the specific determinants of these associations, particularly when distantly related fungi are involved, remain poorly understood. In this study, we investigated the impact of different drivers on the association patterns between taxonomically diverse lichenized fungi and their trebouxioid symbiotic partners. We collected 200 samples from four biomes and identified 41 species of lichenized fungi, associating them with 16 species of trebouxioid green algae, of which 62% were previously unreported. The species identity of both the fungal and algal partners had the most significant effect on the outcome of the symbiosis, compared to abiotic factors like climatic variables and geographic distance. Some obviously specific associations were observed in the temperate zone; however, the nestedness value was lower in arid regions than in cold, polar, and temperate regions according to interaction network analysis. Cophylogenetic analyses revealed congruent phylogenies between trebouxioid algae and associated fungi, indicating a tendency to reject random associations. The main evolutionary mechanisms contributing to the observed phylogenetic patterns were "loss" and "failure to diverge" of the algal partners. This study broadens our knowledge of fungal-algal symbiotic patterns in view of Trebouxia -associated fungi.

Cynanotophyllosides E-F, two new minor pregnane glycosides were isolated from the antidepressant active fraction of cultivated Cynanchum otophyllum , and their structures were determined as 12- O -vanilloyl-deacetylmetaplexigenin 3- O - β -D-glucopyranosyl-(1→4)- β -D-glucopyranosyl-(1→4)- β -D-cymaropyranosyl-(1→4)- β -D-oleandropyranosyl-(1→4)- β -D-digitoxopyranoside, and 12- O -nicotinoyl-deacetylmetaplexigenin 3- O - β -D-glucopyranosyl-(1→4)- β -D-glucopyranosyl-(1→4)- β -D-cymaropyranosyl-(1→4)- β -D-oleandropyranosyl-(1→4)- β -D-cymaropyranoside respectively, with the combination of spectroscopic and chemical analysis.

While investigating the diversity of lignicolous fungi in Yunnan Province, China, six fresh collections of Torulaceae were collected and identified based on morphological examination and phylogenetic analyses of combined LSU, ITS, SSU, tef1-α , and rpb2 sequence data. Two new species, viz. Neopodoconisyunnanensis and Torulasuae , and three new records, viz. T.canangae (new freshwater habitat record), T.masonii (new host record), and T.sundara (new freshwater habitat record) are reported. Detailed descriptions, illustrations, and a phylogenetic tree to show the placement of these species are provided., Competing Interests: The authors have declared that no competing interests exist., (Wen-Peng Wang, Hong-Wei Shen, Dan-Feng Bao, Yong-Zhong Lu, Qiu-Xia Yang, Xi-Jun Su, Zong-Long Luo.)

Background: An increasing number of studies on physicians' professionalism have been done since the 2002 publication of Medical Professionalism in the New Millennium: A Physician Charter. The Charter proposed three fundamental principles and ten responsibilities. However, most studies were done in developed countries, and few have been done in China. Additionally, few studies have examined the effect of patient-centered hospital culture (PCHC) on physicians' professionalism. We aimed to investigate physicians' medical professionalism in public hospitals in China, and to assess mediating effect of professional attitudes in the relationship of PCHC with professional behaviours., Methods: Self-administered questionnaires including professional attitudes (20 items) and behaviours (10 items) survey and PCHC scale (22 items) were given to clinical physicians in five public hospitals, China. The mediating effect of professional attitudes in the relationship of PCHC with professional behaviours was tested., Result: 232 valid questionnaires were collected. More than 90% (208) respondents agreed with 15 of 20 specific statements on medical professionalism. As for the responsibility of improving quality of care, 54 (23%) respondents disagreed with reporting of incompetent colleagues and as for the responsibility of maintaining professional competence, 49 (21%) disagreed with recertification. More than 185 (83%) respondents reported that they sometimes, usually, or always showed the four positive behaviours on the questionnaire, and 173 (77%) reported that they never showed the six negative behaviours. Mediating effect analysis revealed that two dimensions of PCHC (i.e. value/institution culture and behaviour/material culture) had a significant positive impact on physicians' professional behaviour, and professional attitude played a complete mediation role between them, but another dimension of PCHC (i.e. negative evaluation of hospital) directly affected professional behaviour without influencing professional attitude., Conclusion: Chinese physicians showed positive professional attitudes and behaviours. Different dimensions of PCHC affected physicians' attitudes and behaviours in different ways., (© 2023. The Author(s).)

Olfactory tests are used for the evaluation of ability to detect and identify common odors in humans psychophysically. Olfactory tests are currently administered by professionals with a set of given odorants. Manual administration of such tests can be labor and cost intensive and data collected as such are confounded with experimental variables, which adds personnel costs and introduces potential errors and data variability. For large-scale and longitudinal studies, manually recorded data must be collected and compiled from multiple sites. It is difficult to standardize the way data are collected and recorded. There is a need for a computerized smell test system for psychophysical and clinical applications. A mobile digital olfactory testing system (DOTS) was developed, consisting of an odor delivery system (DOTS-ODD) and a mobile application program (DOTS-APP) connected wirelessly. The University of Pennsylvania Smell Identification Test was implemented in DOTS and compared to its commercial product on a cohort of 80 normosmic subjects and a clinical cohort of 12 Parkinson's disease patients. A test-retest was conducted on 29 subjects of the normal cohort. The smell identification scores obtained from the DOTS and standard UPSIT commercial test are highly correlated (r = 0.714, P < 0.001), and test-retest reliability coefficient was 0.807 (r = 0.807, P < 0.001). The DOTS is customizable and mobile compatible, which allows for the implementation of standardized olfactory tests and the customization of investigators' experimental paradigms. The DOTS-APP on mobile devices offers capabilities for a broad range of on-site, online, or remote clinical and scientific chemosensory applications., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Regulations limiting the sale of flavored e-cigarette products are controversial for their potential to interfere with e-cigarette use as a cessation aid in addition to curbing youth use. Limited research suggests that flavor might enhance the addictive potential of e-cigarettes; however, the acute effects of flavored aerosols on brain function among humans have not been assessed. The present study aimed to isolate and compare the neural substrates of flavored and unflavored e-cigarette aerosols on brain function among nine female daily smokers. Participants inhaled aerosolized e-liquid with 36 mg/mL of nicotine with and without a strawberry-vanilla flavor while undergoing functional magnetic resonance imaging. We used general linear modeling to compare whole-brain mean neural activation and seed-to-voxel task-based functional connectivity between the flavored and unflavored inhalation runs. Contrary to our hypothesis, the flavored aerosol was associated with weaker activation than the unflavored aerosol in the brain stem and bilateral parietal-temporal-occipital region of the cortex. Instead, the flavor engaged taste-related brain regions while suppressing activation of the neural circuits typically engaged during smoking and nicotine administration. Alternatively, functional connectivity between subcortical dopaminergic brain seeds and cortical brain regions involved in motivation and reward salience were stronger during the flavored compared to unflavored aerosol run. The findings suggest that fruity and dessert-flavored e-cigarettes may dampen the reward experience of aerosol inhalation for smokers who initiate e-cigarette use by inhibiting activation of dopaminergic brain circuits. These preliminary findings may have implications for understanding how regulations on flavored e-cigarettes might impact their use as cessation aids. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double-blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane-based or propofol-based anesthesia groups. The Mini-Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholinesterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini-Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane- or propofol-based general anesthesia did not differ regardless of Mini-Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane-based anesthesia has short-term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley‐VCH GmbH.)

Background: Acteoside, a water-soluble active constituent of diverse valuable medicinal vegetation, has shown strong anti-inflammatory property. However, studies on the anti-inflammatory property of acteoside in complement-induced acute lung injury (ALI) are limited. Therefore, this study aims to evaluate the anti-inflammatory activity of acteoside in cobra venom factor (CVF)-stimulated human microvascular endothelial cells (HMEC) and in ALI mice model., Methods: In this study, we investigated the effects of acteoside (20, 10, and 5 μg/mL) in vitro in CVF induced HMECs and the activity of acteoside (100, 50, and 20 mg/kg/day bodyweight) in vivo in CVF induced ALI mice. Each eight male mice were orally administered acteoside or the positive drug PDTC (100 mg/kg/day) for 7 days before CVF (35 μg/kg) injection. After injection for 1 h, the pharmacological effects of acteoside were investigated by spectrophotometry, pathological examination, enzyme-linked immunosorbent assay, and immunohistochemistry., Results: In vitro , acteoside (20, 10, and 5 μg/mL) reduced the protein expression of adhesion molecules and pro-inflammatory cytokines and transcriptional activity of NF-κB ( P < 0.01). In vivo studies showed that acteoside dose-dependently alleviated lung histopathologic lesion, inhibited the production of the protein content of BALF, leukocyte cell number, lung MPO activity, and expression levels of IL-6, TNF-α, and ICAM-1, and suppressed the C5b-9 deposition and NF-κB activation in CVF-induced acute lung inflammation in mice ( P < 0.05, 0.01)., Conclusion: This study demonstrates that acteoside exerts strong anti-inflammatory activities in the CVF-induced acute lung inflammation model and suggests that acteoside is a potential therapeutic agent for complement-related inflammatory diseases., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Background: Alexithymia is common in patients with type 2 diabetes mellitus (T2DM). Although the estimated prevalence of alexithymia in patients with T2DM is widely reported, these results have not been synthesized., Aim: To systematically assess the prevalence and characteristics of alexithymia in patients with T2DM., Methods: We searched for relevant publications in PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database, and Weipu Database. The prevalence of alexithymia, the mean scores, and standard deviations of the total scale of the 20-item Toronto Alexithymia Scale (TAS-20) were pooled using random effects meta-analysis in Stata 13.0, with studies stratified by study location in this meta-analysis., Results: This meta-analysis included thirteen articles. Pooled prevalence of alexithymia (TAS-20 total scores ≥61) were 43.0% (95%CI 35.0-51.0%), and the prevalence of alexithymia was higher in China (45.0%, 95%CI 36.0-54.0%) compared with non-China (41.0%, 95%CI 29.0-54.0%). The pooled mean score for the TAS-20 total scale was 57.70 (95% CI 55.25-60.15). Leave-one-out analysis showed that none of the studies significantly impacted the overall pooled results., Conclusions: This meta-analysis indicated a high prevalence of alexithymia in patients with T2DM. Thus, clinicians need to be aware of and assess appropriately for alexithymia in patients with T2DM., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Seed dormancy is an adaptive strategy for environmental evolution. However, the molecular mechanism of the breaking of seed dormancy at cold temperatures is still unclear, and the genetic regulation of germination initiated by exposure to cold temperature requires further investigation. In the initial phase of the current study, the seed coat characteristics and embryo development of Fritillaria taipaiensis P.Y.Li at different temperatures (0°C, 4°C, 10°C & 25°C) was recorded. The results obtained demonstrated that embryo elongation and the dormancy-breaking was most significantly affected at 4°C. Subsequently, transcriptome analyses of seeds in different states of dormancy, at two stratification temperatures (4°C and 25°C) was performed, combined with weighted gene coexpression network analysis (WGCNA) and metabolomics, to explore the transcriptional regulation of seed germination in F. taipaiensis at the two selected stratification temperatures. The results showed that stratification at the colder temperature (4°C) induced an up-regulation of gene expression involved in gibberellic acid (GA) and auxin biosynthesis and the down-regulation of genes related to the abscisic acid (ABA) biosynthetic pathway. Thereby promoting embryo development and the stimulation of seed germination. Collectively, these data constitute a significant advance in our understanding of the role of cold temperatures in the regulation of seed germination in F. taipaiensis and also provide valuable transcriptomic data for seed dormancy for other non-model plant species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Chen, Zhao, Zhang, Zhao, Peng, Sun, Baldwin, Yang and Liang.)

Microbial cultivation is the current gold standard for the clinical diagnosis of bacterial infections. However, this method sometimes produces false negative results. We present a case study of multisite Pseudomonas aeruginosa infections detected by metagenomic next-generation sequencing in a child with aplastic anemia, highlighting the rapid and accurate advantages of this technique., (Published by Oxford University Press on behalf of American Society for Clinical Pathology 2022.)

In this study, we explored the effect of the hydrophile-lipophile balance (HLB) in the linker unit of Galactose (Gal)/N-acetylgalactosamine (GalNAc) ligands on their affinity toward asialoglycoprotein receptors (ASGPRs). Two Gal/GalNAc ligands with lipophilic linkers-{(5-cholesten-3b-ol)[(2-acetamido-2-deoxy-d-galactopyranose-6-o)sebacate]} (CHS-6-GalNAc) and {(5-cholesten-3b-ol)[(d-galactopyranose-6-o)sebacate]} (CHS-6-Gal)-and two with hydrophilic linkers-{(5-cholesten-yl)[(4-O-b-D-galactopyranosyl)-D-glucitol-6-yl]sebacate} (CHS-1-Gal) and {(5-cholesten-3a-ol)[(2-acetamido-2-deoxy-d-galactopyranose-6-o)3,6-dioxa-octanedioate]} (CHS-PEG 2 -6-GalNAc)-were synthesized by enzymatic catalysis. Compared with unmodified liposomes, all Gal/GalNAc ligand-modified liposomes showed higher efficiency toward the hepatocyte target as evaluated by weighted-average overall drug-targeting efficiency (Te*) in vivo and HepG2 cell uptake efficiency in vitro. The ligands containing linkers with high HLB values (i.e., CHS-PEG 2 -6-GalNAc and CHS-1-Gal) exhibited higher ASGPR affinity than those containing linkers with low HLB values (i.e., CHS-6-GalNAc and CHS-6-Gal). We used molecular-dynamics (MD) simulations to investigate the structure-activity relationship between the HLB value of the linker in a ligand and ASGPR affinity. MD simulation results indicated that a Gal/GalNAc ligand with a more hydrophilic linker (i.e., higher HLB value) unit tended to have a higher solvent-accessible surface area (SASA), leading to lower steric hindrance for effective ASGPR recognition. The results of this study will provide an improved design for Gal/GalNAc ligand-based surface-modified liposomes with high ASGPR affinity., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Dysfunction of the cingulo-frontal-parietal (CFP) cognitive attention network has been associated with the pathophysiology of chronic low back pain (cLBP). However, the direction of information processing within this network remains largely unknown. We aimed to study the effective connectivity among the CFP regions in 36 cLBP patients and 36 healthy controls by dynamic causal modeling (DCM). Both the resting-state and task-related (Multi-Source Interference Task, MSIT) functional magnetic resonance imaging (fMRI) data were collected and analyzed. The relationship between the effective connectivity of the CFP regions and clinical measures was also examined. Our results suggested that cLBP had significantly altered resting-state effective connectivity of the prefrontal cortex (PFC)-to-mid-cingulate cortex (MCC) (increased) and MCC-to-left superior parietal cortex (LPC) (decreased) pathways as compared with healthy controls. MSIT-related DCM suggested that the interference task could significantly increase the effective connectivity of the right superior parietal cortex (RPC)-to-PFC and RPC-to-MCC pathways in cLBP than that in healthy controls. The control task could significantly decrease the effective connectivity of the MCC-to-LPC and MCC-to-RPC pathways in cLBP than that in healthy controls. The endogenous connectivity of the PFC-to-RPC pathway in cLBP was significantly lower than that in healthy controls. No significant correlations were found between the effective connectivity within CFP networks and pain/depression scores in patients with cLBP. In summary, our findings suggested altered effective connectivity in multiple pathways within the CFP network in both resting-state and performing attention-demanding tasks in patients with cLBP, which extends our understanding of attention dysfunction in patients with cLBP., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change > 1.5 and P < 0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in "regulation of synaptic plasticity and structure" and "calmodulin-dependent protein kinase activity," which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII- α , CaMKII- β , and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE., Competing Interests: None of the authors has any conflict of interest to disclose., (Copyright © 2022 Xu Qian et al.)

Chronic nonspecific low back pain (cNLBP) is a leading contributor to disease burden worldwide that is difficult to treat due to its nonspecific aetiology and complexity. The amygdala is a complex of structurally and functionally heterogeneous nuclei that serve as a key neural substrate for the interactions between pain and negative affective states. However, whether the functions of amygdalar subcomponents are differentially altered in cNLBP remains unknown. Little attention has focused on effective connectivity of the amygdala with the cortex in cNLBP. In this study, thirty-three patients with cNLBP and 33 healthy controls (HCs) were included. Resting-state functional connectivity (rsFC) and effective connectivity of the amygdala and its subregions were examined. Our results showed that the patient group exhibited significantly greater rsFC between the left amygdala and left dorsal medial prefrontal cortex (mPFC), which was negatively correlated with pain intensity ratings. Subregional analyses suggested a difference located at the superficial nuclei of the amygdala. Dynamic causal modelling revealed significantly lower effective connectivity from the left amygdala to the dorsal mPFC in patients with cNLBP than in HCs. Both groups exhibited stronger effective connectivity from the left amygdala to the right amygdala. In summary, these findings not only suggested altered rsFC of the amygdala-mPFC pathway in cNLBP but also implicated an abnormal direction of information processing between the amygdala and mPFC in these patients. Our results further highlight the involvement of the amygdala in the neuropathology of cNLBP., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the incidence and types of thalassemia in Xiangxi Tujia and Miao Autonomous Prefecture., Methods: Automatic capillary electrophoresis was used to screen the thalassemia phenotypes of 22 940 blood samples of pregnant women and puerperants collected in our hospital and some other medical institutions in the prefecture during 2017-2019, among which there were 3 356 cases of Tujia ethnicity, 2 821 cases of Miao ethnicity, and 2 233 cases of Han ethnicity included, whose ethnicity were indicated. The samples with positive result would undergo further genetic testing., Results: There were 2 314 cases of suspicious thalassemia were screened from 22 940 cases by the electrophoresis, thus the positive rate was 10.1% (hematological phenotypes from some other institutions were not included). Specifically, there were 1 706 cases with HBA 2 less than 2.5%, 255 cases with HBA 2 ranged from 2.5% to 3.5%, which displayed abnormal hematology (MCV or/and MCH) or other abnormal bands, and 353 cases with HBA 2 >3.5%. There were 436 suspected positive patients in 2 314 suspicious samples received further thalassemia gene testing in our hospital, among them 48 cases were diagnosed with α-thalassemia, 85 cases with β-thalassemia, and 2 cases as compound type. The positive diagnosis rate of α-thalassemia gene test was 11.0%, β-thalassemia was 19.4%, and positive pregnant women was 31.0%., Conclusion: The positive rate of thalassemia screening in Xiangxi Autonomous Prefecture is roughly the same as that in other regions of Hunan. The positive predictive value of β-thalassemia screening is as high as 86%. Compared with the missed screening data, it is recommended to use hematology (MCV, MCH) method combined with capillary hemoglobin electrophoresis for thalassemia screening.

Purpose: Investigating the designs and effects of high dielectric constant (HDC) materials in the shape of a conformal helmet on the enhancement of RF field and reduction of specific absorption rate at 10.5 T for human brain studies., Methods: A continuous and a segmented four-piece HDC helmet fit to a human head inside an eight-channel fractionated-dipole array were constructed and studied with a phantom and a human head model using computer electromagnetic simulations. The simulated transmit efficiency and receive sensitivity were experimentally validated using a phantom with identical electric properties and helmet-coil configurations of the computer model. The temporal and spatial distributions of displacement currents on the HDC helmets were analyzed., Results: Using the continuous HDC helmet, simulation results in the human head model demonstrated an average transmit efficiency enhancement of 66%. A propagating displacement current was induced on the continuous helmet, leading to an inhomogeneous RF field enhancement in the brain. Using the segmented four-piece helmet design to reduce this effect, an average 55% and 57% enhancement in the transmit efficiency and SNR was achieved in human head, respectively, along with 8% and 28% reductions in average and maximum local specific absorption rate., Conclusion: The HDC helmets enhanced the transmit efficiency and SNR of the dipole array coil in the human head at 10.5 T. The segmentation of the helmet to disrupt the continuity of circumscribing displacement currents in the helmet produced a more uniform distribution of the transmit field and lower specific absorption rate in the human head compared with the continuous helmet design., (© 2021 International Society for Magnetic Resonance in Medicine.)

The present study aimed to investigate the regulatory mechanism of chemokine (C-X-C motif) receptor 4 (CXCR4) on endothelial progenitor cells (EPCs) through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway under hypoxic conditions. Mononuclear cells were isolated from the bone marrow (BM) of young Sprague-Dawley (SD) rats. Bone marrow-derived endothelial progenitor cells (BM-EPCs) were characterized by using Dil-labeled acetylated low-density lipoprotein (Dil-ac-LDL) and fluorescein isothiocyanate-labeled UEA (FITC-UEA-1). Phenotype identification of BM-EPCs was based on red cytoplasm and green cytomembrane. Flow cytometry was employed to examine the markers CD14, CD34, and KDR. Expression level of the EPC-specific surface marker CD14 was found to be negative, while the expression level of CD34 and KDR was positive. In addition, CXCR4 was stably overexpressed in BM-EPCs after transfection with adenovirus-CXCR4. Cell proliferation, migration and apoptosis abilities were measured through the application of CCK-8, followed by Transwell and flow cytometry assays. The expression level of CXCR4, PI3K and Akt was determined by reverse transcription-quantitative PCR and western blotting assays. Functional experiments demonstrated that hypoxia inhibited BM-EPC proliferation and migration, while accelerating BM-EPC apoptosis. Additionally, CXCR4 was found to promote proliferation and migration, and suppress apoptosis in BM-EPCs with or without hypoxia treatment. Evidence also demonstrated that CXCR4 markedly upregulated the expression levels of PI3K and Akt. Furthermore, PI3K inhibitor (LY294002) and CXCR4 inhibitor (AMD3100) effectively inhibited the proliferation, migration and resistance to apoptosis of CXCR4-mediated BM-EPCs under hypoxic conditions., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Liu et al.)

Purpose: Although it is known that peripheral arterial disease (PAD) is associated with chronic myopathies, the acute muscular responses to exercise in this population are less clear. This study used diffusion tensor imaging (DTI) to compare acute exercise-related muscle damage between PAD patients and healthy controls., Methods: Eight PAD patients and seven healthy controls performed graded plantar flexion in the bore of a 3T MRI scanner. Exercise began at 2 kg and increased by 2 kg every 2 min until failure, or completion of 10 min of exercise. DTI images were acquired from the lower leg pre- and post-exercise, and were analyzed for mean diffusivity, fractional anisotropy (FA), and eigenvalues 1-3 (λ 1-3 ) of the medial gastrocnemius (MG) and tibialis anterior (TA)., Results: Results indicated a significant leg by time interaction for mean diffusivity, explained by a significantly greater increase in diffusivity of the MG in the most affected legs of PAD patients (11.1 × 10 -4  ± 0.5 × 10 -4 mm 2 /s vs. 12.7 × 10 -4  ± 1.2 × 10 -4 mm 2 /s at pre and post, respectively, P = 0.02) compared to healthy control subjects (10.8 × 10 -4  ± 0.3 × 10 -4 mm 2 /s vs. 11.2 × 10 -4  ± 0.5 × 10 -4 mm 2 /s at pre and post, respectively, P = 1.0). No significant differences were observed for the TA, or λ 1-3 (all P ≥ 0.06). Moreover, no reciprocal changes were observed for FA in either group (all P ≥ 0.29)., Conclusion: These data suggest that calf muscle diffusivity increases more in PAD patients compared to controls after exercise. These findings are consistent with the notion that acute exercise results in increased muscle damage in PAD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To demonstrate that strategic use of materials with high electric permittivity along with integrated head-sized coil arrays can improve SNR in the entire brain., Methods: Numerical simulations were used to design a high-permittivity material (HPM) helmet for enhancing SNR throughout the brain in receive arrays of 8 and 28 channels. Then, two 30-channel head coils of identical geometry were constructed: one fitted with a prototype helmet-shaped ceramic HPM helmet, and the second with a helmet-shaped low-permittivity shell, each 8-mm thick. An eight-channel dipole array was used for excitation. In vivo maps of excitation flip angle and SNR were acquired., Results: Simulation results showed improvement in transmit efficiency by up to 65% and in receive-side SNR by up to 47% on average through the head with use of an HPM helmet. Experimental results showed that experimental transmit efficiency was improved by approximately 56% at the center of brain, and experimental receive-side SNR (SNR normalized to flip angle) was improved by approximately 21% on average through orthogonal planes through the cerebrum, including at the center of the brain, with the HPM., Conclusion: Although HPM is used increasingly to improve transmit efficiency locally in situations in which the transmit coil and imaging volume are much larger than the HPM, here we demonstrate that HPM can also be used to improve transmit efficiency and receive-side SNR throughout the brain by improving performance of a head-sized receive array. This includes the center of the brain, where it is difficult to improve SNR by other means., (© 2021 International Society for Magnetic Resonance in Medicine.)

Objective: To investigate the clinical characteristic of coagulation, possible causes and countermeasures of patients with severe corona virus disease 2019 (COVID-19)., Methods: The clinical data of the 142 patients diagnosed as COVID-19 at Wuhan Third Hospital in Wuhan, China, from February 10 to February 16, 2020 were collected and analyzed retrospective. Among the patients, 17 cases of dead patients were divided into observe group, and 125 cases of cured patients were divided into control group. The clinical characteristics, laboratory tests, influencing factors, anticoagulant therapy, embolization and bleeding events of the two groups were observed., Results: The average hospital stay time in 142 patients was 22 d. For the 17 dead patients in the observe group, the average hospital stay time was 9.9 d, and the D-dimer, prothrombin time, WBC count and Padua score of the patients in the observe group were significantly higher as compared with the patients in the control group. PT(OR=1.064, 95%CI 1.012-1.119) and D-D(OR=1.045, 95%CI 1.027-1.064) were the independent risk factors that causing the death of COVID-19 patients. Among the patients, 36(25.4%) patients received low-molecular-weight heparin for anticoagulant therapy, with the average course of 9.6 d. The cumulative incidence of the embolism of the patients in the observe group was 7（41.2%）, while 2(11.8%) patients developed to deep vein thrombosis (DVT) and pulmonary embolism (PE), 3 (17.6%) patients occurred acute cerebral infarction and 2 (11.8%) patients occurred acute myocardial infarction. 3 (17.6%) dead patients revealed dominant disseminated intravascular coagulation (DIC)., Conclusion: Most patients with severe COVID-19 shows a variety of risk factors for thrombus, and those with coagulation dysfunction shows a high dead rate and rapid disease progression. Therefore, coagulation indicators should be dynamically monitored, and mechanical and drug prevention should be actively carried out.

Objective: Preeclampsia (PE) is one of common pregnancy diseases, which has seriously threatened the health of the gravidas. Although upregulated miR-269-3p has been found in the placentas of the patients with PE, the regulation mechanisms of miR-296-3p remain unclear., Patients and Methods: In this study, the placentas of the patients and normal gravidas were used to observe the difference in miR-296-3p expression level, and HTR-8/Svneo and JAR cells were used to investigate the role of miR296-3p in trophoblast cells. Besides, qRT-PCR, Western blot, CCK-8 assay, Dual-Luciferase reporter gene assay and transwell assay were used to explore the functions and regulation mechanisms of miR-296-3p on PE., Results: The results showed that miR-296-3p was upregulated in the PE-placentas, and increased miR-296-3p could inhibit the proliferation, invasion and migration of HTR-8/Svneo and JAR cells. Besides, miR-296-3p could directly target the 3'-UTR of CEMIP, and the phenomena induced by increased miR-296-3p, including decreased β-catenin and p-AKT and weakened proliferation, invasion and migration abilities, could be reversed by upregulating the expression level of CEMIP., Conclusions: To summarize, this study suggests that miR-296-3p inactivates the Wnt/β-catenin and PI3K/AKT pathways to promote the progression of PE via targeting the CEMIP.

Purpose: In this work, we investigated how the position of the radiofrequency (RF) shield can affect the signal-to-noise ratio (SNR) of a receive RF coil. Our aim was to obtain physical insight for the design of a 10.5T 32-channel head coil, subject to the constraints on the diameter of the RF shield imposed by the head gradient coil geometry., Method: We used full-wave numerical simulations to investigate how the SNR of an RF receive coil depends on the diameter of the RF shield at ultra-high magnetic field (UHF) strengths (≥7T)., Results: Our simulations showed that there is an SNR-optimal RF shield size at UHF strength, whereas at low field the SNR monotonically increases with the shield diameter. For a 32-channel head coil at 10.5T, an optimally sized RF shield could act as a cylindrical waveguide and increase the SNR in the brain by 27% compared to moving the shield as far as possible from the coil. Our results also showed that a separate transmit array between the RF shield and the receive array could considerably reduce SNR even if they are decoupled., Conclusion: At sufficiently high magnetic field strength, the design of local RF coils should be optimized together with the design of the RF shield to benefit from both near field and resonant modes., (© 2021 International Society for Magnetic Resonance in Medicine.)

In this study, we describe a novel synthesis of galactosylated lipids by lipase catalysis. Lactitol (Lac), galactose (Gal), or N -acetyl galactosamine (GalNAc) was coupled with cholesterol (CHS) as target head groups by enzyme-catalyzed regioselective esterification to produce three kinds of lipids: CHS-1-Gal, CHS-6-Gal, or CHS-6-GalNAc 1 . The biological effects of galactosylated lipids carrying different constitutional isomers of the pendent sugar species were investigated. LP-1-Gal (liposomes containing 5.0 molar% of CHS-1-Gal) showed strong binding to tetrameric lectins of Ricinus communis agglutinin (RCA120) in vitro , while LP-6-Gal (liposomes containing 5.0 molar% of CHS-6-Gal) and LP-6-GalNAc (liposomes containing 5.0 molar% of CHS-6-GalNAc) did not. After intravenous injection, LP-6-GalNAc, LP-1-Gal and LP-6-Gal rapidly disappeared from the blood and accumulated rapidly in liver (up to 74.88 ± 4.11%, 58.67 ± 5.75%, and 47.66 ± 4.56% of injected dose/g organ within 4 h, respectively). This is significantly higher than the uptake of unmodified liposomes (Unmod-LP) (18.67 ± 6.07%). Pre-injection of asialofetuin significantly inhibits liver uptake of Gal-liposomes ( P  < 0.01), with the degree of inhibition appearing in the following order: LP-6-GalNAc (73.29%) > LP-1-Gal (67.06%) > LP-6-Gal (53.61%). More importantly, LP-6-GalNAc was preferentially taken up by hepatocytes and the uptake ratio by parenchymal cells (PC) and nonparenchymal cells (NPC) (PC/NPC ratio) was 11.03 higher than LP-1-Gal (7.32), LP-6-Gal (5.83) and Unmod-LP (2.39). We suggest that liposomes containing the novel galactosylated lipid CHS-6-GalNAc have potential as drug delivery carriers for hepatocyte-selective targeting.

One in three Americans suffer from kidney diseases such as chronic kidney disease, and one of the etiologies is suggested to be long-term renal hypoxia. Interestingly, sympathetic nervous system activation evokes a renal vasoconstrictor effect that may limit oxygen delivery to the kidney. In this report, we sought to determine if sympathetic activation evoked by lower body negative pressure (LBNP) would decrease cortical and medullary oxygenation in humans. LBNP was activated in a graded fashion (LBNP; -10, -20, and -30 mmHg), as renal oxygenation was measured (T2*, blood oxygen level dependent, BOLD MRI; n = 8). At a separate time, renal blood flow velocity (RBV) to the kidney was measured ( n = 13) as LBNP was instituted. LBNP significantly reduced RBV ( P = 0.041) at -30 mmHg of LBNP (Δ-8.17 ± 3.75 cm/s). Moreover, both renal medullary and cortical T2* were reduced with the graded LBNP application (main effect for the level of LBNP P = 0.0008). During recovery, RBV rapidly returned to baseline, whereas medullary T2* remained depressed into the first minute of recovery. In conclusion, sympathetic activation reduces renal blood flow and leads to a significant decrease in oxygenation in the renal cortex and medulla. NEW & NOTEWORTHY In healthy young adults, increased sympathetic activation induced by lower body negative pressure, led to a decrease in renal cortical and medullary oxygenation measured by T2*, a noninvasive magnetic resonance derived index of deoxyhemoglobin levels. In this study, we observed a significant decrease in renal cortical and medullary oxygenation with LBNP as well as an increase in renal vasoconstriction. We speculate that sympathetic renal vasoconstriction led to a significant reduction in tissue oxygenation by limiting oxygen delivery to the renal medulla.

Objective: To investigate the feasibility of in vitro inflammatory wound microenvironment simulated by using inflammatory wound tissue homogenate of mice. Methods: (1) Ten eight-week-old C57BL/6 male mice were collected and full-thickness skin tissue with diameter of 1.0 cm on both sides of the midline of the back was taken with a perforator to make the normal skin tissue homogenate supernatant. At 48 h after the full-thickness skin defect wound was established, the wound tissue within 2 mm from the wound edge was taken to make inflammatory wound tissue homogenate supernatant. Two kinds of tissue homogenate supernatant were taken to adjust the total protein concentration to 1 mg/mL, and the tumor necrosis factor α (TNF-α) content was detected by enzyme-linked immunosorbent assay. The number of sample was 6. (2) The primary passage of human umbilical cord mesenchymal stem cells (hUCMSCs) were collected and cultured to the 3rd passage with the normal exosomes being extracted from the hUCMSCs after cultured for 48 h. Another batch of hUCMSCs in the 3rd passage was collected and stimulated with inflammatory wound tissue homogenate supernatant of 30, 50, and 100 μg/mL total protein and normal skin tissue homogenate supernatant of 30, 50, and 100 μg/mL total protein, respectively. After cultured for 48 h, the exosomes stimulated with normal protein of 30, 50, and 100 μg/mL and exosomes stimulated with inflammatory protein of 30, 50, and 100 μg/mL were extracted. Normal exosomes, exosomes stimulated with 30 μg/mL normal protein, and exosomes stimulated with 30 μg/mL inflammatory protein were collected, the morphology was observed by transmission electron microscope, the particle size was detected by nanoparticle tracking analyzer, and the expressions of CD9 and CD63 were detected by Western blotting. (3) Twenty one-day-old C57BL/6 mice were taken to isolate the primary passage of fibroblasts (Fbs) and the 3rd passage of Fbs, whose morphology was observed under the inverted phase contrast microscope. The Fbs of 3rd passage were collected to observe the expression of vimentin by cell crawling method combined with immunofluorescence method at culture hour (CH) 2. (4) The Fbs of 3rd passage were divided into control group, normal exosome group, 30, 50, 100 μg/mL normal protein stimulating exosome group, and 30, 50, 100 μg/mL inflammatory protein stimulating exosome group according to the random number table, with 4 wells in each group. Cells in control group received no treatment, and cells in the other 7 groups were respectively added with normal exosomes, exosomes stimulated with normal protein of 30, 50, and 100 μg/mL, and exosomes stimulated with inflammatory protein of 30, 50, and 100 μg/mL prepared in experiment (2). The final mass concentration of exosomes was adjusted to 10 μg/mL. The cell viability was detected by cell count kit 8 at CH 48. (5) Two batches of Fbs in the 3rd passage were divided and treated as those in experiment (4), with 4 wells in each group, and the final mass concentration of exosomes was adjusted to 1 and 10 μg/mL, respectively. The cell mobility was detected by cell scratch test at CH 6, 12, and 24. (6) Two batches of the Fbs of 3rd passage were collected, divided, and treated as those in experiment (4) except with no control group, with 3 wells in each group, and the final mass concentration of exosomes was respectively adjusted to 1 and 10 μg/mL. The mRNA expression levels of transforming growth factor β(1) (TGF-β(1)), TGF-β(3), and α smooth muscle actin (α-SMA) were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction at CH 48. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and Bonferroni method. Results: (1) The content of TNF-α in inflammatory wound tissue homogenate supernatant of mice was (116±3) pg/mL, significantly higher than (97±5) pg/mL in normal skin tissue homogenate supernatant at post injury hour 48 ( t =3.306, P <0.05). (2) Normal exosomes, exosomes stimulated with 30 μg/mL normal protein, and exosomes stimulated with 30 μg/mL inflammatory protein of hUCMSCs showed the typical saucer-like shape. The particle sizes of the three exosomes of hUCMSCs were 30-150 nm, which were all within the normal particle size range of exosome. Three exosomes of hUCMSCs positively expressed CD9 and CD63. (3) The primary passage of cells were clearly defined and showed protruding spindle shape, irregular polygon shape, or slender strip shape. The morphology of the 3rd and the primary passage of cells is similar. At CH 2, vimentin in cells was positively expressed, and the cells were identified as Fbs. (4) At CH 48, the cell viability was (137.4±2.8)% in 30 μg/mL inflammatory protein stimulating exosome group, obviously higher than 100%, (107.5±2.4)%, (113.3±3.2)%, (104.0±2.0)%, and (101.9±1.5)% in control group, normal exosome group, 30 μg/mL normal protein stimulating exosome group, and 50 and 100 μg/mL inflammatory protein stimulating exosome groups, respectively ( P <0.01), and cell viability in 30 μg/mL normal protein stimulating exosome group was obviously higher than that in control group, normal exosome group, and 50 and 100 μg/mL normal protein stimulating exosome groups [(103.4±2.2)% and (102.5±1.4)%], respectively ( P <0.01). (5) At CH 6, 12, and 24, the mobility rate of cells in 30 μg/mL inflammatory protein stimulating exosome group was significantly higher than that in control group, normal exosome group, 30 μg/mL normal protein stimulating exosome group, and 50 and 100 μg/mL inflammatory protein stimulating exosome groups, respectively, when the final mass concentrations of exosome was 1 μg/mL ( P <0.05) . At CH 12, the mobility rate of cells in 30 μg/mL normal protein stimulating exosome group was obviously higher than that in control group, normal exosome group, and 50 and 100 μg/mL normal protein stimulating exosome groups, respectively, when the final mass concentration of exosome was 1 μg/mL ( P <0.05). At CH 6, the mobility rate of cells in 30 μg/mL inflammatory protein stimulating exosome group was significantly higher than that in control group and normal exosome group ( P <0.05), and the mobility rate of cells in 30 μg/mL normal protein stimulating exosome group was significantly higher than that in 50 and 100 μg/mL normal protein stimulating exosome groups, respectively, when the final mass concentration of exosome was 10 μg/mL ( P <0.05). At CH 12 and 24, the mobility rate of cells in 30 μg/mL inflammatory protein stimulating exosome group was significantly higher than that in control group, normal exosome group, and 50 and 100 μg/mL inflammatory protein stimulating exosome groups ( P <0.05), and the mobility rate of cells in 30 μg/mL normal protein stimulating exosome group was significantly higher than that in control group, normal exosome group, and 50 and 100 μg/mL normal protein stimulating exosome groups, respectively, when the final mass concentration of exosome was 10 μg/mL ( P <0.05). (6) There were no statistically significant differences in mRNA expression levels of TGF-β(1), TGF-β(3), and α-SMA of cells among the 7 groups at CH 48 when the final mass concentration of exosome was 1 μg/mL ( F =1.123, 1.537, 1.653, P >0.05). There were no statistically significant differences in mRNA expression levels of TGF-β(1) and α-SMA of cells among the 7 groups at CH 48 when the final mass concentration of exosome was 10 μg/mL ( F =1.487, 1.308, P >0.05), and mRNA expression level of TGF-β(3) of cells in 50 μg/mL inflammatory protein stimulating exosome group at CH 48 was significantly higher than that in normal exosome group, 50 μg/mL normal protein stimulating exosome group, and 30 and 100 μg/mL inflammatory protein stimulating exosome groups when the final mass concentration of exosome was 10 μg/mL ( P <0.05). Conclusions: The pretreatment with inflammatory wound tissue homogenate supernatant of mice has no significant effect on the total protein of hUCMSCs exosomes. The hUCMSCs exosomes stimulated by low concentration inflammatory wound tissue homogenate supernatant can significantly promote the proliferation and migration ability of Fbs. The content of inflammatory mediators in the wound tissue homogenate supernatant during the inflammatory phase is extremely low, which may be the reason that the anti-inflammation and tissue repair paracrine effects of mesenchymal stem cell cannot be effectively started.

This work introduces an innovative magnetic resonance (MR) imaging technology that incorporates radiofrequency (RF) coil(s) with permittivity-tunable ultrahigh dielectric constant (tuHDC) ceramics to significantly improve RF coil transmission and reception efficiencies, MR imaging sensitivity and signal-to-noise ratio (SNR). The tuHDC ceramics made of composite barium strontium titanate (BST) compounds (Ba 0.6 Sr 0.4 TiO 3 ) have low dielectric loss and very high permittivity tunability from 2,000 to 15000 by varying the ceramic temperature between 0°C and 40°C to achieve an optimal permittivity for MR imaging application. We demonstrated for the first time the proof of concept using the BST-based tuHDC-RF-coil technology to improve MR spectroscopic imaging performance of 17 O nuclide at 10.5 Tesla (T) at a low ceramic temperature and 23 Na nuclide at 7T at room temperature. We discovered a large and spatially independent noise reduction under an optimal ceramic temperature, which synergistically resulted in an unprecedented SNR improvement. Large improvements were also demonstrated for 1 H MRI on a 1.5T clinical scanner using the same ceramics. The tuHDC-RF-coil technology is robust, flexible and cost-effective; it presents a technical breakthrough to significantly improve imaging sensitivity and resolution for broad MR imaging applications; which is critical for advancing biomedical and neuroscience research, and improving diagnostic imaging.