Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

BACKGROUND: Iron deposition plays a crucial role in the pathophysiology of Parkinson's disease (PD), yet the distribution pattern of iron deposition in the subcortical nuclei has been inconsistent across previous studies. We aimed to assess the difference patterns of iron deposition detected by quantitative iron-sensitive magnetic resonance imaging (MRI) between patients with PD and patients with atypical parkinsonian syndromes (APSs), and between patients with PD and healthy controls (HCs). METHODS: A systematic literature search was conducted on PubMed, Embase, and Web of Science databases to identify studies investigating the iron content in PD patients using the iron-sensitive MRI techniques (R2 * and quantitative susceptibility mapping [QSM]), up until May 1, 2023. The quality assessment of case-control and cohort studies was performed using the Newcastle-Ottawa Scale, whereas diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Standardized mean differences and summary estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for iron content, using a random effects model. We also conducted the subgroup-analysis based on the MRI sequence and meta-regression. RESULTS: Seventy-seven studies with 3192 PD, 209 multiple system atrophy (MSA), 174 progressive supranuclear palsy (PSP), and 2447 HCs were included. Elevated iron content in substantia nigra (SN) pars reticulata ( P <0.001) and compacta ( P <0.001), SN ( P <0.001), red nucleus (RN, P <0.001), globus pallidus ( P <0.001), putamen (PUT, P = 0.021), and thalamus ( P = 0.029) were found in PD patients compared with HCs. PD patients showed lower iron content in PUT ( P <0.001), RN ( P = 0.003), SN ( P = 0.017), and caudate nucleus ( P = 0.017) than MSA patients, and lower iron content in RN ( P = 0.001), PUT ( P <0.001), globus pallidus ( P = 0.004), SN ( P = 0.015), and caudate nucleus ( P = 0.001) than PSP patients. The highest diagnostic accuracy distinguishing PD from HCs was observed in SN (AUC: 0.85), and that distinguishing PD from MSA was found in PUT (AUC: 0.90). In addition, the best diagnostic performance was achieved in the RN for distinguishing PD from PSP (AUC: 0.86). CONCLUSIONS: Quantitative iron-sensitive MRI could quantitatively detect the iron content of subcortical nuclei in PD and APSs, while it may be insufficient to accurately diagnose PD. Future studies are needed to explore the role of multimodal MRI in the diagnosis of PD. REGISTRISION PROSPERO (CRD42022344413).
Humans ; Parkinson Disease/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Iron/metabolism*

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Background::Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. Methods::Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.Results::3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) ( n = 2) or risk of compression coronary artery ( n = 2). Concerning sizing, we found that an oversize of 2-5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P <0.001). Conclusions::In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2-5 mm sufficed.

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
Humans ; Receptors, Antigen, T-Cell, gamma-delta ; Immunotherapy, Adoptive ; T-Lymphocytes ; Immunotherapy ; Neoplasms/therapy*

[摘 要] γδT细胞是一类表达γδTCR异源二聚体的特殊固有免疫T细胞。过去，缺乏对其全面系统的基础研究，在其发育、分化、增殖、活化、效应和耗竭等所有环节仍有很多问题尚不清楚。然而，因为成熟的γδT细胞优势定植于皮肤、消化道、呼吸道、生殖道等肿瘤高发的黏膜组织，能以MHC非限制性的方式直接识别和杀伤多种肿瘤细胞，在肿瘤免疫治疗领域具有不可替代的优势，近年来其应用异军突起，发展迅速，也因此反过来促进了基础研究的深入，取得了一些亮眼的进展。本文对2023年γδT细胞在肿瘤免疫治疗领域的重大进展进行述评，主要集中在γδT细胞肿瘤抗原识别机制、肿瘤微环境中γδT细胞的功能调控、γδT细胞抗肿瘤细胞毒活性的机制、新型基于γδT细胞的肿瘤免疫治疗协同增效策略四个方面，以期推动γδT细胞在肿瘤免疫治疗领域的进一步发展，为临床γδT细胞应用协同增效的策略提供新的思路。

Objective To construct chimeric antigen receptors modified γδT cells targeting at BCMA(BCMA CAR-γδT)and to evaluate its efficacy of anti-multiple myeloma in vitro.Methods Lentiviral vectors containing BCMA single-chain variable fragment were constructed and transiently transfected into 293T cells.The expression of foreign genes was verified by fluorescence microscopy and Western blot;the lentivirus was packaged and the virus titer was determined by flow cytometry.Human peripheral blood αβT cells were infected and γδT cells were examined for its infection efficiency;LDH release method was used to detect the cytotoxic activity of BCMA CAR-γδT cells against human multiple myeloma cell lines in vitro,and the difference of cytotoxic activity between CAR-γδT cells and CAR-αβT cells was compared by Incucyte S3 Live-Cell Analysis Instrument.Results Twenty-four hours after BCMA-CAR lentiviral vector was transferred into 293T cells,the expression of exogenous ZsGreen was microscopied by fluorescence microscope;CD3ζ was detected by Western blot,which showed that BCMA-CAR could be success-fully expressed.The lentivirus was packaged,collected and concentrated(virus titer of 2.23×108 Tu/mL).Infected αβT cells and γδT cells from human peripheral blood in MOI=5,and the results of flow cytometry showed that infection efficiency of αβT cells was 59.18%±2.56%,γδT cells was 48.15±9.86%.The cytotoxic activity of CAR-γδT cells against human myeloma cell lines MM1.S,H929 with high expression of BCMA and K562 cells with over-expression of BCMA was higher than that of empty vector control γδ T cells,which were signifi-cantly enhanced(P＜0.001),but there was no difference in cell lines negative for BCMA expression;Live-Cell Analysis Instrument results showed that the cytotoxic activity of BCMA CAR-γδT cells and BCMA CAR-αβT cells against H929 in vitro was significantly better than their vector control cells.There was no difference in the cytotoxic activities of BCMA CAR-γδT cells as compared with against BCMA negative cell lines,and so do BCMA CAR-T cells.Conclusions Cytotoxic activity of BCMA CAR-γδT targeting at BCMA in vitro was significantly enhanced,which is expected to serve as a novel allogeneic γδT cell product for cell a-doptive immunotherapy of multiple myeloma.