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Na Li,1 Xuefei Li,1 Rui Su,1 Ruihe Wu,1 Hong-Qing Niu,1 Jing Luo,1 Chong Gao,2 Xiaofeng Li,1 Caihong Wang1 1Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Pathology, Joint Program in Transfusion Medicine, Brigham and Women’s Hospital/Children’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Caihong Wang, Tel +8613603515399, Fax +863513365551, Email snwch@sina.comPurpose: Low-dose interleukin-2 (ld-IL-2) has been shown to regulate the balance between effector T and regulatory T (Treg) cells and has been used in several clinical trials to treat autoimmune diseases including rheumatoid arthritis (RA). In this study, we investigated the effects of ld-IL-2 on collagen-induced arthritis (CIA) in mice.Methods: Arthritis severity in CIA mice was measured using the arthritis index (AI), radiographs, and hematoxylin and eosin staining. Cytokines were detected using enzyme-linked immunosorbent assay. Gut microbiota alterations and short-chain fatty acid production were analyzed through 16S rRNA sequencing and gas chromatography.Results: The AI scores of CIA mice treated with ld-IL-2 were significantly lower compared to the model group, which significantly reduced the severity of arthritis. Ld-IL-2 also altered the gut microbiota in CIA mice. The diversity, composition, and dominant species of gut microbiota were altered by ld-IL-2 treatment. Ld-IL-2 also increased short-chain fatty acid levels. There was a strong correlation between ld-IL-2 treatment and improved gut microbiota.Conclusion: Ld-IL-2 significantly ameliorated joint inflammation and bone damage and improved gut microbial dysbiosis in CIA, indicating that it may be a promising therapy for RA patients.Keywords: low-dose IL-2, CIA, gut microbiota, SCFA, 16sRNA

Background: Currently, tumor budding (TB) is defined as an important factor for a poor prognosis in various types of cancers. The authors identified a significant presence of TB-like structures at the tumor invasive front in giant cell tumor of bone (GCTB), which may have the same biologic function as TB. The objective of this report was to describe the distribution of TB in GCTB and investigate its correlation with clinicopathologic characteristics, the immune microenvironment, survival prognosis, and response to denosumab treatment., Methods: This multicenter cohort study included 426 patients with GCTB who received treatment between 2012 and 2021 at four centers. Two independent pathologists performed visual assessments of TBL structures in hematoxylin-and-eosin-stained tumor sections. Immunohistochemistry was used to evaluate tumor-infiltrating lymphocyte subtypes (CD3-positive, CD4-positive, CD8-positive, CD20-positive, programmed cell death protein-1-positive, programmed cell death-ligand 1positive, and FoxP3-positive) as well as Ki-67 expression levels in 426 tissue samples. These parameters were then analyzed for associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]), clinicopathologic characteristics, and response to denosumab treatment., Results: High-grade TB was associated with poorer LRFS and OS in both patient groups. In addition, TB was correlated with various clinicopathologic features, tumor-infiltrating lymphocyte expression, and response to denosumab treatment. TB outperformed the traditional Enneking and Campanacci staging systems in predicting patient LRFS and OS., Conclusions: The current data support the assessment of TBL structures as a reliable prognostic tool in GCTB, potentially aiding in the development of personalized treatment strategies for patients., (© 2024 American Cancer Society.)

Purpose: The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis., Methods: Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness., Results: Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex ( P = .046), Enneking staging ( P < .001), Ki-67 expression ( P = .007), and denosumab treatment responsiveness ( P = .005). Lower CD8 + (tumor interior [TI]) NNDTC, and CD3 + (TI) NNDTC were associated with worse PFS ( P = .003 and .038, respectively), whereas lower CD8 + (TI) NNDTC was associated with worse OS ( P = .001), but CD8 + (tumor infiltrating margin) NNDTC had the opposite effect ( P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB., Conclusion: These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

Plants face a relentless onslaught from a diverse array of pathogens in their natural environment, to which they have evolved a myriad of strategies that unfold across various temporal scales. Cell surface pattern recognition receptors (PRRs) detect conserved elicitors from pathogens or endogenous molecules released during pathogen invasion, initiating the first line of defence in plants, known as pattern-triggered immunity (PTI), which imparts a baseline level of disease resistance. Inside host cells, pathogen effectors are sensed by the nucleotide-binding/leucine-rich repeat (NLR) receptors, which then activate the second line of defence: effector-triggered immunity (ETI), offering a more potent and enduring defence mechanism. Moreover, PTI and ETI collaborate synergistically to bolster disease resistance and collectively trigger a cascade of downstream defence responses. This article provides a comprehensive review of plant defence responses, offering an overview of the stepwise activation of plant immunity and the interactions between PTI-ETI synergistic signal transduction., (© 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Chordoma, a rare bone tumor, presents limited treatment options and patients typically exhibit poor survival outcomes. While immunotherapy has shown promising results in treating various tumors, research on the immune microenvironment of chordomas is still in its early stages. Therefore, understanding how the immune microenvironment of chordomas influences the outcomes of immunotherapy is crucial., Methods: We employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, CellChat, gene set variation analysis, as well as calculation of immune features to further dissect the complex immune microenvironment of chordoma., Results: Previous research by van Oost et al argued that compared with other sarcomas, chordomas typically exhibit an immunologically "hot" microenvironment, a conclusion with which we concur based on their research findings. Additionally, the authors suggest that T cell-mediated immunotherapy is feasible for the majority of chordomas. However, we are inclined to categorize them as an immune-excluded phenotype according to the latest classification methods, rather than persisting with the concepts of "cold" and "hot". Unlike them, we explored immune infiltration scores (IS), T lymphocyte scoring (TLS), and human leucocyte antigen class I (HLA-I) using Bulk RNA-seq data from 126 chordoma patients and found that higher IS, TLS, and higher HLA-I expression were associated with poorer patient prognosis. Additionally, CellChat analysis of scRNA-seq results from six chordoma patients revealed no direct interaction between T cells and tumor cells., Conclusions: These findings suggested that the efficacy of T cell-based immunotherapy may be limited or even ineffective for patients with chordoma., Competing Interests: Competing interests: The authors declare that they have no competing interests, (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Traumatic brain injury (TBI) is a major health concern globally, which is characterized by high morbidity and mortality rates. Since the 21st century, TBI has received increasing attention and the number of publications is growing rapidly. This study aimed to characterize the volume and quality of scholarly output on TBI and identify the most impactful literature, research trends, and hotspots from the year 2000-2022. We searched publications on TBI through the Web of Science Core Collection-Science Citation Index Expanded database which were published from 2000 to 2022. Basic information of each paper, including publication year, countries, authors, affiliations, journal, fundings, subject areas, and keywords were collected for further analysis by using Microsoft Excel, VOSviewer, and CiteSpace software. A total of 47231 TBI-related publications were identified through database retrieval. The annual number of publications on TBI has increased steadily over the past twenty years and the number in the year 2022 is sevenfold higher than that in 2000. The United States of America (USA) was the leading country in both numbers of publications and citations, which is consistent with the finding that it had the most funding agencies. Menon DK was the author with the highest influence and the University of California System was the most productive affiliation. Moreover, keywords analysis suggested that the research topics can be mainly divided into six categories: management, rehabilitation, mechanisms, concussion, neuroimaging, and neuroendocrine. This study visualized the trends and focuses of scientific research related to TBI, both quantitatively and qualitatively. The USA had a relatively high academic impact owing to its productive experts and institutions in this field. Neuroinflammation, machine learning, tranexamic acid, and extracellular vesicles are currently hot topics in the field of TBI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The WUSCHEL-related Homeobox (WOX) genes, which encode plant-specific homeobox (HB) transcription factors, play crucial roles in regulating plant growth and development. However, the functions of WOX genes are little known in Eucalyptus, one of the fastest-growing tree resources with considerable widespread cultivation worldwide., Results: A total of nine WOX genes named EgWOX1-EgWOX9 were retrieved and designated from Eucalyptus grandis. From the three divided clades marked as Modern/WUS, Intermediate and Ancient, the largest group Modern/WUS (6 EgWOXs) contains a specific domain with 8 amino acids: TLQLFPLR. The collinearity, cis-regulatory elements, protein-protein interaction network and gene expression analysis reveal that the WUS proteins in E. grandis involve in regulating meristems development and regeneration. Furthermore, by externally adding of truncated peptides isolated from WUS specific domain, the transformation efficiency in E. urophylla × E. grandis DH32-29 was significant enhanced. The transcriptomics data further reveals that the use of small peptides activates metabolism pathways such as starch and sucrose metabolism, phenylpropanoid biosynthesis and flavonoid biosynthesis., Conclusions: Peptides isolated from WUS protein can be utilized to enhance the transformation efficiency in Eucalyptus, thereby contributing to the high-efficiency breeding of Eucalyptus., (© 2023. The Author(s).)

Background: A scientific and comprehensive analysis of the current status and trends in the field of cancer-associated fibroblast (CAF) research is worth investigating. This study aims to investigate and visualize the development, research frontiers, and future trends in CAFs both quantitatively and qualitatively based on a bibliometric approach., Methods: A total of 5518 publications were downloaded from the Science Citation Index Expanded of Web of Science Core Collection from 1999 to 2021 and identified for bibliometric analysis. Visualized approaches, OriginPro (version 9.8.0.200) and R (version 4.2.0) software tools were used to perform bibliometric and knowledge-map analysis., Results: The number of publications on CAFs increased each year, and the same tendency was observed in the RRI. Apart from China, the countries with the largest number of publications and the most cited frequency were mainly Western developed countries, especially the USA. Cancers was the journal with the largest number of articles published in CAFs, and Oncology was the most popular research orientation. The most productive author was Lisanti MP, and the University of Texas System was ranked first in the institutions. In addition, the topics of CAFs could be divided into five categories, including tumor classification, prognostic study, oncologic therapies, tumor metabolism and tumor microenvironment., Conclusions: This is the first thoroughly scientific bibliometric analysis and visualized study of the global research field on CAFs over the past 20 years. The study may provide benefits for researchers to master CAFs' dynamic evolution and research trends., (© 2023. The Author(s).)

Background: ChatGPT, powered by the GPT model and Transformer architecture, has demonstrated remarkable performance in the domains of medicine and healthcare, providing customized and informative responses. In our study, we investigated the potential of ChatGPT in the field of neurosurgery, focusing on its applications at the patient, neurosurgery student/resident, and neurosurgeon levels., Method: The authors conducted inquiries with ChatGPT from the viewpoints of patients, neurosurgery students/residents, and neurosurgeons, covering a range of topics, such as disease diagnosis, treatment options, prognosis, rehabilitation, and patient care. The authors also explored concepts related to neurosurgery, including fundamental principles and clinical aspects, as well as tools and techniques to enhance the skills of neurosurgery students/residents. Additionally, the authors examined disease-specific medical interventions and the decision-making processes involved in clinical practice., Results: The authors received individual responses from ChatGPT, but they tended to be shallow and repetitive, lacking depth and personalization. Furthermore, ChatGPT may struggle to discern a patient's emotional state, hindering the establishment of rapport and the delivery of appropriate care. The language used in the medical field is influenced by technical and cultural factors, and biases in the training data can result in skewed or inaccurate responses. Additionally, ChatGPT's limitations include the inability to conduct physical examinations or interpret diagnostic images, potentially overlooking complex details and individual nuances in each patient's case. Moreover, its absence in the surgical setting limits its practical utility., Conclusion: Although ChatGPT is a powerful language model, it cannot substitute for the expertise and experience of trained medical professionals. It lacks the capability to perform physical examinations, make diagnoses, administer treatments, establish trust, provide emotional support, and assist in the recovery process. Moreover, the implementation of Artificial Intelligence in healthcare necessitates careful consideration of legal and ethical concerns. While recognizing the potential of ChatGPT, additional training with comprehensive data is necessary to fully maximize its capabilities., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: A comprehensive understanding of the clinical characteristics and prognostic factors associated with axial chondroblastoma (ACB) is still lacking. This study aimed to understand the clinical characteristics and prognostic factors of axial chondroblastoma (ACB) and compare them with extra-axial chondroblastoma (EACB)., Methods: A retrospective review of our institution's local database was conducted, encompassing a total of 132 CB patients, of which 61 were diagnosed with ACB and 71 with EACB. Immunohistochemistry was employed to evaluate the expression levels of vimentin, S100, and cytokeratin., Results: ACB and EACB shared similar characteristics, with the exception of advanced age, tumor size, elevated Vim expression, incidence of surrounding tissue invasion, and postoperative sensory or motor dysfunction. While wide resection and absence of surrounding tissue invasion consistently showed a favorable association with survival in both ACB and EACB cohorts during univariate analysis, most parameters exhibited differential prognostic significance between the two groups. Notably, the significant prognostic factors for local recurrence-free survival in the ACB cohort included the type of resection and the presence of chicken-wire calcification. In the multivariate analysis of overall survival, the type of resection emerged as a significant predictor in the ACB cohort, whereas in the EACB group, the type of resection and the occurrence of postoperative sensory or motor dysfunction were predictive of overall survival., Conclusion: There may exist distinct biological behaviors between ACB and EACB, thereby providing valuable insights into the prognostic characteristics of ACB patients and contributing to enhanced outcome prediction in this particular patient population., (© 2023. The Author(s).)

Background: Currently, little is known about the prognostic value of tumor growth rate (TGR) in spinal giant cell tumors of bone (GCTB)., Objective: To investigate the correlation of TGR with clinicopathological features, immune microenvironment, prognosis, and response to denosumab treatment of spinal GCTB., Methods: A total of 128 patients with spinal GCTB treated at 5 centers from 2011 to 2021 were included. TGR was assessed by 2 independent neuroradiologists using at least 2 preoperative thin-section magnetic resonance imaging scans at a minimum interval of 2 months. Immunohistochemistry was used to assess tumor-infiltrating lymphocyte subtypes for CD3, CD4, CD8, CD20, PD-1, PD-L1, and Foxp3. Then, these parameters were analyzed for their associations with patient outcomes (progression-free survival and overall survival), clinicopathological features, and denosumab treatment responsiveness., Results: High TGR predicted both poor progression-free survival and overall survival (both P < .001). In addition, TGR was associated with postoperative neurological dysfunction ( P < .001), Enneking staging ( P = .016), denosumab treatment responsiveness ( P = .035), and the number of CD3 + ( P < .001), PD-1 + ( P = .009), PD-L1 + ( P < .001), and FoxP3 + tumor-infiltrating lymphocyte ( P = .02). Importantly, TGR outperformed the traditional Enneking, Campanacci, and American Joint Committee on Cancer staging systems in predicting the clinical outcomes of spinal GCTB., Conclusion: These data support the use of TGR as a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy of spinal GCTB, which may be helpful in guiding prognostic risk stratification and therapeutic optimization of patients., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Corneal tissue engineering has developed rapidly in recent years, with a large number of publications emerging worldwide. This study focused on exploring the global status and research trends in this field. Publications related to corneal tissue engineering from 1991 to 2021 were acquired from the Science Citation Index-Expanded (SCI-Expanded) of Web of Science (WoS). Firstly, the VOS viewer software was chosen for visualizing bibliometric networks, including bibliographic coupling analysis, co-citation analysis, co-authorship analysis, and co-occurrence analysis, and the CiteSpace software was used to detect burst keywords. Subsequently, the publication trends in corneal tissue engineering research were also predicted. In present study, 953 publications were selected and analyzed. The number of annual publications was increasing globally and was predicted to continue the current trend. While Japan ranked top 1 in terms of average citation, the USA contributed the most to the corneal tissue engineering research with highest number of citations and highest H -index. The journal of Biomaterials contributed the largest publication number. The top-ranked institutions were National University of Singapore and Singapore National Eye Center. Additionally, researches could be manually divided into four clusters: "biomaterial related research," "cell related research," "transplantation therapy," and "mechanism research on biomaterials." Specifically, the research topic "hydrogel" was predicted to be hotspots which may help researchers to explore new directions for future research., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objectives: The contributing factors for spondylitis after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) remain unclear. Here, we sought to investigate the factors affecting spondylitis occurrence after PVP/PKP. We also compared the clinical characteristics between patients with tuberculous spondylitis (TS) and nontuberculous spondylitis (NTS) following vertebral augmentation., Methods: Literature searches (from January 1, 1982 to October 16, 2020) using MEDLINE, EMBASE, Google Scholar and Web of science databases were conducted to identify eligible studies according to predefined criteria. The local database was also retrospectively reviewed to include additional TS and NTS patients at our center., Results: Thirty studies from the literature and 11 patients from our local institute were identified, yielding a total of 23 TS patients and 50 NTS patients for analysis. Compared with NTS group, patients in the TS group were more likely to have a history of trauma before PVP/PKP treatment. Univariate analyses of risk factors revealed pulmonary tuberculosis and diabetes were significant factors for TS after PVP/PKP. Analyzing NTS, we found obesity, a history of preoperative trauma, urinary tract infection, diabetes and multiple surgical segments (≥2) were significantly associated with its occurrence following PVP/PKP treatment. Multivariate logistic analyses showed a history of pulmonary tuberculosis and diabetes were independent risk factors for TS after PVP/PKP, while diabetes and the number of surgically treated segments independently influenced NTS development., Conclusions: A history of pulmonary tuberculosis and diabetes were independent risk factors for TS. For NTS, diabetes and the number of surgically treated segments significantly influenced the occurrence of postoperative spinal infection. These data may be helpful for guiding risk stratification and preoperative prevention for patients, thereby reducing the incidence of vertebral osteomyelitis after PVP/PKP., 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., (© 2022 Zheng, Liu, Zheng, Niu, Li, Lv, Zou and Xu.)

Introduction: Osteoporosis (OP) is one of the major comorbidities of rheumatoid arthritis (RA). Recent studies have shown that immune cells modulate bone health and regulate bone remodeling. However, the alterations of lymphocyte subsets in RA patients with OP are unclear. Here, we assessed the absolute numbers and proportions of the subsets in RA sufferers with OP and investigated the clinical significance., Methods: A total of 777 RA patients and 117 gender- and age-matched healthy controls (HCs) were enrolled in this study. Patients were divided into RA-non-OP and RA-OP group according to their bone mineral density (BMD) and the history of fragility fracture. Peripheral lymphocyte subsets of participants were assessed by flow cytometry., Results: Among 220 (28.31%) RA-OP patients, there were higher levels of erythrocyte sedimentation rate (ESR) (P = 0.011), C-reactive protein (CRP) (P = 0.028), rheumatoid factor (RF) (P = 0.013) and anti-cyclic citrullinated peptide antibody (ACPA) (P = 0.010), while red blood cells (RBC) (P = 0.039) were lower than those in RA-non-OP group. Compared with those of HCs and RA-non-OP group, the level of circulating Th17 cells in RA-OP patients was significantly increased (P < 0.05), while those of Tregs decreased (P < 0.01), leading to a higher ratio of Th17/Treg (P < 0.01). Notably, the level of B cells in both RA-non-OP and RA-OP group was reduced, this alteration was more obvious in patients with OP (P < 0.05)., Conclusions: Immune disorders characterized by peripheral Th17/Treg imbalance and reduced B cells may contribute directly or indirectly to OP in RA, and this deserves more clinical attention., (© 2022. The Author(s).)

Microorganism exerts a profound impact on the development and function of human immunity. Vice versa, immunity also affects the constitution and function of human microbiota. Hence, a new concept, immunomicroecology, has been put forward as an inevitable consequence of the development in the fields of microecology and immunology. Here, we describe the reciprocities between immunological system and microecological system, and elaborate the concept, developing course, and prospects of immunomicroecology.

Members of the interferon regulatory factor (IRF) gene family are crucial regulators of type I interferon signaling, which may play a role in the resistance of glioma to immune checkpoint blockade. However, the expression profiles, potential functions, and clinical significance of IRF family members remain largely unknown. Here, we examined IRF transcript levels and clinicopathological data from glioma patients using several bioinformatic databases, including ONCOMINE, GEPIA, TCGA, and cBioPortal. We found that IRF1, IRF2, IRF5, IRF8 and IRF9 were significantly upregulated in glioma compared to normal brain tissue. Higher IRF1, IRF2, IRF3, IRF4, IRF5, IRF7, IRF8 and IRF9 mRNA levels correlated with more advanced tumor grades and poorer outcomes. Moreover, although IRFs mutation rates were low (ranging from 0.5% to 2.3%) in glioma patients, genetic alterations in IRFs were associated with more favorable patient survival. Functional analysis showed that IRFs participated in glioma pathology mainly through multiple inflammation- and immunity-related pathways. Additionally, correlations were identified between IRFs and infiltration of immune cells within glioma tissues. Collectively, these results indicate that IRF family members, including IRF1, IRF2, IRF5, IRF8 and IRF9, may serve as prognostic biomarkers and indicators of immune status in glioma patients.

Aims: CD4 + T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4 + T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4 + T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA., Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4 + T cell subpopulations were determined by flow cytometric analysis., Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males., Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Background: Immunophenotyping of blood lymphocytes is an essential tool to evaluate the immune function of patients with immunodeficiency or autoimmunity. Predominately identified CD4 + T cell subsets, Th1, Th2, Th17, as well as regulatory T (Treg) cells, play crucial roles in several immunological and pathological conditions. Considering the variations in cell counts among populations and ethnicities, specific CD4 + T cell subset reference values need to be locally established to enable meaningful comparisons and accurate data interpretation in clinical and research settings. Therefore, the aim of this study was to establish distributions and reference ranges for blood CD4 + T cell subpopulations in age- and sex-balanced healthy adults of a Han Chinese population in Shanxi Province, North China., Methods: Peripheral blood CD4 + T cell subsets were examined in 150 healthy volunteers (75 males, 75 females) aged 20-70 years with a four-color FACSCalibur flow cytometer., Results: Reference value percentages (absolute counts, cells/μl) were defined as 95% of the population for cell types as follows: CD4 + T, 23.78-51.07 (360-1127); Th1, 0.43-39.62 (2.64-276.21); Th2, 0.27-3.57 (1.80-27.14); Th17, 0.22-2.62 (1.10-19.54); and Treg, 2.17-7.94 (13.47-64.58). The ranges for the Th1:Th2 and Th17:Treg ratios were 0.59-52.37 and 0.04-0.76, respectively. Notably, a significant increase was observed in the values of Treg cells in older individuals, and the numbers of Treg cells in females also tended to decrease when compared to those in males. Therefore, we established the distribution and reference range of CD4 + T cell subsets based on age and sex, demonstrating the lowest values of Treg cells in younger females., Conclusions: Collectively, our data provide population-, age-, and sex-specific distributions and reference ranges of circulating CD4 + T cell subpopulations, which can be adopted to guide clinical decisions and interpretation of immunophenotyping data in the Han Chinese population in Taiyuan, Shanxi Province, China. In addition, the low expression of peripheral Treg cells in younger females may be associated with the predisposition of females to autoimmune diseases.

Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) has posed significant threats to the public health and life in China. Unlike the other 6 identified coronaviruses, the SARS-Cov-2 has a high infectious rate, a long incubation period and a variety of manifestations. In the absence of effective treatments for the virus, it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission. Hereby we focused on the surgical practice in Neurosurgery Department, Tongji Hospital, Wuhan, and drafted several recommendations based on the latest relevant guidelines and our experience. These recommendations have helped us until now to achieve 'zero infection' of doctors and nurses in our department, we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.

Objectives: Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity. Mechanistic target of rapamycin (mTOR) signalling negatively controls the development and function of Treg cells. The aim of the present study was to evaluate the effects of rapamycin, under the generic name sirolimus, on CD4+CD25+FoxP3+ Treg cells in rheumatoid arthritis (RA) patients with low disease activity or in DAS28 remission., Methods: Fifty-five RA patients and 60 healthy controls were enrolled in this study. All patients had previously received conventional disease-modifying anti-rheumatic drugs (DMARDs) and were considered to have a low DAS28 score (≤3.2). Peripheral blood samples and clinical information were obtained at baseline and following 6 and 12 weeks of sirolimus treatment, or after 12 weeks of conventional treatment. Peripheral blood samples were also obtained from the healthy controls. The circulating levels of lymphocyte subpopulations were assessed by flow cytometry., Results: Thirty-five patients received sirolimus and 20 patients continued treatment with conventional DMARDs. The absolute counts and proportions of CD4+CD25+FoxP3+ Treg cells were significantly lower in all RA patients with DAS28 ≤ 3.2 as compared with those in healthy controls. By contrast, the difference in circulating Th17 cell numbers was not significant. Sirolimus administration resulted in elevations in circulating Treg cell numbers and significant reductions in the Th17/Treg cell ratio, whereas the circulating level of Treg cells and the Th17/Treg cell ratio in patients under conventional treatment both showed a tendency of reduction. Furthermore, a greater proportion of patients under sirolimus treatment achieved DAS28-based remission at 12 weeks., Conclusions: Sirolimus can favourably expand Treg cells in RA patients with DAS28 ≤3.2, consequently restoring a healthy balance of Th17/Treg cells, which might improve the likelihood of long-term and sustained clinical remission and reduce the probability of disease flare-ups in RA.

Parenchymal neurocysticercosis is the most common form of neurocysticercosis in the central nervous system (CNS), which mainly causes epilepsy and usually responses well to routine medications. However, there are appreciable cases of relapses refractory to medical treatment. We investigated microsurgical treatment of epilepsy with parenchymal neurocysticercosis. Nine cases of epilepsy caused by parenchymal neurocysticercosis from 2002 to 2018 were analyzed retrospectively. Cysts in 7 cases were completely removed. No case died of operation and no new dysfunction of the nervous system was observed after surgery. Among the other 9 cases, 8 cases became seizure-free or controlled by medicine according to the postoperative follow-up for 6 months to 9 years. One case was lost for follow-up. It was suggested that epilepsy with parenchymal neurocysticercosis can usually be controlled after routine medications. However, surgery is still indicated in some cases and careful microsurgery is associated with satisfactory clinical outcomes in appropriately selected cases.

Background: We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance., Methods: In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2 : 1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4 + T subsets were compared before and after the treatment., Results: Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints ( p < 0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone ( p < 0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups ( p > 0.05)., Conclusions: Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245)., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 Hong-Yan Wen et al.)

Although conventional combination therapy is effective for most patients with rheumatoid arthritis (RA), many still do not respond to current therapies. Therefore, novel combination regimens that better target cellular processes involved in RA pathogenesis are required. Preliminary studies have demonstrated the beneficial effects of a combination of cyclophosphamide (CTX) and methotrexate (MTX) in models of RA. Using western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and immunofluorescent staining, we demonstrated that the combination of 4-hydroperoxy CTX (4-H-CTX) and MTX inhibited the expression of receptor activator of nuclear factor-κB ligand (RANKL) in fibroblast-like synoviocytes (FLS) treated with the interleukin (IL)-6/soluble IL-6 receptor (sIL-6R) complex. To elucidate the mechanisms underlying this effect, we treated RA-FLS with the JAK2/STAT3 inhibitor AG490 or p38MAPK inhibitor SB203580. The results showed that IL-6/sIL-6R-induced RANKL upregulation required phosphorylation-mediated activation of STAT3 and p38 signaling, and that 4-H-CTX and/or MTX inhibited RANKL expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3 and p38MAPK signaling. This study demonstrated for the first time the inhibitory effects of 4-H-CTX and MTX on RANKL expression in IL-6/sIL-6R-stimulated FLS via suppression of STAT3 and p38MAPK phosphorylation. These results identify promising therapeutic agents that might have clinical applications in patients with RA who are at high risk of bone erosion or do not respond well to conventional therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To summarize the initial experiences of applying sacral neuromodulation (SNM) for refractory interstitial cystitis/pelvic pain syndrome (IC/PPS). Methods: From January 2013 to August 2016, 26 patients with refractory IC/PPS (including 5 males and 21 females) treated with SNM were recruited in Beijing Chaoyang Hospital and Hebei Yanda Hospital in this retrospective study. The data before operation, after implantation of stage Ⅰ tined lead, and during short-term follow-up after implantation of stage Ⅱ implanted pulse generator (IPG) were compared in order to observe the improvement of relevant symptoms, and to summarize the effectiveness and safety of SNM for IC/PPS. Results: All the 26 patients received stage Ⅰ tined lead implantation under local anesthesia, of whom 7 patients finally had the tined lead removed under local anesthesia because of poor testing effects. And 19 patients chose embedding of IPG at the end of stageⅠ, with the conversion rate from stage Ⅰto stage Ⅱ being 73.1%. The mean follow-up time after stage Ⅱ was 12.1 months. The data at the end of follow-up compared with those before treatment were: voiding frequency in 24 hours 24.3±9.6 vs 13.5±5.7, nocturia 4.6±2.2 vs 2.7±1.5, average voiding amount (109.4 ±45.3)vs(172.6±61.6) ml, O'leary-sant scale score 26.0±3.1 vs 17.0±3.8, quality of life (QOL) score 5.7±0.4 vs 3.3±1.3, sex rating 5.4±1.4 vs 2.9±1.6, and Numeric Pain Intensity Scale 8.4±1.7 vs 3.9±1.2 (all P <0.05). During the follow-up period for the 19 patients, 11 showed symptoms relieve without recurrence, 5 patients had slightly symptoms recurrence and 3 patients had severe recurrence of pelvic pain and frequent urination. About 42.1%(8/19) patients received reprogramming, the average reprogramming rate being 1.73/person. And 84.2% (16/19) patients had symptoms improvement greater than 50% after stage Ⅱ IPG implantation. Conclusions: SNM is an effective, safe and minimally invasive procedure for refractory IC/PPS. IC/PPS is a good indication for SNM with a high conversion rate from stage Ⅰ to stage Ⅱ. Patients should be followed up regularly after operation, and reprogramming should be arranged according to the degree of symptom improvement.

Background: Clostridium acetobutylicum can propagate on fibrous matrices and form biofilms that have improved butanol tolerance and a high fermentation rate and can be repeatedly used. Previously, a novel macroporous resin, KA-I, was synthesized in our laboratory and was demonstrated to be a good adsorbent with high selectivity and capacity for butanol recovery from a model solution. Based on these results, we aimed to develop a process integrating a biofilm reactor with simultaneous product recovery using the KA-I resin to maximize the production efficiency of biobutanol., Results: KA-I showed great affinity for butanol and butyrate and could selectively enhance acetoin production at the expense of acetone during the fermentation. The biofilm reactor exhibited high productivity with considerably low broth turbidity during repeated batch fermentations. By maintaining the butanol level above 6.5 g/L in the biofilm reactor, butyrate adsorption by the KA-I resin was effectively reduced. Co-adsorption of acetone by the resin improved the fermentation performance. By redox modulation with methyl viologen (MV), the butanol-acetone ratio and the total product yield increased. An equivalent solvent titer of 96.5 to 130.7 g/L was achieved with a productivity of 1.0 to 1.5 g · L-1 · h-1. The solvent concentration and productivity increased by 4 to 6-fold and 3 to 5-fold, respectively, compared to traditional batch fermentation using planktonic culture., Conclusions: Compared to the conventional process, the integrated process dramatically improved the productivity and reduced the energy consumption as well as water usage in biobutanol production. While genetic engineering focuses on strain improvement to enhance butanol production, process development can fully exploit the productivity of a strain and maximize the production efficiency.

Objective: To evaluate the effectiveness and safety of the meridian three-combined therapy for treatment of ordinary psoriasis., Methods: A multi-central, randomized and positive drug controlled trial was adopted, and 233 cases were divided into an observation group of 116 cases and a control group of 117 cases. The observation group was treated with thread embedding at points, blood-letting puncture on the back of ear and auricular point pressing (i.e. meridian three-combined therapy). For thread embedding, 3-4 local points such ear points as Fei (CO14), Gan (CO12), Pizhixia (AT4), Shenmen (TF4) , cephalic and symmetric points of severe parts of the limb skin were selected according to the skin lesion position, and the treatment was given once each two weeks. For ear point tapping and pressing, 3-5 points were selected in each session. And the control group was treated with oral administration of Di yin Tablets, 5 tablets each time, twice each day. After treatment of 6 weeks, the clinical therapeutic effects, the score of skin lesion area, the scores for skin lesion severity and safety were compared in the two groups., Results: The markedly effective rate was 57.8 % in the observation group and 51.3% in the control group with no significant difference between the two groups (P>0.05); after treatment the scores for both the skin lesion area and the skin lesion severity were significantly decreased in the two groups compared with those before treatment (P<0.01), and with a significant difference between the two groups (P>0.05). And the incidence rate of the adverse reaction in the observation group was significantly lower than that in the control group., Conclusion: The meridian three-combined therapy is effective and safe for treatment of ordinary psoriasis.

Background & Objective: Leucine-rich repeats and immunoglobulin-like domains 1(LRIG1)is a kind of transmembrane glycoprotein,which is induced by epidermal growth factor (EGF),and develops inhibitory negative feedback by specific binding with epidermal growth factor receptor (EGFR). This research was to explore the molecular mechanism of LRIG1 inhibiting EGFR signal pathway., Methods: Plasmid p3XFLAG-CMV9-LRIG1 was transfected into neuroglioma cell line H4. Changes of LRIG1 and EGFR expression at mRNA and protein levels were measured by RT-PCR and Western blot, respectively. Changes of cell proliferation and apoptosis were analyzed by MTT and flow cytometry methods., Results: LRIG1 mRNA level in p3XFLAG-CMV9-LRIG1 transfected H4 cells (1.997+/-0.114) was significantly higher than that in control H4 cells (0.500+/-0.031),and p3XFLAG-CMV9 transfected group (0.357+/-0.035) (P< 0.001). LRIG1 protein level in p3XFLAG-CMV9-LRIG1 transfected H4 cells (1.790+/-0.119) was significantly higher than that in control H4 cells (0.717+/-0.038, P< 0.001), and p3XFLAG-CMV9 transfected H4 cells (0.930+/-0.076, P=0.001). EGFR mRNA level in p3XFLAG-CMV9-LRIG1 transfected H4 cells (0.463+/-0.033) was significantly lower than that in control H4 cells (1.157+/-0.067, P< 0.001), and p3XFLAG-CMV9 transfected H4 cells (0.933+/-0.058, P=0.002). EGFR protein level in p3XFLAG-CMV9-LRIG1 transfected H4 cells (0.703+/-0.067) was significantly lower than that in control H4 cells (1.280+/-0.078, P=0.003),and p3XFLAG-CMV9 transfected H4 cells (1.163+/-0.068,P=0.009). Apoptosis rate in LRIG1-transfected H4 cells (18.89%)was lower than that in control H4 cells (3.11%), and vector-transfected H4 cells (5.42%, P< 0.001)., Conclusion: LRIG1 participates in construction of negative feedback loop of EGFR, which may inhibits growth of glioma cells.

The standard surgical treatment of hydrocephalus by cerebrospinal fluid (CSF) shunt is accompanied by numerous complications. The search for alternative treatment methods includes resection, coagulation and irradiation of part of the plexus choroideus. The reduction of CSF secretion after choroid plexus (CP) irradiation has been investigated only on the experimental level. The new Photon Radiosurgery System (PRS) now also provides clinically the opportunity to induce selective radionecrosis on the CP with high efficiency and safety. In order to achieve a basic understanding of the reaction of CP cells after PRS irradiation, we investigated the cell death after different irradiation doses using TB dye-exclusion and MTT assay on sheep choroid plexus (SCP) cells. We observed a dose-dependent decrease in cell survival with increasing doses of irradiation (9, 18, 27 and 36 Gy). Lower irradiation doses (9, 18 Gy) induced an initial decrease of cell survival. Cells were able to recover from day 6 on and achieved a similar cell viability compared to non-irradiated cells on day 12. In contrast, higher doses (27 and 36 Gy) of irradiation induced a constant decrease of the cell survival over 12 days. These results clearly demonstrate that PRS irradiation is able to induce radionecrosis of CP cells which are responsible for the secretion of CSF. Interstitial photon radiosurgery can provide the opportunity to deliver the irradiation dose locally to CP with minimal exposure of surrounding tissue. Our basic data support further studies investigating this concept in animal models and clinically.