Multi-omics and Multi-VOIs to predict esophageal fistula in esophageal cancer patients treated with radiotherapy.

OBJECTIVE: This study aimed to develop a prediction model for esophageal fistula (EF) in esophageal cancer (EC) patients treated with intensity-modulated radiation therapy (IMRT), by integrating multi-omics features from multiple volumes of interest (VOIs). METHODS: We retrospectively analyzed pretreatment planning computed tomographic (CT) images, three-dimensional dose distributions, and clinical factors of 287 EC patients. Nine groups of features from different combination of omics [Radiomics (R), Dosiomics (D), and RD (the combination of R and D)], and VOIs [esophagus (ESO), gross tumor volume (GTV), and EG (the combination of ESO and GTV)] were extracted and separately selected by unsupervised (analysis of variance (ANOVA) and Pearson correlation test) and supervised (Student T test) approaches. The final model performance was evaluated using five metrics: average area under the receiver-operator-characteristics curve (AUC), accuracy, precision, recall, and F1 score. RESULTS: For multi-omics using RD features, the model performance in EG model shows: AUC, 0.817 ± 0.031; 95% CI 0.805, 0.825; p < 0.001, which is better than single VOI (ESO or GTV). CONCLUSION: Integrating multi-omics features from multi-VOIs enables better prediction of EF in EC patients treated with IMRT. The incorporation of dosiomics features can enhance the model performance of the prediction.

Genome-wide analysis of the TIFY family in Lycium and the negative regulation of stomatal development by LrJAZ2 gene.

Stomata are ports that facilitate gas and water vapor exchange during plant photosynthesis and transpiration. Stomatal development is strictly regulated by endogenous hormone. Jasmonate, an important signal that modulates multiple physiological processes in plants, has been found to negatively regulate stomatal development in Arabidopsis thaliana, yet the molecular mechanisms underlying stomata development signaling remain to be understood. Jasmonate ZIM-domain (JAZ) proteins are the members of TIFY family and the key component of JA signaling pathway. Its function in stomatal development is unclear to data. Here, we screened out 24 TIFY family members against the genome of Lycium, and identified a JAZ member by combination analyses of evolutionary tree, cis-elements in promoter and gene expression patterns. Overexpression of this gene (LrJAZ2) in Lycium ruthenicum and Arabidopsis thaliana indicated LrJAZ2 negatively regulates stomatal development. Microscopic observations revealed that overexpression of LrJAZ2 negatively regulated stomatal development by decreasing stomatal density and index, which may lead to lower leaf transpiration rates. Transcriptome data indicated the overexpression of LrJAZ2 up-regulated the stomatal related genes such as LrERL2, LrPYL4, and down-regulated the LrSPCH. Collectively, our study found that LrJAZ2 is a key gene in stomatal development regulation in L. ruthenicum and provided new insights into the regulation of stomatal development.

Comparison of glial fibrillary acidic protein-immunoglobulin G-associated myelitis with myelin oligodendrocyte glycoprotein-immunoglobulin G-associated myelitis.

Objective: Glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG)-associated myelitis and myelin oligodendrocyte glycoprotein-IgG (MOG-IgG)-associated myelitis have rarely been compared. Therefore, this study aimed to explore the clinical, laboratory, and imaging features of them to identify the differences. Methods: Overall, 14 and 24 patients with GFAP-IgG-and MOG-IgG-associated myelitis, respectively, were retrospectively screened and included in the study. Results: Among the 14 patients with GFAP-IgG-associated myelitis, the condition was more common in males (71.4%), with a median age of onset of 36.5 years, and more common in adults than in children (35.7%). In contrast, among the 24 patients with MOG-IgG-associated myelitis, the condition was equally divided between males and females, with a median age of onset of 9.5 years and more in children (66.7%) than in adults. The median age of onset of GFAP-IgG-associated myelitis was later than that of the MOG-IgG group. Isolated myelitis was rare in both groups. Elevated cerebrospinal fluid (CSF) protein levels were more prevalent in patients with GFAP-IgG-associated myelitis (64.3%) than in those with MOG-IgG-associated myelitis (16.7%) (p < 0.05), whereas patchy gadolinium enhancement of the cerebral lesion site was less common in patients with GFAP-IgG-associated myelitis than in those with MOG-IgG associated myelitis (p < 0.05). Six patients had a combination of other neurological autoantibodies, the specific mechanism of the overlapping antibodies remains unclear. Conclusion: Cerebrospinal fluid analysis and gadolinium enhanced MRI examination may help to distinguish the two kinds of myelitis.

Light-Driven Conversion of Silicon Nitride Nanopore to Nanonet for Single-Protein Trapping Analysis.

The single-molecule technique for investigation of an unlabeled protein in solution is very attractive but with great challenges. Nanopore sensing as a label-free tool can be used for collecting the structural information of individual proteins, but currently offers only limited capabilities due to the fast translocation of the target. Here, a reliable and facile method is developed to convert the silicon nitride nanopore to a stable nanonet platform for single-entity sensing by electrophoretic or electroosmotic trapping. A nanonet is fabricated based on a material reorganization process caused by electron-beam and light-irradiation treatment. Using protein molecules as a model, it is revealed that the solid-state nanonet can produce collision and trapping flipping signals of the protein, which provides more structural information than traditional nanopore sensing. More importantly, thanks to the excellent stability of the solid-state silicon nitride nanonet, it is demonstrated that the ultraviolet-light-irradiation-induced structural-change process of an individual protein can be captured. The developed nanonet supplies a robust platform for single-entity studies but is not limited to proteins.

Efficacy and cerebral mechanism of acupuncture and moxibustion for treating primary dysmenorrhea: study protocol for a randomized controlled clinical trial.

BACKGROUND: Acupuncture or moxibustion has been proven to be effective for patients with primary dysmenorrhea (PDM). However, the respective advantages and potential central mechanism of acupuncture and moxibustion are worthy of investigating to promote their further application. METHODS: In this randomized controlled neuroimaging trial, 72 patients with PDM will be randomly assigned to three groups: acupuncture treatment group, moxibustion treatment group, and waiting list group. The acupuncture treatment group and moxibustion treatment group will receive acupuncture or moxibustion, respectively, for a total of 3 sessions over 3 consecutive menstrual cycles, and the waiting list group will not take acupuncture or moxibustion during these 3 menstrual cycles. The COX Menstrual Symptom Scale (CMSS), visual analog scale (VAS), and Pain Catastrophizing Scale (PCS) will be used to evaluate the clinical efficacy. The Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and 36-Item Short Form Health Survey (SF-36) will be used to assess the mental state and quality of life at baseline and at the end of treatment. Functional magnetic resonance imaging (fMRI) will be performed for detecting the cerebral activity changes at baseline and at the end of the treatment. The clinical data and imaging data will be analyzed among the groups. Correlation analysis will be conducted to investigate the relationship between brain functional changes and symptom improvement. DISCUSSION: The application of the randomized controlled neuroimaging trial will provide objective and valid evidence about how acupuncture and moxibustion treatment relieve menstrual pain. The results of this study would be useful to confirm the potential similarities and differences between acupuncture and moxibustion in clinical efficacy and central mechanism for patients with PDM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100043732 . Registered on 27 February 2021.

Proteomic and phosphorylated proteomic landscape of injured lung in juvenile septic rats with therapeutic application of umbilical cord mesenchymal stem cells.

Acute lung injury (ALI) is the most common complication of sepsis. Intravenous injection of HUMSCs can regulate the level of circulating endothelial cytokines and alleviate lung injury in juvenile septic rats. In this study, we performed proteomic and phosphorylated proteomic analysis of lung tissue of juvenile septic rats after Human Umbilical Cord Mesenchymal Stem Cells (HUMSCs) intervention for the first time, and screened the potential proteins and pathways of HUMSCs for therapeutic effect. The 4D proteome quantitative technique was used to quantitatively analyze the lung tissues of septic rats 24 hours (3 biological samples) and 24 hours after HUMSCs intervention (3 biological samples). A total of 213 proteins were identified as differentially expressed proteins, and 971 phosphorylation sites changed significantly. Based on the public database, we analyzed the functional enrichment of these proteins and phosphorylated proteins. In addition, Tenascin-C may be the key differential protein and ECM receptor interaction pathway may be the main signal pathway by using various algorithms to analyze the protein-protein interaction network. Phosphorylation analysis showed that tight junction pathway was closely related to immune inflammatory reaction, and EGFR interacted most, which may be the key differential phosphorylated protein. Finally, 123 conserved motifs of serine phosphorylation site (pS) and 17 conserved motifs of threonine (pT) phosphorylation sites were identified by motif analysis of phosphorylation sites. Results from proteomics and phosphorylated proteomics, the potential new therapeutic targets of HUMSCs in alleviating lung injury in juvenile septic rats were revealed.

Classification of primary dysmenorrhea by brain effective connectivity of the amygdala: a machine learning study.

BACKGROUND: The amygdala plays a crucial role in the central pathogenesis mechanism of primary dysmenorrhea (PDM). However, the detailed pain modulation principles of the amygdala in PDM remain unclear. Here, we applied the Granger causality analysis (GCA) to investigate the directional effective connectivity (EC) alterations in the amygdala network of PDM patients. METHODS: Thirty-seven patients with PDM and 38 healthy controls were enrolled in this study and underwent resting-state functional magnetic resonance imaging scans during the pain-free stage. GCA was employed to explore the amygdala-based EC network alteration in PDM. A multivariate pattern analysis (MVPA)-based machine learning approach was used to explore whether the altered amygdala EC could serve as an fMRI-based marker for classifying PDM and HC participants. RESULTS: Compared to the healthy control group, patients with PDM showed significantly decreased EC from the amygdala to the right superior frontal gyrus (SFG), right superior parietal lobe/middle occipital gyrus, and left middle cingulate cortex, whereas increased EC was found from the amygdala to the bilateral medial orbitofrontal cortex. In addition, increased EC was found from the bilateral SFG to the amygdala, and decreased EC was found from the medial orbitofrontal cortex, caudate nucleus to the amygdala. The increased EC from the right SFG to the amygdala was associated with a plasma prostaglandin E2 level in PDM. The MVPA based on an altered amygdala EC pattern yielded a total accuracy of 86.84% for classifying the patients with PDM and HC. CONCLUSION: Our study is the first to combine MVPA and EC to explore brain function alteration in PDM. The results could advance understanding of the neural theory of PDM in specifying the pain-free period.

[Effect of acupuncture on brain functional connectivity strength in patients with primary dysmenorrhea].

OBJECTIVE: To investigate the effect of acupuncture on the brain functional activities of the patients with primary dysmenorrhea based on the resting-state functional magnetic resonance imaging (rs-fMRI), and to provide visual evidence for the central mechanism of acupuncture in treatment of primary dysmenorrhea. METHODS: Forty-two patients of primary dysmenorrhea were enrolled and randomly divided into an observation group (21 cases, 1 case dropped off) and a control group (21 cases, 2 cases dropped off, 3 cases withdrawal). In the observation group, acupuncture was exerted at Sanyinjiao (SP 6) and Guanyuan (CV 4), started 5-7 days before menstrual flow, once a day till menstrual onset, for a total of 3 menstrual cycles. No intervention was applied in the control group. The scores of visual analogue scale (VAS) and Cox menstrual symptom scale (CMSS) were observed in both groups before and after treatment. Based on rs-fMRI, the data of resting-state functional magnetic resonance were collected from two groups before and after treatment. Combined with functional connectivity strength (FCS) and functional connectivity (FC) analysis, the differences of brain regions before and after treatment were compared between the two groups and the correlation was analyzed between their functional connectivity changes and the improvements in VAS and CMSS scores of the patients in the observation group. RESULTS: In the observation group, the scores of VAS and CMSS were all decreased after treatment (P<0.05), while the scores related to the symptom time in CMSS was reduced in comparison with that before treatment in the control group (P<0.05). The score reducing ranges of VAS and CMSS in the observation group were larger than the control group (P<0.05). Compared before treatment, FCS of the right middle cingulate cortex and the left cuneus was increased, while FCS of the left inferior parietal lobule was decreased after treatment in the observation group. In the control group, FCS of the left orbital frontal cortex was increased after treatment. Compared with the control group, FCS of the left anterior insula was increased in the observation group after treatment. FC analysis was performed using the left anterior insula as the seed point. In comparison with the control group, FC of the left anterior insula was increased either with the inferior temporal gyrus or with the right hippocampus; and was decreased either with the middle occipital lobe or with the right dorsolateral prefrontal cortex in the observation group after treatment. In the observation group, FC between the left anterior insula and the right hippocampus was positively correlated with the improvements in symptom severity (r =0.385, P<0.05) and symptom time (r =0.510, P<0.05) of CMSS, and FC between the right dorsolateral prefrontal cortex and the left anterior insula was negatively correlated with the improvement in symptom severity of CMSS after treatment (r =-0.373, P<0.05). CONCLUSION: The anterior insula may be the key brain region in treatment of primary dysmenorrhea with acupuncture. Acupuncture may relieve dysmenorrhea and the related symptoms through strengthening the functional connectivity of anterior insula-limbic system and anterior insula-control network.

Single-cell RNA sequencing reveals the potential mechanism of heterogeneity of immunomodulatory properties of foreskin and umbilical cord mesenchymal stromal cells.

BACKGROUND: Mesenchymal stromal cells (MSCs) are heterogeneous populations. Heterogeneity exists within the same tissue and between different tissues. Some studies have found enormous heterogeneity in immunomodulatory function among MSCs derived from different tissues. Moreover, the underlying mechanism of heterogeneity in immunomodulatory abilities is still unclear. METHODS: Foreskin mesenchymal stromal cells (FSMSCs) and human umbilical cord mesenchymal stromal cells (HuMSCs) were isolated and cultured until the third passage. According to the International Association for Cell Therapy standard, we confirmed the cell type. Then, FSMSCs and HuMSCs were cocultured with human peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) in vitro. Furthermore, the supernatant was sampled for an enzyme-linked immunosorbent assay to investigate the secretion of IL-1ß, IL-6, IL-10, TNF-α, and TGF-ß1. Finally, we performed single-cell RNA sequencing (scRNA-seq) of FSMSCs and HuMSCs. RESULTS: We successfully identified FSMSCs and HuMSCs as MSCs. When cocultured with LPS pretreated PBMCs, FSMSCs and HuMSCs could effectively reduced the secretion of IL-1ß and TNF-α. However, FSMSCs stimulated the PBMCs to secrete more IL-10, TGF-ß1, and IL-6. Furthermore, 4 cell subsets were identified from integrated scRNA-seq data, including proliferative MSCs (MKI67+, CD146low+, NG2+, PDGFRB-), pericytes (CD146high+, PDGFRB+, MKI67-, CD31-, CD45-, CD34-), immune MSCs (CXCL12high+, PTGIShigh+, PDGFRB+, CD146-, MKI67-) and progenitor proliferative MSCs (CXCL12low+, PTGISlow+, PDGFRB+, CD146-, MKI67-). Among them, we found that immune MSCs with strengthened transcriptional activity were similar to pericytes with regard to the degree of differentiated. Various of immune-related genes, gene sets, and regulons were also enriched in immune MSCs. Moreover, immune MSCs were determined to be close to other cell subsets in cell-cell communication analysis. Finally, we found that the proportion of immune MSCs in foreskin tissue was highest when comparing the subset compositions of MSCs derived from different tissues. CONCLUSIONS: FSMSCs show better immunomodulatory capacity than HuMSCs in vitro. Moreover, immune MSCs may play a vital role in the heterogeneity of immunoregulatory properties. This study provides new insights suggesting that immune MSCs can be isolated to exert stable immunoregulatory functions without being limited by the heterogeneity of MSCs derived from different tissues.

Trends in Corneal Transplantation and Characteristics of Donors in the Chongqing Eye Bank, China: A Retrospective Study, 1999-2018.

Aim: This study aimed to analyze corneal transplantation trends and voluntary donor characteristics at the Chongqing Eye Bank in China. Methods: We retrospectively reviewed and analyzed data from January 1, 1999, to December 31, 2018, covering 5,397 preregistered voluntary donors, 1,955 actual donors, 3,910 donated tissues, and 2,374 corneal transplantations. Results: The 5,397 preregistered donors included 13 ethnic groups, with an overall mean age of 39.6 years (SD 21.5) and 3,010 were women (55.8%). The most prevalent education level was college and above (2,546, 47.2%), and the most common ethnic group was Han (5,335, 98.85%). Of the 1,955 actual donors, the male-to-female ratio was 3.3, and the mean age was 57.1 (SD 23.0 years). Based on population size in 2018, Jiangbei county was the most active in donation willingness, with ~60 × 10-6 per capita, and the Yuzhong county was the most active in cornea donations, with ~451 × 0-6 per capita. Of the 3,910 donated corneas, 2,540 (65.0%) were clinically used. Of those not used, 978 (71.4%) were rejected for poor corneal quality. The 2,374 (93.5%) corneal transplantation procedures were done at the Department of Ophthalmology of the First Affiliated Hospital of Chongqing Medical University and the rest (n = 166, 6.5%) were performed in other centers. Of those 2,374 corneal transplantations, there were 1,671 penetrating keratoplasty (70.39%), 700 anterior lamellar keratoplasty (29.49%), and three corneal endothelial transplantations in our center (0.13%). The number of annual corneal transplantations increased by nearly 10 times, from 35 cases in 1999 to 327 cases in 2018. Among them, cases of penetrating keratoplasty and anterior lamellar keratoplasty increased from 27, and eight cases in 1999 to 230 and 94 cases in 2018, respectively. Infectious keratitis (37.0%) was the leading indication for keratoplasty, followed by corneal scar (19.8%). Over the study period, corneal scars dropped from the first (41.1% in 1999-2003) to the second indication (20.5% in 2014-2018), while infectious keratitis advanced to take the lead, ranging from 12.2% in 1999-2003 to 26.3% in 2014-2018. Conclusion: Our study reports corneal donation and transplantation trends in Chongqing over 20 years, showing that infectious keratitis is a leading indication for keratoplasty and that penetrating keratoplasty and anterior lamellar keratoplasty show upward trends. The analysis further suggests that a potential preregistered cornea donor is a female Han, with a higher education level.

Exploring the long-term vegetation dynamics of different ecological zones in the farming-pastoral ecotone in northern China.

The vegetation in the farming-pastoral ecotone in northern China is influenced by both natural and anthropogenic factors and has undergone drastic changes in the past decades. The farming-pastoral ecotone is the transition zone from agriculture to animal husbandry. The ecological environment of this ecotone is complex and fragile. Most researches have primarily focused on the entire farming-pastoral ecotone, seldomly considering the differences between different ecological zones characterized by soil, climate, and biome conditions. Based on the long time series of leaf area index (LAI) data, meteorological data, and land-use dataset, this study analyzed LAI variation trends, the correlations between LAI and climate factors, and the impact of land-use type change on vegetation in the farming-pastoral ecotone in northern China. Moreover, this paper makes a full study of the changes of the whole study area from the perspective of the differences between different ecological zones. The results showed that over 36 years, areas with vegetation improvements were considerably larger than those with degradations. However, there were still 49.56% of the total area showing no significant vegetation change. There are differences in vegetation change and response to climate between the forest ecological zones and the grassland ecological zones. The vegetation improvement trends of the forest ecological zones were larger and more sensitive to temperature, while the vegetation improvements of the grassland ecological zones were relatively small, and were more sensitive to precipitation. Human activities promote LAI changes in areas close to the forest ecological zones. The change of land use indicates that the decrease of the overall natural vegetation area has not resulted in decreasing LAI. And there is a growing trend of woodland area in the grassland ecological zones. The study provides a theoretical basis for the management of the environment and vegetation in the farming-pastoral ecotone in northern China.

Transfer Learning for Toxoplasma gondii Recognition.

Toxoplasma gondii, one of the world's most common parasites, can infect all types of warm-blooded animals, including one-third of the world's human population. Most current routine diagnostic methods are costly, time-consuming, and labor-intensive. Although T. gondii can be directly observed under the microscope in tissue or spinal fluid samples, this form of identification is difficult and requires well-trained professionals. Nevertheless, the traditional identification of parasites under the microscope is still performed by a large number of laboratories. Novel, efficient, and reliable methods of T. gondii identification are therefore needed, particularly in developing countries. To this end, we developed a novel transfer learning-based microscopic image recognition method for T. gondii identification. This approach employs the fuzzy cycle generative adversarial network (FCGAN) with transfer learning utilizing knowledge gained by parasitologists that Toxoplasma is banana or crescent shaped. Our approach aims to build connections between microscopic and macroscopic associated objects by embedding the fuzzy C-means cluster algorithm into the cycle generative adversarial network (Cycle GAN). Our approach achieves 93.1% and 94.0% detection accuracy for ×400 and ×1,000 Toxoplasma microscopic images, respectively. We showed the high accuracy and effectiveness of our approach in newly collected unlabeled Toxoplasma microscopic images, compared to other currently available deep learning methods. This novel method for Toxoplasma microscopic image recognition will open a new window for developing cost-effective and scalable deep learning-based diagnostic solutions, potentially enabling broader clinical access in developing countries.IMPORTANCE Toxoplasma gondii, one of the world's most common parasites, can infect all types of warm-blooded animals, including one-third of the world's human population. Artificial intelligence (AI) could provide accurate and rapid diagnosis in fighting Toxoplasma So far, none of the previously reported deep learning methods have attempted to explore the advantages of transfer learning for Toxoplasma detection. The knowledge from parasitologists is that the Toxoplasma parasite is generally banana or crescent shaped. Based on this, we built connections between microscopic and macroscopic associated objects by embedding the fuzzy C-means cluster algorithm into the cycle generative adversarial network (Cycle GAN). Our approach achieves high accuracy and effectiveness in ×400 and ×1,000 Toxoplasma microscopic images.

Potassium Transporter LrKUP8 Is Essential for K+ Preservation in Lycium ruthenicum, A Salt-Resistant Desert Shrub.

Salt stress is a major constraint for many crops and trees. A wild species of Goji named Lycium ruthenicum is an important economic halophyte in China and has an extremely high tolerance to salinity. L. ruthenicum grows in saline soil and is known as a potash-rich species. However, its salt adaptation strategies and ion balance mechanism remains poorly understood. Potassium (K+) is one of the essential macronutrients for plant growth and development. In this study, a putative salt stress-responsive gene encoding a HAK (high-affinity K+)/KUP (K+ uptake)/KT (K+ transporter) transporter was cloned and designated as LrKUP8. This gene belongs to the cluster II group of the KT/HAK/KUP family. The expression of LrKUP8 was strongly induced under high NaCl concentrations. The OE-LrKUP8 calli grew significantly better than the vector control calli under salt stress conditions. Further estimation by ion content and micro-electrode ion flux indicated a relative weaker K+ efflux in the OE-LrKUP8 calli than in the control. Thus, a key gene involved in K+ uptake under salt condition was functionally characterized using a newly established L. ruthenicum callus transformation system. The importance of K+ regulation in L. ruthenicum under salt tolerance was highlighted.

The cerebral mechanism of acupuncture for treating knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Acupuncture is safe and effective for reducing the symptoms of knee osteoarthritis (KOA), but the underlying mechanisms of acupuncture for treating KOA are not fully understood. METHODS/DESIGN: In total, 108 participants diagnosed with KOA will be recruited. They will be blinded to group assignment and randomized to either verum acupuncture, sham acupuncture or waiting-list groups with 36 patients in each group. Each patient in the acupuncture group will receive five treatments per week for 2 weeks. This study will focus on detecting the cerebral functional connectivity changes elicited by acupuncture treatment. The Visual Analog Scale and the short form of the McGill Pain Questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index, the Attention Test Scale, the Pain Assessment of Sphygmomanometer and the 12-Item Short Form Health Survey will be used to evaluate the symptoms and quality of life improvement at the baseline and the end of treatment. The Self-rating Anxiety Scale and the Self-rating Depression Scale will be used at the baseline and the end of treatment to investigate the influence of emotional state on brain activity and clinical variable. To ensure the consistency of acupuncture manipulation, the deqi scale will be performed after each acupuncture treatment. During the procedure of outcome evaluation and data analysis, the evaluators and statisticians will be blinded to the group allocation. The repeated measures analysis of variance (3 groups × 2 time points ANOVA) will be employed to analyze numerical variables of the clinical and neuroimaging data generated in the study, then the t test will be used in the post-hoc analysis. DISCUSSION: The results of this randomized, sham- and waiting-list-controlled functional magnetic resonance imaging (fMRI) study will help to investigate the influence of verum acupuncture treatment on the brain activities of patients with KOA, which might provide evidence for the clinical application of verum acupuncture for KOA management. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCT-IOR-17012364 . Registered on 14 August 2017.