OBJECTIVE: To investigate the changes in the functional connectivity (FC) in the right insula between migraine without aura (MWoA) and healthy controls by using resting-state functional magnetic resonance imaging (rs-fMRI), and to observe the instant alteration of FC in MWoA during electroacupuncture (EA) stimulation at Shuaigu (GB8). METHODS: A total of 30 patients with MWoA (PM group) and 30 healthy controls (HC group) underwent rs-fMRI scans. The PM group underwent a second rs-fMRI scan while receiving EA at GB8. The right insula subregions, including the ventral anterior insula (vAI), dorsal anterior insula (dAI) and posterior insula (PI), were selected as the seed points for FC analysis. RESULTS: Aberrant FC, including dAI with right postcentral gyrus, PI with left precuneus, was found among PM before EA (PMa), PM during EA (PMb) and HC. Meanwhile, decreased FC between dAI and the right postcentral gyrus was found in the PMa compared to the HC and PMb. Increased FC between the PI and left precuneus was found in the PMa compared to the HC and PMb. Correlation analysis showed that the FC value of the right postcentral gyrus in PMa was negatively correlated with the scores of Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. The FC value of the left precuneus in PMa was positively correlated with the visual analogue scale score. CONCLUSION The alteration of FC between the right insula subregions and multiple brain regions may be an important index for MWoA. EA at GB8 was able to adjust the FC between the right insula subregions and parietal lobe, namely, the right dAI and right postcentral gyrus, and the right PI and left precuneus, thereby rendering an instant effect in the management of MWoA.
Brain/diagnostic imaging* ; Electroacupuncture ; Humans ; Magnetic Resonance Imaging/methods* ; Migraine without Aura

The pharmacokinetics of traditional Chinese medicine is a subject that studies the dynamic changes of the absorption, distribution, metabolism and excretion of complex components of traditional Chinese medicine, which is an important method for elucidating the pharmacodynamic material basis, action characteristics, and compatibility mechanisms of traditional Chinese medicine. However, given on the fact that traditional Chinese medicine is a multi-dimensional and complex system with multiple components, multiple pathways, multiple targets, and an unclear pharmacodynamic material basis, the research on the pharmacokinetics of traditio-nal Chinese medicine has become a scientific and technological problem. Although the pharmacokinetics of traditional Chinese medicine has achieved remarkable development with the emergence of new theories, methods and technologies, there are still some problems in the application of the research direction of the pharmacokinetics of traditional Chinese medicine judging from the current application of the National Natural Science Foundation of China. Therefore, this article discussed the current research status on pharmacokinetics of traditional Chinese medicines by analyzing the projects funded by the National Natural Science Foundation of China in the past 5 years from 2016 to 2020, mainly including the application and funding analysis, main research contents of the projects in pharmacokinetics of traditional Chinese medicines. And the research hotspots, difficulties and deficiencies were focused in order to provide certain reference for researchers engaged in pharmacokinetics of traditional Chinese medicine.
China ; Financial Management ; Foundations ; Medicine, Chinese Traditional ; Natural Science Disciplines

Alzheimer′s disease is a progressive neurodegenerative disease that requires medication to improve patient symptoms, but there is an individual difference in the efficacy. In this paper, the correlation between single nucleotide polymorphism and the drug efficacy of Alzheimer′s disease (AD) in the past 20 years was searched through the databases of China National Knowledge Infrastructure, VIP Database, Wanfang Database, Pubmed, Springer Link and Cochrane Library with key words of Alzheimer′s disease, drug efficacy, single nucleotide polymorphism. The correlation between AD drug efficacy difference and gene single nucleotide polymorphism was reviewed, including ABCA1, ApoE, ChAT, CHRNA7, IL-6, A2M, CYP2D6, BChE, 5HT2a, PON-1 and ESR1 genes, so as to provide a reference basis for clinicians to select drugs in the treatment of AD.

BACKGROUND: We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice. METHODS: Intestinal epithelial CCL7 overexpression (CCL7) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing. RESULTS: We found that the CCL7 mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7 mice compared to WT. Furthermore, HFD-fed CCL7 mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis. CONCLUSIONS Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

OBJECTIVE: To explore the clinical effects of convolution method in treating displaced midshaft clavicle fracture. METHODS: From January 2018 to July 2019, 32 patients (21 males and 11 females) with displaced midshaft clavicle fracture were treated, ranging in age from 18 to 65 years old, with a median age of 41.5 years old. Nineteen patients had fractures on the left side and 13 patients had fractures on the right side. The duration from injury to treatment ranged from 30 minutes to 5 days. The patients were treated with convolution method and repeated push and rotation of the affected upper limb, followed by external fixation of clavicle band. The reduction and healing of the fracture and the functional recovery of shoulder joint were observed. RESULTS: After operation, fracture reduction was evaluated by X ray film. Seven patients had an excellent result, 20 good and 5 fair. All the patients were followed up, and the duration ranged from 14 to 18 weeks. The mean Neer score was 89.75±6.88, which included pain score of 32.66±2.54, functional score of 26.44±2.91, range of motion score of 22.38±2.06, and anatomy score of 8.43±0.84;17 patients receive an excellent result, 14 good and 1 fair. CONCLUSION The rotation method combined with the repeated pushing and rotating of the upper limb of the affected side can well reduce the displaced fracture of the middle clavicle. Bandage and clavicle band can be performed after reduction. Functional exercise runs through the whole course of treatment. Functional recovery of shoulder joint is good and satisfactory therapeutic effect is achieved.
Adolescent ; Adult ; Aged ; Bone Plates ; Clavicle ; Female ; Fracture Fixation ; Fracture Fixation, Internal ; Fracture Healing ; Fractures, Bone ; Humans ; Male ; Middle Aged ; Shoulder Joint ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the clinical effects of modified lamina osteotomy replantation versus traditional lamina osteotomy replantation in the treatment of lumbar disc herniation with lumbar instability.

METHODSThe clinical data of 146 patients with unilateral lumbar disc herniation with lumbar instability underwent surgical treatment from March 2008 to March 2013 were retrospectively analyzed. Patients were divided into two groups according to osteotomy replantation pattern. There were 77 patients in the traditional group (underwent traditional lamina osteotomy replantation), including 42 males and 35 females with an average age of (49.4±18.5) years;the lesions occurred on L₄,₅ in 46 cases, on L₅5S₁ in 31 cases. There were 69 patients in modified group (underwent modified lamina osteotomy replantation), including 37 males and 32 females with an average age of (49.8±17.9) years;the lesions occurred on L₄,₅ in 40 cases, on L₅S₁ in 29 cases. The operation time, intraoperative blood loss, complication rate during operation, lamina healing rate, recurrence rate of low back and leg pain were compared between two groups. Visual analogue scales (VAS) and Japanese Orthopadic Association (JOA) scores were used to evaluate the clinical effects.

RESULTSThe operation time and intraoperative blood loss were similar between two group (>0.05). There was significantly different in nerve injury rate(5.80% vs 16.9%) and dural injury rate(1.45% vs 9.09%) between modified group and traditional group(<0.05). The recurrent rate of low back pain of modified group was higher (91.30%, 63/69) than that of traditional group (76.62%, 59/77), and the intervertebral fusion rate of modified group was lower(8.70%, 6/69) than that of traditional group (29.9%, 23/77) at 3 years after operation. Postoperative VAS scores of all patients were significantly decreased at 6 months, 1, 2, 3 years, and JOA scores were obviously increased (<0.05). At 1, 2, 3 years after operation, VAS scores of modified group were significantly lower than that of traditional group(<0.05), and JOA scores of modified group were higher than that of traditional group(<0.05).

CONCLUSIONSModified lamina osteotomy replantation has better long-term efficacy(in the aspect of recurrent rate of low back pain, intervertebral fusion rate, VAS and JOA score at three years follow-up) in treating lumbar disc herniation with instability.

Objective To research the monoclonal antibody KMP1 inhibited bladder cancer EJ cell lines growth and metastasis in vivo by bioluminescence imaging. Methods Immunohistochemistry was used to determine the KMP1 binding to EJ and EJ-GFP cell lines. The xenograft tumor cell growth and distribution were measured by vernier calipers and dynamic in vivo fluorescence imaging. Immunohistochemistry and H&E counterstaining researched the feature of the xenograft tumor. Results Cell growth curves of EJ and EJ-GFP cells were similar. EJ-GFP had a green fluorescence. In EJ-GFP nude mouse tumor model, the addition of KMP1 significantly inhibited tumor growth and extended the average life span of nude mice. Both EJ and EJ-GFP cells can bind to KMP1,and the weight of transplanted tumors in the KMP1 treatment group was significantly lower than that of the mIgG control group (P＜0.001).Conclusion KMP1 has a promising antitumor effect in vivo. It might be valuable for development as a promising targeted agent for bladder cancer.

The main pathogenesis of saphenous vein graft neointimal hyperplasia after coronary artery bypass grafting (CABG) is inflammation-caused migration and proliferation of vascular smooth muscle cells (VSMCs). Janus kinase 2/signal transducer and activators of transcription 3 (JAK2/STAT3) pathway is an important signaling pathway through which VSMCs phenotype conversion occurs. Suppressor of cytokine signaling 3 (SOCS3) is the classic negative feedback inhibitor of JAK2/STAT3 pathway. Growing studies show that SOCS3 plays an important anti-inflammatory role in numerous autoimmune diseases, inflammatory diseases and inflammation-related tumors. However, the effect and mechanism of SOCS3 on vein graft disease is unclear. The purpose of this study was to investigate the effects of SOCS3 on the inflammation, migration and proliferation of VSMCs in vitro and the mechanism. The small interference RNA plasmid targeting rat SOCS3 (SiRNA-rSOCS3) and the recombinant adenovirus vector carrying rat SOCS3 gene (pYrAd-rSOCS3) were constructed, and the empty plamid (SiRNA-control) and vector (pYrAd-GFP) only carrying GFP reported gene were constructed as control. The rat VSMCs were cultured. There were two large groups of A (SOCS3 up-regulated): control group, IL-6/IFN-γ group, IL-6/IFN-γ+pYrAd-rSOCS3 group, IL-6/IFN-γ(+)pYrAd-GFP group; and B (SOCS3 down-regulated): control group, IL-6/IFN-γ group, IL-6/IFN-γ+SiRNA-rSOCS3 group and IL-6/ IFN -γ+SiRNA-control group. The pYrAd-rSOCS3 and SiRNA-rSOCS3 were transfected into VSMCs induced by IL-6/IFN-γ. After 24 h, real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expression of SOCS3, STAT3 (only by Western blotting), P-STAT3 (only by Western blotting), IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1. The MTT, Transwell assay and flow cytometry were used to examine VSMCs proliferation, migration and cell cycle progression, respectively. As compared with control group, the mRNA and protein expression of SOCS3, STAT3, P-STAT3, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 was significantly up-regulated in VSMCs stimulated by IL-6/IFN-γ. However, in VSMCs transfected with pYrAd-rSOCS3 before stimulation with IL-6/IFN-γ, the expression of SOCS3 mRNA and protein was further up-regulated, and that of STAT3, P-STAT3, IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 was significantly down-regulated as compared with IL-6/IFN-γ group and IL-6/IFN-γ+pYrAd-GFP group. The expression of those related-cytokines in IL-6/IFN-γ+SiRNA-rSOCS3 group was markedly increased as compared with IL-6/IFN-γ group and IL-6/IFN-γ+SiRNA-control group. The absorbance (A) values, the number of cells migrating to the lower chamber, and percentage of cells in the G2/M+S phase were increased in VSMCs stimulated by IL-6/IFN-γ. In VSMCs incubated with pYrAd-rSOCS3 or SiRNA-rSOCS3 before IL-6/IFN-γ stimulation, the A values, the number of cells migrating to the lower chamber, and the percentage of cells in the G2/M+S phase were significantly decreased, and increased respectively. These results imply that IL-6/IFN-γ, strong inflammatory stimulators, can promote transformation of VSMCs phenotype form a quiescent contractile state to a synthetic state by activating JAK2/STAT3 pathway. Over-expresssed SOCS3 might inhibit pro-inflammatory effect, migration and growth of VSMCs by blocking STAT3 activation and phosphorylation. These data in vitro confirm that SOCS3 may play a negatively regulatory role in development and progression of vein graft failure. These conclusions can provide a novel strategy for clinical treatment of vein graft diseases and a new theoretic clue for related drug development.
Animals ; Blotting, Western ; Cell Cycle ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Cytokines ; genetics ; metabolism ; Flow Cytometry ; Gene Expression ; Inflammation Mediators ; metabolism ; Interferon-gamma ; genetics ; metabolism ; pharmacology ; Interleukin-6 ; genetics ; metabolism ; pharmacology ; Janus Kinase 2 ; metabolism ; Male ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Phosphorylation ; RNA Interference ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; genetics ; metabolism

Objective To study investigate the dose accuracy that can be achieved with the method of bulk density assignment.Methods Sixteen cases of nasopharyngeal cancer patients and nineteen cases of esophageal cancer patients who accept radiotherapy in our department were selected.The planning CT images with bulk density assignment to different classes of tissues were applied to calculate the dose distributions,and then the resulting dose volume histograms (DVH) of the tumor and organs of risk were compared with the original treatment plan.The paired t-test was taken for dose comparison between two plans.Results The DVH comparison based on the planning CT and the bulk density assignment CT showed good agreements.With nasopharyngeal cancer patients,differences between the two plans about target and normal tissue were less than 1％.With esophageal cancer patients,the dose differences were less than 2％.Conclusion Preliminary results confirm that the bulk density assignment method can be applied to calculate the dose distributions.

Culturing cells on planar substrate in vitro is a conventional cell biology method. However, each type of physiological tissues has its specific three-dimensional micro-structure, which provides various micro environment to regulate such biological processes as cell proliferation and differentiation. To date, a growing body of researches on the impacts of substrate micro-topography on cellular responses has been documented in the literature. It is found that micro-topograhical substrate can manipulate cell spreading, migrating, orientating, cytoskeleton remodeling, and stem cell differentiation, which are crucial to ex vivo tissue construction and surface modification of medical implanting materials. This review discusses the recent progresses of the effects of substrate micro-topography on cellular responses and the underlying mechanisms of mechano-biological coupling.