Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

AIM:To explore the molecular mecha-nism of Fuyangjing gel in the treatment of chronic eczema rats model based on janus protein kinase 1(JAK1)/signal transducer and activator of transcrip-tion 5(STAT5)signaling pathway.METHODS:Thirty-six SPF Wistar rats were randomly divided into nor-mal group,model group,Qingpeng ointment group,Fuyangjing gel low,medium and high dose groups.Except the normal group,the other groups of rats were treated with 2,4-dinitrochlorophenone solution to induce chronic eczema-like lesions on the back.After 3 weeks of modeling,Qingpeng ointment group and Fuyangjing gel low,medium and high dose groups were respectively treated with corresponding drugs.The model group was smeared with blank gel matrix once a day for 2 weeks,while the normal group was not treated.The severity and pathological changes of back le-sions in chronic eczema rats were observed.The ex-pression of phosphorylated protein tyrosine kinase 1(p-JAK1)and phosphorylated signal transduction and transcriptional activator 5(p-STAT5)in rat dor-sal skin was detected by Western blot.Detection of thymic stromallymphopietin(TSLP),JAK1,STAT5,in-terleukin-10(IL-10)and IL-17 mRNA expression lev-els in rat back skin by qRT-PCR;The levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in serum of rats were deter-mined by enzyme-linked immunosorbent assay(ELI-SA).RESULTS:Compared with normal group,the se-rum levels of IL-4,IL-6,IL-13 and IL-17 in model group were significantly increased,while IL-10 lev-els were significantly decreased(P＜0.05).The ex-pression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significantly increased,while IL-10 mRNA levels were significantly decreased(P＜0.05).Compared with model group,serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng ointment group and Fuy-angjing gel low,medium and high dose groups were significantly decreased,while IL-10 levels were significantly increased(P＜0.05).The expres-sion levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significantly decreased,while the mRNA levels of IL-10 were significantly increased(P＜0.05).The serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng oint-ment group were decreased,while IL-10 levels were increased(P＜0.05).The expression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were decreased,while the mRNA levels of IL-10 were increased(P＜0.05).Com-pared with Qingpeng ointment group,there were no significant differences in serum levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in Fuyangjing gel high-dose group(P＞0.05).There were no significant differenc-es in the expression levels of p-JAK1,p-STAT5 pro-tein and TSLP,JAK1,STAT5,IL-10 and IL-17 mRNA in back lesions(P＞0.05).CONCLUSION:Fuyangjing gel may play a role in the treatment of chronic eczema by regulating the expression of JAK1/STAT5 signal-ing pathway related inflammatory factors,proteins and genes.

BACKGROUND:Three-point mechanics is an effective method for ankle foot orthosis correction and prevention of various foot diseases.At present,the clinical application research on 3D printing ankle foot orthosis has been widespread;however,there are relatively few reports on numerical simulation and finite element analysis involving three-point mechanical correction.There is a lack of relevant biomechanical experimental verification. OBJECTIVE:Three-point force was loaded to analyze the composite model of ankle foot orthosis and foot by finite element method,observing the effect of foot correction with ankle foot orthosis under three-point force intervention,verifying the effectiveness of three-point force and the reliability of ankle foot orthosis. METHODS:A three-dimensional foot and ankle model of a healthy volunteer was constructed based on the medical image processing software Mimics.Rodin 4D and Geomagic reverse engineering software were used to optimize the models and design personalized ankle foot orthosis models.Solidworks software was utilized to turn the ankle model inside for 10° to simulate the foot varus disease.Static loading was carried out on the foot force application area by ANSYS software combined with the three-point mechanics principle.The deformation and stress changes of the foot and ankle tissues were analyzed when the human foot pain threshold was met.The display dynamics was used to further verify the effectiveness of the three-point force applied by the ankle foot orthosis. RESULTS AND CONCLUSION:(1)The personalized ankle foot orthosis designed in this paper had the effect of preventing and fixing foot and ankle varus.The ankle varus was 1.81 mm after being loaded with 1 N·m of varus when not wearing ankle foot orthosis,while it was only 0.44 mm after wearing ankle foot orthosis,the deformation rate was reduced by 75.7%,and the effect of preventing varus was significantly enhanced.(2)When only coronal correction was performed,the low calcaneal force would aggravate the varus angle of the front foot.After adjusting the correction force on the inside of the heel and above the medial malleolus,the varus angle of the front foot and the calcaneus position were improved;however,the medial phalangeal region of the foot still had different degrees of adduction and displacement,which would aggravate the adduction deformity of the patient's front foot.(3)The correction effect of the coronal plane and horizontal plane was better than that of the single coronal plane.There was no adduction and displacement of the medial phalanges of the front foot and the varus angle of the front foot decreased under the force(25,10,10,20 N)of the medial heel,the medial shaft of the first metatarsal,below the lateral malleolus and above the medial malleolus,and the valgus along the X-axis was corrected by 1.395 mm,the calcaneus valgus was corrected by 1.227 mm.The calcaneus varus angle was corrected from 10.21° to 7.25°,and the varus angle was improved by 28.9%.(4)The lateral plantar metatarsal load decreased,the medial plantar metatarsal load increased under the action of a two-plane three-point force,and the plantar bone stress was significantly improved after correction.Thus,the reliability of the three-point force principle was further verified.This study provides an important theoretical support for the implementation of ankle foot orthosis in the treatment of varus in clinical practice.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION This cell-based vascular graft is ready to undergo clinical trials for human patients.

Humans ; Female ; Breast Neoplasms/genetics* ; Prognosis ; Gene Expression Profiling ; Biomarkers, Tumor/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Receptor, ErbB-2/metabolism* ; Gene Regulatory Networks/genetics*

Objective:To explore the characteristics of imaging findings and related risk factors of small vessel cerebral vascular disease (CSVD) in patients with systemic lupus erythematosus (SLE) with different disease activity.Methods:One hundred and ninty four SLE patients were included. Patients were divided into three groups according to systemic lupus erythematosus disease activity index (SLEDAI): stable or mild active disease group (0~9 points) ( n=107), moderate active group (10~14 points) ( n=41), severe active group (≥ 15 points) ( n=46). Imaging findings, general clinical information laboratory tests of all patients were collected, and the imaging data were scored according to the small cerebral vessel score scale. CSVD-related risk factors of SLE patients in the three groups were analyzed by using ordered Logistic regression. Results:There were significant differences in TWMH score, TPVS score and CSVD score among the three groups ( H=6.07, 6.00, 9.63, P<0.05). Orderly logistic regression showed that age [ OR(95% CI)=1.119 (1.051, 1.891), P<0.001], HCT [ OR (95% CI)=1.531 (1.158, 2.026), P=0.003], anti-PM-Scl antibody [ OR (95% CI)=17.271 (1.442, 206.851), P=0.025] were risk factors for CSVD in the severe active disease group. RBC [ OR(95% CI)=0.011 (0.001, 0.155), P=0.001]、anti-Rib.p antibody [ OR(95% CI)=0.093 (0.018,0.047), P=0.004] were protective factors for CSVD. Conclusion:The manifestations of CSVD in SLE patients with different disease activity are different, and are affected by age, part of blood indicators and lupus antibodies.

Objective:To observe and analyze the effect of peripore cavity size on visual function of macular area before and after surgery for idiopathic macular hole (IMH).Methods:A retrospective clinical study. From July 2020 to February 2021, a total of 25 patients with 25 eyes with monocular IMH (operation group) diagnosed by ophthalmology examination in Department of ophthalmology, Fourth Hospital of Hebei Medical University were included in the study. The control group was contralateral healthy eyes. All subjects were examined by best corrected visual acuity (BCVA), microfield of vision, frequency domain optical coherence tomography (SD-OCT), and OCT angiography (OCTA). The diameter of macular hole was measured by SD-OCT. The cystic morphology of deep capillary plexus (DCP) was detected by en face OCT, and the cystic area was measured by Image J software. MP-3 microperimeter was used to measure central macular retinal light sensitivity (MS) and mean macular retinal light sensitivity (MMS). Central macular retinal light sensitivity (CMS), MMS and cystic cavity MS were measured in the operation group. MMS was measured in the control group. The microperimetry images were superimposed on the DCP layer of OCTA to identify and calculate the average MS within the lumen and compare it with the control group. Standard three incisions were performed in all affected eyes by vitrectomy of the flat part of the ciliary body + stripping of the inner boundary membrane + intraocular sterile air filling. Three months after the operation, the same equipment and methods were used to perform relevant examinations. Paired sample t test was used to compare MS between operation group and control group. Pearson correlation analysis was used to analyze the correlation between capsular area, macular hole diameter before and after operation and MS before and after operation. The correlation between BCVA and capsular area before and after surgery was analyzed by Spearman correlation analysis. Results:In the surgical group, the retinal MS was (4.24±3.07) dB. The MMS of control group was (19.08±6.11) dB. The MS in the surgical group was significantly lower than that in the control group, and the difference was statistically significant ( t=10.832, P<0.01). Before operation, the area of cyst was (1.04±0.55) mm 2, and the diameter of macular hole was (564.80±166.59) μm. CMS and MMS were (2.27±2.29) dB and (9.08±3.65) dB, respectively. The diameter of macular hole ( r=0.50, P=0.010) and BCVA before operation ( r=0.57, P<0.001) were positively correlated with peripore cavity area. Before operation, CMS and MMS were negatively correlated with peripore cavity area ( r=-0.53, -0.47; P=0.010, 0.020). At 3 months after surgery, the capsular area was negatively correlated with CMS and MMS ( r=-0.65,-0.76; P=0.020, 0.030). There was no correlation with BCVA ( r=0.23, P=0.470). Conclusions:Retinal MS is decreased in the peri-capsular area of IMH pore. There is a positive correlation between capsule area, BCVA and macular hole diameter before operation. The capsular area is negatively correlated with CMS and MMS before operation.

Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.
Curcumin/pharmacology* ; Escherichia coli/genetics* ; Fermentation

Objective:To investigate and analyze the current status of multimodality therapy for resectable gastric cancer, aiming to provide reference for optimizing the multimodality treatment strategy for gastric cancer.Methods:Clinical data of patients diagnosed with gastric adenocarcinoma undergoing radical gastrectomy in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. Clinical characteristics, preoperative medical comorbidities, pathological features, surgical and perioperative status and clinical efficacy were recorded. The gap between the diagnosis and treatment procedures and the standard guidelines was analyzed. The changes in the multimodality treatment patterns for gastric cancer were understood.Results:A total of 265 patients were included in this study. All patients were divided into two cohorts: early[2008] and late[2013] cohorts. In the early cohort, 127 patients were assigned, and 138 cases in the late cohort. In the early cohort, 67 patients (52.8%) underwent D 2 lymph node dissection, significantly less than 83 patients (60.1%) in the late cohort ( P<0.01). In the early and late cohorts, the proportion of patients with the number of lymph node dissection of ≥15 was 5.5% and 52.8%( P<0.01). The median number of lymph node dissection was increased from 6 to 16. The proportion of patients receiving neoadjuvant chemotherapy in the early and late cohorts was 2.4% and 3.6%( P=0.55). In the early cohort, the proportion of patients treated with postoperative chemotherapy and postoperative adjuvant chemoradiotherapy was 62.6% and 2.4%, significantly higher compared with 58.0% and 8.0% in the late cohort ( P=0.04). In addition, the proportion of patients receiving postoperative chemotherapy in the early cohort was 62.2%( n=79) and 58.0%( n=80) in the late cohort ( P=0.48). Conclusions:Although the level of radical gastrectomy has been continuously improved and standardized in China, which still lags behind the standard D 2 radical gastrectomy in Japan and South Korea. Adjuvant therapies including postoperative adjuvant radiotherapy can bring clinical benefits. However, the proportion of patients receiving adjuvant therapy is still low, and the multimodality therapy of gastric cancer should be widely applied.

Objective:To investigate the mid-term clinical efficacy and imaging changes of Waveflex semi-rigid internal fixation system combined with posterior lumbar interbody fusion (PLIF) in the treatment of double segmental lumbar degenerative diseases.Methods:The data of 51 patients with lumbar degenerative diseases who underwent surgery from September 2014 to September 2015 were retrospectively analyzed, including 29 males and 22 females, aged 65.5±5.6 years (range 58-73 years). Preoperative intervertebral space degeneration grade by University of California at Los Angeles (UCLA) and Pfirrmann intervertebral disc degeneration grade were recorded. 23 cases of primary responsible segments were treated with decompression, fixation and fusion, and adjacent secondary responsible or degenerative segments were treated with Waveflex semi-rigid internal fixation (combined group); 28 cases of double segments were treated with decompression, fixation and fusion (fusion group). Disc height index (DHI) and intervertebral foramina height (IFH) of the semi-rigid fixation segments, DHI and IFH of the upper adjacent intervertebral space, and horizontal displacement of the upper adjacent vertebral body (HD) were measured on lateral X-ray films of lumbar spine; In the fusion group, DHI and IFH adjacent to the upper vertebral space and HD adjacent to the upper vertebral body were measured. The efficacy was evaluated by short-form McGill Pain Questionnaire (SF-MPQ) and Oswestry disability index (ODI).Results:51 cases were followed up for 5.4±0.3 years (range 5.2-6.3 years). The low back and leg pain and function in the combined group and fusion group were significantly improved compared with those before operation. SF-MPQ and ODI at 3 months, 1 year, 5 years after operation were significantly different from those before operation ( P<0.05). In the combined group, the DHI of semi-rigid internal fixation segments before operation and 3 months, 1 year, 5 years after operation were 37.8%±7.6%, 37.9%±7.4%, 36.5%±6.9% and 36.0%±7.1% respectively ( P>0.05); The IFH of semi-rigid internal fixation segments before operation and 3 months, 1 year, 5 years after operation were 21.5±2.8, 21.4±2.8, 20.4±2.7, 19.4±2.4 mm respectively ( P<0.05); The DHI of the upper segment adjacent to semi-rigid internal fixation before operation and 3 months, 1 year, 5 years after operation were 37.1%±9.3%, 36.8%±9.1%, 35.2%±9.1%, 33.9%±8.8% respectively ( P>0.05); The IFH of the upper segment adjacent to semi-rigid internal fixation before operation and 3 months, 1 year, 5 years after operation were 21.9±3.0, 21.4±3.0, 20.4±2.9, 19.5±2.7 mm, respectively ( P<0.05). The HD of upper vertebral body adjacent to semi-rigid internal fixation before operation and 3 months, 1 year, 5 years after operation were 2.2±0.7, 2.3±0.5, 2.5±0.5, 2.8±0.5 mm respectively ( P<0.05). At the last follow-up, one case of semi-rigid titanium rod fracture, one case of screw loosening at semi-rigid internal fixation segment, three cases with unsatisfied numbness relief, and 2 cases of facet joint spontaneous fusion at semi-rigid fixation segment occurred in the combined group. Conclusion:Waveflex semi-rigid internal fixation can protect the degenerative lumbar intervertebral disc, and delay the degeneration of semi-rigid internal fixation segment and adjacent upper segment after interbody fusion, but long-term follow-up and study are needed.