Implanted brain-computer interface (iBCI) is a system that establishes a direct communication channel between human brain and computer or an external devices by implanted neural electrode. Because of the good functional extensibility, iBCI devices as a platform technology have the potential to bring benefit to people with nervous system disease and progress rapidly from fundamental neuroscience discoveries to translational applications and market access. In this report, the industrialization process of implanted neural regulation medical devices is reviewed, and the translational pathway of iBCI in clinical application is proposed. However, the Food and Drug Administration (FDA) regulations and guidances for iBCI were expounded as a breakthrough medical device. Furthermore, several iBCI products in the process of applying for medical device registration certificate were briefly introduced and compared recently. Due to the complexity of iBCI in clinical application, the translational applications and industrialization of iBCI as a medical device need the closely cooperation between regulatory departments, companies, universities, institutes and hospitals in the future.
Humans ; Brain-Computer Interfaces ; Brain/physiology* ; Electrodes, Implanted

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

Objective:To explore the level of tibial growth plate chondrocyte mitophagy in young rats with chronic renal failure (CRF) and its effect on chondrocyte apoptosis.Methods:Male 4-week-old Sprague-Dawley rats were randomly divided into two groups according to random number table method: normal control group ( n=20, intragastric administration with distilled water) and CRF group ( n=20, given adenine suspension 150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavage for 6 weeks. The length of tibia was measured on X ray film, the width of tibia growth plate was measured and compared on histological section, and the apoptosis rate of chondrocytes in growth plate was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The growth plate chondrocytes of two groups were isolated and cultured to the third generation in vitro, and the apoptosis rate of chondrocytes was detected by TUNEL assay. The co-localization of mitochondria and autophagy lysosomes in chondrocytes was observed by double fluorescence staining. Western blotting was used to detect the level of mitochondrial marker protein translocate of the outer mitochondrial membrane-20 (Tom-20) and autophagy marker light chain-3 protein (LC-3). The mitophagy of growth plate chondrocytes was observed by transmission electron microscope. Results:Compared with the normal control group, the tibia length of CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], and the relative width of growth plate in histological section was narrower (0.56±0.19 vs 1.00±0.21, t=6.744, P<0.001). The apoptosis rate of chondrocytes in growth plate in CRF group was higher than that in the normal control group (17.2%±4.8% vs 5.1%±3.4%, t=6.505, P<0.001). The apoptosis rate of chondrocytes cultured in vitro in CRF group was higher than that in the normal control group (11.8%±6.2% vs 3.1%±1.2%, t=4.357, P<0.001). The result of double influorescence staining showed that there was co-localization between mitochondria and autophagy lysosomes in CRF group. Western blotting results showed that the levels of LC-3 protein ( t=8.944, P<0.001) and Tom-20 protein ( t=6.708, P<0.001) in CRF group were lower than those in the normal control group. Conclusion:The level of tibial growth plate chondrocyte mitophagy in young rats with CRF increases, which will lead to a decrease in the number of mitochondria, an increase in the apoptosis and a decrease in the number of chondrocytes, and eventually lead to dysplasia of tibia.

Objective:To explore the preoperative 68Ga-PSMA PET/CT examination on the guidance of surgical strategies for high-risk prostate cancer patients and the influence of positive surgical margins after surgery. Methods:The clinical data of 118 patients with high-risk prostate cancer who underwent robot-assisted laparoscopic radical prostatectomy from June 2019 to December 2020 in Xijing Hospital of Air Force Military Medical University was retrospectively analyzed. 47 patients received 68Ga-PSMA PET/CT examination before surgery (study group), and 71 cases without 68Ga-PSMA PET/CT examination before operation ( control group). There was no statistically significant difference in the age [69 (63, 76) vs. 67 (64, 74) years], PSA [PSA≤20ng/ml: 9.91 (6.00, 13.67) vs. 11.64 (8.15, 15.44) ng/ ml, PSA> 20ng/ml: 66.53 (53.66, 195.30) vs. 63.18 (30.08, 148.05) ng/ml], preoperative clinical staging (T 2/≥T 3: 21/26 cases vs. 34/37 cases), and Gleason score [8 (7, 9) vs. 8 (7, 9) points] (all P>0.05) between study group and control group. Both groups underwent robot-assisted laparoscopic radical prostatectomy. The surgical plan was based on the PSMA PET/CT and MRI results in study group and control group respectively. First, ensure that all tumors are removed, and secondly, preserve the patient's urethral length as much as possible to ensure postoperative urinary control.If there is seminal vesicle invasion, expand the scope of resection as needed. If lymph node metastasis is shown, lymph node dissection is performed. For those with negative lymph nodes in imaging studies, if enlarged lymph nodes are found during the operation, lymph node dissection is also performed. After the operation, the perioperative results and surgical margins of the two groups were compared, and the correlation between the PSA value and the SUVmax value of prostate cancer tissue was analyzed. Results:The operations of the two groups were successfully completed, and there was no transfer to open surgery. The operation time of the study group was shorter than that of the control group [175 (155, 205) min vs. 205 (155, 235) min, P=0.003], and the positive rate of resection margin was significantly lower than that of the control group [23.40% (11/47) vs. 45.07%(32/71), P=0.017]. For patients with pathological stage ≥pT 3, the positive rate of surgical margins in the study group was significantly lower than that in the control group [30.77%(8/26) vs. 62.16%(23/37), P=0.014]. In the study group, 11 cases of PSMA-PET showed positive lymph nodes before operation, 10 cases were pathologically positive after operation (90.91%). PSMA-PET showed negative lymph nodes in 1 case, which was pathologically positive after operation. In the control group, 26 cases underwent lymph node dissection, and 16 cases (61.54%) were pathologically positive after operation. The preoperative PSA value of 47 cases in the study group was positively correlated with the SUVmax value of prostate cancer tissue ( r=0.579, P<0.01). Conclusions:Preoperative 68Ga-PSMA PET/CT for high-risk prostate cancer patients can guide the surgeon to optimize the surgical plan, reduce the positive rate of resection margins, and effectively remove the metastatic lymph nodes, which will benefit the patients.

Objective:To explore the effect of Wnt/β-catenin signaling pathway on growth plate development of tibial growth plate in young chronic renal failure (CRF) rats.Methods:Four-week-old male SD rats were randomly divided into control group and CRF group ( n=20/per group). Control group was intragastric administration with distilled water, and CRF group was given adenine suspension (150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavages for 6 weeks. The full length of tibia was compared between the two groups. The width of tibia proximal growth plates was measured by micro-CT scanning, and the width of the growth plate was also measured in histological sections. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. Immunohistochemical staining was used to detect the expression of collagen Ⅱ, matrix metalloproteinase 13 (MMP-13) and β-catenin in chondrocytes. Western blotting was used to detect the protein expressions of collagen Ⅱ, MMP-13 and β-catenin. Results:Compared with the control group, the tibial length of rats in the CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], the width of growth plate in micro-CT picture was more narrow [(0.72±0.22) mm vs (1.13±0.27) mm, t=5.096, P<0.001], and the relative width of the growth plate was also more narrow ( t=6.744, P<0.001) in histological sections. The results of immunohistochemistry and Western blotting showed the expressions of collagen Ⅱ in the CRF group decreased significantly ( t=8.212, P<0.001), MMP-13 ( t=13.091, P<0.001) and β-catenin ( t=7.534, P<0.001) increased significantly compared the control group in chondrocytes. Conclusion:The Wnt/β-catenin signaling pathway is highly expressed in the tibial growth plate of young rats with chronic renal failure, which leads to accelerated degeneration and differentiation of chondrocytes and a closure tendency of growth plate.

42 cases with gastroesophageal varices were prospectively included. The groups were treated with endoscopic band ligation or combined with tissue adhesive. The results showed that the left gastric vein internal diameter, average blood flow velocity and blood flow volume after the treatment of band ligation combined with tissue adhesive were significantly lower than that of the treatment of band ligation alone, and the differences were statistically significant ( P < 0.05). Spleen and portal vein internal diameter, blood flow and average velocity, the liver and spleen size, shear wave velocity and liver function grade of the two groups after treatment did not change significantly ( P > 0.05). The effective rate of band ligation combined with tissue adhesive in the treatment of esophageal and gastric varices (66.67%, 52.38%) were higher than that of band ligation alone (42.85%, 23.81%) ( P > 0.05), and the re-bleeding rate of the latter was higher (9.52% and 19.05%, P > 0.05). Hence, it is suggested that the combined therapy is safe and more effective, and has no apparent effect on liver function and portal hypertension.

Objective To evaluate the factors related to contralateral hip fracture in the elderly patients with hip fracture by meta analysis.Methods Pubmed,Cochrane,CBMdisc,CNKI Chinese Journal Full Text Database and Wan Fang Database were searched for publications at home and abroad from January 2005 to April 2018 on factors related to contralateral hip fracture after hip fractures in the elderly.The publication quality was strictly evaluated before the data were extracted concerning gender and age(＞ 65years) of the patients,concomitant osteoporosis (Singh sign ≥ 4),primary fracture type,concomitant Parkinson disease,concomitant stroke,concomitant senile dementia,concomitant cataract,concomitant rheumatoid arthritis,concomitant diabetes,type of internal fixation for primary fracture and therapeutic compliance.Revman5.0 was used to perform the statistical analysis and the OR value and 95％ CI were calculated fore each index.Results A total of 17 studies were included involving 1,504 patients with contralateral hip fracture among 13,717 elderly patients with hip fracture.The factors related to the refracture of the contralateral hip were the age of the patients (OR ＝-3.55,95％ CI:-5.60 ～-1.50,P ＜ 0.001),osteoporosis (OR=2.38,95％CI:1.36～4.17,P=0.002),Parkinson disease (OR=4.54,95％CI:2.74～7.53,P ＜0.001),stroke (OR=0.33,95％ C I:0.18～0.59,P ＜ 0.001),senile dementia (OR=0.43,95％CI:0.29～0.62,P ＜0.001),cataract (OR=0.37,95％CI:0.22～0.63,P ＜0.001),rheumatoid arthritis (OR =0.32,95％ CI:0.21 ～ 0.50,P ＜ 0.001),diabetes (OR =0.65,95％ CI:0.47～0.91,P=0.01),type of internal fixation for primary fracture (OR=0.51,95％ CI:0.30 ～ 0.85,P =0.01),and therapeutic compliance (OR =0.36,95％ CI:0.21 ～ 0.64,P ＜ 0.001).However,the refracture of the contralateral hip was not related to gender (OR =1.07,95％ CI:0.45 ～2.56,P=0.88),smoking (OR=0.86,95％CI:0.40～1.86,P=0.70),fracture type (OR=0.97,95％ CI:0.60～1.57,P=0.90),or hypertension (OR=0.70,95％ C I:0.41～1.21,P=0.20).Conclusions In elderly patients with hip fracture,the risks for contralateral hip fracture may be advanced age,concomitant osteoporosis,Parkinson disease,stroke,senile dementia,cataract,rheumatoid arthritis and diabetes,type of internal fixation for primary fracture,and poor therapeutic compliance.However,no sufficient evidence has suggested that gender,smoking,type of hip fracture or concomitant hypertension might be associated with the contralateral hip fracture.

Objective To observe the expression of parathyroid hormone - related peptide (PTHrp) receptor in tibial growth plate and its effects on tibial extension in chronic renal insufficiency rats. Methods Two-week-old male Sprague-Dawley rats were randomly divided into sham group, model group and enalapril group, each with 20 rats. In model group and enalapril group rats had chronic renal insufficiency induced by left ureteral obstruction, and rats were respectively given saline and enalapril by gavage after the operation. In sham group, left ureter was only exposed without ligation, and rats were given saline. The urine was collected 4 weeks after the operation and the total protein content was measured. Then all rats were killed. The concentrations of PTHrp, creatinine and urea nitrogen in intracardiac blood were detected. HE staining and Masson staining were performed on the left kidney to observe pathological changes of glomeruli and renal tubules. The total length of bilateral tibia was measured. The number of columnar cells in the growth plate proliferative zone was measured by safranin O staining and the expression of PTHrp receptor in the growth plate was detected by immunohistochemistry. Results The 24 h urine total protein, creatinine and urea nitrogen in model group were higher than those in sham group (all P＜0.05), while these 3 renal functional parameters in enalapril group were lower than those in model group (all P＜0.05). In model group and enalapril group rats had higher blood concentrations of PTHrp than that in sham group (all P＜0.05), but blood PTHrp in enalapril group was lower than that in model group (P＜0.05). HE staining and Masson staining showed that in the model group rats had severe tubular dilation, inflammatory cell infiltration and the tissue fibrosis, while in enalapril group renal tubules slightly dilated and had a few inflammatory cell infiltration and tissue fibrosis. Compared with those in the sham group, in model group the tibia length, the chondrocyte number of column structure in the growth plate proliferative zone and the PTHrp receptor decreased (all P＜0.05). But in enalapril group those indexes increased than model group (all P＜0.05). Conclusions Chronic renal insufficiency rats had increased PTHrp concentration in the blood but decreased PTHrp receptors expression in tibial growth plate, which lead to their limited tibial extension.

Objective To study the association between the expression of periostin and the occurrence and progression of knee osteoarthritis (OA) in synovial fluid.Methods The expression level of periostin in the synovial fluid of healthy people and patients with different stages of OA was tested.Furthermore,60 surgical-induced OA rat model were divided into two groups,the sham operation group had only implemented slit suture,and the OA model group had one side anterior cruciate ligament transected.The expression of periostin in intra-articular injection samples were analyzed at 1,2,4,8,12 week.Fluorescence molecular tomography (FMT) were performed after surgery at 4,8,12 week on the surgery knee.Gross morphologic lesions on the tibial plateau in rats were visualized by India ink staining,toluidine blue staining,cartilage permeation test.The synovium were visualized by HE staining and periostin were detected by immunohistoc hemistry.The measurement data were compared by one factor analysis of variance test.Results The expression of periostin in cartilage was lower in late-stage OA than the one from normal and early-stage OA (F=13.95,P＜0.01).The FMT showed that there was no obvious change in the extent of chronic inflammation in the sham operation group,and the chronic inflammatory degree of the OA model group gradually increased as time went on.Toluidine blue staining and cartilage permeation test showed that the cartilage degeneration in rat model of OA became more and more serious with time.There was no stastically significant difference of the periostin in control groutp at different time stage (F=0.67,P=0.53).The periostin in the intra-articular increased at first and then decreased with the development of OA (F=11.0,P＜0.05).HE staining of synovial tissue showed that the degree of synovial hyperplasia was consistent with the degree of degeneration of joints.With the extension of time,the expression of periostin in synovial tissue increased gradually.Conclusion The expression of periostin in human synovial fluid is low in normal knee joint,increases in early and middle stages,and decreases in late stage.The rat model indicates that the expression of periostin increases first and then decreases with the development of OA,but the expression in synovium increases gradually with the development of OA.The increased expression of periostin in synovial fluid may serve as an early diagnostic marker for OA and downregulation of the periostin may be a start marker for the late OA.

Objective To investigate the effect of POSTN protein on the proliferation of chondrocytes of tibial plateau in old rats.Methods Cartilage cells collected from the tibial plateau of old rats were cultured in vitro to the third generation.Then the cells were divided into 3 groups:POSTN group,PBS group and POSTN antibody group.The proliferations of the three groups at 24 h,48 h and 72 h were determined by EDU method.The expression of Notch1 protein was detected by immunohistochemistry in all groups at the same time.Female 20-month-old Sprague-Dawley rats were randomly divided into 3 groups:POSTN protein injection group,Phosphate Buffered Saline (PBS) injection group and POSTN antibody injection group.Twelve weeks after the operation,related reagents were injected 3 times consecutively at day 1,day 3,day 5 and EDU was injected into joints at day 1.At 2 weeks after injection,the rats were killed and the knee tibial plateau was taken to observe the proliferation of the cartilage cells.Results At 24 h,there were differences between the three groups O(F=27.32,P=0.017).The proliferation rates of POSTN group [(23±8)％] and PBS group [(21±10)％] were higher than that of POSTN antibody group (16±5)(P=0.003,P=0.011).At 48 h,there were differences between the three groups (F=35.34,P＜0.01).The proliferation rate of POSTN group [(36±11)％] was higher than that of the other groups [(22±6)％],(18±6)％(P=0.021,P＜0.01).At 72h,there were differences between the three groups (F=52.62,P=0.000).The proliferation rate of POSTN group [(56±17)％] was the highest one,the proliferation rate of PBS group [(31±8)％] was the medium,and the POSTN antibody group [(26±7)％] was the lowest one (all P＜0.05).As for Notch1 protein expression in chondrocytes,there were differences between the three groups (F=26.72,P＜0.01).The Notch1 protein was the most frequently expressed in POSTN protein-injection group and the least in the anti-POSTN group.In rats,the proliferation rate of the chondrocytes in the medial tibia plateau of the knee of POSTN protein injection group [(36±14)％],which was the highest,and that of the POSTN antibody injection group [(10 ±4)％] was the lowest (all P＜0.05).Conclusion POSTN protein can promote the proliferation of chondrocytes knee OA rats.POSTN antibody injection has been shown to induce the proliferation of chondrocytes.The POSTN protein may promote the proliferation of chondrocytes by activating the Notch signaling pathway.