A series of laws and regulations are the essential legal requirement in the field of clinical trial of medical device currently in China, especially the Provision for Clinical Trial of Medical Device. On the basis of current situation of medical device clinical trial, systemic analysis on the hot spot topics in the regulations was conducted to explore the way of improving the control system of clinical trial of medical device in China, which will provide the reference for medical device industry and the investigators of the clinical trial of medical device.
China ; Device Approval ; legislation & jurisprudence

OBJECTIVE: To evaluate the efficacy of oblique lumbar interbody fusion combined with unilateral pedicle screw fixation via Wiltse approach in the treatment of lumbar spinal stenosis. METHODS: From July 2017 to January 2019, 90 patients with lumbar spinal stenosis, including 38 males and 52 females, aged from 43 to 75 years old with an average of(59.9±8.8) years old, and were treated with oblique lumbar interbody fusion(OLIF) combined with Wiltse unilateral pedicle screw fixation. Surgical decompression and fixation was performed in 50 cases of single segment, 32 cases of double segments and 8 cases of three segments. The distribution of responsible segments included 8 cases of L₂-L₃, 12 cases of L₃-L₄ and 30 cases of L₄-L₅ on single segment, 10 cases of L₂-L₄ and 22 cases of L₃-L₅ on double segments, and 8 cases of L₂-L₅ on three segments. The operation time, blood loss and occurrence of complications were recorded, Visual analogue scale(VAS), Oswestry Disability Index(ODI) and SF-36 scale were used to evaluate clinical efficacy. Lumbar X-ray and MRI were taken at three days after operation, interverterbral space height, intervertebral foraminal height, interverterbral foraminal area, and spinal canal area were measured, and interbody fusion was evaluated according to CT at half a year after operation. RESULTS: All patients were followed up from 12 to 33 months, with an average of (20.2±6.6) months. Mean operation time was (103.3±35.9) min, and mean intraoperative blood loss was (70.4±17.8) ml. VAS of low back pain leg pain, and ODI decreased from 6.2±1.1, 6.1±0.9 and (59.9±4.2)% to 2.7±0.5, 2.5±0.5 and (31.3±8.8)%. SF-36 scale significantly increased from (37.2±3.1) to (54.9±6.1) at the six months postoperation(P<0.05). The intervertebral space height, intervertebral foraminal height, intervertebral foraminal area, and spinal canal area were significantly improved at 3 days after operation(P<0.05). Six months after operation, CT scan showed well fusion in 87 cases, but 3 cases with poor fusion, including 1 case of single segment, 2 cases of multi-segments. The total fusion rate was 96.7% (87/90), the single segment fusion rate was 98.0% (49/50), and the multi-segments fusion rate was 95.0%(38/40). The overall incidence of complications was 17.8%(16/90), including transient iliopsoas muscle weakness in 5 cases (5.6%), endplate fracture in 2 cases (2.2%), peritoneal injury in 1 case (1.1%), postoperative hematoma in 1 case (1.1%), adjacent segment disease in 1 case(1.1%), and fusion cage subsidence in 6 cases (6.7%). Three patients was followed up for recurrent nerve root pain and the symptoms were relieved after revision operation. All complications were relieved or disappeared in varying degrees during the follow-up period, and there were no complications such as cage displacement and screw fracture. CONCLUSION OLIF combined with unilateral pedicle screw fixation via Wiltse approach is effective in treating lumbar spinal stenosis with minimally invasive advantages such as less trauma and less complications. Under the premise of strictly grasping the indications, this method could also achieve satisfactory clinical results in multi-segments oprations.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Spinal Stenosis/surgery* ; Pedicle Screws ; Spinal Fusion/methods* ; Lumbar Vertebrae/surgery* ; Treatment Outcome ; Low Back Pain

Objective: To investigate the inhibitory effect and mechanism of the extracts from fresh Lycii Fructus (LBL) on hepatoma HepG2 cell-induced cachexia in mouse.Method: The human hepatoma cell line HepG2 was injected into BALB/C mice to establish the cachexia model.Then the LBL was fed to the models respectively in low dose (5 mg·kg^-1) or high dose (25 mg·kg^-1).After 28 days of continuous feeding,the mice's body weight was detected.The expression levels of creatine kinase (CK),interleukin-1β (IL-1β),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were evaluated by enzyme linked immunosorbent assay (ELISA).The muscle degradation and the expression of p38 mitogen-activated protein kinase (p38 MAPK) were detected by immunohistochemistry staining.The expression levels of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-κB (NF-κB) were determined by Western blot.Result: Compared with cachexia group,the loss of body weight and muscle decomposition were significantly inhibited both in the low dose LBL group and high dose LBL group (P<0.05,P<0.01).The level of plasma CK decreased significantly both in the low-dose LBL group and the high-dose LBL group (P<0.01).ELISA tests revealed lower expression levels of IL-1β,IL-6 and TNF-α in both the low-dose LBL group and the high-dose LBL group (P<0.05,P<0.01).Immunohistochemistry staining showed that the expression of p38 MAPK was inhibited both in the low-dose LBL group and the high-dose LBL group (P<0.05).Western blot indicated that the expressions of p-p38 MAPK and NF-κB were inhibited both in the low-dose LBL group and the high-dose LBL group (P<0.01).We found that the high-dose LBL group shows a higher inhibitory capability than the low-dose LBL group.Conclusion: LBL could inhibit the cachexia induced by hepatoma HepG2 cell line in mouse,suggesting LBL could reduce major cytokine and plasma inflammatory factors through p-p38 MAPK pathway.

Arthritis, Rheumatoid/complications* ; Biomarkers ; Humans ; Lung Diseases, Interstitial/etiology* ; Prognosis

It is known that SMAD specific E3 ubiquitin protein ligase 1 (SMURF1) mediates autophagy through its E3 ubiquitin ligase activity, but the ubiquitinated substrates of SMURF1 need to be further explored. In this paper, the interacting proteins of SMURF1 in THP-1 cells were captured and identified by co-immunoprecipitation (Co-IP) combined with mass spectrometry. It was found that SMURF1 could physically bind to 222 proteins in THP-1 cells, and Adenosine deaminase acting on RNA 1 (ADAR1) had a higher peptide binding score. SMURF1 overexpression vectors were constructed and transfected into HEK-293T cells, then Co-IP and Western blotting assays verified the interaction between exogenous SMURF1 and endogenous ADAR1. qRT-PCR and Western blotting assays were carried out after transfecting SMURF1 overexpression vectors in HEK-293T cells, which identified that overexpression of SMURF1 attenuated the protein levels of ADAR1 (P<0. 05). However, there was no significant difference in the mRNA level of ADAR1. HEK-293T cells with normal and overexpressing SMURF1 were treated with cycloheximide (CHX), respectively, and Western blotting assays showed a shortened half-life of ADAR1 after overexpression of SMURF1 (P < 0. 05). Furthermore, overexpression of SMURF1 increased the polyubiquitination level of ADAR1 as detected by Co-IP and Western blot (P<0. 05). After the proteasome inhibitor (MG132) treatment, the Western blotting assay was performed to demonstrate that the negative regulatory effect of SMURF1 on ADAR1 was weakened after the proteasome degradation pathway was attenuated (P<0. 05). This study shows that SMURF1 interacts with ADAR1, catalyzes the polyubiquitination of ADAR1 and mediates its degradation through the proteasome pathway, which provides a theoretical basis for exploring the various biological functions of SMURF1 by affecting the stability of ADAR1.

Objective　To investigate the role of fatty acid binding protein 4 (FABP4) in the apoptosis of mouse podocytes induced by hyperhomocysteinemia (HHcy).　Methods　Nine wild male C57BL/6J mice (Cbs+/+) and nine C57BL/6J male mice with cystathionine beta synthase gene knockout heterozygote (Cbs+/-) were used as the control group and HHcy model group, respectively. All mice were fed with 2% high methionine diet for 8 weeks to replicate the HHcy model. The ultrastructure of glomerular podocytes was observed by transmission electron microscopy. Glomerular podocytes were cultured in vitro and divided into blank control group (Control group) podocytes treated with Hcy concentration of 0 μmol•L-1 for 48 hours. The podocytes of homocysteine group (Hcy group) were treated with Hcy concentration of 80 μmol•L-1 for 48 hours. Podocytes were infected with GFP-labeled adenovirus (Ad-GFP group) and FABP4 overexpression adenovirus (Ad-FABP4 group), respectively. Podocytes were treated with Hcy and FABP4 adenovirus, named as Hcy+Ad-FABP4 group. The expression of FABP4 was detected by qRT-PCR and Western blot. The changes of apoptosis-related proteins Bax, Bcl-2 and Caspase-12 were analyzed by Western blot. The apoptosis rate of cells was measured by flow cytometry.　Results　Compared with the control group, the podocyte injury was aggravated and accompanied by the increasing number of apoptotic cells in the kidney tissues of model group mice. At the same time, the expression of FABP4 mRNA (3.20±0.42) and protein (4.98±1.12) in model group were higher than those in control group (2.09±0.13, 3.04±0.11)(P<0.05). The expression of FABP4 mRNA (5.34±0.28) and the expression of FABP4 protein (11.94±0.22) in Hcy group were higher than those in control group (4.00±0.17, 5.10±0.20)(P<0.05). After infection with FABP4 adenovirus, the mRNA expression levels (3.05±0.22) and protein expression (4.07±0.20) of FABP4 in Ad-GFP group were not significantly different from those in control group (3.07±0.15, 3.93±0.15) (P>0.05); the mRNA expression levels (4.59±0.28) and protein expression (10.07±0.82) of FABP4 in Ad-FABP4 group were higher than those in Ad-GFP group (P<0.05). Bax/Bcl-2 value (3.15±0.65) and Caspase-12 protein expression (4.30±0.89) in Hcy group were higher than those in control group (2.19±0.10, 3.19±0.47) (P<0.05). The Bax/Bcl-2 values (5.42±0.55) and Caspase-12 protein expression (7.87±1.27) in the Hcy+Ad-FABP4 group were significantly higher than those in the Hcy+Ad-GFP group (3.19±0.47, 4.34±0.64) (P<0.05).　FABP4 plays an important role in the apoptosis of mouse podocytes induced by HHcy. Flow cytometry analysis showed that the total apoptotic rate of Hcy group was (10.85±1.25) higher than that of control group (3.77±0.12) (P<0.05). Hcy + Ad-FABP4 group (15.72±1.60) was higher than that of Hcy+Ad-GFP group (11.22±0.43) (P< 0.05).　Conclusion　FABP4 promotes the apoptosis of podocytes in mice treated with HHcy.

Objective: To investigate the influence of the Rho/ROCK signaling pathway on the anti-cryodamage ability of human sperm and provide some theoretical evidence for the development of high-efficiency semen cryoprotectants. METHODS: We collected semen samples from 25 healthy males, each divided into a fresh, a normal cryopreservation control and an Rho-inhibition group. Before and after freezing, we detected sperm motility, viability, membrane integrity, morphology, DNA fragmentation index (DFI), acrosomal enzyme activity (AEA) and mitochondrial membrane potential (MMP) and determined the expressions of RhoA and ROCK proteins in the sperm by immunofluorescence staining. RESULTS: Compared with the normal cryopreservation control, the frozen-thawed sperm of the Rho-inhibition group showed significantly increased sperm motility （ ［51.20 ± 7.70］% vs ［57.50 ± 6.83］%, P = 0.002), survival rate ( ［52.87 ± 5.07］% vs ［60.24 ± 5.53］%, P = 0.001), membrane integrity (［59.78±5.56］% vs ［67.10 ± 4.43］%, P = 0.001), percentage of morphologically normal sperm (［4.83 ± 1.11］% vs ［7.46 ± 1.28］, P = 0.001) and MMP (56.30 ± 4.28 vs 63.11 ± 2.97, P = 0.001), but decreased DFI (［27.64 ± 6.64］% vs ［18.87 ± 4.07］%, P = 0.001). There was no statistically significant difference in the AEA of the frozen-thawed sperm between the control and Rho-inhibition groups (97.65 ± 9.31 vs 98.30 ± 11.33, P > 0.05). Immunofluorescence staining revealed extensive expressions of RhoA and ROCK proteins in the head and neck of the sperm. CONCLUSIONS The Rho/ROCK signaling pathway plays a role in the cryodamage to human sperm, and inhibiting the activity of Rho/ROCK can significantly improve the ability of sperm to resist cryodamage.

AIM: To investigate the efficacy of epithelial-off accelerated corneal cross-linking(CXL)in the treatment of advanced keratoconus.METHODS: A retrospective study was performed on data collected from 32 patients(43 eyes)with advanced keratoconus who underwent epithelial-off accelerated CXL at Ningxia Eye Hospital from April 2020 to December 2021. Slit-lamp, intraocular pressure, uncorrected visual acuity(UCVA), corrected visual acuity, specular microscope, Pentacam and Corvis ST were tested before and at 1, 3 and 6mo after surgery. Preoperative and postoperative corneal condition, UCVA, best corrected visual acuity(BCVA)and the values of corneal endothelial, maximum keratometry(Kmax), thinnest corneal thickness(TCT), anterior and posterior surfaces of the cornea K1, K2, biomechanically corrected intraocular pressure(bIOP), applanation time 1(A1T), applanation length 1(A1L), applanation velocity 1(A1V), applanation time 2(A2T), applanation length 2(A2L), applanation velocity 2(A2V), highest concavity deformation amplitude(HCDA), radius at highest curvature(HCR), highest concavity peak distance(HCPD)and stiffness parameter at first applanation(SP-A1)were recorded.RESULTS: There were differences between UCVA(LogMAR; 1.06±0.49, 0.78±0.39)and BCVA(LogMAR; 0.48±0.34, 0.38±0.29)before and at 6mo after surgery(P<0.05), but there were no differences in corneal endothelial cells(2917.39±288.38 vs. 2959.19±336.27 cells/mm2, P=0.477). There were differences among Kmax, TCT, anterior surface K1 and K2 and posterior surface K1 before and after surgery(P<0.05), and all increased at 1mo after surgery then returned to preoperative level at 3mo after surgery, while there was no difference in the posterior K2. Furthermore, there were statistical significance in A1T, HCPD and SP-A1 before and after surgery(P<0.05), while there were no statistical significance in A1L, A1V,A2T, A2L, A2V, HCDA, HCR and bIOP(P>0.05).CONCLUSION: Epithelial-off accelerated CXL can prevent the progression of keratoconus within half year after surgery, and it has certain safety.

Objective To verify the biomechanical stability of oblique lateral interbody fusion ( OLIF) combinedwith different fixation methods for treating degenerative lumbar scoliosis (DLS) by three-dimensional (3D) finite element analysis. Methods The L1-S1 3D finite element DLS model ( Model 1) was established, and then the OLIF (L2-5) at 3 contiguous levels of fusion and its combination with different internal fixation methods were simulated, namely, stand-alone OLIF model ( Model 2), vertebral screw fixation model ( Model 3), unilateral pedicle screw fixation model (Model 4) and bilateral pedicle screw fixation model (Model 5) were established,respectively. Under upright, flexion, extension, lateral bending and axial rotation states, range of motion (ROM) of fusion segments, as well as cage stress, internal fixation stress, and stress distribution were recorded and analyzed. Results Under six motion states, the overall ROM of fusion segments in Models 2-5 was smaller than that of Model 1. Compared with Model 1, the overall ROM reduction of Model 3 and Model 4 was larger than that of Model 2 and smaller than that of Model 5. Under flexion and extension, the overall ROM reduction of Model 4 and Model 5 was basically equal. Under left and right lateral bending, the overall ROM reduction of Model 3 and Model 5 was basically equal. Under all motion states, the peak stress of Model 3 and Model 4 fusion cage was larger than that of Model 5 and smaller than that of Model 2. The peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 3 increased by 5. 52% , 10. 96% and 7. 99% respectively compared with Model 5 under left lateral bending, and the peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 4 increased by 8. 70% , 7. 00% and 6. 99% respectively under flexion. Under all motion states, the peak stress of screw rod in Model 5 was smaller than that of Model 3 and Model 4, and the peak stresses of screw rod in Models 3-5 were the smallest in upright state. Conclusions The OLIF with unilateral pedicle screw fixation or vertebral screw fixation can provide favorable biomechanical stability of the fusion segment. The results provide some references for clinical application of OLIF technology in the treatment of DLS.

ObjectiveTo acquire the basic information of trainees and analyze the training results and it' s influence factors in the training of rural health appropriate technology in Jiangsu.MethodsWe used the questionnaire to collect data of the trainees' personal information and training results after training.Results A total of 2284 valid questionnaires were collected. There were 73.6％ trainees came from township hospitals,95.1 ％ of them under 45 years old,62.9％ for females,79.2％ have been working for 8 years,3％ with senior professional titles,only 0.4％ had acquire the master's degree or above.Multiple regression analysis showed that the different level of hospitals,the training needs, suitable degree,knowledge familiarity before the training,expert instruction and learning were the main influence factors for the master of the technology; The influence factors for the wish to be re-training were working age,education,the demand for training technology,ease of learning,expert instruction,grasp of this time,appliance of the technology.Conclusionlong-term mechanism for trainning and continue education should be established,and medical workers in rural areas should be strengthen to take the technical training to further improve the rural medical services.