Objective To investigate the mechanisms of erythropoietin-producing hepatocellular A3 (EphA3) in the invasion of hepatocellular carcinoma (HCC) cells.Methods Hepatic cell HL-7702 and HCC cell and HCC cell lines HepG2 and MHCC97H were cultured.The expression of EphA3 in the HepG2 and MHCC97H cells was suppressed by siRNA interference,and then were divided into the untreated group,the control group and the siRNA intervention group.The expression of EphA3 was detected by RT-PCR and Western blot.The invasion ability of HepG2 and MHCC97H was detected by Transwell chamber.The protein expression of VEGF and activity of vascular endothelial growth factor (VEGF) were detected by western blot and ELISA.All data were analyzed using the analysis of variance or LSD-t test.Results The relative mRNA expressions of EphA3 in HL-7702,HepG2,and MHCC97H cells were 0.94 ±0.13,1.76 ±0.16 and 3.62 ±0.14,respectively,and the protein expressions of EphA3 in the 3 cells were 0.96 ±0.12,1.59 ±0.11 and 3.82 ±0.11.There was significant difference in the EphA3 expression between HL-7702 cells and HepG2,MHCC97H cells (t =2.511,6.437 ; 2.321,6.895,P ＜ 0.05).The relative mRNA expressions of EphA3 in the HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.95 ±0.11,0.96 ±0.12 and 0.31 ±0.15,respectively.There was significant difference in the mRNA expression of EphA3 in the HepG2 cells between the siRNA intervention group and the control group (t =4.051,P ＜ 0.05).The relative mRNA expressions of EphA3 in the MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.97 ± 0.16,0.95 ± 0.14 and 0.40 ± 0.11,respectively.There was significant difference in the mRNA expression of EphA3 in the MHCC97H cells between the siRNA interference group and the control group (t =5.237,P ＜0.05).The relative protein expressions of EphA3 in the HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.97 ± 0.16,0.95 ± 0.15 and 0.32 ± 0.17,respectively.There was significant difference in the protein expression of EphA3 in the HepG2 cells between the siRNA interference group and the control group (t =4.145,P ＜ 0.05).The relative protein expressions of EphA3 in the MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.95 ± 0.11,0.96 ± 0.12 and 0.38 ±0.17,respectively.There was significant difference in the protein expressions of EphA3 in the MHCC97H cells between the siRNA interference group and the control group (t =4.327,P ＜ 0.05).The numbers of HepG2 cells penetrated the Watrigel in the untreated group,the control group and the siRNA intervention group were (111 ±4)/10HPF,(109 ±5)/10HPF and (51 ±3)/10HPF,respectively.There was significant difference in the number of HepG2 cells between the siRNA interference group and the control group (t =7.582,P ＜ 0.05).The numbers of MHCC97H cells penetrated the Watrigel in the untreated group,the control group and the siRNA intervention group were (402 ± 6)/10HPF,(397 ± 7)/10HPF and (152 ± 7)/10HPF,respectively.There was significant difference in the number of MHCC97H cells between the siRNA interference group and the control group (t =9.479,P ＜ 0.05).The relative protein expressions of VEGF in the HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.98 ± 0.11,0.96 ± 0.13 and 0.57 ± 0.11,respectively.There was significant difference in the protein expression of VEGF of the HepG2 cells between the siRNA interference group and the control group (t =3.167,P ＜ 0.05).The relative protein expression of VEGF in the MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.97 ±0.14,0.98 ±0.12 and 0.34 ± 0.15,respectively.There was significant difference in the protein expression of VEGF of the MHCC97H cells between the siRNA interference group and the control group (t =4.278,P ＜ 0.05).The relative activities of VEGF proteins of HepG2 cells in the untreated group,the control group and the siRNA intervention group were 0.96 ±0.15,0.94 ±0.11 and 0.47 ±0.13,respectively.There was significant difference in the activity of VEGF protein in the HepG2 cells between the siRNA interference group and the control group (t =3.981,P ＜ 0.05).The relative activities of VEGF proteins in MHCC97H cells in the untreated group,the control group and the siRNA intervention group were 0.98 ±0.12,0.97 ±0.12 and 0.38 ±0.14,respectively.There was significant difference in the activity of VEGF protein in the MHCC97H cells between the siRNA interference group and the control group (t =4.059,P ＜ 0.05).Conclusions EphA3 plays an important role in the invasion of HCC cells via regulating the protein expression and activity of VEGF.EphA3 might be a new target for the treatment of HCC.

With the development of life science and technology, neuroscience has become one of the fastest growing fields in life science. The application range of neurotechnology involving medical treatment, education, life style and national security, etc. With the development of neuroscience, the ethical problems encountered in the development of neuroscience and neurotechnology have gradually become hot issues, including the research on the ethical issues of neuroscience and its technology applications, and the research on the neural basis of ethics, etc. The discipline of neuroethics has gradually emerged. Based on the horizon of neuroethics, this paper discussed three risks brought by neurotechnology, namely, physical and psychological risk, social risk and future risk. With the application of neurotechnology ethics as the core, the ethical risk should be considered from the aspects of accelerating the development of the discipline of neuroethics, emphasizing respect for the right to life and prudence in the research and application of neurotechnology, and strengthening the ethical governance of neurotechnology.

Alzheimer’s disease is a progressive， fatal， and neurodegenerative disease， clinically characterized by gradually developed cognitive and memory function decline， language and visuospatial disorders， and other aspects. It remains incurable and irreversible to date. In clinical settings， Alzheimer’s disease usually faces the possibility of untimely diagnosis， causing difficulties in the early intervention of the disease. Thus， it is essential to improve diagnostic efficiency and help patients diagnose Alzheimer’s disease as early as possible. With the continuous development of artificial intelligence （AI） technology， its application in Alzheimer’s disease imaging diagnosis has shown great potential. Meanwhile， it is also accompanied by many ethical issues. By exploring the ethical challenges brought by AI in the research and application of Alzheimer’s disease imaging diagnosis， such as data security， interpretability， algorithmic discrimination， and disclosure of incidental findings， the paper proposed the corresponding countermeasures， with a view to providing certain ethical guidance for the AI application in medical imaging diagnosis， protecting the rights and interests of subjects/patients， and promoting the healthy development of technology.

Addiction is a state of chronic neurological dysfunction with repetitive and compulsive behavior as the main manifestation. One of the characteristics of this state is that addicts have significantly reduced autonomy for compulsive behaviors. The emergence of addictive behavior is based on the impaired autonomy of addicts, so the assessment of their condition, prognosis, and related moral responsibility are all related to their autonomy. By exploring whether the treatment of addicts should be based on autonomy as the core indicator to evaluate whether they can end treatment, and exploring the debate on addicts’ autonomy based on the disease model and moral model of addiction, it is believed that whether addicts have autonomy cognition is influenced by the causes of addiction. Furthermore, the issue of moral responsibility of addicts after treatment termination and the quantitative feasibility of autonomy were discussed, and it was advocated to determine the moral responsibility after addiction treatment based on their autonomy.

Objective:To investigate the effect of teriparatide on residual back pain (RBP) after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective cohort study was used to analyze the clinical data of 90 OVCF patients sustaining RBP after PKP admitted to Second Affiliated Hospital of Kunming Medical University from September 2015 to March 2019, including 18 males and 72 females, at age of 57-85 years［(68.0±5.9) years］. Teriparatide treatment was applied regularly in 32 patients (teriparatide group) and antiosteoporosis drug was administered routinely in 58 patients (routine treatment group). Visual analogue scale (VAS) and Oswestry disability index (ODI) were compared between the two groups before operation, at 24 hours, 1 month, 3 months, 6 months and 12 months after operation. Anterior vertebral body height (ABH), middle vertebral body height (MBH), kyphosis angle (KA), maintenance rate of anterior vertebral body height (MRABH), maintenance rate of middle vertebral body height (MRMBH) and difference of kyphosis angle (DKA) were measured at 24 hours and 12 months after operation to evaluate the maintenance of vertebral height and incidence of vertebral refracture. Levels of type I collagen carboxy-terminal peptide (β-CTX) and serum N-terminal osteocalcin (N-MID) were measured before operation and at 12 months after operation to evaluate the improvement of bone metabolism. The adverse reactions of teriparatide group were observed.Results:All patients were followed up for 12-36 months［(14.3±0.6)months］. VAS and ODI were decreased gradually with time in both groups (all P<0.01). There were no significant differences in VAS between the two groups before operation and at 24 hours after operation (all P>0.05). Teriparatide group showed VAS of (4.4±0.6)points, (3.2±0.5)points, (2.0±0.5)points, (1.1±0.1)points at 1, 3, 6 and 12 months after operation, significantly lower than those in routine treatment group［(4.9±0.6)points, (4.0±0.6)points, (3.2±0.7)points, (2.7±0.1)points, respectively］(all P<0.01). Teriparatide group showed ODI of 26.5±1.3 and 20.6±1.2 at 6 months and 12 months after operation, significantly lower than those in routine treatment group (28.2±1.6, 23.6±1.6) (all P<0.01). There were no significant differences in ODI between the two groups at other time points (all P>0.05). Both groups presented significantly lowered levels of ABH and MBH at 12 months after operation as compared with those at 24 hours after operation (all P<0.01). There were no significant differences in ABH or MBH between the two groups at 24 hours after operation (all P>0.05). ABH, MBH, MRABH and MRMBH in teriparatide group were (1.9±0.2)cm, (1.7±0.2)cm, 0.91±0.02 and 0.92±0.02 at 12 months after operation, significantly higher than those in routine treatment group［(1.7±0.2)cm, (1.6±0.2)cm, 0.86±0.02 and 0.87±0.02］(all P<0.01). KA in both groups showed significant increase at 12 months after operation as compared with that at 24 hours after operation (all P<0.01). There was no significant difference in KA between the two groups at 24 hours after operation ( P>0.05). KA in teriparatide group was (7.3±0.7)° at 12 months after operation, significantly lower than (9.5±0.5)° in routine treatment group ( P<0.01). DKA in teriparatide group was (5.3±1.3)° at 12 months after operation, significantly lower than (6.6±1.4)° in routine treatment group ( P<0.01). Incidence of vertebral refracture in teriparatide group was 7% (2/32), significantly lower than 35% (15/58) in routine treatment group ( P<0.05). Level of β-CTX was not significantly different between and within the two groups before operation and at 12 months after operation (all P>0.05). There was no significant difference in N-MID between the two groups before operation ( P>0.05). After treatment for 12 months, level of N-MID in teriparatide group was significantly increased［19.5 (17.6, 20.9)pg/ml］as compared with that before operation［18.2 (14.6, 21.0)pg/ml］( P<0.01), and was significantly higher than that in routine treatment group［17.6 (15.3, 19.9)pg/ml］( P<0.01). Routine treatment group showed no significant difference in level of N-MID before operation and at 12 months after operation ( P>0.05). Two patients in teriparatide group had orthostatic hypotension after treatment. Conclusion:For OVCF patients with RBP after PKP, teriparatide can effectively alleviate pain, improve motor dysfunction, maintain the height of bone cement vertebral body, reduce incidence of vertebral refracture and enhance the activity of osteoblasts, with less adverse reactions.

Objective:To explore the risk factors of adjacent segment diseases (ASDis) after lumbar fusion, summarize the prevention strategies and provide reference for clinical treatment.Methods:All of 258 patients who underwent lumbar interbody fusion from March 2014 to March 2019 were retrospectively analyzed, including 95 males and 163 females, the age of whom was 61.8±8.4 years (range, 39-77 years). The patients were divided into ASDis group and non-ASDis group according to whether ASDis occurred at the follow-up of 24 months after operation. The patient's individual factors [gender, age, body mass index (BMI), main diagnosis, preoperative paraspinal muscle fatty degree, etc.] and surgical factors (operation type, fixed segment, fusion segment, etc.), sagittal parameters [lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL] were recorded. After univariate analysis of potential risk factors, the factors with P<0.05 were substituted into logistic regression model for multivariate analysis to determine the risk factors of ASDis after lumbar fusion. Results:ASDis occurred in 24 patients after lumbar fusion, with an incidence of 9.3% (24/258); univariate analysis showed that age ≥ 60 years old, complicated with osteoporosis, preoperative fatty degree of paraspinal muscle (GCS grade≥3), PLIF operation, suspension fixation, total laminectomy and multi-segment fusion (≥ 3 segments) were the potential risk factors for ASDis after operation (P<0.05); Gender, education level, partner status, type of work, BMI, obesity (BMI≥24 kg/m 2) , smoking, use of bisphosphonates, concomitant lumbar spinal stenosis, lumbar lordosis angle, pelvic incidence angle, pelvic tilt angle, sacral slope angle, and PI-LL had no significant correlation with ASDis. Logistic regression analysis showed that age ≥ 60 years ( OR=5.63, 95% CI: 1.56, 20.29, P=0.008), preoperative paravertebral muscle fatty GCS ≥ 3 ( OR=4.82, 95% CI: 1.36, 17.13, P=0.015), combined with osteoporosis ( OR=14.04, 95% CI: 2.53, 77.79, P=0.002), PLIF ( OR=9.69, 95% CI: 1.91, 49.03, P=0.001), and multi-segment fixation ( OR=9.36, 95% CI: 1.77, 49.41, P=0.008) were the risk factors for ASDis after lumbar fusion; Incomplete laminectomy ( OR=0.09, 95% CI: 0.02, 0.37, P=0.001) and suspension fixation ( OR=0.16, 95% CI: 0.02, 0.94, P=0.042) were the protective factors of ASDis after lumbar fusion. Conclusion:The patients with age ≥ 60 years old, osteoporosis and preoperative paraspinal muscle fatty degree ≥ 3 grade GCS should be more careful in choosing the surgical methods, and try to choose transforaminal interbody fusion, posterolateral fusion, short segment fusion, decompression with preservation of vertebral lamina, suspension fixation and other surgical methods to reduce the incidence of postoperative ASDis.

The introduction of vitrectomy has solved a difficult and intractable problem in the ophthalmology community for the treatment of fundus oculi diseases. To date, minimally invasive vitrectomy(MIV)is the main surgery for the treatment of fundus oculi diseases. Clinically, patients develop dry eye symptoms after MIV, including lacrimation, foreign body sensation, and visual disturbances. We speculates that MIV may damage the conjunctival and corneal epithelium as well as related sensory nerves, disrupting the tear film and causing a local inflammation response, thereby further affecting the ocular surface microenvironment and inducing or aggravating dry eye symptoms. At present, there are few studies on the changes of ocular surface after MIV. This article aims to analyze the effects of different factors on the microenvironment of the ocular surface before, during and after MIV, and to provide preventive and curative measures that can be taken to guide the clinic to make good preparations for the operation, to choose the appropriate surgical procedure, and to reduce the risk of dry eye in the postoperative period.