Objective:To investigate the expression of SLIT2/ROBO1 in prostate cancer and its clinical significance.Methods:A total of 100 cases of radical prostatectomy paraffin specimens at Department of Clinical Pathology, the average age of the patients was (71.8±7.8) years, the People?s Hospital of Baoan Shenzhen from January 2015 to December 2019 were collected and immunohistochemical staining was used to analyze the correlation between SLIT2/ROBO1 expression and clinicopathological features in prostate cancer.COX regression was used to analyze the influencing factors of biochemical recurrence in patients with prostate cancer after radical treatment.Prostate cancer cells PC3 and LNCaP were used as research objects, ROBO1 was silenced by small interfering RNA specific to human ROBO1, and its effect on the growth rate of prostate cancer was observed by CCK8 assay.Transwell cell migration and invasion assay was used to detect the effect of ROBO1 knock-down on the migration and invasion ability of prostate cancer cells.Protein immunoimprinting assay was used to detect the expression of TGF-β/SMAD pathway-related proteins after ROBO1 knockdown.Results:The expressions of SLIT2 and ROBO1 in prostate cancer were increased with the increase of prostate cancer Gleason score system (Gleason score) and International Society of Urology Pathology score (ISUP)( P<0.05). The expression was significantly up-regulated in prostate cancer tissues with lymph node metastasis ( P<0.01) and T3 stage.In addition, COX regression univariate analysis showed that age, preoperative PSA level, Gleason and ISUP scores, T stage, lymph node metastasis and ROBO1 protein expression status were correlated with postoperative biochemical recurrence.COX regression multivariate analysis showed that ROBO1 high expression, age, preoperative PSA value and T stagewere risk factors for the prognosis of prostate cancer ( P<0.05).The results of cell experiments showed that ROBO1 promoted the proliferation, migration and invasion of prostate cancer cells.The expression of TGF-β/SMAD was decreased after ROBO1 knockdown and SLIT2/ROBO1 inhibitor (P144)treatment, respectively. Conclusions:The high expression of SLIT2 and ROBO1 is associated with the progression and differentiation of prostate cancer.The high expression of ROBO1 is a risk factor for biochemical recurrence of prostate cancer.At the same time, ROBO1 can inhibit the migration and invasion of prostate cancer cells by regulating the TGF-β/SMAD signaling pathway.

Objective:To observe and preliminarily analyze the risk factors related to silicone oil dependence after pars plana vitrectomy (PPV) in open globe injuries (OGI) .Methods:A retrospective clinical study. This study included 211 patients with OGI who received PPV treatment from January 1, 2005 to December 31, 2016 in Eye Injury Vitrectomy Study database. Silicone oil dependence was defined as the intraocular pressure <10 mm Hg (1 mm Hg= 0.133 kPa) in silicone oil tamponade eye 6 months after PPV. The patient's age, intraocular pressure, type of injury, length of eyeball wound, as well as the presence of ciliary body injury, choroidal injury, and retinal resection and/or defect area were recorded in detail. Logistic multifactorial regression analyzed the correlation between age, eye wound length and ciliary body iinjury, choroidal injury and retinal resection and/or defect severity and silicone oil dependence.Results:211 OGI eyes underwent vitrectomy were included, the mean age of the study population was 32.93 years (range 1-73 years), and the median follow-up period was 20.06 months (range 5.85-90.58 months). Among the 211 eyes, 121 (57.3%, 121/211), 52 (24.6%, 52/211), 23 (10.9%, 23/211) and 15 (7.1%, 15/211) were rupture, perforation, intraocular foreign bodies and penetrating injury, respectively. 98 eyes (46.4%, 98/211) of silicone oil dependence in total, among them, 64 (65.3%, 64/98), 19 (19.4%, 19/98), 9 (9.2%, 9/98) and 6 (6.1%, 6/98) eyes were rupture, perforation, intraocular foreign body and penetrating injury, respectively. Correlation analysis revealed that silicone oil dependence was significantly associated with ciliary body injury [odds ratio ( OR) = 2.150, 95% confidence interval ( CI) 1.052-4.393], choroidal injury ( OR=3.233, 95% CI 1.454-7.191), and retinal injury ( OR=2.731, 95% CI 1.393-5.353). No correlation was found with age ( OR= 0.981, 95% CI 0.960-1.002) or ocular wound length ( OR=1.716, 95% CI 0.987-2.984) ( P> 0.05). Conclusion:Silicone oil dependency following PPV in OGIs are associated with ciliary body, choroidal, and retinal injuries, but no association with age or length of the ocular wound.

Objective:To investigate the expression of SLIT2/ROBO1 in prostate cancer and its clinical significance.Methods:A total of 100 cases of radical prostatectomy paraffin specimens at Department of Clinical Pathology, the average age of the patients was (71.8±7.8) years, the People?s Hospital of Baoan Shenzhen from January 2015 to December 2019 were collected and immunohistochemical staining was used to analyze the correlation between SLIT2/ROBO1 expression and clinicopathological features in prostate cancer.COX regression was used to analyze the influencing factors of biochemical recurrence in patients with prostate cancer after radical treatment.Prostate cancer cells PC3 and LNCaP were used as research objects, ROBO1 was silenced by small interfering RNA specific to human ROBO1, and its effect on the growth rate of prostate cancer was observed by CCK8 assay.Transwell cell migration and invasion assay was used to detect the effect of ROBO1 knock-down on the migration and invasion ability of prostate cancer cells.Protein immunoimprinting assay was used to detect the expression of TGF-β/SMAD pathway-related proteins after ROBO1 knockdown.Results:The expressions of SLIT2 and ROBO1 in prostate cancer were increased with the increase of prostate cancer Gleason score system (Gleason score) and International Society of Urology Pathology score (ISUP)( P<0.05). The expression was significantly up-regulated in prostate cancer tissues with lymph node metastasis ( P<0.01) and T3 stage.In addition, COX regression univariate analysis showed that age, preoperative PSA level, Gleason and ISUP scores, T stage, lymph node metastasis and ROBO1 protein expression status were correlated with postoperative biochemical recurrence.COX regression multivariate analysis showed that ROBO1 high expression, age, preoperative PSA value and T stagewere risk factors for the prognosis of prostate cancer ( P<0.05).The results of cell experiments showed that ROBO1 promoted the proliferation, migration and invasion of prostate cancer cells.The expression of TGF-β/SMAD was decreased after ROBO1 knockdown and SLIT2/ROBO1 inhibitor (P144)treatment, respectively. Conclusions:The high expression of SLIT2 and ROBO1 is associated with the progression and differentiation of prostate cancer.The high expression of ROBO1 is a risk factor for biochemical recurrence of prostate cancer.At the same time, ROBO1 can inhibit the migration and invasion of prostate cancer cells by regulating the TGF-β/SMAD signaling pathway.

Objective:To observe and preliminarily analyze the risk factors related to silicone oil dependence after pars plana vitrectomy (PPV) in open globe injuries (OGI) .Methods:A retrospective clinical study. This study included 211 patients with OGI who received PPV treatment from January 1, 2005 to December 31, 2016 in Eye Injury Vitrectomy Study database. Silicone oil dependence was defined as the intraocular pressure <10 mm Hg (1 mm Hg= 0.133 kPa) in silicone oil tamponade eye 6 months after PPV. The patient's age, intraocular pressure, type of injury, length of eyeball wound, as well as the presence of ciliary body injury, choroidal injury, and retinal resection and/or defect area were recorded in detail. Logistic multifactorial regression analyzed the correlation between age, eye wound length and ciliary body iinjury, choroidal injury and retinal resection and/or defect severity and silicone oil dependence.Results:211 OGI eyes underwent vitrectomy were included, the mean age of the study population was 32.93 years (range 1-73 years), and the median follow-up period was 20.06 months (range 5.85-90.58 months). Among the 211 eyes, 121 (57.3%, 121/211), 52 (24.6%, 52/211), 23 (10.9%, 23/211) and 15 (7.1%, 15/211) were rupture, perforation, intraocular foreign bodies and penetrating injury, respectively. 98 eyes (46.4%, 98/211) of silicone oil dependence in total, among them, 64 (65.3%, 64/98), 19 (19.4%, 19/98), 9 (9.2%, 9/98) and 6 (6.1%, 6/98) eyes were rupture, perforation, intraocular foreign body and penetrating injury, respectively. Correlation analysis revealed that silicone oil dependence was significantly associated with ciliary body injury [odds ratio ( OR) = 2.150, 95% confidence interval ( CI) 1.052-4.393], choroidal injury ( OR=3.233, 95% CI 1.454-7.191), and retinal injury ( OR=2.731, 95% CI 1.393-5.353). No correlation was found with age ( OR= 0.981, 95% CI 0.960-1.002) or ocular wound length ( OR=1.716, 95% CI 0.987-2.984) ( P> 0.05). Conclusion:Silicone oil dependency following PPV in OGIs are associated with ciliary body, choroidal, and retinal injuries, but no association with age or length of the ocular wound.

Objective:To explore the association between mild cognitive impairment(MCI)and the risk of all-cause death among community middle-aged and older adults, and to provide evidence for early identification of high-risk populations.Methods:From September to November 2011, the residents aged 55 years and middle-aged and older in five urban communities were selected as the research objects by typical sampling method.The baseline survey of general information questionnaire, Mini-Mental State Examination(MMSE), activity of daily Living Scale(ADL), Geriatric Depression Scale(SDS)was carried out and the physical examination was performed.Mild cognitive impairment at the time of enrollment was the exposure factor.In 2017, 2019 and 2021, Deaths were followed up through home visits and search for death surveillance information systems.COX regression model was used to analyze the influencing factors for death.Results:A total of 1046 participants completed the follow-up and were included in the study.The baseline age was(66.4±6.6)years, and 199(19.0%)of them met the criteria for MCI.The average follow-up time was 112±16 months.During the follow-up period, 106 deaths were observed.The mortality rate was higher in participants with MCI(40 deaths, 21.1%)than those without MCI [(66 deaths, 10.1%), χ2=26.80, P<0.001)]. Participants with MCI had a shorter median survival time than those without MCI[(108.0±1.5) vs.(113.0±0.5)months, χlog-rank2=28.02, P<0.001]using the Kaplan-Meier method.Controlling for gender, age, and ethnicity, the Cox regression model revealed that MCI is associated with an increased risk of all-cause death( HR=1.98, 95% CI: 1.30-3.02, P=0.023). Conclusions:Mild cognitive impairment is an independent risk factor for all-cause death among community older adults.Early identification and intervention of MCI may have potential value in preventing premature death and prolonging life in middle-aged and older adults.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Borderline personality disorder (BPD) is characterized by emotional regulation, interpersonal relationship, self-image and impulse control instability. It is a mental disorder with high morbidity, high mortality and difficult treatment. Psychotherapy is the main treatment for this disease. However, current mainstream psychotherapy, such as dialectical behavior therapy (DBT), has certain limitations, so it is necessary to find a more convenient and effective treatment method. Acceptance and commitment therapy (ACT), as the representative therapy of the third generation of cognitive therapy, aims to make individuals accept inevitable pain, find their own value and commit to action, and finally improve their psychological flexibility to live a meaningful life. ACT has been used in the treatment of a variety of mental disorders, and the effect is significant. By expounding the pathogenesis of BPD and the theoretical model of ACT, this paper analyzed the rationality and feasibility of ACT intervention in BPD from the pathological model and treatment model of ACT. Finally, the research results of ACT treating BPD in recent years were summarized. The results show that ACT provides a promising method for the treatment of BPD patients, however, more studies are needed to prove its use in this group and its specific mechanism.

Objective:To systematically evaluate the intervention effect of acceptance commitment therapy on anxiety disorder.Methods:The full-text databases of Web of Science Core Collection, MEDLINE, KCI-Korean Journal Database, SciELO Citation Index, SpringerLink, Pubmed, EMBASE, Cochrane Library, CNKI Wanfang and Weipu were searched and randomized controlled studies related to acceptance commitment therapy for patients with anxiety disorder were collected.All randomized controlled studies met the criterion were included.Meanwhile, the literature quality of the included literatures was evaluated.The outcome indicators such as anxiety index, psychological flexibility and quality of life index were selected, and RevMan 5.3 software was used to analyze the literature data that met the inclusion criteria.Results:A total of 12 studies with 1 062 patients were included, including 513 cases in ACT group and 549 cases in control group.Meta analysis showed that ACT can effectively reduce anxiety level of patients with anxiety disorder (MD=-0.58, 95% CI: -0.85- -0.32, P<0.001), anxiety level in follow-up period (MD=-0.42, 95% CI: -0.75- -0.08, P=0.01), improving psychological flexibility (MD=0.46, 95% CI: 0.24~0.68, P<0.001); In the study of CBT(cognitive behavioral therapy) as the control group, there was no significant difference between ACT group and control group, among which after intervention (MD =-0.06, 95% CI: -0.47- 0.36, P=0.79), follow-up period (MD = 0.17, 95% CI: -0.07-0.41, P=0.16) .In the study with the control group as the blank control, ACT can reduce the anxiety level of patients with anxiety disorder (MD =-0.76, 95% CI: -0.97- -0.56, P<0.001), and the difference is statistically significant.Excluding the non-blank control study, ACT can reduce the anxiety level of patients with anxiety disorder (MD =-0.82, 95% CI: -1.09--0.55, P<0.001) in the studies where the proportion of women is greater than or equal to 70%.In the study of 50%-70% females, ACT can reduce the anxiety level of patients with anxiety disorder (MD =-0.68, 95% CI: -1.09 --0.28, P=0.01). All the differences were statistically significant.There was no significant difference between ACT and the control group for quality of life(MD=0.24, 95% CI: -0.01-0.49, P=0.06). Conclusion:ACT has a certain effect on patients with anxiety disorder, which not only improves the anxiety level of patients, but also keeps the effect of anxiety improvement during the follow-up period, and the improvement of psychological flexibility has also been verified.The immediate and long-term efficacy of ACT is similar to that of CBT, which further improve the reliability of ACT curative effect.Gender difference has not been confirmed for the therapeutic effect.ACT has no obvious improvement on the quality of life, and the conclusion of this study needs more randomized controlled studies with large samples and high quality to verify it.

Objective The present study aimed to explore the expression and purification of a fusion protein of human TIM-4 and EGFP in Escherichiacoli(E.coli)and evaluate its bioactivity.Methods The cDNA fragments of human TIM-4 and EG-FP genes were respectively amplified by RT-PCR and cloned into prokaryotic expression vector pET-28a. The constructed re-combinant plasmid pET-28a-TIM-4-EGFP was transformed to E. coli BL21 (DE3)for the expression under the induction of IPTG.The expressed protein was purified by Ni-NTA resin.Recombinant protein was analyzed by SDS-PAGE and Western blotting ,and its binding activity to the apoptotic cells was detected under the fluorescence microscope.Results The TIM-4-EG-FP vector was constructed and expressed in E. coli. The TIM-4-EGFP fusion protein was identified and verified by SDS-PAGE and Western blotting.Our results demonstrated that all the TIM-4-EGFP fusion proteins recognize and bind directly to apoptot-ic cells ,but not to viable cells.We further verified that the interactions of TIM-4-EGFP with apoptotic cells were blocked by TIM-4-Ig fusion proteins.Conclusion We successfully constructed a fusion protein encoding human TIM-4 and EGFP ,and ex-pressed it in E.coli. The fusion protein shows a readily obtainable source of biologically active TIM-4 ,which has considerable potential for further studies on human TIM-4 and its receptor.

Objective To analyze the etiologies of severe vitreous hemorrhage in venerable age patients.Methods A retrospective series case study was adopted.Medical records of 30 cases 30 eyes severe vitreous hemorrhage venerable age patients were analyzed in Xuanwu Hospital Capital Medical University,Peking University Third Hospital and Beijing Tsinghua Chang Gung Hospital from July in 1999 to June in 2015.Visual acuity,intraocular pressure,anterior segment slit lamp microscopy,mydriasis funduscopy and ophthalmic B type ultrasound examination were used to evaluate 30 cases 30 eyes.Thirty eyes were all treated with pars plans vitrectomy (PPV).Results Mydriasis funduscopy examination showed that vitreous hemorrhage was so dense in 30 eyes that the fundus cannot be observed.The initial visual acuity examination showed that 8 eyes were count finger,5 eyes were hand move,16 eyes were light perception,and 1 eye was no light perception.There were dense light spots or clusters of high echoes in vitreous cavities,complete/incomplete posterior vitreous detachment (PVD) of all eyes;retinal detachment with different degrees in 5 eyes;proliferating cord adhesion to the wall of eyeball in 3 eyes.The etiologies included retinal vein occlusion (RVO) in 10 eyes (33.33％),retinal tear or retinal detachment in 7 eyes (23.33％),polypoidal choroidal vasculopathy (PCV) in 7 eyes (23.33％),proliferative diabetic retinopathy (PDR) in 4 eyes (13.33％).The above 4 etiologies were in 28 eyes,accounting for 93.33％.The others were ocular trauma in 2 eyes (6.67％).Conclusions The main cause to severe vitreous hemorrhage venerable age patients is RVO,followed by retinal tear or retinal detachment,PCV and PDR.Ocular trauma is rare.Vitrectomy is a diagnostic treatment,which can remove vitreous hemorrhage,improve the visual acuity of the patients,and determine the etiologies of the vitreous hemorrhage.