AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

BACKGROUND:Increasing evidence supports the association between different exercise intensities and the risk of osteoarthritis,but this may be affected by confounding and reverse causality,and the conclusions have not been unified. OBJECTIVE:To explore the causal association between different exercise intensities and osteoarthritis using Mendelian randomization method. METHODS:Data from genome-wide association studies associated with different exercise intensities were selected,and instrumental variables were screened with a threshold of P＜5×10-8.Causal associations between exposure and risk of outcome were assessed using five analysis methods of Mendelian randomization with inverse variance weighting as the primary analysis method.Selected instrumental variables were used to assess causal associations between different exercise intensities and osteoarthritis,and sensitivity analyses with inverse Mendelian randomization were performed. RESULTS AND CONCLUSION:In the analysis results of the inverse variance weighting method,low-intensity exercise showed a significant protective effect on knee osteoarthritis[odds ratio(OR)=0.14,95%confidence interval(CI):0.06-0.32,P＜0.001],while sedentary behavior without exercise intensity,such as watching TV,was confirmed to be a risk factor for knee osteoarthritis and hip osteoarthritis(OR=2.24,95%CI:1.74-2.88,P＜0.001;OR=1.34,95%CI:1.01-1.78,P=0.04).Through the reverse Mendelian randomization analysis of osteoarthritis to different exercise intensities,it was found that osteoarthritis was negatively correlated with low-intensity exercise and positively correlated with watching TV.The analysis results show that there is a two-way causal relationship between different exercise intensity and osteoarthritis risk.

Objective To design a mobile personnel radiation protection equipment for operation in environments with high radiation such as spent fuel reprocessing plants, to achieve simultaneous protection against γ radiation, neutron radiation, and radioactive aerosol, to reduce the internal and external exposure dose of radioactive workers, and to meet the requirement of operation for two hours. Methods The core parts of the mobile personnel radiation protection equipment included a shielding chamber and a respiratory maintenance system. An automated chassis was used for the movement and lifting of the shielding chamber. MCNP software was used to simulate and calculate the protective effects of shielding chamber made of different materials and material thicknesses. Experimental verification of the shielding chamber design was conducted. Mathematical models were established to describe the variations in the content of various gases in the chamber with personnel operation time. A respiratory maintenance system, a harmful gas absorption device, and an automated mobile chassis were designed. Results The shielding chamber made of polyethylene with a thickness of 80 mm achieved an 80% neutron shielding rate. The respiratory maintenance system could support workers for 2 hours of operation inside the equipment. The mobile chassis allowed operation of the equipment with one person. Conclusion This mobile personnel radiation protection equipment can solve the problem in simultaneous protection against γ radiation, neutron radiation, and radioactive aerosol. The equipment can provide radiation protection for radioactive workers, reduce exposure dose, and reduce personnel burden. This system provides technical means for the operation and maintenance of equipment in high-radiation sites such as spent fuel reprocessing plants.

Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.

Objective:To investigate the safety of the use of the intermediate catheter in the endovascular treatment (EVT) of patients with acute anterior circulation large vessel occlusive stroke and its impact on the outcomes.Methods:From May 2015 to September 2018, patients with anterior circulation large vessel occlusive stroke received EVT in Nanjing First Hospital, Nanjing Medical University were enrolled retrospectively. According to whether intermediate catheter was used during the procedure, they were divided into intermediate catheter group and non-intermediate catheter group. The demographics, clinical data and procedure related information were collected. The outcome evaluation indicators included secondary embolization, symptomatic intracranial hemorrhage, clinical outcome and death at 90 d after onset. A good outcome was defined as the modified Rankin Scale score of 0-2. Multivariate logistic regression analysis was used to determine the independent predictor of clinical outcome. Results:A total of 195 patients with anterior circulation large artery occlusive stroke received EVT were enrolled, including 161 in the intermediate catheter group and 34 in the non-intermediate catheter group. There were no significant differences in demographics and clinical characteristics between the intermediate catheter group and the non-intermediate catheter group. In terms of procedure related information, the number of mechanical thrombectomy passes in the intermediate catheter group was significantly decreased (2 [1-3] times vs. 2.5 [1.75-4] times; Z=2.218, P=0.017), the recanalization rate of one-pass thrombectomy was significantly higher (38.5% vs. 20.6%; χ2=3.943, P=0.047), and the rate of thrombus escape and secondary embolism was significantly lower (19.3% vs. 35.3%; χ2=4.202, P=0.041). In terms of clinical outcome, there were no significant differences in the incidence of symptomatic intracranial hemorrhage, mortality and good outcome at 90 d between the intermediate catheter group and the non-intermediate catheter group. Multivariate logistic regression analysis showed that the use of intermediate catheter was an independent predictor of good outcome at 90 d (odds ratio 0.430, 95% confidence interval 0.196-0.947; P=0.036). Conclusion:In EVT of patients with acute anterior circulation large vessel occlusive stroke, the use of intermediate catheter can reduce the number of mechanical thrombectomy passes, improve recanalization rate of one-pass thrombectomy, reduce the rate of thrombus escape and second embolization, and then improve the outcome of patients.

Objective:To investigate the correlation between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and outcomes after endovascular mechanical thrombectomy (EMT) in patients with anterior circulation large vessel occlusive stroke.Methods:Using " Nanjing First Hospital Stroke Database" , consecutive patients with anterior circulation large vessel occlusive stroke received EMT treatment from June 2015 to December 2018 were enrolled retrospectively. Before EMT treatment, the distal FVH grade and the American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral circulation grade were evaluated. The modified Rankin Scale was used to evaluate the functional outcome of patients at 3 months after onset, and 0-2 was defined as a good outcome. Spearman correlation analysis was used to analyze the correlation between the distal FVH grade and the ASITN/SIR collateral circulation grade. Multivariate logistic regression analysis was used to identify the independent predictors of the outcomes. Results:A total of 117 patients with acute anterior circulation large vessel occlusive stroke were enrolled, aged 70.74±12.50 years, 72 (61.5%) were male. The baseline National Institutes of Health Stroke Scale (NIHSS) score was 13.73±4.91. Seventy-four patients (63.2%) had a good outcome and 43 (36.8%) had a poor outcome. The distal FVH grade was grade 0 in 8 cases (6.84%), grade 1 in 34 cases (29.06%), and grade 2 in 75 cases (64.10%). Compared with the distal FVH low-grade group (grade 0-1), the high-grade group (grade 2) had a higher ASITN/SIR collateral circulation grade ( P<0.001) and lower baseline National Institutes of Health Stroke Scale (NIHSS) score ( P=0.026). Spearman correlation analysis showed that the distal FVH grade was significantly positively correlated with the ASITN/SIR collateral circulation grade ( r=0.620, P<0.001). Multivariate logistic regression analysis showed that the high distal FVH grade (odds ratio [ OR] 0.336, 95% confidence interval [ CI] 0.128-0.879; P=0.026) was independently associated with the good outcomes, while the higher baseline NIHSS score ( OR 1.036, 95% CI 0.988-1.229; P=0.048) and symptomatic cerebral hemorrhage ( OR 5.597, 95% CI 1.052-29.761; P=0.043) were independently associated with the poor outcomes. Conclusion:The distal FVHs can reflect the state of collateral circulation. The high grade of distal FVHs is associated with the good outcomes after EMT in patients with anterior circulation large vessel occlusive stroke.

Objective: To compare the effects of modified Thrombolysis in Cerebral Infarction score (mTICI) 2b and mTICI 3 reperfusion on lesions′ changes and prognosis in patients who underwent endovascular therapy within six hours after onset. Methods: A retrospective analysis was conducted on 94 patients with acute large intracranial artery occlusion of the anterior circulation who achieved reperfusion sucesssfully by endovascular therapy within 6 hours after onset in the Department of Neurology, Nanjing First Hospital from October 2016 to March 2019. The effects of mTICI 2b and mTICI 3 reperfusion on lesions′ changes and prognosis of patients were compared. The primary endpoint was the modified Rankin Scale (mRS) score at 90 days; the secondary endpoints were the early neurological deficit score, the mortality at 90 days, the volume of infarction at 24 hours, the changes in infarct volume for 24 hours and the rate of symptomatic intracerebral hemorrhage (sICH) , reocclusion and hemorrhagic transformation. Results: In all patients, 35 cases received mTICI 2b reperfusion and 59 cases received mTICI 3 reperfusion. Compared with mTICI 2b group (10.00 (3.00, 16.00)), the early neurological deficit score at seven days of mTICI 3 group (6.00 (1.00,11.50)) was lower (Z=-2.004, P=0.045) . However, there were no statistically significant differences in mRS score at 90 days, early neurological deficit score at 24 hours and 3 days, mortality at 90 days, volume of infarction at 24 hours, the changes in infarct volume for 24 hours, and the rate of sICH, reocclusion, and hemorrhagic transformation between the two groups. Conclusion For patients with large intracranial artery occlusion of the anterior circulation within six hours after onset, achieving mTICI 3 reperfusion after endovascular therapy can improve the early neurological function more effectively, but the effects on 90-day functional outcome are similar to that of mTICI 2b reperfusion.

Objective: To investigate the effect of the time from onset to recanalization on the outcomes after endovascular treatment (EVT) in patients with acute stroke due to posterior circulation large vessel occlusion. Methods: From May 2015 to May 2019, patients with acute ischemic stroke due to posterior circulation large vessel occlusion receiving EVT in the Department of Neurology, Nanjing First Hospital, Nanjing Medical University were enrolled retrospectively. According to the modified Rankin Scale (mRS) score at 90 d after procedure, they were divided into good outcome group (≤2) and poor outcome group (>2). Demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent correlation between the time from onset to recanalization and the outcomes. Results: A total of 64 patients with acute ischemic stroke due to posterior circulation large vessel occlusion treated by EVT were enrolled in this study. There were 50 males (78.0%) and 14 females (22.0%). The age was 67.52±10.30 years. The National Institutes of Health Stroke Scale (NIHSS) score was 22.04±4.17, and the time from onset to recanalization was 370.53±78.59 min. Thirty-one patients (48.0%) were in the good outcome group and 33 (52.0%) were in the poor outcome group. There were significant differences in baseline NIHSS score, systolic blood pressure, time from onset to revascularization, and the proportions of patients with tandem lesion and symptomatic intracranial hemorrhage between the two groups (all P<0.05). Multivariate logistic regression analysis showed that the longer time from onset to recanalization (odds ratio [OR] 1.317, 95% confidence interval [CI] 1.001-3.034; P=0.041) and symptomatic intracranial hemorrhage (OR 4.207, 95% CI 1.931-10.761; P=0.004) were the independent predictors of poor outcomes, while the lower baseline NIHSS score (OR 0.302, 95% CI 0.056-0.743; P=0.047) was the independent protective factor of poor outcomes. Conclusions The longer time from onset to recanalization is an independent risk factor for poor outcomes after EVT in patients with acute ischemic stroke caused by posterior circulation large vessel occlusion.

Objective To investigate the effect and safety of intravenous thrombolytic therapy in the endovascular treatment of acute anterior circulation vascular occlusive stroke.Methods The clinical data of 226 patients with acute anterior circulation vascular occlusive stroke who underwent endovascular treatment in Nanjing First Hospital,Nanjing Medical University from May 2015 to May 2018 were retrospectively collected.According to whether or not intravenous thrombolysis was performed,the patients were classified into simple thrombectomy group (n=112) and bridging treatment group (n=114).The modified Thrombolysis in Cerebral Infarction Score (mTICI) was used to evaluate the vascular opening effect,and the blood vessel recanalization time,mTICI,the symptomatic intracranial hemorrhage rate,and the modified Rankin Scale (mRS) score at 90 days after surgery were evaluated.Results There were no statistically significant differences in gender,age,past history and National Institute of Health Stroke Scale score between the two groups (P＞0.05).There was no statistically significant difference in door-to-recanalization time between the two groups (P＞0.05).Excluding the patients with post-wake stroke and unexplained onset time,the simple thrombectomy group (n=63) and the bridging treatment group (n=1 11) showed statistically significant differences in onset-to-door time ((235.04± 182.64) min vs (102.48±60.51) min,t=7.01,P＜0.01)and onset-to-recanalization time ((405.31 ± 148.89) min vs (337.31 ± 117.65) min,t=3.32,P=0.01).The difference in number of thrombectomy between the simple thrombolysis group (2.55± 1.52) and the bridging treatment group (2.11± 1.48) was statistically significant (t=2.246,P=0.026).The total reperfusion (mTICI 2b/3) rate was 89.8％ (203/226),88.4％ (99/112) in the simple thrombectomy group and 91.2％ (104/114) in the bridging treatment group,with no statistically significant difference between the two groups (P＞0.05).The differences in symptomatic intracranial hemorrhage rate (8.93％ (10/112) vs 11.4％ (13/114)),mortality rate (12.5％ (12/112) vs 16.7％ (19/114)) and 90-day good functional outcome (mRS score 0-2;54.5％ (61/112) vs 55.8％ (63/114)) between the two groups were not statistically significant (P＞0.05).Conclusions In patients with acute anterior circulation vascular occlusive stroke undergoing endovascular treatment,intravenous thrombolysis can reduce the number of thrombectomy,not increase the door-to-recanalization time,the risk of symptomatic intracranial hemorrhage and mortality,and has similar good functional outcome as the simple thrombeetomy group.Therefore,intravenous thrombolysis is safe and effective for endovascular treatment of acute anterior circulation large vessel occlusive stroke.