Fabry disease, a rare genetic disorder affecting multiple organs, has understudied correlations among enzyme activity, genotype, and clinical manifestations in patients of different sexes with classical and late-onset phenotypes. In this study, clinical data, α-Gal A activity, and GLA gene test results of 311 patients, who were categorized by classical and late-onset phenotypes, ⩽5% and > 5% of the normal mean value of enzyme activity, and truncated and nontruncated mutation groups, were collected. The common clinical manifestations of Fabry disease included acroparesthesia, hypohidrosis/anhidrosis, neuropsychiatric system, and renal and cardiovascular involvement. Multiorgan involvement was higher in males and classical phenotype patients. In both sexes, classical patients commonly presented with acroparesthesia and multiorgan involvement, whereas late-onset patients showed renal, neuropsychiatric, and cardiovascular involvement. Male and classical patients had lower enzyme activity than female and late-onset patients, respectively. Classical males with enzyme activity of ⩽5% of the normal mean level showed higher multiorgan involvement frequency than those with enzyme activity of > 5%, whereas no significant difference was observed among females. Ninety-five gene mutation sites were detected, with significant phenotype heterogeneity in patients with the same mutation. No significant difference in enzyme activity or clinical manifestations was observed between truncated and nontruncated mutations. Overall, male patients with Fabry disease, regardless of classical or late-onset phenotype, have a higher frequency of multiple-organ involvement and lower α-Gal A activity than female patients. α-Gal A activity was closely correlated with clinical symptoms in males but weakly correlated with clinical manifestations in females. The clinical manifestations of patients with the same mutation are heterogeneous, and the correlation between gene mutation and enzyme activity or clinical manifestation is weak.
Adolescent ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Age of Onset ; alpha-Galactosidase/metabolism* ; China ; Fabry Disease/enzymology* ; Genotype ; Mutation ; Phenotype ; Sex Factors ; East Asian People/genetics*

Objective:To investigate the effects of low-frequency and high frequency repetitive transcranial magnetic stimulation (rTMS) combined with levodopa and benserazide hydrochloride on mild cognitive impairment in patients with Parkinson disease (PD).Methods:Totally 90 PD patients with mild cognitive impairment who visited from January 2020 to June 2022 were included , and they were divided into a simple drug group ( n=30), drug+ low-frequency group ( n=30), and drug+ high-frequency group ( n=30) according to the order of admission.The patients in the simple drug group were treated with oral levodopa and benserazide hydrochloride, while the patients in drug+ low-frequency and drug+ high-frequency groups were treated with low-frequency or high-frequency rTMS on the basis of oral levodopa and benserazide hydrochloride.Montreal cognitive assessment(MoCA), digital span (DS), Chinese auditory learning test (CALT), the judgment of line orientation test (JLOT) and verbal fluency test (VFT) were used to evaluate the cognitive function of patients before and after 4 weeks of treatment.SPSS 26.0 was used for statistical analysis.The paired t-test was used for intra-group comparison before and after treatment, while one-way ANOVA was used for inter-group comparison. Results:There were no significant differences in MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT, and VFT scores among patients in the simple drug group before and after 4 weeks of treatment( t=-1.157, -0.648, -0.215, -0.290, -0.154, -0.782, -0.960, all P>0.05). After 4 weeks of treatment, MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT scores in drug+ low-frequency group and drug+ high-frequency group were higher than before treatment (drug+ low frequency group: t=-16.357, -11.379, -7.999, -11.805, -16.624, -15.996, -17.241, all P<0.05; drug+ high-frequency group: t=-25.198, -13.971, -13.904, -25.831, -26.382, -20.108, -15.643, all P<0.05). There were no statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups before treatment (all P>0.05). After treatment, there were statistically significant differences in the scores of MoCA, DS anterograde, DS backward, CALT immediate recall, CALT delayed recall, JLOT and VFT among the three groups (simple drug group : (20.37±1.96), (4.37±1.19), (2.80±0.55), (6.93±1.70), (5.17±1.09), (15.50±2.69), (10.73±1.55); drug+ low-frequency group: (23.83±2.32), (5.87±0.94), (3.87±0.73), (9.17±1.74), (8.13±1.50), (20.77±2.19), (13.30±1.73); drug+ high-frequency group: (27.17±1.64), (6.73±1.01), (4.80±0.81), (11.20±2.06), (10.03±1.54), (25.17±3.14), (15.87±2.05)) (all P<0.05). Further analysis showed that both the drug+ low-frequency and drug+ high-frequency groups had higher scores than the simple drug group, and the drug+ high-frequency group had higher scores than the drug+ low-frequency group(all P<0.05). Conclusion:The combination of drug+ low-frequency or drug+ high-frequency rTMS and drug therapy can help improve cognitive function in patients with PD, and the efficacy of drug+ high-frequency rTMS may be more significant, which provides a new therapeutic idea for clinical treatment of patients with PD.

Objective:To construct a predictive model for the risk of major adverse cardiovascular events(MACE) after surgery in patients with symptomatic arteriosclerosis obliterans(ASO) .Methods:From Jan 2018 to Dec 2021, 957 patients with symptomatic ASO admitted to Nanjing Drum Tower Hospital were selected and divided into MACE and non-MACE groups according to whether they had a post-op MACE. A risk prediction model was constructed based on a stepwise regression method with multi-factor COX regression analysis. The model was evaluated using the receiver operating characteristic curve (ROC), the calibration curve to assess the model fit, and the Bootstrap method for internal validation.Results:MACE occurred in 143 patients (14.94%). After COX regression analysis, BMI, creatinine clearance, fibrinogen, rivaroxaban and previous history of surgery were enrolled into model constructing. The ROC curve assessed the model with a C-statistic of 0.690 (95% CI: 0.644-0.736), sensitivity and specificity of 49.2% and 80.7% respectively, a Jorden index of 0.299 and an optimal cut-off value of 0.086. Calibration curves showing agreement between predicted and actual observed values. Internally validated C-statistic of 0.689 (95% CI: 0.672-0.700). The population was divided into high and low risk groups based on the best cut-off value and analysed for survival. The difference between the two groups was statistically different. Conclusion:The risk prediction model for the occurrence of MACE based on clinical parameters is simple and convenient, with good predictability and good discriminatory ability, and can provide reference for the assessment and treatment of MACE in ASO patients.

Objective: To explore the intervention effect of 12 week spinal health exercise on adolescents high and low shoulders, in order to provide empirical evidence for exploring simple and feasible measures to intervene. Methods: In February 2023, 60 high and low shoulder students from a vocational high school in a certain county of Luzhou City were randomly selected as the research subjects by convenient sampling method. Paired sampling was used to randomly divide participants into an intervention group and a control group with 30 students each group. The intervention group received spinal health gymnastics intervention during 12 weeks of morning exercises and large break exercises for twice a day, with two groups each time; the control group maintained their previous morning exercises and large break exercises. A follow up study was conducted on the height difference between the left and right shoulder peaks of the intervention group and the control group students before intervention, after 12 weeks intervention, at 4 weeks post intervention. The t-test was used to analyze the changes in shoulder peak height difference between the intervention group and the control group. Results: Before intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(2.50±1.19)cm] and the control group [(2.49±1.20)cm] adolescents ( t=0.05, P > 0.05). After 12 weeks of intervention, the difference in shoulder height between the left and right sides of adolescents in the intervention group decreased, compared to that before intervention [(1.43±1.15, 2.50±1.19)cm], while the control group increased compared to that before intervention [(2.58±1.19, 2.49±1.20) cm], and the differences were both statistically significant ( t= -78.17 , 20.15, P <0.05). At 4 weeks post intervention, there was no statistically significant difference in the height of the left and right shoulder peaks between the intervention group [(1.44±1.15)cm] and the control group [(2.59±1.18)cm] compared to 12 weeks after the intervention ( t=1.80, 1.05, P >0.05). The intervention group [(2.49±1.26, 2.52±1.16) (1.43±1.21, 1.44±1.13) (1.44±1.21, 1.45±1.14)cm] and the control group [(2.45±1.24, 2.52±1.20) (2.55±1.24, 2.61±1.18) (2.55±1.22, 2.62±1.18)cm] showed no statistically significant difference in the height of the left and right shoulder peaks between males and females before intervention, after 12 weeks of intervention, and after stopping intervention for 4 weeks ( t =-0.08, -0.03, -0.02; -0.15, -0.12, -0.15, P >0.05). Conclusions Spinal health gymnastics has a good effect on correcting high and low shoulders in adolescents. Spinal health gymnastics should be promoted on campus to promote adolescent posture health.

Objective:To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in different regions of the kidney in distinguishing IgA nephropathy (IgAN) patients from healthy volunteers.Methods:This study was a cross-sectional study. Eighty-four patients diagnosed with IgAN (IgAN group) who underwent renal biopsy (lower pole of the left kidney) and were pathologically confirmed at the First Medical Center of PLA General Hospital from February 2022 to September 2023 and thirty-four healthy volunteers (control group) were included prospectively. The regions of interest were outlined in the right renal cortex, medulla, and parenchyma for all subjects, and the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D *), and perfusion fraction (f) were measured in the corresponding regions. The differences in IVIM-DWI parameters between the IgAN group and the control group were compared using the student′s t-test or the Mann-Whitney U test. Receiver operating characteristic curve analysis was performed on the parameters with statistically significant differences, and the area under the curve (AUC) was calculated. Results:There were statistically significant differences in renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values between the IgAN group and the control group ( Z=-3.03, -2.21, -2.62, -2.03, -2.03; P=0.002, 0.027, 0.009, 0.043, 0.042). The AUCs (95% CI) for diagnosing IgAN using renal cortical ADC, renal parenchymal ADC, renal cortical D, renal parenchymal D, and renal medullary f values were 0.679 (0.586-0.762), 0.630 (0.537-0.717), 0.654 (0.535-0.774), 0.619 (0.497-0.742), and 0.620 (0.495-0.745), respectively. There were no statistically significant differences in renal medullary ADC, D, renal cortex, medulla and parenchyma D *, renal cortical and renal parenchymal f values between the two groups ( P>0.05). Conclusion:The quantitative parameters of renal IVIM-DWI are influenced by different measurement regions, among which the ADC, D of renal cortex and parenchyma, and f of renal medulla can be used for the initial diagnosis of IgAN.

OBJECTIVE To compare the safety of polysaccharide iron complex and ferrous sulfate in the treatment of anemia during pregnancy. METHODS Retrieved from Cochrane Library， PubMed， Embase， SinoMed， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about polysaccharide iron complex （trial group） versus ferrous sulfate （control group） in the treatment of anemia during pregnancy were collected from the inception to May 20th， 2022. After literature screening， data extraction and quality evaluation， meta-analysis， sensitivity analysis and publication bias analysis were conducted with RevMan 5.3 software. RESULTS A total of 13 RCTs were included， with a total of 1 318 patients. Results of meta-analysis showed that the total incidence of adverse drug reactions （ADR） [RR＝0.11， 95%CI （0.06， 0.18）， P＜0 000 01]， gastrointestinal adverse reactions [RR＝0.08， 95%CI （0.05， 0.12）， P＜0.000 01]， anorexia and nausea [RR＝0.21， 95%CI （0.09， 0.54）， P＝ 0.001]， abdominal pain [RR＝0.18， 95%CI （0.04， 0.78）， P＝0.02]， diarrhea [RR＝0.18， 95%CI （0.04， 0.79）， P＝0.02]， vomiting [RR＝0.24， 95%CI （0.06， 0.89）， P＝0.03] and gingival melanosis [RR＝0.09， 95%CI （0.03， 0.28）， P＜0.000 1] in the trial group were all significantly lower than the control group. The results of sensitivity analysis showed that the conclusions obtained in this study were relatively robust. The results of publication bias analysis indicated that there was a high possibility of publication bias in this study. CONCLUSIONS The polysaccharide iron complex is safer than ferrous sulfate for treatment of anemia during pregnancy.

Objective:To investigate the feasibility of multi-slice spiral CT (MSCT) imaging feature of gastric stromal tumor (GST) in evaluating Ki-67 index expression .Methods:The clinical and CT imaging data of 501 patients with GST confirmed by surgery and pathology were retrospectively studied in Zhongshan Hospital affiliated to Fudan University and the Affiliated TCM Hospital of Southwest Medical University from Nov 2014 to Nov 2021. By immunohistochemical results, tumors were divided into Ki-67 low expression group (Ki-67≤6%, 335 lesions) and high expression group (Ki-67>6%, 168 lesions). Multivariate logistic regression analysis was conducted.Results:Between the two groups,there were statistical differences in the longest and shortest diameter of tumor, CT value on venous phase, CT attenuation value ( Z=4.80, 4.91, 3.21, 3.29, all P<0.01) and tumor location,morphology, necrosis, ulcer, feeding artery, vascular enhancement, positive fat sign around disease, gastrointestinal bleeding ( χ2=10.77, 13.49, 8.59, 22.87, 7.59, 7.23, 7.76, 8.58, all P<0.05). Tumor ulceration positive ( OR=1.88, 95%CI: 1.17-3.03) was independent risk factor of Ki-67 high expression ( P=0.009). Gastric antrum was used as the reference for tumor location, cardia ( OR=5.41, 95% CI:1.25-23.46) was independent risk factor of Ki-67 high expression ( P=0.024). Conclusion:MSCT has a definite predictive value for the expression in Ki-67 index of GST cases.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective:To apply the best evidence for the prevention of radial artery occlusion after transradial coronary angiography or intervention to clinical practice and evaluate its effect.Methods:This was a quasi-experimental study. Based on the evidence continuous quality improvement model, evidence-based practice method was used to obtain the best evidence, formulated review indicators, analyzed the obstacles in the practice process and took action strategies. The 88 patients who underwent transradial coronary angiography or intervention in the Cardiology Department of Qilu Hospital of Shandong University (Qingdao) from June 1 to 30, 2020 were selected as the baseline review group by convenience sampling. The 94 patients who underwent this treatment from September 1 to 30, 2020 were selected as the evidence application group. The baseline review group used the original perioperative management plan, and the evidence application group used the perioperative management plan based on the best evidence. The implementation rate of each review indicator, the incidence of radial artery occlusion, the degree of compression pain, and the comfort level of patients were compared between the two groups.Results:The implementation rates of review indicators 1, 2, 3, 5, 6, 7, 8 in the evidence application group were 100.0% (94/94), 100.0% (94/94), 11.7(11/94), 88.3% (83/94), 100.0% (94/94), 100.0%(94/94), 85.1%(80/94), respectively, which were higher than those in the baseline review group(all 0), except for the review indicator 4, the differences were statistically significant ( χ2 values were 9.00-178.02, all P<0.05). The incidence of radial artery occlusion and the incidence of pain Numerical Rating Scale>3 points in the evidence application group were 2.1% (2/94) and 3.2% (3/94), respectively, which were lower than 14.8% (13/88) and 23.9% (21/88) in the baseline review group; the comfort level of patients in the evidence application group was 96.8% (91/94), which was higher than 63.6% (56/88) in the baseline review group. The differences were statistically significant ( χ2 = 8.01, 15.21, 30.10, all P<0.05). Conclusions:The best evidence for the prevention of radial artery occlusion after transradial coronary angiography or intervention can be applied to clinical practice, which can standardize the behavior of medical staff, reduce the incidence of postoperative radial artery occlusion, reduce the degree of compression pain, and improve the comfort of patients.