Objective:To validate the usefulness of copy number variation sequencing (CNV-seq) in detecting the deletion/duplication of the DMD gene in Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients. Methods:One hundred and seventy-seven cases who visited the Department of Medical Genetics, Affiliated Hospital of Kunming University of Science and Technology/the First People′s Hospital of Yunnan Province from April 2018 to November 2023 were collected. All patients had previously accepted multiplex ligation-dependent probe amplification (MLPA) to detect the deletion/duplication of the DMD gene, including 90 cases of normal control with a negative result of MLPA and 87 cases with the deletion or duplication of the DMD gene (61 cases of DMD and 26 cases of BMD). CNV-seq was performed in a single-blind manner to detect DMD gene deletion or duplication for all of 177 cases to obtain the detection efficiency of CNV-seq in comparison with MLPA. Results:Comparing to MLPA, CNV-seq had a coincidence rate of 88.7% (157/177) for detecting DMD gene deletion/duplication, with a sensitivity of 77.0% (67/87), a specificity and a positive predictive value of both 100.0% (90/90 and 67/67, respectively), a negative predictive value of 81.8% (90/110), and a Kappa value of 0.773. Of the 87 patients with the deletion or duplication of the DMD gene, CNV-seq detected 67 cases with DMD gene deletion/duplication, including 62 cases with deletion and 5 cases with duplication, with fragment ranging from 150 to 750 kb. While CNV-seq missed 23.0% (20/87) of positive cases, mainly due to the involved fragments spanning only 1 to 4 exons, and with a variation size less than 50 kb, below the resolution (100 kb) of CNV-seq. The detection rate of CNV-seq in BMD cases (84.6%, 22/26) was a little higher than that in DMD cases (73.8%, 45/61), but there was no significant difference between 2 subgroups ( χ2=1.211, P=0.271). The results of CNV-seq in normal controls were all negative, and consistent with the results of MLPA. Conclusion:CNV-seq can detect 77.0% (67/87) of deletion/duplication of the DMD gene in patients with DMD/BMD, while the deletion/duplication less than 100 kb may be inevitably unidentified, therefore it is recommended as an assistant screening technique in prenatal diagnosis for DMD gene deletion or duplication.

Objective:To investigate the correlation between thyroid function and the total cerebral small vessel disease score in the elderly.Methods:This cross-sectional study included elderly people who underwent physical examinations at the Geriatrics Department of Beijing Hospital from April 2019 to December 2020. Participants were devided into 5 groups based on the total score of cerebral small vessel disease: 0, 1, 2, 3, and 4. General clinical data were collected through physical examination reports and outpatient medical records. All participants underwent a 3T brain magnetic resonance imaging (MRI), scan and data were collected to calculate the total cerebral small vessel disease score. Fasting venous blood samples were taken in the morning to measure thyroid hormone levels. Relationships between thyroid hormone levels and lacunar infarcts, microbleeds, white matter hyperintensities (WMH), enlarged perivascular spaces, and total cerebral small vessel disease score were analyzed using Spearman correlation. Multivariate ordinal logistic regression was also used to analyze factors associated with total cerebral small vessel disease score.Results:A total of 545 elderly individuals were included, with a mean age of (75.16±9.18) years, and 505 (92.7%) were male. The number of subjects with a total cerebral small vessel disease score of 0 were 207 (38.0%), 1 were 182 (33.4%), 2 were 99 (18.2%), 3 were 41 (7.5%), and 4 were 16 (2.9%). Statistical significant differences were found in age, fasting blood glucose, systolic blood pressure, triiodothyronine (TT3), free triiodothyronine (FT3), and the proportion of hypertensive patients among the groups (all P<0.05). Spearman correlation analysis showed that TT3 ( r=-0.138, P=0.001) and FT3 ( r=-0.213, P<0.001) were negatively correlated with total cerebral small vessel disease score. Multivariate ordinal logistic regression analysis revealed that age was independently and positively associated with total cerebral small vessel disease score ( OR=1.139, 95% CI: 1.087-1.193, P<0.001), while FT3 was independently and negatively associated with total cerebral small vessel disease score ( OR=0.331, 95% CI: 0.118-0.929, P=0.009). Conclusion:In the elderly population, FT3 levels are independently and negatively associated with total cerebral small vessel disease score.

Objective:To investigate the correlation between thyroid function and the total cerebral small vessel disease score in the elderly.Methods:This cross-sectional study included elderly people who underwent physical examinations at the Geriatrics Department of Beijing Hospital from April 2019 to December 2020. Participants were devided into 5 groups based on the total score of cerebral small vessel disease: 0, 1, 2, 3, and 4. General clinical data were collected through physical examination reports and outpatient medical records. All participants underwent a 3T brain magnetic resonance imaging (MRI), scan and data were collected to calculate the total cerebral small vessel disease score. Fasting venous blood samples were taken in the morning to measure thyroid hormone levels. Relationships between thyroid hormone levels and lacunar infarcts, microbleeds, white matter hyperintensities (WMH), enlarged perivascular spaces, and total cerebral small vessel disease score were analyzed using Spearman correlation. Multivariate ordinal logistic regression was also used to analyze factors associated with total cerebral small vessel disease score.Results:A total of 545 elderly individuals were included, with a mean age of (75.16±9.18) years, and 505 (92.7%) were male. The number of subjects with a total cerebral small vessel disease score of 0 were 207 (38.0%), 1 were 182 (33.4%), 2 were 99 (18.2%), 3 were 41 (7.5%), and 4 were 16 (2.9%). Statistical significant differences were found in age, fasting blood glucose, systolic blood pressure, triiodothyronine (TT3), free triiodothyronine (FT3), and the proportion of hypertensive patients among the groups (all P<0.05). Spearman correlation analysis showed that TT3 ( r=-0.138, P=0.001) and FT3 ( r=-0.213, P<0.001) were negatively correlated with total cerebral small vessel disease score. Multivariate ordinal logistic regression analysis revealed that age was independently and positively associated with total cerebral small vessel disease score ( OR=1.139, 95% CI: 1.087-1.193, P<0.001), while FT3 was independently and negatively associated with total cerebral small vessel disease score ( OR=0.331, 95% CI: 0.118-0.929, P=0.009). Conclusion:In the elderly population, FT3 levels are independently and negatively associated with total cerebral small vessel disease score.

Objective:To validate the usefulness of copy number variation sequencing (CNV-seq) in detecting the deletion/duplication of the DMD gene in Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients. Methods:One hundred and seventy-seven cases who visited the Department of Medical Genetics, Affiliated Hospital of Kunming University of Science and Technology/the First People′s Hospital of Yunnan Province from April 2018 to November 2023 were collected. All patients had previously accepted multiplex ligation-dependent probe amplification (MLPA) to detect the deletion/duplication of the DMD gene, including 90 cases of normal control with a negative result of MLPA and 87 cases with the deletion or duplication of the DMD gene (61 cases of DMD and 26 cases of BMD). CNV-seq was performed in a single-blind manner to detect DMD gene deletion or duplication for all of 177 cases to obtain the detection efficiency of CNV-seq in comparison with MLPA. Results:Comparing to MLPA, CNV-seq had a coincidence rate of 88.7% (157/177) for detecting DMD gene deletion/duplication, with a sensitivity of 77.0% (67/87), a specificity and a positive predictive value of both 100.0% (90/90 and 67/67, respectively), a negative predictive value of 81.8% (90/110), and a Kappa value of 0.773. Of the 87 patients with the deletion or duplication of the DMD gene, CNV-seq detected 67 cases with DMD gene deletion/duplication, including 62 cases with deletion and 5 cases with duplication, with fragment ranging from 150 to 750 kb. While CNV-seq missed 23.0% (20/87) of positive cases, mainly due to the involved fragments spanning only 1 to 4 exons, and with a variation size less than 50 kb, below the resolution (100 kb) of CNV-seq. The detection rate of CNV-seq in BMD cases (84.6%, 22/26) was a little higher than that in DMD cases (73.8%, 45/61), but there was no significant difference between 2 subgroups ( χ2=1.211, P=0.271). The results of CNV-seq in normal controls were all negative, and consistent with the results of MLPA. Conclusion:CNV-seq can detect 77.0% (67/87) of deletion/duplication of the DMD gene in patients with DMD/BMD, while the deletion/duplication less than 100 kb may be inevitably unidentified, therefore it is recommended as an assistant screening technique in prenatal diagnosis for DMD gene deletion or duplication.

Objective:To investigate the relationship between cerebral small vessel disease and thyroid hormones in the elderly.Methods:A total of 314 subjects aged ≥60 years with records of head magnetic resonance image(MRI), serum thyroid function tests and physical examinations collected in the Department of Health Care Neurology of Beijing Hospital from May 2019 to November 2020 were consecutively included for this cross-sectional study.Participants were assigned into the cerebral small vessel disease group if their head MRI presentations met the following standards: the Fazekas score ≥3 points; the Fazekas score ≥2 points, with 1 cavity; new subcortical infarcts; or cerebral microhemorrhage.Differences in thyroid function were compared between the cerebrovascular disease group(n=129)and the group without cerebrovascular disease(control group, n=185).Results:A total of 314 subjects were enrolled, of whom 129 met the head MRI standards for cerebrovascular disease, and 185 who did not meet the standards entered the control group.Comparison of thyroid function found a statistically significant difference in FT3( t=3.270, P=0.001)between the two groups.As for the association of a specific type of cerebral small vessel disease with thyroid function, there was a statistically significant difference in the FT3 level between the lacunar infarction group and the non-lacunar infarction group( t=3.106, P=0.002)and between the cerebral microhemorrhage group and the non-cerebral microhemorrhage group( t=2.125, P=0.034). Groups with different Fazekas scores in white matter hyperintensity showed statistically significant differences in rT3( F=3.092, P=0.027), FT3( F=5.427, P=0.001)and FT4( F=2.646, P=0.049). After correction for hyperlipidemia, rT3 and FT4, it was found that age( OR=1.044, 95% CI: 1.022-1.067, P=0.000), hypertension( OR=0.533, 95% CI: 0.294-0.963, P=0.037)and FT3( OR=0.276, 95% CI: 0.159-0.478, P=0.000)were related to cerebral small vessel disease. Conclusions:FT3 levels at the lower end of the normal range are associated with cerebral small vessel disease in the elderly.

PurposeTo investigate the relationship between the serum oxidized low-density lipoprotein (ox-LDL) level and carotid vulnerable plaque in patients with acute cerebral ischemic stroke, and to evaluate the ability of serum ox-LDL in identifying vulnerable carotid plaques.Materials and Methods 181 patients with history of acute cerebral ischemic stroke were recruited. According to the results of carotid ultrasound patients were divided into non plaque group (n=48), stable plaque group (n=38) and vulnerable plaque group (n=95). The serum total cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, fasting plasma glucose and ox-LDL were measured. Carotid intima-medial thickness (CIMT), total carotid plaque area (TPA) and the characters of plaque were examined with color Doppler ultrasound.Results The serum ox-LDL and the number of patients with hypertension in plaque group were significantly higher than that in the non-plaque group (P<0.05). The serum ox-LDL and TPA in the vulnerable plaque group were significantly higher than that in the stable plaque group (P<0.05). Serum ox-LDL in patients with acute cerebral infarction was positively correlated with CIMT, serum total cholesterol and LDL-C (r1=0.154,P<0.05;r2=0.338, P<0.05;r3=0.385,P<0.05). Logistic regression analysis showed that serum ox-LDL was an independent risk factor for carotid vulnerable plaque (OR=1.038, 95%CI 1.008-1.069, P<0.01).Conclusion The serum ox-LDL is independently associated with the formation of vulnerable plaque in patients with acute cerebral infarction. This study suggests that ox-LDL can be used as a biomarker in screening for vulnerable carotid plaque in clinical practice. Carotid ultrasound combined with serology can early identify carotid artery vulnerable plaque that may lead to cerebral ischemic events.

Objective To compare the curative effect and safety of high-frequency and low-frequency repetitive tran-scranial magnetic stimulation(r-TMS) in the treatment of Parkinson's disease complicated with depressive disorder. Methods All 92 patients with Parkinson's disease complicated with depressive disorder were randomly allocated to three groups. High frequency group received antiparkinsonian drugs combined with high frequency r-TMS (5 Hz);Low frequency group received antiparkinsonian drugs combined with low frequency r-TMS (0.5 Hz);Sham group re-ceived antiparkinsonian drugs combined with sham r-TMS (s-rTMS). Each group received r-TMS twice a week for four weeks. UPDRS and HAMD-17 were assessed every two weeks , adverse events were recorded , and clinical global im-pression was carried out four weeks after the treatment. Results Upon enrollment, scores of HAMD and UPDRS among the three groups were not significantly different (P>0.05). During the second week of the intervention, the HAMD score in high frequency group improved significantly , and the differences between three groups were statistically signif-icant according to one-way ANOVA (P=0.0144). The differences changed larger in the fourth week, with greatly sig-nificant differences between the two groups (P=0.0000);During the second week of the intervention, the differences of UPDRSⅡscores in high frequency, low frequency and sham group were not statistically significant according to one-way ANOVA (P=0.1981). The differences appeared in the fourth week, but the differences between groups were not statistically significant according to one-way ANOVA (P=0.0219). During the second week and the fourth week of the intervention, UPDRS Ⅲ scores in the three groups were not significantly different (P=0.6105, 0.4248 respectively). Adverse events in the three groups were rare, and the differences were not statistically significant. Conclusion High-frequency stimulation on dorsal-lateral left prefrontal cortex is effective in alleviating depression for patients with Parkinson's disease, and is also effective in improving capabilities in daily life, which shows exact clinical effect and rare adverse events.