Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

Objective:To summarize the clinical and genetic characteristics of late-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients, and to compare the differences between late-onset and classic-onset FSHD1 patients.Methods:A retrospective analysis was conducted on the clinical and genetic data of genetically confirmed late-onset FSHD1 patients (age at onset30 years) between January 2007 and June 2024 from the Department of Neurology of Peking University First Hospital and the First Affiliated Hospital of Fujian Medical University. Classic-onset FSHD1 patients (10 yearsage at onset≤30 years) were matched 1∶1 according to sex and disease duration for comparison. The demographic information, the number of D4Z4 repeat units, the distal D4Z4 methylation levels, FSHD Clinical Score (CS), Clinical Severity Score (CSS), and Age-Corrected Clinical Severity Score (ACSS) of these patients were collected. Survival analysis was performed to compare the outcome of lower extremity involvement between late-onset and classic-onset FSHD1 patients. The correlation of the number of D4Z4 repeat units and D4Z4 methylation level with CS and ACSS was analyzed in late-onset FSHD1 patients.Results:A total of 61 patients with late-onset FSHD1 were enrolled, 33 (54.1%) of whom are female, with an age of 54.0 (46.0, 62.0) years and a disease duration of 14.0 (5.5, 22.5) years. Compared to classic-onset FSHD1 patients, late-onset patients exhibited significantly lower CS [7.0 (5.6, 8.4) vs 6.0 (4.4, 7.7), U=1 416.000, P=0.013], CSS [3.0 (2.8, 3.3) vs 3.0 (2.0, 4.0), U=2 352.000, P=0.010], and ACSS [189.2 (137.1, 241.3) vs 96.8 (61.3, 132.2), U=3 225.500, P0.001], and higher proportion of patients with limb girdle involvement but no facial muscle involvement [18.0% (11/61) vs 6.6% (4/61), χ2=3.725, P=0.054]. Kaplan-Meier survival analysis showed that the onset age of lower extremity involvement in late-onset patients (45 years, 95% CI 42-48 years) was significantly higher than that in classic-onset patients (24 years, 95% CI 21-27 years, χ2=61.012, P0.001). The duration from symptom onset to lower extremity involvement in late-onset patients (15 years, 95% CI 10-20 years) was significantly longer than that in classic-onset patients (8 years, 95% CI 3-13 years, χ2=9.105, P=0.003). Late-onset FSHD1 patients carried higher average distal D4Z4 methylation levels compared to those with classic-onset FSHD1 [46.68% (40.79%,52.57%) vs 41.02% (34.03%,48.00%), U=1 378.500, P=0.014]. Among late-onset FSHD1 patients, cytosine-phosphate-guanine 6 (CpG6) methylation levels were significantly negatively correlated with ACSS ( r=-0.278, P=0.025); the number of D4Z4 repeat units were significantly negatively correlated with ACSS ( r=-0.272, P=0.034);CpG6 methylation levels were significantly negatively correlated with CS ( r=-0.441, P=0.003), while no correlation was found between number of D4Z4 repeat units and CS ( r=-0.161, P=0.310). Conclusions:Compared with classic-onset FSHD1 patients, late-onset FSHD1 patients are associated with a higher degree of distal D4Z4 methylation, along with a milder muscle weakness phenotype, slower disease progression and a higher proportion of cases without facial muscle involvement. The age at onset can be used as a marker of the severity and prognosis in FSHD1.

Objective To analyze the correlation between sleep disorder and bone mineral density(BMD)and fracture risk in middle-aged and elderly patients with type 2 diabetes mellitus(T2DM).Methods 150 T2DM patients over 50 years old who were hospitalized in the Endocrine Metabolism Department of Changsha First Hospital from September 2022 to April 2023 were selected.According to the Pittsburgh Sleep Quality Index(PSQI),they were divided into a non-sleep disorder group(66 cases)and a sleep disorder group(84 cases).The general data and biochemical indicators of the two groups were compared.The relationship between sleep disorder and BMD,fracture risk was analyzed.Results Compared with the non-sleep disorder group,HbA1c,FPG,female proportion,the proportion of hypnotics and risk scores of vertebral fracture in the sleep disorder group were higher,and BMI,BMD of femoral neck and hip were lower(P<0.05).Pearson correlation analysis showed a negative correlation between PSQI score and BMD of femoral neck and hip(P<0.05).Pearson or Spearman correlation analysis showed that the risk scores of vertebral fracture was positively correlated with age,duration of DM,use of hypnotics and sleep disorder(P<0.05 or P<0.01),and negatively correlated with BMD of femoral neck and hip(P<0.01).Binary logistic regression analysis showed that FPG,use of hypnotics and hip BMD were influencing factors of sleep disorders,while sleep disorders and PSQI scores were influencing factors of osteoporosis.Conclusions For middle-aged and elderly T2DM patients,improving sleep may help reduce the occurrence of osteoporosis and reduce the risk of fractures.

Objective To study the clinical, laboratorial, histopathological, imaging features of two cases of hypothyroid myopathy. Method Clinical manifestations, thyroid function, electromyography, muscle MRI, muscle biopsy and follow-up results were collected, and analyzed with the literature. Result These two patients were middle-age to old age and the onset of disease was insidious. Their common clinical manifestations included subacute progressive weakness in the proximal muscles,myalgia after sports and reduction in tendon reflex.The blood test showed an increase in serum concentration of CK and TSH, and a decrease in FT3 and FT4. The electromyography showed suspicious myogenic damage.Muscle histopathological findings were largely nonspecific,such as type I fiber predominance and type 2 atrophy. The MRI revealed extensive muscular dystrophy and fatty filtration in the posterior group of thighs. Treatment of replacement therapy with L-T4 relieved the myopathic symptoms quickly. Conclusion When a patient presents with a subacute progressive weakness in the proximal muscles, the hypothyroidism should be consideration. Muscle histopathological findings may be nonspecific. The muscle MRI have a value of differential diagnosis and lesion assessment.

Euphorbia factor L2, a lathyrane diterpenoid isolated from caper euphorbia seed (the seeds ofL.), has been traditionally applied to treat cancer. This article focuses on the cytotoxic activity of Euphorbia factor L2 against lung carcinoma A549 cells and the mechanism by which apoptosis is induced. We analyzed the cytotoxicity and related mechanism of Euphorbia factor L2 with an MTT assay, an annexin V-FITC/PI test, a colorimetric assay, and immunoblotting. Euphorbia factor L2 showed potent cytotoxicity to A549 cells. Euphorbia factor L2 led to an increase in reactive oxygen species (ROS) generation, a loss of mitochondrial electrochemical potential, release of cytochromeactivation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase, suggesting that Euphorbia factor L2 induced apoptosis through a mitochondrial pathway. The cytotoxic activity of Euphorbia factor L2 in A549 cells and the related mechanisms of apoptotic induction provide support for the further investigation of caper euphorbia seeds.

Objective To study the clinical, pathological, imaging features of two cases of central core disease (CCD) with different inheritance and to explore the similarities and differences between autosomal recessive CCD (AR-CCD) and autosomal dominant CCD (AD-CCD). Methods Clinical manifestations, family history, muscle MRI and muscle biopsy were collected. Targeted next generation sequencing (NGS) and sanger sequencing were applied for genetic analysis. Co-segregation analysis was further conducted in one family. Results Their common clinical manifestations included childhood early-onset proximal limbs muscle weakness and dystrophy accompanied with facial involvement. The MRI revealed extensive muscular dystrophy and fatty filtration in the both thighs, but not in rectus femoris. Pathology of skeletal muscle showed typical central cores in type Ⅰ muscle fibers and eccentric cores only in AR-CCD. Targeted NGS identified 3 missense mutations in RYR1, including one novel mutation. Conclusion The present study has described clinical and pathological features of two typical CCD patients with different inheritance, which may be associated with the different mutations in RYR1 gene. Targeted NGS apparently improves the genetic diagnosis of CCD.

OBJECTIVETo assess the association of genetic polymorphisms of CYP2C19*2,*3,*17 with the recurrence risk of ischemic stroke during clopidogrel prevention in ethnic Han Chinese from Fujian Province.

METHODSClinical data of 985 patients with acute ischemic stroke was collected. After 1 year postdischarge follow-up evaluations, only 114 patients with persistence of clopidogrel were enrolled. CYP2C19 genetic polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and direct sequencing ,then we analysis the correlation between polymorphisms and the recurrence of stroke.

RESULTSAmong the 114 patients, 23 had a second onset whilst receiving clopidogrel treatment. During the antiplatelet therapy with clopidogrel, carriers of CYP2C19 poor metabolizer (CYP2C19*2/*2 or *2/*3) had a higher rate of recurrent stroke compared with extensive metabolizers (CYP2C19*1/*1) (OR=4.71, 95%CI: 1.18-18.80, P<0.05). Carriers of CYP2C19 *2 mutant allele had increased recurrence compared with those carrying none loss-of-function allele (OR=2.31, 95%CI: 1.20-4.46, P<0.05). The rate of recurrent stroke in those carrying homozygous mutant *2 allele (CYP2C19*2/*2) was 6.14 times greater than the rate of wild-type homozygotes (CYP2C19*1/*1) (95%CI: 1.54-24.54, P<0.05). Patients with previous stroke history had increased risk of recurrence (OR= 4.146, 95%CI: 1.259-13.655, P<0.05). However, CYP2C19*17 was not detected in the group.

CONCLUSIONFor ethnic Han Chinese patients receiving clopidogrel treatment, carriers of poor metabolizer or homozygous mutant *2 allele (CYP2C19*2/*2) have a higher risk of recurrent stroke. The CYP2C19 *2 allele is an independent risk factor for recurrent stroke. Those with previous history of stroke are more prone to the recurrence.

Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Brain Ischemia ; complications ; ethnology ; China ; Cytochrome P-450 CYP2C19 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; Logistic Models ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Recurrence ; Risk Factors ; Sequence Analysis, DNA ; Stroke ; ethnology ; etiology ; genetics ; prevention & control ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Time Factors

Objective To investigate the extracellular polysaccharide distribution and components of Ureaplasma urealyticum (Uu) after biofilm having been developed in.Methods The standard serotype 3 and serotype 14 belong to biovar Parvo,and the standard serotype 4 and serotype 8 belong to biovar T960 were employed to form biofilrns in vitro.Scanning electron microscope and confocal laser scanning microscope were used to analysis the biofilms and extracellular polysaccharide.We used combination of two different labeled lectins,Canavalia ensiformis(FITC-ConA) and Erythrina cristagalli(ECA) which bind to specific polysaccharide residues to visualize extracellular polysaccharide in biofilms,and average uorescence intensity was evaluated Results All the strains can form the biofilmsin vitro.The biofilm was honeycomb-Like structures mainly,and extracellular polymeric substances accounts for majority of proportions.All the extracellular polysaccharide could be combined with FITC-ConA and ECA,and the total average fluorescence intensity of FITC-ConA was higher than ECA( P＜0.001 ).Conclusion Ureaplasma urealyticum biofilm is honeycomb-like structures mainly.The extracellular polysaccharide contains,galactose,and N-acetyl glucan residual,and the glucose,mannose residual are the main components.

ObjectiveTo study whether the abductor pollicis brevis been effected by the reinnervation of the Riche-Cannieu anastomosis in the median nerve injury cases.MethodsCollect 43 cases (29male,14 female,mean age 32.6)corresponds with the study needs: (1)The traumatic median nerve injury (proved by the results of electrophysiological examine and the clinic diagnose)on or below the forearm.(2)The existence of RCA was verified by the electrophysiological examine results,and the amplitude of electric potential was under 1mv.(3) Rule out the cases with the other injure of nerve or nervous system disease and cervical vertebra disease,diabetes patient.The analysis base on the results of 43 case's periodical examine,the periodical criteria as following: within 2-4th week,within the 2-4thmonth and 1 year after the injury.Results Forty-three cases had not obvious recovery indication of the median nerve under the clinical and electrophysiological aspect,eight cases of abductor pollicis brevis function improved quickly in 3 months,the relevant CMAP amplitude of Riche-Cannieu anastomosis increased apparently,the EMG (Electromyography)results of abductor pollicis brevis ameliorated accordingly.ConclusionIn the case of RCA combined with the median nerve injury,the abductor pollicis brevis fibra might be dominated by RCA reinnervation when losing domination of median nerve,the reinnervation process will much faster than the regeneration process of the broken nerve.

Objective To analyze the dystrophin gene in patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and their family members by multiplex ligation-dependent probe amplification (MLPA) method and to evaluate the application of this method in the mutations detection. Methods The whole dystrophin gene (79 exons) was analyzed by MLPA in 355 patients with DMD/BMD, the mothers of 46 patients with deletion mutation and the mothers of 8 patients with duplication mutation. The results were verified by PCR and sequencing when single exon deletion was found. Results One hundred and ninety cases were found to have deletion of one or more dystrophin exons, and 34 patients were identified to have duplication mutations. In 46 mothers of patients with deletion mutations, 28 were identified the mutations;and of 8 mothers of patients with duplication mutations, 6 were identified the mutations. There was no statistical significance between the carrier incidences in the 2 groups. A 23 bp deletion of AGGGAACAGATCCTGGTAAAGCA fragment in exon 17 was found in a patient. Conclusions Comparing with the traditional quantitative methods, MLPA can detect the deletion and duplication mutation in all the 79 exons of dystrophin gene in DMD/BMD patients, and can identify the carrier status in their family members. Furthermore, MLPA is not apt to be interfered by the concentration and purity of DNA template.