BACKGROUND:Duchenne muscular dystrophy is recognized as a fatal X-linked recessive inheritance. It is caused by the dystrophin gene mutation, resulting in the deficiency of dystrophin and consequent degeneration and necrosis of muscle fibers gradual y. Becker muscular dystrophy is also caused by the mutation of the same gene, but presented with less severe clinical symptoms compared with Duchenne muscular dystrophy. Frameshift mutation destroys the reading frames, and thus the translation cannot proceed smoothly to transcript functional proteins. In-frame mutation cannot destroy the reading frames and hence the translation can proceed smoothly. But in-frame mutation involves the whole hydrophobic regions. The three-dimensional structure of these regions and their functionality are not interpreted clearly. The effects of these regions on disease development need to be clarified in detail from the point of structure and function.
OBJECTIVE:By analyzing Kate and Dolittle scale mean hydrophobicity profile, to investigate the dystrophin hydrophobic regions using Swiss-model so as to provide the supplement explanation on the reading frame rule.
METHODS:Form 2002 to 2013, 1 038 cases diagnosed as Duchenne muscular dystrophy or Becker muscular dystrophy were col ected in the First Hospital of Sun Yat-sen University in China and Leiden DMD information database was searched with deletion of codon mutation information available. The correlation between clinical types and genotypes was analyzed upon resources col ected above. The mean hydrophobicity profile of dystrophin was analyzed by Bioedit as wel as the reconstruction of hydrophobic domains using Swiss-model. Thus, the important functional domain of dystrophin was confirmed by analysis and the correlation between clinical types and genotypes.
RESULTS AND CONCLUSION:Four hydrophobic regions were confirmed:Calponin homology domain CH2 on actin-binding domain, repeat 16 domain, Hinge Ⅲ domain and EF Hand domain. Duchenne muscular dystrophy was developed as a result of the destruction of the 1st, 2nd and 4th hydrophobic regions which were the conjunction of dystrophin and associated protein in dystrophin-glycoprotein complex. When the 3rd hydrophobic was deleted, the repeat domain located on central rob domain remained its continuity so that the clinical symptoms were less severe. These findings indicate that the dystrophin hydrophobic regions act as an important role on the pathogenesis of Duchenne muscular dystrophy.

Objective To assess the interference by calcium dobesilatein 7 peroxidase-baseduric acid assays and to determine its clinical significance.Methods In the in vitro experiments, uric acid in pooled serum with final concentrations of calcium dobesilate additions (0, 2, 4, 8, 16, 32, and 64μg/ml) were measured by 7 peroxidase-based assays.Percent Bias (%) was calculated relative to the drug-free specimen.In the in vivo experiments, changes in serum uric acid and calcium dobesilate concentrations were observed before and after calcium dobesilate administration ( baseline, 0 h, 1 h, 2 h, 3 h, 4 h, 6 h ) involunteers.The interference in different assays was assessed compared with LC-IDMS/MS method. Calcium dobesilate levels in 40 specimens from those taking calcium dobesilate were measured by HPLC method.Of the 40 specimens, 10 were selected to analyse the levels of uric acid by both peroxidase and UV measurement method to assess the impact in clinical status.Results In the in vitro study, concentrations of uric acid measured by 7 peroxidase-based assays were reduced by -6.3%to -21.2%compared with drug-free serum, when theconcentration of calcium dobesilate was16μg/ml.In the in vivo study, comparedto UA levels at 0 h, the biasesof serum uric acid determined by peroxidase method after calcium dobesilate administration(1 h, 2 h, 3 h, 4 h, 6 h) were of -3.33%, -6.79%, -7.49%, -6.07%, -4.09%, respectively.The observed uric acid concentrations for 8 participants measured by enzymatic assays were inhibited by -3.75% to -6.89% at 0 hour and by -16.9% to-22.22% at 2 hours relative to the concentrations measured by the LC-IDMS/MS method. Conclusions Calcium dobesilate produced a clinically significant negative interference with uric acid in all peroxidase-based uric acid assays,which may result in false evaluation of uric acid level in clinical status.Significant differences in the degree of interference were observed among the assays.

ObjectiveTo explore the protective effect of hearing protectors worn by noise-exposed workers and its influencing factors. Methods A total of 329 occupational noise-exposed workers were selected as the research subjects by judgment sampling method. A questionnaire survey on the use of ear protectors and individual suitability tests was conducted. Intervention was carried out for those whose personal attenuation rating (PAR) did not pass the baseline standard. Results The median (M) and the 25th and 75th percentiles of baseline PAR were 17.0 (5.0, 22.5) dB. The baseline PAR of the workers who were male, aged 25-<35 years, with a working experience of 5-<15 years, with a college degree or above, wearing ear protectors for 5-<15 years, knowing the right way to wear ear protectors, and workers who wore ear protectors correctly during work was relatively high (all P<0.01). The unqualified rate of baseline PAR of the study subjects was 32.8%. The unqualified rate of baseline PAR of workers in automobile manufacturing enterprises was lower than that of workers in plastic enterprises and textile enterprises (9.2% vs 43.6%, and 9.2% vs 50.0%, both P<0.01). The M of the 108 unqualified worker on baseline PAR was improved after intervention (22.0 vs 1.0 dB, P<0.01). The rates of knowing the right way to wear ear protectors, wearing ear protectors correctly during work, and receiving training on wearing ear protectors correctly for the research subjects were 88.1%, 84.8%, and 86.6%, respectively. Workers in automobile manufacturing enterprises and plastic enterprises had higher rates of knowing the right way to wear ear protectors, wearing ear protectors correctly during work, and receiving training on wearing ear protectors correctly than those in textile enterprises (all P<0.01). Conclusion Gender, age, working experience, education level, duration of wearing ear protectors, knowledge and use of ear protectors correctly are influencing factors of the protective effect of ear protectors for noise-exposed workers.

OBJECTIVETo study genotype-phenotype correlation of a family with late infantile metachromatic leukodystrophy(MLD).

METHODSClinical data were collected and ARSA gene was tested by PCR and sequencing in a pedigree.

RESULTSThe male proband onset with walking dysfunction at 19 months, arylsulfatase A activity of leucocyte from his peripheral blood was 20.2 nmol/mg.17h, and his cranial MRI showed wildly symmetrical demyelination. Homozygosis for novel c.622delC (p.His208Metfs46X) in exon 3 of ARSA gene was identified in proband, and heterozygous for the same mutation in parents and grandma of the proband.

CONCLUSIONLate infantile metachromatic leukodystrophy is characterized by rapid and progressive regression of neuropsychiatric and motor development. There is a significant correlation between the mutation of c.622delC(p.His208Metfs*46) in the ARSA gene and the phenotype presenting as O/O patients.

Base Sequence ; Cerebroside-Sulfatase ; deficiency ; genetics ; DNA Mutational Analysis ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Infant ; Leukodystrophy, Metachromatic ; diagnostic imaging ; enzymology ; genetics ; Magnetic Resonance Imaging ; Male ; Mutation ; Pedigree ; Phenotype ; Polymerase Chain Reaction ; Radiography ; Sequence Deletion

Objective To evaluate the effects of Traditional Chinese Medicine (TCM) nursing training based on Kirkpatrick's model relying on TCM hospitals.Methods Totally 77 clinical nurses from 50 medical institutions in Hangzhou were enrolled for TCM training.The four levels of Kirkpatrick's model including reaction,learning,behavior and results were applied for the evaluation together with questionnaires,paper-based exams,scene simulation method and semi-structured interviews.Results Nurses' attendance was over 85％,and average score of training satisfaction was 96.32±5.91 which lied between highly satisfied and very satisfied.TCM knowledge and skills were higher after training(P＜0.05).The scores of self-evaluation and peer evaluation were higher after training(P＜0.05).The numbers of projectsand personnel to practice TCM in the department or outpatient clinic were higher after training (P＜0.05).The patient satisfaction was over 82％.The themes of training benefits among nurses were reaching the expected values,growth and harvest,and expectation of continuous learning.Conclusion Using Kirkpatrick's model as the evaluation tool can evaluate the effects of TCM nursing training relying on TCM hospitals in a comprehensive and long-term manner,and improve the quality of training.

ObjectiveTo analyze the results of fit testing and its influencing factors on half-mask respirator among workers exposed to organic solvents. Methods A total of 84 workers exposed to organic solvents were selected as the research subjects using a convenience sampling method. The qualitative fit test apparatus of respiratory protection was tested after the workers had put on the half-mask respirats, and 11 facial indicators of the subjects were measured. Results The overall pass rate of the respirator fit testing was 71.4% (60/84). The lowest pass rate was 63.1% (53/84), which occurred during bending movements of workers. The head width, minimum forehead width, face length, nose length, nose depth, head circumference and head length were higher in workers who passed respirator fit testing, compared with those in the failing group (all P<0.05). The result of binary logistic regression analysis showed that gender and face width were influencing factors of the respirator fit testing (both P<0.05). Female workers had a lower pass rate of the fit testing than male workers, and workers with larger face width had a lower pass rate in the fit testing. Conclusion Drastic movement may lead to a decrease in the seal of half-mask respirator of workers exposed to organic solvents. When providing half-mask respirator to workers exposed to organic solvents, employers need to pay attention to the fit of respirators of female works and those with larger face width to ensure the effectiveness of respiratory protection for workers.

BackgroundMajor depressive disorder is one of the most disabling mental diseases. Currently， medication in combination with physiotherapy and psychotherapy remains the most commonly used treatment modality for the disease， whereas only a few randomized controlled studies have been conducted on physiotherapy， and even fewer studies have focused on medication combined with physiotherapy. ObjectiveTo explore the efficacy and safety profile of repetitive transcranial magnetic stimulation （rTMS） versus modified electroconvulsive therapy （MECT） in combination with antidepressants in the treatment of major depressive disorder， so as to provide an optimized treatment plan for patients with major depressive disorder. MethodsPatients with major depressive disorder （n=335） hospitalized in Shandong Daizhuang Hospital from January 1， 2019 to April 30， 2023 were included， all of whom met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10）. Depending on their disease condition， patients were subjected to either MECT in combination with drugs （n=141） or rTMS in combination with drugs （n=194） after admission. Depressive symptoms were assessed using Hamilton Depression Scale-24 item （HAMD-24） at the baseline and the end of the 1^st， 2^nd， 3^rd and 4^th week of treatment， and the adverse reactions were documented in patient's medical records. ResultsAnalysis of variance on HAMD-24 revealed a significant effect of time （F=3.081， P=0.042）， but no effect of group （F=1.023， P=0.313）， and the interaction effect between the time and the groups was not statistically significant （F=1.642， P=0.191）. No statistical difference was reported between two groups in response rate and full remission rate （P>0.05）. Throughout the course of treatment， 58 cases （41.13%） of recent memory impairment and 74 cases （52.48%） of headache or neck muscle pain occurred in MECT combined with drugs group， and 27 cases （13.92%） in rTMS combined with drugs group experienced headache or head skin discomfort. ConclusionAntidepressants in combination with rTMS or MECT show equivalent efficacy in the treatment of major depressive disorder， while rTMS combined with antidepressants demonstrates a superior safety profile compared to MECT.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.