Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, making it one of the most common forms of hereditary muscular dystrophy. The DMD gene, which encodes dystrophin, is the largest known gene in the human genome. Mutations in the DMD gene are highly diverse, including exon deletions, duplications, point mutations, and small insertions or deletions, posing significant challenges for treatment. Currently, there is no cure for DMD, and existing treatment strategies focus primarily on symptom management, which cannot reverse or halt disease progression. Advances in biotechnology position nucleic acid drugs and gene therapies at the forefront of DMD treatment research. These treatments aim to restore dystrophin expression by repairing or replacing mutated genes, thereby improving muscle function or slowing muscle degeneration. Preclinical studies in animal models and early-phase clinical trials demonstrate promising efficacy and offer new hope for DMD patients. This review briefly outlines the pathological mechanisms and genetic characteristics of DMD before delving into recent progress in therapeutic strategies, with a particular focus on nucleic acid drugs (including antisense oligonucleotides for exon skipping therapy and translation readthrough inducers) and gene therapy approaches (including gene replacement therapy and gene editing). The development and application of these therapies not only provide new treatment options for DMD patients, but also offer valuable insights for addressing other genetic disorders. However, numerous challenges impede the clinical translation of DMD treatments. Future studies must optimize existing therapeutic strategies, improve their efficacy and applicability, and explore innovative approaches to deliver more effective and sustainable treatments for DMD patients.

Objective To compare the contents of alkaloid in Aconiti Kusnezoffii Radix with different degrees of processing and their effects on electrocardiogram and vagus nerve action potential in SD rats;To establish a toxicity evaluation method for Aconiti Kusnezoffii Radix and its processed products.Methods HPLC was used to determine the contents of six alkaloid components,including benzoyl neoaconitine,benzoyl aconitine,benzoyl subeaconitine,neoaconitine,subeaconitine and aconitine in Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix Cocta of soaking and boiled for 30 minutes,boiled for 4 h without soaking,soaking and boiled for 4 h,and soaking and boiled for 8 h.SD rats were subjected to sublingual drainage with Aconiti Kusnezoffii Radix and four types of processed products.The vagus nerve action potential and electrocardiogram of rats before and after administration were recorded,and the correlation analysis between alkaloid content and vagus nerve action potential and heart rate was conducted.Results The contents of alkaloid of the four processed products showed that the content of diester alkaloids was soaking and boiled for 30 min>boiled for 4 h without soaking>soaking and boiled for 4 h>soaking and boiled for 8 h;monoester alkaloid content:boiled for 4 h without soaking>soaking and boiled for 30 min>soaking and boiled for 4 h>soaking and boiled for 8 h.After the administration of each sample,compared with the basal discharge,the vagus nerve discharge of rats with different processed products was changed by sublingual administration,heart rate increased,the degree of arrhythmia increased,and it varied with the degree of processing;the results of correlation analysis showed that there was a significant correlation between the nerve discharge area and the contents of diester alkaloids and total alkaloids.Conclusion The action potential of the vagus nerve and electrocardiogram of rats after sublingual drainage administration can reflect the degree of numbness in the tongue,which can provide reference for the study of tongue sensation of Aconiti Kusnezoffii Radix.

Objective:To assess the value of culture of epidermal melanocytes from negative-pressure suction blisters in the auxiliary diagnosis of segmental vitiligo-like nevus depigmentosus.Methods:Between June 2019 and March 2020, 8 patients with segmental vitiligo-like nevus depigmentosus, who met the Coupe′s clinical diagnostic criteria, were enrolled from Department of Dermatology, Hangzhou Third People′s Hospital. All patients were evaluated by the Wood′s lamp, reflectance confocal microscopy (RCM) , 308-nm excimer laser radiation, and in vitro culture of epidermal melanocytes from negative-pressure suction blisters. Results:Among the 8 patients, fluorescence was observed in 6 under the Wood′s lamp, dermal papillary rings were incomplete or absent in 4 as shown by RCM, and 5 experienced no repigmentation after 308-nm excimer laser radiation. Among the 8 patients, in vitro cultured lesional melanocytes were all positive for ferrous sulfate staining, yellowish-white precipitates were obtained after digestion and centrifugation of the melanocytes, and stage Ⅰ-Ⅲ melanosomes were observed in the cytoplasm of melanocytes under the electron microscope; however, the precipitates were black in color after digestion and centrifugation of the melanocytes collected from the normal skin tissues at the contralateral anatomical site, and stageⅠ-Ⅳ melanosomes were seen in the cytoplasm of the melanocytes under the electron microscope. Conclusion:Culture of epidermal melanocytes from negative-pressure suction blisters may facilitate the diagnosis of segmental vitiligo-like nevus depigmentosus.

Objective To investigate the clinical and epidemiological characteristics of crayfish associated rhabdomyolysis syndrome in Baiyun District, Guangzhou, and explore the related factors, and to provide evidence for the prevention of crayfish rhabdomyolysis syndrome. Methods The cases of crawfish associated rhabdomyolysis syndrome were found through the foodborne disease surveillance and reporting system, and a field epidemiological investigation was carried out to analyze the clinical and epidemiological characteristics of the cases. Results A total of 25 cases of crayfish associated rhabdomyolysis syndrome occurred in 2020. The intake of crayfish of the cases ranged from 5 to 25, the incubation period was 1 to 9.5h, and the interval from onset to medical treatment was 0.17 to 9h. All the cases had muscle pain, and the content of creatine kinase (CK) in the cases increased to varying degrees (128-17851 U/L). Retrospective cohort analysis of 10 crayfish events found no correlation between the consumption of different parts of crayfish and the incidence of crayfish-related rhabdomyolysis syndrome. Conclusion The incidence of rhabdomyolysis syndrome reported in Baiyun District of Guangzhou is related to the consumption of crayfish, but the pathogenic factors need to be further studied. It is suggested to strengthen the supervision of crayfish breeding, transportation, sales, and processing to ensure the health of consumers.

Targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for treating melanoma, gastric cancer (GC) and bladder cancer with clinical benefit. Nevertheless, many patients failed to respond to anti-PD-1/PD-L1 treatment, so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy. Here with the data from The Cancer Genome Atlas (TCGA) and our in-house tissue library, PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7 (USP7) in GC. Furthermore, USP7 directly interacted with PD-L1 in order to stabilize it, while abrogation of USP7 attenuated PD-L1/PD-1 interaction and sensitized cancer cells to T cell killing

Objective: To clarify the correlation between the clinical characteristics, esophageal motility features and esophageal acid exposure in patients with ineffective esophageal motility (IEM). Methods: From January 2016 to March 2018, at Peking University First Hospital, 22 IEM patients diagnosed by esophagus high-resolution manometry (HRM) and 24 individuals with normal HRM results were enrolled. Clinical features, parameters of esophageal HRM and results of esophageal 24-hour pH monitoring of IEM patients and the individuals with normal HRM results were compared. According to the median distal contraction integral (DCI) of ten swallows, the IEM patients were divided into mild-IEM group (DCI 250-450 mmHg·s·cm (1 mmHg=0.133 kPa)) (14 cases) and severe-IEM group (DCI<250 mmHg·s·cm) (eight cases). The clinical features and esophageal motility were compared between normal HRM group, mild-IEM group and severe-IEM group. T test, chi-square test and one-way analysis of various were used for statistical analysis. Results: The age of IEM group was older than that of normal HRM group ((64.5±11.2) years vs. (50.3±18.2) years), and the difference was statistically significant (t=-3.135, P=0.003). The lower esophageal sphincter pressure (LESP) of IEM group was lower than that of normal HRM group ((17.0±6.8) mmHg vs. (22.3±7.2) mmHg), and the difference was statistically significant (t=2.516, P=0.016). There were 15 cases in normal HRM group and 14 patients in IEM group who underwent esophageal 24-hour pH monitoring and there were five and two patients with abnormal acid exposure time (AET) in normal HRM group and IEM group, respectively. The length of proximal esophageal body (PEB) pressure zone of severe-IEM group was shorter than those of normal HRM group and mild-IEM group ((2.8±1.5) cm vs.(4.2±0.7) cm and (4.6±0.9) cm), and the differences were statistically significant (t=2.397 and 3.432, P=0.044 and 0.003). The integrated relaxation pressure (IRP) and LESP of normal HRM group were both higher than those of mild-IEM group ((9.3±2.9) mmHg vs. (7.2±3.3) mmHg, (22.3±7.2) mmHg vs. (15.4±7.1) mmHg), and the differences were statistically significant (t=2.148 and 2.843, P=0.038 and 0.007). There were six and eight patients in mild-IEM group and severe-IEM group who underwent esophageal 24-hour pH monitoring, respectively, and two patients in mild-IEM had abnormal AET. Conclusions The LESP of IEM patients is low. The clinical features and AET of IEM patients are not associated with the severity of IEM. In patients with severe IEM, the proximal and distal esophageal contractility is weakened, and the length of PEB pressure zone is shortened.

OBJECTIVETo detect potential mutation of TCOF1 gene in a Chinese family affected with Treacher-Collins syndrome.

METHODSClinical data of the patient was collected. The analysis included history taking, clinical examination and genetic testing. All coding regions of the TCOF1 gene were subjected to PCR amplification and Sanger sequencing.

RESULTSA novel mutation c.2261ins G (p.E95X) of the TCOF1 gene was discovered in the patient. The same mutation was not found in his parents and 100 healthy controls.

CONCLUSIONThe c.2261insG (p.E95X) mutation of the TCOF1 gene probably underlies the disease in the patient. Genetic testing can facilitate diagnosis and genetic counseling for families affected with TCS.

OBJECTIVETo compare the clinical efficacy of treating different diseases with the same acupuncture comprehensive therapy and intramuscular injection of ranibizumab in the treatment of macular edema, and to explore an effective treatment.

METHODSA retrospective study was conducted, ①Acupuncture combined with EA at Xinming one (Extra), Sizhukong (TE 23), Tongziliao (GB 1), once every other day; ②acupoint injection, alternation with compound anisodine and mecobalamine injection at Qiuhou (EX-HN 7), Taiyang (EX-HN 5), once every other day; ③auricular acupressure at yan (LO), gan (CO), shen (CO) and other points; ④plum-blossom needle at Zhengguang 1 (Extra), Zhengguang 2 (Extra), once every other day were given in the acupuncture group (20 cases, 24 affected eyes). Intramuscular injection of 0.5 mg ranibizumab was given in the ranibizumab group (22 cases, 23 affected eyes). The macular foveal thickness, early treatment diabetic retinopathy study of (ETDRS) visual acuity chart, self-evaluation scores of visual function impairment ophthalmopathy patient's quality of life scale were observed before treatment, after 3, 6, 9 and 12 months of treatment, and the clinical efficacy was evaluated.

RESULTS①At all the observation time points of the treatment, the macular thickness was lower than that before treatment in the two groups (all <0.05), and there was no significant difference between the acupuncture group and the ranibizumab group (all >0.05). ②Visual acuity was higher than that before treatment at all the time points in the two groups (all <0.05). After 3-months treatment, there was no statistical significance between the two groups (>0.05). After 6, 9, and 12 months treatment, the visual acuity in the acupuncture group was better than that in the ranibizumab group (<0.05, <0.01). ③At all the time points, the quality of life scores were lower than those before treatment in the two groups (all <0.05). There was no statistical significance in the ranibizumab group compared with those before treatment (all >0.05). In 3, 6, 9 and 12 months of treatment, the quality of life scores in the acupuncture group was better than those in the ranibizumab group (<0.05, <0.01). ④The total effective rate of the acupuncture group was 79.2% (19/24), which was better than 30.4% (7/23) in the ranibizumab group (<0.05). ⑤The improvement of visual acuity before and after treatment was negatively correlated with the course of disease (<0.05), ie, the longer the disease course of the eyes, the worse the visual acuity and the worse the effect.

CONCLUSIONAcupuncture comprehensive treatment can effectively treat macular edema, significantly improve the patient's vision, improve the subjective experience and the quality of life, and the shorter the course of the disease the more significant effect. Acupuncture comprehensive treatment is better than intramuscular injection of ranibizumab.

Objective To observethe clinical efficacy of comprehensive acupuncture treatment in treating primary open-angle glaucoma, and to objectively evaluate the therapeutic efficacy.Method Twenty-eight patients (53 eyes) who received acupuncture treatment were recruited. By adopting a self-control design, the changes of intraocular tension, mean defect (MD) of vision field, mean sensitivity (MS), vision, and score of Quality of Life Scale for Patients with Visual Impairment (QLSPVI) were observed after 3-month acupuncture treatment.ResultThe intraocular tension of the 28 patients declined obviously after the treatment (P<0.01); MD, MS and vision didn't show significant improvements after the treatment (P>0.05); the QLSPVI score dropped significantly after the treatment (P<0.01);the total effective rate was 86.8%; the therapeutic efficacy wasn't correlated with age, disease duration, and treatment duration (P>0.05).Conclusion Acupuncture treatment can effectively reduce the intraocular tension, control the deterioration of MD and MS, maintain the level of vision, and enhance the quality of life of patients with primary open-angle glaucoma; with the same disease duration, the longer the treatment, the better the therapeutic efficacy.