Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.

Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

Objective:To summarize the characteristics of neuralgia in Fabry disease and explore the effects of genders and alpha-galactosidase A (GLA) gene mutation types on neuralgia.Methods:Questionnaires and Brief Pain Inventory evaluations were conducted on the recruited patients diagnosed as Fabry disease in Department of Neurology, Peking University First Hospital from January 2001 to April 2020. The characteristics of the neuralgia were summarized, and the portrait of neuralgia between male and female patients, and the patient groups carrying truncated mutations and non-truncated mutations of GLA gene was compared.Results:A total of 93 patients with Fabry disease were enrolled. The incidence of neuralgia was 91.4% (85/93),and the average onset age of pain was 9 years. The average remission age was 20 years with the remission incidence of 22.8% (18/79). Pain attack on extremities [96.5%(82/85)] was the most common form. The neuralgia relieving rate of male patients [17.5%(11/63)] was lower than that of females (7/16, χ2=5.01, P=0.025).Brief Pain Inventory scores showed that the degree of most severe pain attack within 24 hours of male patients (4.16±3.20) was higher than that of females (2.07±2.02, t=3.03, P=0.004),and the impact of pain on daily life [male 4 (7) vs female 0 (4), Z=-2.33, P=0.020], walking ability [male 5 (8) vs female 0 (2), Z=-2.87, P=0.004], daily work [male 5 (8) vs female 0 (2), Z=-3.10, P=0.002], relationship [male 2 (6) vs female 0 (3), Z=-2.67, P=0.008] and interests [male 4 (8) vs female 0 (3), Z=-2.81, P=0.005] of male patients was also higher than female patients. The truncated mutation group [1 (2)] only showed higher score on the current pain level than the non-truncated mutation group [0(0), Z=-2.89, P=0.003]. Conclusions:The neuralgia in Chinese patients with Fabry disease showed high incidence and early onset. Male patients presented more severe pain than female which led to a greater impact on life, while the type of GLA gene mutation had less impact on neuralgia.

The necessity of WeChat public platform-based subject service in medical college and university libraries was analyzed according to its characteristics and problems, followed by an elaboration with the application of We-Chat public platform in common information release, personal information push, reference service, interactive ex-change,information network navigation, educational training, and its management and maintenance, with sugges-tions put forward for improving WeChat public platform-based subject service.

2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.

The application of HPLC-NMR-MS hyphenated technique in the structural identification of trace substances from complex mixtures and the identification of endogenous and exogenous substances in the establishment process of metabolic profiling have become effective analytical tools in pharmaceutical chemistry, pharmacological and pharmacokinetic studies of active substances from natural products. Metabolomics method based on NMR technology can accurately portray metabolic phenotypes with the characteristics of diseases and a variety of disease-related pathways, and it can greatly enrich and supplement the traditional disease evaluation methods. So it can be used for pharmacological studies of active substances from natural products, such as toxicological studies, the dose optimization, active substances screening and pharmacodynamic evaluation. Hyphenated technique associated with metabolomics method based on NMR technology will accelerate the speed of the discovery of active substances from natural products, and improve the efficiency of their pharmacological evaluation.

To obtain a better understanding of the progression of atherosclerosis and identify potential biomarkers, proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabonomics was used to study the metabolic changes in the plasma of hamster fed with a high-fat/cholesterol diet. Plasma samples were collected at different time points during the progression of atherosclerosis and individual proton NMR spectra were visually and statistically assessed using multivariate analyses. NMR results for all samples showed a time-dependent development from physiological to pathophysiological status during atherosclerosis. Analysis of the identified biomarkers of atherosclerosis suggests that lipid and amino acid metabolisms are significantly disturbed, together with inflammation, oxidative stress, following cholesterol overloading. The results enriched our understanding of the mechanism of atherosclerosis and demonstrated the effectiveness of the NMR-based metabonomics approach to study such a complex disease.

Objective:The 11?-hydroxysteroid dehydrogenase(11?-HSD) plays an important role in tumor biological behavior,and the 11?-HSD inhibitor Glycyrrhetinic acid(GA) may have an anticancer effect,although its mechanism remains unkown.This study aimed to observe the expressions of 11?-HSD 1 and 2 in colorectal cancer and the effects of glucocorticoid and GA on colorectal cancer cells.Methods: The mRNA expressions of 11?-HSD1 and 2 in the human colorectal cancer cell line HCT-8 were detected by reverse transcription polymerase chainreaction(RT-PCR),and the protein expressions of 11?-HSD1 and 2 were detected by Western blot.The inhibition of the growth of the HCT-8 cells was determined by MTT assay after treated with glucocorticoid,cosubstrate,GA only or their combination.Results: The expression of 11?-HSD2 mRNA and proteins but not that of 11?-HSD1 mRNA and proteins was expressed in the HCT-8 cells.The rate of cell growth inhibition was(40.87 ? 1.47)% after a 12-hour treatment with cortisol,and it was(5.79 ? 0.20)% in the cortisol + NAD group,with statistically significant difference(P