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.

Objective To evaluate the predictive value of a dose-surface histogram (DSH) for radiation cystitis (RC) in patients with cervical cancer. Methods We retrospectively included 190 patients with cervical cancer who underwent image-guided radiotherapy (IGRT) from the HIS system of The First Affiliated Hospital of Hebei North University from May 2013 to May 2023. The patients were divided into test group (n = 100) and control group (n = 90). The dose distribution in the bladder was evaluated by using a DSH for the test group and using a dose-volume histogram (DVH) for the control group. Receiver operating characteristic curves were used to evaluate the predictive value of DSH for RC in comparison with DVH. Results There were no significant differences in baseline data and RC incidence between the two groups (all P＞0.05). All evaluation indicators were significantly different between DSH and DVH (all P＜0.05). The predictive value of S₄₅ and V₄₅ for the incidence of grade-I, -II, and -III RC was low (all P＜0.05). The predictive value of S₅₀ and V₅₀ for the incidence of grade-I, -II, and -III RC was moderate (all P＜0.05). S₅₅−S₅₇ and V₅₅−V₅₇ showed high value for predicting the incidence of grade-I, -II, and -III RC (all P＜0.05). Conclusion DSH shows basically the same predictive value for the incidence of RC caused by IGRT in cervical cancer as DVH, which is expected to become a new tool for evaluating radiotherapy plans.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1). METHODS: A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3). CONCLUSION The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.
Adolescent ; Humans ; Male ; China ; Computational Biology ; Genomics ; Genotype ; Mutation

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

In 2016, a national one million general population cohort project was set up in China for the first time in "Precision Medicine Research" Key Project, National Key Research and Development Program of China, which consists of general population cohorts in seven areas in China. As one of the seven major areas in China, northeastern China has unique climate and specific dietary patterns, and population aging is serious in this area. And the burden of chronic and non-communicable diseases ranks tops in China. Therefore, it is of great significance to establish a large general population cohort in northeastern China to explore the area specific exposure factors related to pathogenesis and prognosis of chronic and non-communicable diseases, develop new prevention strategies to reduce the burden of the diseases and improve the population health in northeastern China. In July 2018, the general population cohort study in northeastern China was launched, the study includes questionnaire survey, health examination and blood, urine and stool sample collection and detection in recruited participants. By now, the cohort has covered all age groups, and the baseline data of 115 414 persons have been collected. This paper summarizes the design and practice of the general population cohort study in northeastern China to provide reference for related research in China.

OBJECTIVE To investigate the effects of different drying methods on the index components in wine-processed Cornus officinalis so as to optimize drying method.METHODS After processed with wine， C. officinalis decoction pieces were dried with different drying methods （blast drying， far infrared drying， microwave drying， freeze drying， sun drying， shade drying and combined drying）. The contents of 5 components such as gallic acid in wine-processed C. officinalis were determined by high- performance liquid chromatography. The contents of total flavonoids in wine-processed C. officinalis were determined by chromogenic method. Analytic hierarchy process was used to evaluate the effects of different drying methods on the contents of components in C. officinalis.RESULTS The contents of gallic acid， 5-hydroxymethylfurfural， monoside， loganin， cornuside and total flavonoids in 22 batches of wine-processed C. officinalis were 1.043 8-1.563 8， 0.648 5-2.358 8， 5.031 0-10.305 7， 6.681 2- 7.534 2， 0.986 5-1.148 8 and 33.657 2-50.741 5 mg/g， respectively. The comprehensive scoring results of analytic hierarchy process showed that the comprehensive score of each component in C. officinalis dried by microwave at 75 ℃ was higher ， followed by blast drying at 60 ℃ and far infrared drying at 60 ℃ .CONCLUSIONS The wine-processed C. officinalis could be dried by microwave drying at 75 ℃， blast drying at 60 ℃ or far infrared drying at 60 ℃.

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To observe the clinical effect of wheat grain-sized cone moxibustion combined with fire needle therapy in the treatment of dorsal wrist ganglion (DWG). Methods:A total of 63 patients with DWG were randomized into a treatment group (n=32) and a control group (n=31). Cases in the control group were treated with fire needle therapy. Based on the therapy given to the control group, cases in the treatment group were additionally given wheat grain-sized cone moxibustion therapy. Then the therapeutic efficacies and recurrence rate were evaluated. Results:After treatment, the overall effective rate was 93.8% in the treatment group, versus 77.4% in the control group, and the between-group comparison showed a statistical significance (P<0.05); 6 months after the treatment, the recurrence rate in the treatment group was obviously lower than that in the control group (P<0.05). Conclusion:The long-term and short-term effects of wheat grain-sized cone moxibustion combined with fire needle therapy in the treatment of DWG are better than those of fire needle therapy alone, and therefore, worth popularizing.