Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ² = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.
Adult ; Humans ; Amyotrophic Lateral Sclerosis/diagnostic imaging* ; Fasciculation/diagnostic imaging* ; Radiculopathy ; Muscle, Skeletal/diagnostic imaging* ; Ultrasonography/methods*

【Objective】 To learn the production efficient of platelet components among prefecture-level blood stations in China, to provide supporting data for those blood stations to optimize the production mode of platelet components and continuously improve production efficiency and supply capacity. 【Methods】 The data from 2017 to 2020 was obtained from 24 prefecture-level blood stations who were the members of the practice comparison network for blood institutes in China. The collection units of apheresis platelets, the number of dual-collections of apheresis platelets and plasma, the average apheresis units of one platelet apheresis procedure, the discarded rate of apheresis platelets, the amount of expired apheresis platelets and the amount of apheresis platelets issued were collected. For concentrated platelets, the prepared amount of platelet concentrates and the amount of expired platelet concentrates were collected; both the quantity of qualified and issued concentrated platelets were submitted for statistical analysis.The total output and efficiency of platelet components were calculated based on the collected data. 【Results】 The average annual growth rate of apheresis platelets collection in 24 prefecture-level blood stations was 12.23%, accounting for 99.80% of the total platelet output; the average collection unit of one platelets apheresis procedure was 1.75; from 2019 to 2020, only 5 blood stations performed dual-collection of platelet and plasma during one apheresis procedure; the discarded rate of apheresis platelets was 0.28%, of which 0.007% was due to expiration. A total of 1 621.2 therapeutic units of concentrated platelets were prepared, and 13.03% of them was discarded due to the expiration. The production efficiency of platelet components was 97.56%, of which the production efficiency of apheresis platelets was 97.61% and the production efficiency of concentrated platelets was 74.43%. 【Conclusion】 There are large regional differences in the supply capacity of platelet components in prefecture-level blood stations. Apheresis platelets are the main resource of platelet components product, and the collection capacity is increasing over the years with the characteristics of high production efficiency and low expiration scrapping rate. However, the preparation of concentrated platelets are still limited with relatively low production and high expiration discarded rate.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective: To analyze the clinical characteristics of 6 children with TTC21B-related nephronophthisis to provide reference for early clinical diagnosis. Methods: The general condition, clinical manifestations, laboratory tests and other clinical data of 6 children from 4 families diagnosed with nephronophthisis by genetic testing in Shanghai Children's Hospital from January 2015 to December 2020 were analyzed retrospectively. Results: A total of 6 children (3 males and 3 females) developed proteinuria and progressive renal dysfunction in early infancy. The onset age of proteinuria was 18 (6, 25) months. The age at the onset of renal impairment was 22 (10, 36) months. All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. Five children had hypertension, 3 children with abnormal liver function, 2 children with visceral translocation and 1 child with growth retardation. The genetic results suggested that all children carried variations TTC21B gene p.C518R. Conclusions: Children with TTC21B gene p.C518R nephronophthisis had proteinuria and progressed to ESRD at the early stage of life. These nephronophthisis patients commonly presented with liver and renal dysfunction.
China ; Female ; Humans ; Kidney Diseases, Cystic/genetics* ; Kidney Failure, Chronic/genetics* ; Male ; Phenotype ; Proteinuria/genetics* ; Retrospective Studies

Objective: To investigate the effect of pesticides and herbicides on lipid metabolism. Methods: In November 2020, Based on the data of the national health and Nutrition Survey (NHANES) (2011-2014) , select the population aged 20~65 who have demographic information, pesticide use and data of four lipid metabolism indicators [total cholesterol (TC) , triglyceride (TG) , high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) ] (n=3039) . The subjects were divided into insecticide group (320 people) and non insecticide group (2719) according to the use of insecticides, and herbicide group (156 people) and non herbicide group according to the use of herbicides. Results: Among the 3039 subjects, the males and female were 1509 (49.7%) and 1530 (50.3%) respectively. The males age was (39.7±12.0) years and the females age was (40.2±12.0) years The concentration of HDLC in the NHANES (55.4±15.0) mg/dl was lower than that of (58.2±14.2) mg/dL in the non herbicide group (P<0.05) (b=-0.044, P<0.05) . The results showed that the use of herbicides was related to the decrease of HDLC and the increase of LDLC and LDLC/HDLC in female population (b=-0.050, 0.062, 0.067, all P<0.05) . Conclusion: Herbicide exposure can cause the change of lipid metabolism, and the effect on female population is more obvious.
Adult ; Cholesterol, HDL ; Cholesterol, LDL ; Female ; Humans ; Lipid Metabolism ; Male ; Middle Aged ; Nutrition Surveys ; Pesticides ; Young Adult

Work-related musculoskeletal disorders (WMSDs) refer to musculoskeletal disorders caused by work or work as the main cause, which are characterized by high prevalence and heavy burden of disease as a global problem. The classification and catalog of occupational diseases is of great significance for guiding the prevention and control of occupational diseases and safeguarding the rights and interests of workers. The types of WMSDs included in the list of occupational diseases vary greatly from country to country, and the regulations on specific pathogenic factors are also inconsistent. By sorting out and analyzing the lists and characteristics of WMSDs at home and abroad, and using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) in occupational health to standardize of WMSDs in various countries, which would lay the foundation for future multi-country WMSDs occupational health registration and disease burden research, and provide a reference for China to revise the WMSDs list.
Humans ; Musculoskeletal Diseases/prevention & control* ; Occupational Diseases/prevention & control* ; Prevalence ; Risk Factors ; Surveys and Questionnaires

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

E3 ubiquitin ligase TRIM21(tripartite motif containing 21) plays an important role in regulating cell biological functions and clinical prognosis as oncogene or tumor suppressor in different types of tumors. However,the biological functions and molecular mechanism of TRIM21 in hypopharyngeal squamous cell carcinoma (HPSCC) are still unclear.Our results showed that TRIM21 is highly expressed in moderately and well differentiated HPSCC, suggesting the role of TRIM21 in tumor differentiation. Overexpression and knockdown of TRIM21 inhibited or promoted cell proliferation and migration. Meanwhile, the expression of differentiation markers including KRT10 (keratin 10), IVL (involucrin) and TGM1 (transglutaminase 1) were increased and decreased upon TRIM21 overexpression or knockdown, respectively. The bioinformatics analysis of TRIM21 interacting protein identified by co-immunoprecipitation combined with mass spectrometry suggested that TRIM21 may be closely related to the regulation of cytoskeleton protein. We further demonstrated that TRIM21 interacted with KRT10. The inhibition of protein synthesis by cycloheximide led to upregulation of KRT10 in TRIM21 overexpressing FaDu cells, and ectopic expression of TRIM21 enhanced the ubiquitination level of KRT10. In summary, our results suggest that TRIM21 may promote the HPSCC differentiation by mediating ubiquitination of cytoskeleton proteins to improve the protein stability.

Objective: To confirm the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on perioperative and long-term outcome in patients with Stanford type A aortic dissection. Methods: From June 2010 to July 2017, the clinical data of 91 patients with Stanford type A aortic dissection were analyzed. Among them, 51 patients with OSAHS were included in the study group and 40 patients without OSAHS were included in the control group. After 36 months follow-up, all-cause death was regarded as the end event. The clinical baseline data, perioperative period and 36 months survival rate of the two groups were compared. Kanplan-Meier method was used to describe the 36 month survival curve of the two groups. Cox proportional risk model was used to evaluate the risk ratio (HR) and 95%CI of 36 month survival rate. Results: The mortality rate during hospitalization was 5.9% (3 cases) in the study group and 5.0% (2 cases) in the control group, and the difference was not statistically significant (χ~2=0.03, P>0.05). The actual follow-up was (36.2±1.5) months, 88 cases were followed up and 3 cases were lost. The all cause mortality rate of 36 months was 27.5% (14/51)in the study group and 10.0%(4/40) in the control group, the difference was statistically significant (χ~2=4.30, P<0.05).By Cox proportional risk model analysis, 36 months after operation, the study group was compared with the control group after adjusting for age, male, bicuspid of aortic valve, chronic obstructive pulmonary disease, anemia, preoperative pericardial tamponade, postoperative organ dysfunction, preoperative LVEF, emergency operation, Sun's operation, coronary artery bypass grafting, hypertension, cardiac arrhythmia, and advanced avulsion of distal aortic dissection The survival rate was lower, the difference was statistically significant (P<0.05).In addition to OSAHS, coronary artery bypass grafting and preoperative pericardial tamponade were also risk factors for the increase of 36 month mortality rate (HR=11.28,95%CI: 1.98-46.25, P=0.009; HR=9.08, 95%CI: 2.22-41.3, P=0.032). Conclusions: There was no significant difference in mortality during hospitalization in patients with Stanford A aortic dissection combined with OSAHS. The survival rate of 36 months after operation was lower than that of the control group.
Aneurysm, Dissecting/surgery* ; Humans ; Hypertension ; Male ; Postoperative Period ; Risk Factors ; Sleep Apnea, Obstructive