OBJECTIVE: To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists. METHODS: By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements. RESULTS: The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development. CONCLUSION Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans ; China ; Surveys and Questionnaires ; Genetic Diseases, Inborn/genetics* ; Cross-Sectional Studies ; Genetics, Medical/education* ; Genetic Testing

Objective:To evaluate the efficacy and safety of transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for erythematotelangiectatic rosacea (ETR).Methods:This was a randomized controlled trial conducted from March to October 2024. At Sichuan Provincial People′s Hospital, 60 patients with newly diagnosed ETR were prospectively enrolled and randomized by a random number table into study group [ n=30; 6 male and 24 female; aged 18-60 (38.9±9.8) years] and control group [ n=30; 4 male and 26 female; aged 18-60 (35.7±10.1) years]. The study group received transdermal delivery of compound glycyrrhizin injection by a medium-frequency drug-delivery therapeutic apparatus together with oral azithromycin and hydroxychloroquine sulfate, whereas the control group received oral azithromycin and hydroxychloroquine sulfate. The efficacy evaluations were conducted at baseline and at weeks 2, 4, 6, and 8 post-treatment. Outcome measures included percentage of erythema area, stratum corneum hydration, transepidermal water loss (TEWL), clinician′s erythema assessment (CEA), erythema and telangiectasia scores, dermatology life quality index (DLQI), and efficacy rate. Adverse reactions during treatment were also recorded. Results:Compared with baseline, both groups exhibited significant reductions in percentage of erythema area, TEWL, CEA, erythema and telangiectasia score, and DLQI, and significant increases in stratum corneum hydration at each post-treatment time point (all P<0.05). After 2, 4, 6, and 8 weeks of treatment, the percentage of erythema area, erythema and telangiectasia scores in the study group were all lower than those in the control group, while the stratum corneum hydration level in the study group was higher than that in the control group (all P<0.05). After 4, 6, and 8 weeks of treatment, TEWL, CEA, and DLQI in the study group were all lower than those in the control group (all P<0.05). After 4 weeks of treatment, the efficacy rate in the study group was 56.7% (17/30), which was higher than that of the control group at 23.3% (7/30, P=0.046). After 6 weeks of treatment, the efficacy rate in the study group was 83.3% (25/30), higher than that of the control group at 50.0% (15/30, P=0.020). After 8 weeks of treatment, the efficacy rate in the study group was 86.7% (26/30), higher than that of the control group at 66.7% (20/30, P<0.001). No severe adverse reactions were observed in either group. Conclusion:Transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for ETR demonstrates favorable efficacy and good safety.

Objective:To analyze the composition and diversity characteristics of facial microbial communities in patients with moderate acne.Methods:This prospective study enrolled 30 patients with moderate acne [12 males, 18 females; aged 21-30 (25.4±2.5) years] from the Department of Dermatology, Sichuan Provincial People′s Hospital from March to July 2021. Thirty healthy controls [13 males, 17 females; aged 24-29 (25.2±1.4) years] were included during the same period. Facial skin swabs were collected from both groups. Total DNA was extracted, followed by PCR amplification, library preparation, and PE250 sequencing. After splicing, filtering, denoising, and chimera removal, amplicon sequence variants (ASV) feature tables and representative sequences were generated to compare microbial community differences between the two groups.Results:A total of 60 samples were sequenced, yielding 2 021 342 valid sequences. The 16S rRNA gene sequences were clustered into 8 379 ASV, with 589 ASV shared between the two groups, while 6 445 ASV were uniquely identified in healthy controls. At the phylum level, both groups showed similar dominant phyla: Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. At the genus level, the acne group was predominantly colonized by Ralstonia (relative abundance 31.85%) and Staphylococcus (28.04%), while healthy controls exhibited more balanced distributions, primarily Staphylococcus (9.18%) and Enhydrobacter (7.37%). Alpha diversity analysis, Beta diversity analysis, and LefSe analysis revealed statistically significant differences in microbial communities between groups ( R2=0.157, P<0.001). The acne group showed lower microbial richness and evenness compared to healthy controls (both P<0.001). Conclusion:Patients with moderate acne exhibit microecological imbalance in facial microbial communities, characterized by reduced microbial richness and evenness.

Objective:To evaluate the efficacy and safety of transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for erythematotelangiectatic rosacea (ETR).Methods:This was a randomized controlled trial conducted from March to October 2024. At Sichuan Provincial People′s Hospital, 60 patients with newly diagnosed ETR were prospectively enrolled and randomized by a random number table into study group [ n=30; 6 male and 24 female; aged 18-60 (38.9±9.8) years] and control group [ n=30; 4 male and 26 female; aged 18-60 (35.7±10.1) years]. The study group received transdermal delivery of compound glycyrrhizin injection by a medium-frequency drug-delivery therapeutic apparatus together with oral azithromycin and hydroxychloroquine sulfate, whereas the control group received oral azithromycin and hydroxychloroquine sulfate. The efficacy evaluations were conducted at baseline and at weeks 2, 4, 6, and 8 post-treatment. Outcome measures included percentage of erythema area, stratum corneum hydration, transepidermal water loss (TEWL), clinician′s erythema assessment (CEA), erythema and telangiectasia scores, dermatology life quality index (DLQI), and efficacy rate. Adverse reactions during treatment were also recorded. Results:Compared with baseline, both groups exhibited significant reductions in percentage of erythema area, TEWL, CEA, erythema and telangiectasia score, and DLQI, and significant increases in stratum corneum hydration at each post-treatment time point (all P<0.05). After 2, 4, 6, and 8 weeks of treatment, the percentage of erythema area, erythema and telangiectasia scores in the study group were all lower than those in the control group, while the stratum corneum hydration level in the study group was higher than that in the control group (all P<0.05). After 4, 6, and 8 weeks of treatment, TEWL, CEA, and DLQI in the study group were all lower than those in the control group (all P<0.05). After 4 weeks of treatment, the efficacy rate in the study group was 56.7% (17/30), which was higher than that of the control group at 23.3% (7/30, P=0.046). After 6 weeks of treatment, the efficacy rate in the study group was 83.3% (25/30), higher than that of the control group at 50.0% (15/30, P=0.020). After 8 weeks of treatment, the efficacy rate in the study group was 86.7% (26/30), higher than that of the control group at 66.7% (20/30, P<0.001). No severe adverse reactions were observed in either group. Conclusion:Transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for ETR demonstrates favorable efficacy and good safety.

Objective:To analyze the composition and diversity characteristics of facial microbial communities in patients with moderate acne.Methods:This prospective study enrolled 30 patients with moderate acne [12 males, 18 females; aged 21-30 (25.4±2.5) years] from the Department of Dermatology, Sichuan Provincial People′s Hospital from March to July 2021. Thirty healthy controls [13 males, 17 females; aged 24-29 (25.2±1.4) years] were included during the same period. Facial skin swabs were collected from both groups. Total DNA was extracted, followed by PCR amplification, library preparation, and PE250 sequencing. After splicing, filtering, denoising, and chimera removal, amplicon sequence variants (ASV) feature tables and representative sequences were generated to compare microbial community differences between the two groups.Results:A total of 60 samples were sequenced, yielding 2 021 342 valid sequences. The 16S rRNA gene sequences were clustered into 8 379 ASV, with 589 ASV shared between the two groups, while 6 445 ASV were uniquely identified in healthy controls. At the phylum level, both groups showed similar dominant phyla: Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. At the genus level, the acne group was predominantly colonized by Ralstonia (relative abundance 31.85%) and Staphylococcus (28.04%), while healthy controls exhibited more balanced distributions, primarily Staphylococcus (9.18%) and Enhydrobacter (7.37%). Alpha diversity analysis, Beta diversity analysis, and LefSe analysis revealed statistically significant differences in microbial communities between groups ( R2=0.157, P<0.001). The acne group showed lower microbial richness and evenness compared to healthy controls (both P<0.001). Conclusion:Patients with moderate acne exhibit microecological imbalance in facial microbial communities, characterized by reduced microbial richness and evenness.

Objective:To investigate the expression levels of serum KLK5, IL-17 and IL-18 in patients with rosacea and their clinical significance.Methods:A prospective study included 65 patients with rosacea from the Department of Dermatology, Sichuan Provincial People＇s Hospital, from May to October 2022. There were 8 males and 57 females with an average age of (30.9±9.8) years, including 47 cases of erythematotelangiectatic type and 18 cases of papulopustular type. Twenty healthy individuals from the same hospital＇s physical examination during the same period were included as control group, consisting of 3 males and 17 females with an average age of (33.8±10.0) years. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum KLK5, IL-17, and IL-18. Investigator＇s global assessment (IGA) score was used to assess the severity of papules and pustules, and clinical erythema assessment (CEA) score was used to assess the severity of persistent erythema. The expression levels of serum KLK5, IL-17, and IL-18 were compared between the two groups, and the correlation between the severity of the disease and the expression levels of KLK5, IL-17, and IL-18 was analyzed. Additionally, the expression levels of KLK5, IL-17, and IL-18 in different subtypes of rosacea were compared.Results:The expression levels of serum KLK5, IL-17, and IL-18 in the rosacea group were (3134.01±448.82), (154.78±37.64), (236.24±38.81) pg/ml, respectively, all of which were higher than those in the healthy control group (2421.54±340.07), (95.36±24.94), (181.61±23.88) pg/ml, with statistically significant differences (all P<0.05). The levels of serum KLK5, IL-17, and IL-18 in patients with rosacea were positively correlated with IGA scores ( r=0.534, 0.767, 0.417) and CEA scores ( r=0.852, 0.459, 0.309) (all P<0.05). There were no statistically significant differences in the expression levels of serum KLK5, IL-17, and IL-18 between the erythematotelangiectatic and papulopustular subtypes of rosacea (all P>0.05). Conclusions:The expression levels of serum KLK5, IL-17 and IL-18 in patients with rosacea are higher than those in the healthy control group and are positively correlated with the severity of rosacea.

Objective: To investigate the effects of long-term hyperglycemia on renal pathology of type 1 diabetic mellitus(T1DM) cynomolgus monkeys by establishing streptozotocin(STZ)-induced T1DM. Methods: Eight 4-year-old male cynomolgus monkeys were randomly divided into control and model groups. Four cynomolgus monkeys were used in the control group, and four cynomolgus monkeys were injected with streptozotocin to create a T1DM model. Hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining were used to observe renal pathological changes.The histological characteristics and changes were observed under transmission electron microscope. Morphometric measurements were used to analyze the glomerular area, the thickness of the glomerular basement membrane, the proportion of glomerular podocyte foot processes and the average area of foot processes. Results: In comparison to the control group, the model group showed pathological changes in the kidneys, including increased glomerular area(P<0.01), thickened basement membrane, capillary loop compression, disordered arrangement of endothelial cell fenestrations, proliferation of mesangial cells, mesangial expansion, accumulation of mesangial matrix glycoproteins, a decrease in the number of foot processes(P<0.001), a decrease in the average size of the foot processes(P<0.05), widened podocyte slit diaphragm, and an increase in the number of fused foot processes(P<0.001). Conclusion Cynomolgus monkeys with T1DM suffer from renal pathological changes due to long-term hyperglycemia.

Objective:Childhood traumatic experiences greatly influenced the brain network activities of patients with depression,and there is an urgent need to explore the temporal dynamics for these changes.This study aims to investigate the abnormalities of resting-state electroencephalogram(EEG)microstates in eye-open state of depressed adolescents and to explore the correlations between their EEG microstates and the childhood traumatic experience. Methods:Using resting-state EEG microstate analysis,we explored the temporal dynamics of brain activity in patients with adolescent depression.This study selected 66 adolescents with depression as a patient group,and 27 healthy adolescents as a healthy control group.A modified k-means clustering algorithm was used to classify the 64-channel resting-state EEG data into different microstates.Independent sample t-tests were used to compare the microstate parameters between the 2 groups and further assciations between these parameters and childhood traumatic experience in patients were explored via using Spearman correlation. Results:In this study,significant differences were observed in the occurrence and transition probabilities of EEG microstates between the healthy control and the patient group.Notably,there was a statistically significant difference(P＜0.05)in the occurrence of microstate A across 2 groups,exhibiting a negative correlation with the emotional abuse component within the childhood trauma scores(Spearman's rho=-0.31,P=0.013).Furthermore,patient-specific,non-random transitions from microstate B to A(Spearman's rho=-0.30,P=0.015)and C to A(Spearman's rho=-0.31,P=0.013)were inversely associated with the scores of emotional abuse factors from childhood trauma in the patient group,showing statistically significant differences when comparing to the healthy controls(P＜0.05).Upon stratification into quartiles based on the emotional abuse factor scores,the occurrence of microstate A,as well as the transition rates from microstates B to A and C to A,retained statistical significance following adjustment for multiple comparisons(all P＜0.05). Conclusion:The abnormal temporal dynamics in brain networks of adolescents with depression are linked to childhood emotional abuse.Those who have suffered severe emotional abuse may show greater impairments in the brain's visual and central executive networks.EEG microstate analysis could be a potential tool for detecting adolescent depression with severe childhood trauma.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects.This study aimed to explore its radio-sensitizing effects and the underlying mechanisms.Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis.Bioinformatic molecular docking prediction and following validation by surface plasmon resonance(SPR)technology,cellular thermal shift assay(CETSA),and isothermal titration calorimetry(ITC)were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha(HSP90α).The effects of ginsenoside Rg5 on HSP90-cell division cycle 37(CDC37)interaction,the client protein stability,and the downstream regulations were further explored.Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis.It could bind to HSP90α with a high affinity,but the affinity was drastically decreased by HSP90α Y61A mutation.Co-immunoprecipitation(Co-IP)and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner.It reduced irradiation-induced upre-gulation of the HSP90-CDC37 client proteins,including SRC,CDK4,RAF1,and ULK1 in A549 cell-derived xenograft(CDX)tumors.Ginsenoside Rg5 or MRT67307(an IKKe/TBK1 inhibitor)pretreatment suppressed irradiation-induced elevation of the LC3-Ⅱ/β ratio and restored irradiation-induced downregulation of p62 expression.In A549 CDX tumors,ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage.In conclusion,ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma.It interacts with HSP90α and reduces the binding between HSP90 and CDC37,thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.